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Fibromyalgia and Risk of Dementia-A Nationwide, Population-Based, Cohort Study
Abstract
Background
Fibromyalgia is a syndrome of chronic pain and other symptoms, which has been associated with patient discomfort and other diseases. This nationwide matched cohort population-based study aimed to investigate the association between fibromyalgia and the risk of developing dementia, and to clarify the association between fibromyalgia and dementia.
Materials and Methods
A total of 41,612 patients of age ≧50 with newly diagnosed fibromyalgia, between January 1, and December 31, 2000, were selected from the National Health Insurance Research Database of Taiwan, along with 124,836 controls matched for sex and age. After adjusting for any confounding factors, Fine and Gray′s competing risk analysis was used to compare the risk of developing dementia during the 10 years of follow-up.
Results
Of the study subjects, 1,704 from 41,612 (21.23 per 1000 person-years) developed dementia when compared to 4,419 from 124,836 (18.94 per 1000 person-years) of the controls. Fine and Gray′s competing risk analysis revealed that the study subjects were more likely to develop dementia (hazard ratio [HR]: 2.29, 95% CI =2.16–2.42, p < .001). After adjusting for gender, age, monthly income, urbanization level, geographic region of residence, and comorbidities, the HR was 2.77 (95% CI: 2.61–2.95, p < .001). Fibromyalgia was associated with increased risk of all types of dementia in this study.
Conclusions
The study subjects with fibromyalgia had a 2.77-fold risk of dementia than the control group. Therefore, further studies are needed to elucidate the underlying mechanisms of the association between fibromyalgia and the risk of dementia.
... The included studies in this meta-analysis were conducted across eight countries: the United States (Wang et al. 2022;Wang and Liu 2021;Khalid et al. 2022Khalid et al. , 2020George et al. 2020), China (Tzeng et al. 2018;Cheng et al. 2022;Kao et al. 2021;Chen et al. 2018;Huang et al. 2015), France (Rouch et al. 2022), the United Kingdom (Kostov et al. 2019), Korea (Kao et al. 2021;Lee et al. 2019), Norway (Hagen et al. 2014), Canada (Morton et al. 2019), and Denmark (Islamoska et al. 2020). All of these studies were population-based and involved a total of 842,806 subjects, including 132,445 patients with chronic pain. ...
... Among the included studies, one was cross-sectional (Wang et al. 2022) and two were case-control designs (Lee et al. 2019;Chen et al. 2018), while the remaining 16 studies were cohort studies. Eighteen studies examined the risk of developing dementia after a diagnosis of chronic pain (Wang and Liu 2021;Khalid et al. 2022Khalid et al. , 2020Rouch et al. 2022;Tzeng et al. 2018;Cheng et al. 2022;Kao et al. 2021;Hurh et al. 2022;Morton et al. 2019;Hagen et al. 2014;Islamoska et al. 2020;George et al. 2020;Lee et al. 2019;Kostov et al. 2019;Chen et al. 2018;Huang et al. 2015), and one study explored the comorbidity of dementia in patients with chronic pain (Wang et al. 2022). ...
... However, due to the nature of cross-sectional study design, it is difficult to (Wang et al. 2022). Furthermore, a majority of the studies included in our analysis indicated that the risk of dementia increased as the age of individuals with chronic pain advanced (Wang and Liu 2021;Khalid et al. 2022Khalid et al. , 2020Rouch et al. 2022;Tzeng et al. 2018;Cheng et al. 2022;Kao et al. 2021;Hurh et al. 2022;Morton et al. 2019;Hagen et al. 2014;Islamoska et al. 2020;George et al. 2020;Lee et al. 2019;Kostov et al. 2019;Chen et al. 2018;Huang et al. 2015). This suggests that older age may be a contributing factor to the development of dementia in individuals with chronic pain. ...
Purpose
Dementia and chronic pain (CP) are prevalent among older adults. However, no study has systematically reviewed the association between dementia and CP. Therefore, we performed this study to gather evidence about the potential relationship between the two.
Methods
Two authors independently searched PubMed, Embase, and Web of Science to identify all records published up to 1 September 2022 that explored the association between CP and dementia. The methodological quality of the studies was assessed using the Newcastle Ottawa Scale (NOS). A fixed or random-effects model was used to pool the risk estimates.
Results
Among the initial 3296 articles retrieved, 19 were included in the review (1 cross-sectional, and 18 cohort). The pooled result showed the risk of dementia was 1.42 times higher in CP patients (HR = 1.42, 95% CI 1.23–1.64, P < 0.001). dementia and CP subtypes, gender, and age did not significantly affect the results.
Conclusion
Our study shows that people who suffered from CP are at an increased risk of developing dementia, regardless of gender, age, and dementia and CP subtypes.
... The extant studies suggest a positive association between different types of chronic pain and incident ADRDs (Ezzati et al., 2019;Innes & Sambamoorthi, 2020a;James & Ferguson, 2019;Khalid et al., 2020;Sangha et al., 2020;Tzeng et al., 2018;Yamada et al., 2019), although studies varied widely in pain sites (e.g., back or knee) and types, study population (mainly focus on aged 65 and older), and length of follow-up (range from 2 to 16.5 years) (Innes & Sambamoorthi, 2020b). Even though the majority of these studies exclude pre-existing cognitive impairment or dementia to prevent the reverse causality, it does not eliminate other potential selection biases such as the predisposing factors of chronic pain being related to the development of ADRDs, which may distort the primary association. ...
... Chronic non-cancer pain. In this study, CNCP included general chronic pain (James & Ferguson, 2019), back pain (Yamada et al., 2019), fibromyalgia (Tzeng et al., 2018), osteoarthritis (Innes & Sambamoorthi, 2020a), arthritis/joint pain (Yamada et al., 2019), and rheumatoid arthritis (Sangha et al., 2020), which have been shown to be associated with cognitive impairment or certain subtypes of dementia. Appendix Table S1 shows the ICD-9-CM and ICD-10-CM diagnosis codes of CNCP. ...
... The main result shows that newly diagnosed CNCP patients aged 50 or older had a higher risk of developing MCI/ADRDs, compared to non-CNCP patients of the same age group, after adjusting for other comorbidities that are known to be related to MCI/ADRDs. In agreement with previously published longitudinal studies (Cao et al., 2019;Ezzati et al., 2019;Innes & Sambamoorthi, 2020a;Khalid et al., 2020;Tzeng et al., 2018), our findings based on newly diagnosed CNCP patients provide empirical evidence that CNCP is indeed a risk factor for incident ADRDs. While previous studies provide inconsistent evidence on the association of CNCP to cognitive decline based on cognitive battery tests (Leeuw et al., 2018;Veronese et al., 2018;Whitlock et al., 2017), our findings indicate that CNCP patients have a greater risk of developing MCI. ...
The goal of this study is to investigate the association between chronic non-cancer pain (CNCP) and mild cognitive impairment (MCI)/Alzheimer’s disease and related dementias (ADRDs) development among adults aged ≥50 using administrative claims data from a national commercial health insurance company during 2007–2017. To reduce selection bias, propensity-score matching was applied to select comparable CNCP and non-CNCP patients. Time-dependent Cox proportional-hazards regressions were conducted to estimate the hazard ratios (HRs) of incident MCI/ADRDs. Of 170,900 patients with/without CNCP, 0.61% developed MCI and 2.33% had been diagnosed with ADRDs during the follow-up period. Controlling for potential confounders, CNCP patients had a 123% increase in MCI risk (HR = 2.23; 95% CI = 1.92–2.58) and a 44% increase in ADRDs risk (HR = 1.44; 95% CI = 1.34–1.54) relative to non-CNCP patients. CNCP is a risk factor for MCI/ADRDs. Promoting awareness and improving early CNCP diagnosis in middle-aged and older adults should be incorporated into cognitive impairment and dementia prevention.
... A growing body of evidence from experimental (Moriarty et al., 2011;Cao et al., 2019) and cross-sectional (Van Der Leeuw et al., 2015;Ikram et al., 2019) studies suggests significant neurocognitive impairment, including deterioration in attention, memory, and executive function with chronic pain and certain NCPCs, as well as adverse neurostructural and neurofunctional changes paralleling those implicated in ADRD pathogenesis (Ng et al., 2018;Cao et al., 2019). Longitudinal studies from North America (Whitlock et al., 2017;van der Leeuw et al., 2018;Ezzati et al., 2019;Khalid et al., 2020), Europe (Veronese et al., 2018), and East Asia (Yang et al., 2016;Tzeng et al., 2018;Yamada et al., 2019) also suggest significant associations of chronic pain and certain NCPCs to subsequent deterioration in memory (Whitlock et al., 2017;van der Leeuw et al., 2018), accelerated cognitive decline (Whitlock et al., 2017), new onset cognitive impairment (Whitlock et al., 2017;van der Leeuw et al., 2018), and incident ADRD (Ezzati et al., 2019;Khalid et al., 2020). ...
... Although longitudinal investigations of rural, disadvantaged populations are lacking, our findings from this study of Appalachian adults are also in broad agreement with those from other previously published observational studies examining the association of chronic pain and/or chronic pain conditions to subsequent adverse cognitive outcomes. For example, findings from recent cross-sectional (Van Der Yang et al., 2016;Tzeng et al., 2018;Yamada et al., 2019), Europe (Hagen et al., 2014;Røttereng et al., 2015), and North America (Morton et al., 2019;Khalid et al., 2020) suggest that those with specific chronic pain conditions including fibromyalgia (Tzeng et al., 2018), headache and migraine (Hagen et al., 2014;Yang et al., 2016;Morton et al., 2019), and osteoarthritis/knee (Yamada et al., 2019;) may be at increased risk for incident ADRD. Likewise, studies of chronic pain symptoms in US (Whitlock et al., 2017;van der Leeuw et al., 2018;Ezzati et al., 2019) and British (Veronese et al., 2018) adults have documented associations of persistent pain (Whitlock et al., 2017), severe chronic pain (van der Leeuw et al., 2018;Veronese et al., 2018), and/or reported pain interference (Ezzati et al., 2019) to subsequent deterioration in memory (Whitlock et al., 2017;van der Leeuw et al., 2018), accelerated cognitive decline (Whitlock et al., 2017), new onset cognitive impairment (Whitlock et al., 2017;van der Leeuw et al., 2018), and incident dementia (Whitlock et al., 2017;Ezzati et al., 2019). ...
... Although longitudinal investigations of rural, disadvantaged populations are lacking, our findings from this study of Appalachian adults are also in broad agreement with those from other previously published observational studies examining the association of chronic pain and/or chronic pain conditions to subsequent adverse cognitive outcomes. For example, findings from recent cross-sectional (Van Der Yang et al., 2016;Tzeng et al., 2018;Yamada et al., 2019), Europe (Hagen et al., 2014;Røttereng et al., 2015), and North America (Morton et al., 2019;Khalid et al., 2020) suggest that those with specific chronic pain conditions including fibromyalgia (Tzeng et al., 2018), headache and migraine (Hagen et al., 2014;Yang et al., 2016;Morton et al., 2019), and osteoarthritis/knee (Yamada et al., 2019;) may be at increased risk for incident ADRD. Likewise, studies of chronic pain symptoms in US (Whitlock et al., 2017;van der Leeuw et al., 2018;Ezzati et al., 2019) and British (Veronese et al., 2018) adults have documented associations of persistent pain (Whitlock et al., 2017), severe chronic pain (van der Leeuw et al., 2018;Veronese et al., 2018), and/or reported pain interference (Ezzati et al., 2019) to subsequent deterioration in memory (Whitlock et al., 2017;van der Leeuw et al., 2018), accelerated cognitive decline (Whitlock et al., 2017), new onset cognitive impairment (Whitlock et al., 2017;van der Leeuw et al., 2018), and incident dementia (Whitlock et al., 2017;Ezzati et al., 2019). ...
Background
There is a growing concern regarding the increasing prevalence of common non-cancer chronic pain conditions (NCPCs) and their possible association with Alzheimer’s disease and related dementias (ADRD). However, large population-based studies are limited, especially in Appalachian and other predominantly rural, underserved populations who suffer elevated prevalence of both NCPCs and known ADRD risk factors.
Objectives
We investigated the relation of NCPC to risk of incident ADRD in older Appalachian Medicare beneficiaries and explored the potential mediating effects of mood and sleep disorders.
Methods
Using a retrospective cohort design, we assessed the overall and cumulative association of common diagnosed NCPCs at baseline to incident ADRD in 161,573 elders ≥65 years, Medicare fee-for-service enrollees, 2013–2015. NCPCs and ADRD were ascertained using claims data. Additional competing risk for death analyses accounted for potential survival bias.
Main Findings
Presence of any NCPC at baseline was associated with significantly increased odds for incident ADRD after adjustment for covariates [adjusted odds ratio (AOR) = 1.26 (1.20, 1.32), p < .0001]. The magnitude and strength of this association increased significantly with rising burden of NCPCs at baseline [AOR for ≥4 vs. no NCPC = 1.65 (1.34, 2.03), p-trend = .01]. The addition of depression and anxiety, but not sleep disorders, modestly attenuated these associations [AORs for any NCPC and ≥4 NCPCs, respectively = 1.16 (1.10, 1.22) and 1.39 (1.13, 1.71)], suggesting a partial mediating role of mood impairment. Sensitivity analyses, multinomial logistic regressions accounting for risk of death, yielded comparable findings.
Conclusion
In this large cohort of older Appalachian Medicare beneficiaries, baseline NCPCs showed a strong, positive, dose–response relationship to odds for incident ADRD; this association appeared partially mediated by depression and anxiety. Further longitudinal research in this and other high-risk, rural populations are needed to evaluate the causal relation between NCPC and ADRD.
... After removal of duplicates, a total of 7,176 potentially relevant records were scanned and 97 potentially eligible papers retrieved for full text review ( Fig. 1). After excluding ineligible studies, a total of 16 papers reporting findings from 16 original studies, including two nested matched case-control studies [86,87], 10 retrospective cohort investigations [87][88][89][90][91][92][93][94], and 4 prospective cohort studies [95][96][97][98][99] met our eligibility criteria and were included in the systematic review (Fig. 1). Table 1 provides a brief synopsis, and Table 2, a more comprehensive summary of the longitudinal studies identified for inclusion, detailing the characteristics, outcomes, and ( Table 2) key findings of each study, stratified by chronic pain measure. ...
... Our search identified only one published longitudinal study to date evaluating the association of fibromyalgia (FMS) to cognitive outcomes, a large retrospective cohort study of over 165,000 Taiwanese nationals [88]. In this retrospective cohort study, the authors examined the association of newly diagnosed FMS to incident dementia in a nationally representative sample of adults ≥50 years of age drawn from the LHID (N = 41,614 with, 124,836 without FMS, of whom 6,213 were subsequently diagnosed with incident dementia) (Tables 1 and 2); the follow-up period ranged from 1 to a maximum of 10 years. ...
... Together, findings of studies to date suggest that chronic pain and certain chronic pain conditions may increase risk for the development of ADRD. Of the 10 studies assessing the relation of OA [87,94,100], FMS [88], or headache [89][90][91]95] [91][92][93] to risk for incident ADRD, all have yielded significant positive findings despite variation in study design, population, length of follow-up, and methodology. Specifically, as detailed above, recent large retrospective matched cohort studies in Taiwanese nationals [87,88,90,91,93,100], a retrospective cohort study of U.S. Medicare beneficiaries [94], prospective cohort studies in Norwegian adults [92,95], and a small retrospective cohort investigation of Manitoba residents [89] reported significantly increased risk for incident all cause dementia in those diagnosed with OA [87,94,100], FMS [88], and headache [89][90][91][92][93]95] after adjustment for demographics, comorbidities, and other factors. ...
Background
Growing evidence suggests that chronic pain and certain chronic pain conditions may increase risk for cognitive decline and dementia.
Objective
In this systematic review, we critically evaluate available evidence regarding the association of chronic pain and specific common chronic pain conditions to subsequent decline in cognitive function, new onset cognitive impairment (CI), and incident Alzheimer’s disease and related dementias (ADRD); outline major gaps in the literature; and provide a preliminary conceptual model illustrating potential pathways linking pain to cognitive change.
Methods
To identify qualifying studies, we searched seven scientific databases and scanned bibliographies of identified articles and relevant review papers. Sixteen studies met our inclusion criteria (2 matched case-control, 10 retrospective cohort, 2 prospective cohort), including 11 regarding the association of osteoarthritis (N = 4), fibromyalgia (N = 1), or headache/migraine (N = 6) to incident ADRD (N = 10) and/or its subtypes (N = 6), and 5 investigating the relation of chronic pain symptoms to subsequent cognitive decline (N = 2), CI (N = 1), and/or ADRD (N = 3).
Results
Studies yielded consistent evidence for a positive association of osteoarthritis and migraines/headaches to incident ADRD; however, findings regarding dementia subtypes were mixed. Emerging evidence also suggests chronic pain symptoms may accelerate cognitive decline and increase risk for memory impairment and ADRD, although findings and measures varied considerably across studies.
Conclusion
While existing studies support a link between chronic pain and ADRD risk, conclusions are limited by substantial study heterogeneity, limited investigation of certain pain conditions, and methodological and other concerns characterizing most investigations to date. Additional rigorous, long-term prospective studies are needed to elucidate the effects of chronic pain and specific chronic pain conditions on cognitive decline and conversion to ADRD, and to clarify the influence of potential confounding and mediating factors.
... Although limited at present, there is evidence from longitudinal studies that chronic pain and common non-cancer chronic pain conditions (NCPC) may increase risk for incident cognitive impairment and ADRD [24][25][26][27][28][29][30][31][32][33][34]. For example, recent retrospective cohort investigations of Taiwanese nationals [26,28,29,34] and prospective cohort studies of Japanese and Norwegian elders [25,27,33] have reported significantly increased risk of incident dementia in adults previously diagnosed with fibromyalgia [28], osteoarthritis or knee pain [26,33], and headache [25,27,29,34]. ...
... Although limited at present, there is evidence from longitudinal studies that chronic pain and common non-cancer chronic pain conditions (NCPC) may increase risk for incident cognitive impairment and ADRD [24][25][26][27][28][29][30][31][32][33][34]. For example, recent retrospective cohort investigations of Taiwanese nationals [26,28,29,34] and prospective cohort studies of Japanese and Norwegian elders [25,27,33] have reported significantly increased risk of incident dementia in adults previously diagnosed with fibromyalgia [28], osteoarthritis or knee pain [26,33], and headache [25,27,29,34]. Likewise, findings from a handful of longitudinal studies in US [24,30,32] and British adults [31] suggest that nonspecific chronic pain may predict subsequent deterioration in memory [30,32], accelerated cognitive decline [32], new onset cognitive impairment [32], and incident dementia [24,32], although studies varied widely in design, study population, length of follow-up, and measures. ...
... Although limited at present, there is evidence from longitudinal studies that chronic pain and common non-cancer chronic pain conditions (NCPC) may increase risk for incident cognitive impairment and ADRD [24][25][26][27][28][29][30][31][32][33][34]. For example, recent retrospective cohort investigations of Taiwanese nationals [26,28,29,34] and prospective cohort studies of Japanese and Norwegian elders [25,27,33] have reported significantly increased risk of incident dementia in adults previously diagnosed with fibromyalgia [28], osteoarthritis or knee pain [26,33], and headache [25,27,29,34]. Likewise, findings from a handful of longitudinal studies in US [24,30,32] and British adults [31] suggest that nonspecific chronic pain may predict subsequent deterioration in memory [30,32], accelerated cognitive decline [32], new onset cognitive impairment [32], and incident dementia [24,32], although studies varied widely in design, study population, length of follow-up, and measures. ...
Accumulating evidence suggests that certain chronic pain conditions may increase risk for incident Alzheimer’s disease and related dementias (ADRD). Rigorous longitudinal research remains relatively sparse, and the relation of overall chronic pain condition burden to ADRD risk remains little studied, as has the potential mediating role of sleep and mood disorders. In this retrospective cohort study, we investigated the association of common non-cancer chronic pain conditions (NCPC) at baseline to subsequent risk for incident ADRD, and assessed the potential mediating effects of mood and sleep disorders, using baseline and 2-year follow-up data using 11 pooled cohorts (2001–2013) drawn from the U.S. Medicare Current Beneficiaries Survey (MCBS). The study sample comprised 16,934 community-dwelling adults aged ≥65 and ADRD-free at baseline. NCPC included: headache, osteoarthritis, joint pain, back or neck pain, and neuropathic pain, ascertained using claims data; incident ADRD (N = 1149) was identified using claims and survey data. NCPC at baseline remained associated with incident ADRD after adjustment for sociodemographics, lifestyle characteristics, medical history, medications, and other factors (adjusted odds ratio (AOR) for any vs. no NCPC = 1.21, 95% confidence interval (CI) = 1.04–1.40; p = 0.003); the strength and magnitude of this association rose significantly with increasing number of diagnosed NCPCs (AOR for 4+ vs. 0 conditions = 1.91, CI = 1.31–2.80, p-trend < 0.00001). Inclusion of sleep disorders and/or depression/anxiety modestly reduced these risk estimates. Sensitivity analyses yielded similar findings. NCPC was significantly and positively associated with incident ADRD; this association may be partially mediated by mood and sleep disorders. Additional prospective studies with longer-term follow-up are warranted to confirm and extend our findings.
... After removal of duplicates, a total of 7,176 potentially relevant records were scanned and 97 potentially eligible papers retrieved for full text review ( Fig. 1). After excluding ineligible studies, a total of 16 papers reporting findings from 16 original studies, including two nested matched case-control studies [86,87], 10 retrospective cohort investigations [87][88][89][90][91][92][93][94], and 4 prospective cohort studies [95][96][97][98][99] met our eligibility criteria and were included in the systematic review (Fig. 1). Table 1 provides a brief synopsis, and Table 2, a more comprehensive summary of the longitudinal studies identified for inclusion, detailing the characteristics, outcomes, and ( Table 2) key findings of each study, stratified by chronic pain measure. ...
... Our search identified only one published longitudinal study to date evaluating the association of fibromyalgia (FMS) to cognitive outcomes, a large retrospective cohort study of over 165,000 Taiwanese nationals [88]. In this retrospective cohort study, the authors examined the association of newly diagnosed FMS to incident dementia in a nationally representative sample of adults ≥50 years of age drawn from the LHID (N = 41,614 with, 124,836 without FMS, of whom 6,213 were subsequently diagnosed with incident dementia) (Tables 1 and 2); the follow-up period ranged from 1 to a maximum of 10 years. ...
... Together, findings of studies to date suggest that chronic pain and certain chronic pain conditions may increase risk for the development of ADRD. Of the 10 studies assessing the relation of OA [87,94,100], FMS [88], or headache [89][90][91]95] [91][92][93] to risk for incident ADRD, all have yielded significant positive findings despite variation in study design, population, length of follow-up, and methodology. Specifically, as detailed above, recent large retrospective matched cohort studies in Taiwanese nationals [87,88,90,91,93,100], a retrospective cohort study of U.S. Medicare beneficiaries [94], prospective cohort studies in Norwegian adults [92,95], and a small retrospective cohort investigation of Manitoba residents [89] reported significantly increased risk for incident all cause dementia in those diagnosed with OA [87,94,100], FMS [88], and headache [89][90][91][92][93]95] after adjustment for demographics, comorbidities, and other factors. ...
Thesis (Ph.D.)--Cornell University, January, 1992. Includes bibliographical references.
... To the best of our knowledge, this is the first study to examine the associations between the number of chronic pain sites and the risk of all-cause dementia and its subtypes. The findings of this study that greater number of chronic pain sites was associated with a higher risk of allcause dementia in part agree with previous longitudinal studies showing an increased risk of dementia in individuals with chronic pain or pain conditions [18][19][20]37], although these studies did not assess the number of painful sites as in the current study. Two recent retrospective US cohort studies found an increased risk of AD and related dementias in individuals with non-cancer chronic pain conditions compared to those without pain conditions during 2 years of follow-up [18,19]. ...
... In a study with a median follow-up of 8.6 years, Whitlock et al. showed that persistent pain was associated with accelerated memory decline and increased probability of dementia [15]. Tzeng et al. also reported that fibromyalgia, a widespread musculoskeletal pain disorder, had a 2.77-fold increased risk of all-cause dementia than the age-and sex-matched control group in a study with 10 years of follow-up [37]. Similarly, analyses of the Framingham Heart Study estimated a 43% increase in all-cause dementia risk in people with widespread pain over a median follow-up of 10 years [20]. ...
Background
Chronic musculoskeletal pain has been linked to dementia; however, chronic pain typically occurs in multiple sites; therefore, this study was to investigate whether greater number of chronic pain sites is associated with a higher risk of dementia and its subtypes.
Methods
Participants (N = 356,383) in the UK Biobank who were dementia-free at baseline were included. Pain in the hip, knee, back, and neck/shoulder or ‘all over the body’ and its duration were assessed. Participants were categorised into six groups: no chronic pain; chronic pain in 1, 2, 3, and 4 sites, and ‘all over the body’. All-cause dementia and its subtypes were ascertained using hospital inpatient and death registry records. Cox regression was used to investigate the associations between the number of chronic pain sites and the incidence of all-cause dementia and its subtypes.
Results
Over a median follow-up of 13 years, 4959 participants developed dementia. After adjustment for sociodemographic, lifestyle, comorbidities, pain medications, psychological problems, and sleep factors, greater number of chronic pain sites was associated with an increased risk of incident all-cause dementia (hazard ratio [HR] = 1.08 per 1 site increase, 95% CI 1.05–1.11) and Alzheimer’s disease (AD) (HR = 1.09 per 1-site increase, 95% CI 1.04–1.13) in a dose–response manner but not vascular and frontotemporal dementia. No significant association was found between the number of chronic pain sites and the risk of incident all-cause dementia among a subsample that underwent a fluid intelligence test.
Conclusions
Greater number of chronic pain sites was associated with an increased risk of incident all-cause dementia and AD, suggesting that chronic pain in multiple sites may contribute to individuals’ dementia risk and is an underestimated risk factor for dementia.
... even after adjustment for confounding and intervening variables [105]. Other conditions, such as fibromyalgia and irritable bowel syndrome (IBS), have also been suggested as possible risk factors for AD [106,107]. The tolerance time in the cold pressor test (4 °C) was lower in patients with AD dementia than in controls [108]. ...
... even after adjustment for confounding and intervening variables [105]. Other conditions, such as fibromyalgia and irritable bowel syndrome (IBS), have also been suggested as possible risk factors for AD [106,107]. The tolerance time in the cold pressor test (4 • C) was lower in patients with AD dementia than in controls [108]. ...
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease worldwide, but therapeutic strategies to slow down AD pathology and symptoms have not yet been successful. While attention has been focused on neurodegeneration in AD pathogenesis, recent decades have provided evidence of the importance of microglia, and resident immune cells in the central nervous system. In addition, new technologies, including single-cell RNA sequencing, have revealed heterogeneous cell states of microglia in AD. In this review, we systematically summarize the microglial response to amyloid-β and tau tangles, and the risk factor genes expressed in microglia. Furthermore, we discuss the characteristics of protective microglia that appear during AD pathology and the relationship between AD and microglia-induced inflammation during chronic pain. Understanding the diverse roles of microglia will help identify new therapeutic strategies for AD.
... Associations of pain or painful chronic conditions with cognitive decline [5,[20][21][22]28,29] and dementia have been documented in several studies [9,15,27,33,36,37,39]; however few studies have examined the temporal nature of this association and the evidence is inconsistent. Most aforementioned studies were conducted amongst older populations and had less than five year mean follow-up. ...
... Pain [9] and chronic painful conditions such as fibromyalgia [27], osteoarthritis [36], head ache [33] have been found to be associated with risk of dementia. Few studies examine both the associations of pain intensity and pain interference, one such study with a four year mean follow-up found pain interference rather than intensity to be associated with dementia [9]. ...
This study examines the importance of length of follow-up on the association between pain and incident dementia. Further objective was to characterize pain trajectories in the 27 years preceding dementia diagnosis and compare them to those among persons free of dementia during the same period. Pain intensity and pain interference (averaged as total pain) were measured on 9 occasions (1991-2016) using the Short-Form 36 Questionnaire amongst 9046 (women=31.4%) dementia-free adults aged 40-64 years in 1991; 567 dementia cases were recorded between 1991-2019. Cox regression were used to assess the association between pain measures at different time points and incident dementia and mixed models to assess pain trajectories preceding dementia diagnosis or end point for dementia-free participants. Results from Cox regression showed moderate/severe compared to mild/no total pain, pain intensity, and pain interference not to be associated with dementia when the mean follow-up was 25.0, 19.6, 14.5, or 10.0 years. These associations were evident for a mean follow-up of 6.2 years: for total pain (hazard ratio=1.72; 95% confidence intervals=1.28-2.33), pain intensity (1.41; 1.04-1.92), and pain interference (1.80; 1.30-2.49). These associations were stronger when the mean follow-up for incidence of dementia was 3.2 years. 27-year pain trajectories differed between dementia cases and non-cases with small differences in total pain and pain interference evident 16 years before dementia diagnosis (difference in total pain score=1.4, 95% confidence intervals=0.1-2.7) and rapidly increasing closer to diagnosis. In conclusion, these findings suggest that pain is a correlate or prodromal symptom rather than a cause of dementia.
... Similarly, our findings parallel those of a growing number of epidemiological studies suggesting certain chronic pain conditions, as well as nonspecific chronic pain symptoms may increase ADRD risk. Notably, recent large retrospective cohort studies in Taiwanese nationals [45][46][47][48] and prospective cohort studies Norwegian adults [49,50] reported significantly increased risk for incident dementia in those diagnosed with fibromyalgia [45] and headache [46][47][48][49][50] after adjustment for demographics, comorbidities, and other factors. While longitudinal studies examining the relation of chronic pain symptoms to adverse cognitive outcomes remain few, and studies, all in U.S. [51][52][53] and British [54] adults, have varied widely in design, study population, measures, length of follow-up, and other factors, overall findings likewise suggest that persistent pain [51], severe chronic pain [53,54], and/or reported pain interference [55] may predict subsequent deterioration in memory [53,54], accelerated cognitive decline [51], and dementia [51,55]. ...
... Similarly, our findings parallel those of a growing number of epidemiological studies suggesting certain chronic pain conditions, as well as nonspecific chronic pain symptoms may increase ADRD risk. Notably, recent large retrospective cohort studies in Taiwanese nationals [45][46][47][48] and prospective cohort studies Norwegian adults [49,50] reported significantly increased risk for incident dementia in those diagnosed with fibromyalgia [45] and headache [46][47][48][49][50] after adjustment for demographics, comorbidities, and other factors. While longitudinal studies examining the relation of chronic pain symptoms to adverse cognitive outcomes remain few, and studies, all in U.S. [51][52][53] and British [54] adults, have varied widely in design, study population, measures, length of follow-up, and other factors, overall findings likewise suggest that persistent pain [51], severe chronic pain [53,54], and/or reported pain interference [55] may predict subsequent deterioration in memory [53,54], accelerated cognitive decline [51], and dementia [51,55]. ...
Background
Emerging evidence suggests osteoarthritis (OA) and related symptom burden may increase risk for Alzheimer’s disease and related dementias (ADRD). However, longitudinal studies are sparse, and none have examined the potential mediating effects of mood or sleep disorders.
Objective
To determine the association of OA and related pain to incident ADRD in U.S. elders.
Methods
In this retrospective cohort study, we used baseline and two-year follow-up data from linked Medicare claims and Medicare Current Beneficiary Survey files (11 pooled cohorts, 2001–2013). The study sample comprised 16,934 community-dwelling adults≥65 years, ADRD-free at baseline and enrolled in fee-for-service Medicare. Logistic regression was used to assess the association of OA and related pain (back, neck, joint, neuropathic) to incident ADRD, explore the mediating inlfuence of mood and insomnia-related sleep disorders, and (sensitivity analyses) account for potential survival bias.
Results
Overall, 25.5% of beneficiaries had OA at baseline (21.0% with OA and pain); 1149 elders (5.7%) were subsequently diagnosed with ADRD. Compared to beneficiaries without OA, those with OA were significantly more likely to receive a diagnosis of incident ADRD after adjustment for sociodemographics, lifestyle characteristics, comorbidities, and medications (adjusted odds ratio (AOR) = 1.23 (95% confidence interval (CI) 1.06, 1.42). Elders with OA and pain at baseline were significantly more likely to be diagnosed with incident ADRD than were those without OA or pain (AOR = 1.31, CI 1.08, 1.58). Sensitivity analyses yielded similar findings. Inclusion of depression/anxiety, but not sleep disorders, substantially attenuated these associations.
Conclusion
Findings of this study suggest that: OA is associated with elevated ADRD risk, this association is particularly pronounced in those with OA and pain, and mood disorders may partially mediate this relationship.
... Our findings are broadly consistent with those of a nested-case control study of Taiwanese Nationals indicating an increased risk for dementia in adults with OA 14 and a cross-sectional study of Appalachian adults, which documented a strong association of OA and related joint pain to perceived memory loss 13 . Our findings are also in general agreement with cross-sectional 5,6,23 , caseecontrol 44,45 , and longitudinal studies 7,8,11 documenting significant associations of non-specific chronic pain 5e8,11 and other (non-OA) chronic pain conditions 5,6,44,45 to impairment in cognitive functioning. Notably, in one recent study of a small US cohort followed for an average of 4.4 years, PI was associated with significantly increased risk for incident dementia 7 . ...
... Our findings are broadly consistent with those of a nested-case control study of Taiwanese Nationals indicating an increased risk for dementia in adults with OA 14 and a cross-sectional study of Appalachian adults, which documented a strong association of OA and related joint pain to perceived memory loss 13 . Our findings are also in general agreement with cross-sectional 5,6,23 , caseecontrol 44,45 , and longitudinal studies 7,8,11 documenting significant associations of non-specific chronic pain 5e8,11 and other (non-OA) chronic pain conditions 5,6,44,45 to impairment in cognitive functioning. Notably, in one recent study of a small US cohort followed for an average of 4.4 years, PI was associated with significantly increased risk for incident dementia 7 . ...
Background:
Emerging evidence suggests that Pain Interference (PI) and certain chronic pain conditions, including Osteoarthritis (OA) may be associated with risk for Alzheimer's disease and Related Dementias (ADRD). However, research exploring the relation of OA and PI to ADRD remains sparse.
Objective:
To assess the association of OA and PI to ADRD using cross-sectional data from a representative sample of USA adults aged ≥65 years.
Design:
Retrospective cross-sectional.
Study sample:
Older adults (age ≥ 65 years) drawn from the Medical Expenditure Panel Survey (MEPS, 2009-2015).
Methods:
OA was identified using both medical conditions files and participant responses to arthritis-specific queries. ADRD was ascertained using the medical conditions files. PI was defined as reported frequent PI with normal activities (PIA). OA and PIA were categorized as a composite variable: 1) OA with PIA; 2) OA without PIA; 3) No OA with PIA; and 4) No OA and no PIA (reference group). Adjusted associations of OA and PIA to ADRD were assessed using logistic regression and adjusted for biological, demographic, socio-economic, lifestyle, and health conditions.
Results:
Overall, 27.1% had OA, of whom 47.6 % reported PIA vs 31.1% of those without OA; 2.8% had diagnosed ADRD. Adults with PIA either with or without OA had significantly higher odds of ADRD relative to those without OA or PIA (Adjusted odd ratios (AOR's) = 1.37, 95%CI - 1.01, 1.86 (p = 0.04) and 1.44, 95%CI - 1.13, 1.82 (p = 0.003), respectively).
Conclusion:
PIA in both the presence and absence of OA remained significantly and positively associated with ADRD after adjustment for multiple confounders.
... There is increasing evidence that CP may be accompanied by an increased risk of objective cognitive impairments and dementia [25]. These cognitive deficits can be observed in several types of CP, including fibromyalgia [26], chronic back pain [27], trigeminal neuralgia [28], post-herpetic neuralgia [29], and others. ...
The coexistence of Alzheimer's disease (AD) and chronic pain (CP) in the elderly population has been extensively documented, and a growing body of evidence supports the potential interconnections between these two conditions. This comprehensive review explores the mechanisms by which CP may contribute to the development and progression of AD, with a particular focus on neuroinflammatory pathways and the role of microglia, as well as the activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome. The review proposes that prolonged pain processing in critical brain regions can dysregulate the activity of the NLRP3 inflammasome within microglia, leading to the overproduction of pro‐inflammatory cytokines and excessive oxidative stress in these regions. This aberrant microglial response also results in localized neuroinflammation in brain areas crucial for cognitive function. Additionally, CP as a persistent physiological and psychological stressor may be associated with hypothalamic‐pituitary‐adrenal (HPA) axis dysfunction, systemic inflammation, disruption of the blood–brain barrier (BBB), and neuroinflammation. These pathophysiological changes can cause morphological and functional impairments in brain regions responsible for cognition, memory, and neurotransmitter production, potentially contributing to the development and progression of CP‐associated AD. Resultant neuroinflammation can further promote amyloid‐beta (Aβ) plaque deposition, a hallmark of AD pathology. Potential therapeutic interventions targeting these neuroinflammatory pathways, particularly through the regulation of microglial NLRP3 activation, hold promise for improving outcomes in individuals with comorbid CP and AD. However, further research is required to fully elucidate the complex interplay between these conditions and develop effective treatment strategies.
... TGF-β is elevated in Alzheimer's disease [46] and Alzheimer's disease progression is accelerated post Covid-19 [47] [48] and in EBV [49], CIRS [50], FM [51], and CMV [52]. [54] and the mechanism appears to involve a Ca:Mg imbalance in the Warburg microenvironment (mitochondrial dysfunction). ...
Long Covid has many symptoms that overlap with ME (myalgic encephalo-myelitis)/CFS (chronic fatigue syndrome), FM (fibromyalgia), EBV (Eps-tein-Barr virus), CMV (cytomegalovirus), CIRS (chronic inflammatory response syndrome), MCAS (mast cell activation syndrome), POTS (postural orthostatic tachycardia syndrome), and post viral fatigue syndrome. They all portend a "long haul" with an antioxidant shortfall and elevated Ca:Mg. Oxidative stress is the root cause. Linkage between TGF (transforming growth factor)-β, IFN (interferon)-γ, the RAS (renin angiotensin system), and the KKS (kallikrein kinin system) is discussed. Technical explanations for the renin aldosterone paradox in POTS, the betrayal of TGF-β, and the commonality of markers for the Warburg effect are offered. The etiology of the common Long Covid symptoms of post exertional malaise, fatigue, and brain fog as well as anosmia, hair loss, and GI symptoms is technically discussed. Ca:Mg is critical to the glutamate/GABA balance. The role of GABA and butyrates from the "good" intestinal bacteria in the gut-brain axis and its correlation with chronic fatigue diseases are explored. The crosstalk between the ENS (enteric nervous system) and the ANS (autonomic nervous system) and the role of the vagus in both are emphasized. HRV (heart rate variability), the fifth vital sign, points to an expanded gut-brain-heart/lung axis. A suggested approach to all of these-Long Covid, chronic fatigue diseases, post viral fatigue syndrome, and general health-is presented.
... TGF-β is elevated in Alzheimer's disease [46] and Alzheimer's disease progression is accelerated post Covid-19 [47] [48] and in EBV [49], CIRS [50], FM [51], and CMV [52]. [54] and the mechanism appears to involve a Ca:Mg imbalance in the Warburg microenvironment (mitochondrial dysfunction). ...
Long Covid has many symptoms that overlap with ME(myalgic encephalomyelitis)/CFS(chronic fatigue syndrome), FM(bromyalgia), EBV(Epstein-Barr virus), CMV(cytomegalovirus), CIRS (chronic in ammatory response syndrome), MCAS(mast cell activation syndrome), POTS(postural orthostatic tachycardia syndrome), and post viral fatigue syndrome. They all portend a "long haul" with an antioxidant shortfall and elevated Ca:Mg. Oxidative stress is the root cause. Linkage between TGF(transforming growth factor)-β, IFN(interferon)-γ, the RAS(renin angiotensin system), and the KKS(kallikrein kinin system) is discussed. Technical explanations for the renin aldosterone paradox in POTS, the betrayal of TGF-β, and the commonality of markers for the Warburg e ect are o ered. The etiology of the common Long Covid symptoms of post exertional malaise, fatigue, and brain fog as well as anosmia, hair loss, and GI symptoms is technically discussed. Ca:Mg is critical to the glutamate/GABA(gamma amino butyric acid) balance. The role of GABA and butyrates from the "good" intestinal bacteria in the gut brain axis and its correlation with chronic fatigue diseases are explored. The crosstalk between the ENS(enteric nervous system) and the ANS(autonomic nervous system) and the role of the vagus in both are emphasized. HRV(heart rate variability), the fth vital sign, points to an expanded gut-brain-heart/lung axis. A suggested approach to all of these-Long Covid, chronic fatigue diseases, post viral fatigue syndrome, and general health-is presented.
... 14 The details of this program were documented in several previous studies. 6,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] The National Health Insurance Research Database (NHIRD) contains comprehensive data of the beneficiaries. Individual identifies were encrypted before release for research under the Personal Information Protection Act. ...
Objective:
There is limited clarity concerning the risk of dementia after pneumonia with intensive care unit (ICU) stay. We conducted a nationwide cohort study, which aimed to investigate the impact of dementia after pneumonia with and without intensive care unit admission.
Methods:
Data was obtained from Taiwan's National Health Insurance Research Database between 2000 and 2015. A total of 7,473 patients were identified as having pneumonia required ICU stay, along with 22,419 controls matched by sex and age. After adjusting for confounding factors, multivariate Cox regression model analysis was used to compare the risk of developing dementia during the 15-years follow-up period.
Results:
The enrolled pneumonia patients with ICU admission had a dementia rate of 9.89%. Pneumonia patients without ICU admission had a dementia rate of 9.21%. The multivariate Cox regression model analysis revealed that the patients with ICU stay had the higher risk of dementia, with a crude hazard ratio of 3.371 (95% confidence interval, 3.093-3.675; p<0.001).
Conclusion:
This study indicated that pneumonia with ICU stay is associated with an increased risk of dementia. A 3-fold risk of dementia was observed in patients admitted to the ICU compared to the control group.
... 1,2 Such neurodegeneration makes cognitive decline a concern in the one in five older adults experiencing persistent pain 3 -especially as they already face inherent risks of cognitive disorders such as Alzheimer's disease (AD) and related dementias that increase with age. 4 In mostly middle-aged clinic samples, studies show that people with pain have poorer cognitive function than controls. [5][6][7] Pain in older adults in the general population may also affect cognition. Cross-sectional studies have had mixed results in older adults, even suggesting that poor cognition may be associated with less reporting of pain in the oldest-old. ...
Background:
No studies have examined the longitudinal association between the persistence of pain and its relationship to cognitive problems in older adults. The objective of this study was to examine how the persistent of pain associates with cognitive performance, cognitive impairment, and subjective memory decline.
Methods:
Across 10 biennial waves, 8515 adults ages 65 and over were assessed from the Health and Retirement Study (Mage = 74.17, SD = 6.87, 59.2% female). At each wave, individuals were asked to report on pain presence, and if present, rate its intensity and interference with daily activities such as housework or chores. Using running frequencies or averages, we calculated the persistence of pain using these three pain measures. Cognition was assessed using cognitive performance and different cognitive impairment cutoffs. Incident subjective memory decline was additionally measured as new self-reported memory change in the last 2 years. General estimating equations examined concurrent associations between persistence of pain and cognitive variables, adjusting for demographics, depressive symptoms, and medical comorbidities.
Results:
Persistence of pain presence was associated with an increased risk of cognitive impairment. Only persistence of pain interference, not pain intensity, was significantly associated with poorer cognitive performance or being classified as cognitively impaired. For every 2 years, persistence of pain interference was associated with 21% increased odds of cognitive impairment. Only one of three pain variables was related to incident subjective memory decline.
Conclusions:
Persistence of pain is associated with poorer cognitive performance in community-dwelling older adults, especially when involving ongoing interference in chores and work. Facilitating pain management might be important for helping to maintain later-life cognition and reduce dementia risk.
... 1 MS often has negative effects on the patients' quality of life as well as their interpersonal relationships, employment, and social life. 2 Neuroimaging research have revealed that symptoms can originate from different brain networks, regardless of the pathological substrate, and from disconnections caused by damage to the strategic white matter tracts. 3 Previous studies have found that some neuropsychiatric disorders are associated with several immune-mediated inflammatory diseases, 4 such as Guillain-Barre syndrome, 5 fibromyalgia, 6 allergic diseases, 7 and periodontal inflammatory diseases. [8][9][10][11] Psychological stressors related to the inflammatory diseases might also contribute to both psychiatric and physical morbidity, 12 and several studies have found that MS is associated with depression, anxiety, bipolar disorder, sleep disorders, alcohol abuse, substance abuse, and psychosis.- ...
Background
Multiple sclerosis (MS) is a demyelinating disease that can damage neurons in the brain and spinal cord and is associated with several psychiatric disorders. However, few studies have evaluated the risk of psychiatric disorders in patients with MS by using a nationwide database. This study investigated the association between MS and the risk of psychiatric disorders.
Methods
Using data from the Taiwan National Health Insurance Research Database from 2000 to 2015, we identified 1066 patients with MS. After adjustment for confounding factors, Fine and Gray’s competing risk model was used to compare the risk of psychiatric disorders during 15 years of follow-up.
Results
Of the patients with MS, 531 (4622.86 per 10⁵ person years) developed psychiatric disorders; by contrast, 891 of the 3198 controls (2485.31 per 10⁵ person years) developed psychiatric disorders. Fine and Gray’s competing risk model revealed an adjusted hazard ratio (HR) of 5.044 (95% confidence interval = 4.448–5.870, p < 0.001) after adjustment for all the covariates. MS was associated with depression, anxiety, bipolar disorder, sleep disorders, schizophrenia, schizophreniform disorder, and other psychotic disorders (adjusted HR: 12.464, 4.650, 6.987, 9.103, 2.552, 2.600, 2.441, and 2.574, respectively; all p < 0.001). Some disease-modifying drugs were associated with a lower risk of anxiety or depression.
Conclusion
Patients with MS were determined to have a higher risk of developing a wide range of psychiatric disorders.
... 9 A nationwide cohort study showed that FM patients have 2.77 times more risk of developing dementia than normal control groups. 10 FM is strongly associated with sleep disorders, headaches, depression, and illness behavior. 11 It is assumed that chronic inflammation can play a significant role in the pathogenesis of FM. ...
Fibromyalgia is a musculoskeletal pain of different parts of the body, which is also associated with fatigue, lack of sleep, cognition deficits, family history, gender bias, and other disorders such as osteoarthritis and rheumatoid arthritis. It is generally initiated after trauma, surgery, infection, or stress. Fibromyalgia often coexists with several other conditions or disorders such as temporomandibular joint disorders, bowel and bladder syndrome, anxiety, depression, headaches, and interstitial cystitis. While there is no permanent cure for fibromyalgia, some interventions are available with multiple side effects. rTMS (repetitive transcranial magnetic stimulation), a noninvasive management strategy is used widely for various pain-related etiologies including fibromyalgia in both the laboratory and clinical settings. In this Review, we discuss the role and mechanism of action of rTMS in fibromyalgia patients and on associated comorbidities including anxiety, pain, depression, neurotransmitter alterations, sleep disorders, and overall quality of life of the patients suffering from this chronic problem. We also provide an update on the rTMS application in the clinical trials of fibromyalgia patients and prospective management therapy for multiple problems that these patients suffer.
... Thus accelerated neuronal aging may also contribute further neuroinflammation. Indirect evidence for this can be the higher rates of dementia seen in patients with FM (adjusted hazard ratio of 2.77) [32]. ...
Introduction: Fibromyalgia (FM) prevalence is much higher in patients with other rheumatic diseases than in the general population. This leads to increase in the perceived disease activity scores and prevents patients from reaching remission. Elucidating the pathogenesis of such “secondary” FM can help alleviate some unmet needs in these diseases.
Methods: MEDLINE and Scopus databases were searched for a scoping review for hypothesis generation regarding the genesis of secondary FM.
Results: FM has been postulated to be due to cytokine dysfunction, neurogenic neuroinflammation, stress, including social defeat, sleep disturbances, sympathetic overactivity, and small fibre neuropathy. These factors increase in most autoimmune and autoinflammatory diseases. Further the evidence for the role of these factors in the pathogenesis of FM is seems strong. Metabolic syndrome and mitochondrial dysfunction are also associated with FM, but it is difficult to distinguish between cause and effect.
Conclusion: FM is the common phenotype arising from the amalgamation of various aetiologies. Recruitment or amplification of the above 6 factors by various rheumatic diseases may thus lead precipitation of secondary FM in susceptible individuals.
... 21 The details of this program were documented in several previous studies. [22][23][24] The NHIRD contains comprehensive and detailed data regarding the total outpatient and a subset of the NHIRD, as a two million Longitudinal Health Insurance Database (LHID), with individual diagnoses coded by the International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM). Several previous studies have confirmed the accuracy and validity of the diagnoses as myocardial infarction, 25 diabetes, 26 oral cancer, 27 and stroke, 28 in the NHIRD. ...
Background
The associations between the human immunodeficiency virus (HIV) and dementias are as yet to be studied in Taiwan. The aim of this study is to clarify as to whether HIV infections are associated with the risk of dementia.
Methods
A total of 1,261 HIV-infected patients and 3,783 controls (1:3) matched for age and sex were selected between January 1 and December 31, 2000 from Taiwan’s National Health Insurance Research Database (NHIRD). Fine and Gray’s survival analysis (competing with mortality) analyzed the risk of dementias during the 15-year follow up. The association between the highly active antiretroviral therapy (HAART) and dementia was analyzed by stratifying the HAART status among the HIV subjects.
Results
During the follow-up period, 25 in the HIV group (N= 1,261) and 227 in the control group (N= 3,783) developed dementia (656.25 vs 913.15 per 100,000 person-years). Fine and Gray’s survival analysis revealed that the HIV patients were not associated with an increased risk of dementia, with the adjusted hazard ratio (HR) as 0.852 (95% confidence interval [CI]: 0.189–2.886, p=0.415) after adjusting for sex, age, comorbidities, geographical region, and the urbanization level of residence. There was no significant difference between the two groups of HIV-infected patients with or without HAART in the risk of dementia.
Conclusion
This study found that HIV infections, either with or without HAART, were not associated with increased diagnoses of neurodegenerative dementias in patients older than 50 in Taiwan.
... 47 Nonetheless, in this study, the rate of obesity is less than 1%, which is lower than the 7.2% obesity rate in adolescents. 48 This observation is similar to that in other studies using the NHIRD, 14,[49][50][51][52] and this might be related to the fact that physicians seldom code obesity in the medical records. The actual reason why they undercode obesity is not known, but we speculate that body image issues and even obesity discrimination in our society might be one of the reasons. ...
Study objectives:
This study has investigated the risk of major adverse cardiovascular events (MACEs), including acute myocardial infarction, coronary artery disease, peripheral artery disease, and acute stroke, among children and adolescents (age younger than 20 years) with obstructive sleep apnea (OSA).
Methods:
In this study, the population-based National Health Insurance Research Database of Taiwan was used to identify patients in whom OSA had been first diagnosed between 2000 and 2015. Children and adolescents with OSA (n = 6,535) were included with 1:3 ratio by age, sex, and index year of control participants without OSA (n = 19,605). The Cox proportional regression model was used to evaluate the risk of MACEs in this cohort study.
Results:
After a 15-year follow-up, the incidence rate of MACEs was higher in the OSA cohort when compared with the non-OSA control cohort (15.97 and 8.20 per 100,000 person-years, respectively). After adjusting for covariates, the risk of MACEs among children and adolescents with OSA was still significantly higher (hazard ratio = 2.050; 95% confidence interval = 1.312-3.107; P = .010). No MACEs were found in the children and adolescents with OSA who received continuous airway positive pressure treatment or pharyngeal surgery.
Conclusions:
This study found a significantly higher risk of MACEs in children and adolescents with OSA. These findings strongly suggest that clinicians should provide careful follow-up and medical treatment for children and adolescents with OSA.
... The third article concerns FM and dementia, pursued by Taiwanese investigators again using the country's insurance data, the rationale being that inflammation-related diseases or other pain disorders, such as headaches, have been shown to be associated with increased risk of dementia. Tzeng et al. (2018b) investigated 41,612 subjects with FM diagnosed between January 1, and December 31,2000, and 124,836 controls without FM, matched for age, sex and index year. All subjects were aged 50 years or over. ...
Strong evidence has emerged recently for the concept that herpes simplex virus type 1 (HSV1) is a major risk for Alzheimer’s disease (AD). This concept proposes that latent HSV1 in brain of carriers of the type 4 allele of the apolipoprotein E gene (APOE-ε4) is reactivated intermittently by events such as immunosuppression, peripheral infection, and inflammation, the consequent damage accumulating, and culminating eventually in the development of AD. Population data to investigate this epidemiologically, e.g., to find if subjects treated with antivirals might be protected from developing dementia—are available in Taiwan, from the National Health Insurance Research Database, in which 99.9% of the population has been enrolled. This is being extensively mined for information on microbial infections and disease. Three publications have now appeared describing data on the development of senile dementia (SD), and the treatment of those with marked overt signs of disease caused by varicella zoster virus (VZV), or by HSV. The striking results show that the risk of SD is much greater in those who are HSV-seropositive than in seronegative subjects, and that antiviral treatment causes a dramatic decrease in number of subjects who later develop SD. It should be stressed that these results apply only to those with severe cases of HSV1 or VZV infection, but when considered with the over 150 publications that strongly support an HSV1 role in AD, they greatly justify usage of antiherpes antivirals to treat AD. Three other studies are described which directly relate to HSV1 and AD: they deal respectively with lysosomal changes in HSV1-infected cell cultures, with evidence for a role of human herpes virus type 6 and 7 (HHV6 and HHV7) in AD, and viral effects on host gene expression, and with the antiviral characteristics of beta amyloid (Aβ). Three indirectly relevant studies deal respectively with schizophrenia, relating to antiviral treatment to target HSV1, with the likelihood that HSV1 is a cause of fibromyalgia (FM), and with FM being associated with later development of SD. Studies on the link between epilepsy, AD and herpes simplex encephalitis (HSE) are described also, as are the possible roles of APOE-ε4, HHV6 and HSV1 in epilepsy.
... 2 16 And the reason why we just enrolled patients with OAB and controls within 1 year, between January 1, 2000 and December 31, 2000 is to make sure all the subjects were followed up in the same period, similar to several previous studies. [17][18][19] All diagnoses of OAB were made by board-certified urologists, and gynecologists (in female patients). Those diagnoses of psychiatric disorders in this study were made by board-certified psychiatrists. ...
Population-based cohort study investigating the risk of depression and other psychiatric disorders for patients with overactive bladder (OAB) syndrome is unavailable. This study investigated the subsequent risk of psychiatric disorders among patients with OAB in an Asian population. Using data from the National Health Insurance Research Database of Taiwan, we established a cohort with 811 patients in an exposed group with OAB between January 1, 2000 and December 31, 2000, and a non-exposed group, without OAB, of 2433 patients without OAB matched by age and year of diagnosis. The occurrence of psychiatric disorders and Cox regression model measured adjusted HRs (aHR) were monitored until the end of 2013. The overall incidence of psychiatric disorders was 41.7% higher in the exposed group with OAB than in the non-exposed group without OAB (14.2% vs 10.1%, p<0.001), with an aHR of 1.34 (95% CI 1.12 to 1.80, p<0.001) for the OAB cohort. OAB was associated with the increased risk of dementia, anxiety, depressive, sleep, and psychotic disorders, with aHRs as 1.53 (p=0.040), 1.61 (p<0.001), 2.10 (p<0.001), 1.43 (p<0.001), and 2.49 (p=0.002), respectively. The risk of psychiatric disorders, including depression and anxiety, is significantly higher in patients with OAB than in those without OAB. Evaluation of psychiatric status in patients with OAB is strongly recommended.
... 9 A nationwide cohort study showed that FM patients have 2.77 times more risk of developing dementia than normal control groups. 10 FM is strongly associated with sleep disorders, headaches, depression, and illness behavior. 11 It is assumed that chronic inflammation can play a significant role in the pathogenesis of FM. ...
Background
Plasma neurofilament light chain (NFL) has been measured as a biomarker of neuronal damage in various neurological disorders. Elevated tau and β‐amyloid levels have been found in patients with fibromyalgia (FM). The aim of the present study was to compare plasma neurofilament levels in fibromyalgia patients with normal controls and to investigate the correlation with clinical features and cognitive tests.
Methods
Plasma NFL levels were assessed in 33 FM patients and compared with 22 age‐matched controls. All patients were also assessed with clinical scales examining fibromyalgia disability, sleep quality and duration, fatigue, anxiety, and depression, and a neuropsychological battery examining executive function, verbal short‐term memory, and working memory, as well as attentional executive function and selective attention, interference sensitivity, and inhibition of automatic responses.
Results
NFL levels were higher in FM patients (controls 6.19± 1.92; FM 17.28± 15.94 pg/mL ANOVA p 0.002). Working memory was the most impaired cognitive function significantly correlated with high NFL scores (Pearson p 0.034). Short sleep times also correlated with higher NFL scores (Pearson p 0.02) and poorer working memory performance (Pearson p 0.02). No correlation was found with indices of disease severity and duration.
Conclusions
Plasma NFL levels are elevated in fibromyalgia patients, suggesting neuronal damage and correlating with a slight decrease in working memory and short sleep duration.
Significance Statement
Plasma neurofilament levels are elevated in patients with fibromyalgia, regardless of disease severity and duration. Neurofilament levels are higher in patients with mild working memory impairment and sleep disorders. Subgroups of patients with primary neuronal damage phenomena could be individualized for prospective evaluation with regard to the possible development of cognitive decline and sleep disturbances, which would justify a tailored therapeutic approach.
Objectives: Chronic pain (CP) remains one of the most incapacitating pathologies among older people. Alzheimer’s disease or Related Dementia (ADRD) is known to disturb pain perception and reduce the ability to report it. No study has yet assessed the prevalence of all types of CP and defined with at least 3 or 6 months duration, among people with ADRD.
Design: To estimate the prevalence of CP among people living with an ADRD from 2017 to 2019 a nationwide cross-sectional study was performed.
Settings: French community-dwelling and nursing home residents.
Participants: People with ADRD, >40 years old, treated with cognitive stimulants (cholinesterase inhibitors and memantine) or with a diagnosis/long-term illness of ADRD and matched with a comparison sample (non-ADRD).
Measurements: The prescription drug, the national hospital discharge, and the French pain center databases of the healthcare system database were used to identify study sample. People treated with analgesic drugs for ≥6 months consecutively or with a medical diagnosis of CP or referred to a pain center (according to ICD-10 codes) were considered as having CP. Using log-linear modeling, capture-recapture analyses were performed to provide prevalence of CP estimates with their 95% confidence intervals.
Results: 48,288 individuals were included. Among the 8 log-linear models generated to estimate the prevalence of CP in people with ADRD, models 3 and 7 was chosen. The estimated prevalence of CP in people with ADRD was from 57.7%[52.9;63.3] to 57.9%[53.0;63.9], and slightly higher than the comparison sample (from 49.9%[47.0;53.2] to 50.4%[47.3;53.9], p<0.001). About 25% of people with ADRD treated for CP before the diagnosis of their ADRD are no longer treated for their CP.
Conclusions: The high prevalence of CP among people living with ADRD should alert practitioners' attention to the need for effective pain assessment and management in this population who has difficulties to express and feel pain.
Objective
Multimorbidity and non-cancer chronic pain conditions (NCPC) are independently linked to elevated risk for cognitive impairment and incident Alzheimer’s Disease and Related Dementias (ADRD)-both - We present the study of potential joint and interactive effects of these conditions on the risk of incident ADRD in older population.
Methods
This retrospective-cohort study drew baseline and 2-year follow-up data from linked Medicare claims and Medicare Current Beneficiary Survey (MCBS). Baseline multimorbidity and NCPC were ascertained using claims data. ADRD was ascertained at baseline and follow-up.
Results
NCPC accompanied by multimorbidity (vs. absence of NCPC or multimorbidity) had a significant and upward association with incident ADRD (adjusted odds ratio (AOR): 1.72, 95% CI 1.38, 2.13, p < 0.0001). Secondary analysis by number of comorbid conditions suggested that the joint effects of NCPC and multimorbidity on ADRD risk may increase with rising number contributing chronic conditions. Interaction analyses indicated significantly elevated excess risk for incident ADRD.
Trigeminal neuralgia (TN) is a stubborn head and face neuropathic pain with complex pathogenesis. Patients with TN have a significantly increased risk of central neurodegeneration, which manifests as cognitive impairment and memory loss, but the specific mechanism underlying central nervous degeneration is still unclear. This study aimed to explore central neurodegeneration and its possible mechanism of action in TN rats based on changes in the brain fatty acid content and microglia-related neuroinflammation. Using a TN neuropathic pain model established by us, we found that TN rats have obvious cognitive impairment. Furthermore, changes in the brain fatty acid content were analyzed using gas chromatography-mass spectrometry (GC-MS). It was found that the docosahexaenoic acid (DHA) content in the central nervous system (CNS) of TN rats was significantly decreased compared to that in the CNS of Sham rats. An important component in maintaining brain cognition, DHA also plays a key role in regulating central neuroinflammation. Here, by continuous supplementation of DHA, the CNS DHA content was increased to a certain extent in TN rats. The cognitive impairment of TN rats was improved after restoring the central DHA level; this may be related to the improvement of neuroinflammation through the DHA-mediated regulation of microglial polarization. Overall, this study provides a theoretical basis for explaining the pathogenesis of central neurodegeneration in TN. It also suggests DHA as a target for protecting the CNS of patients with TN from damage.
Introduction
Dementia is associated with many comorbidities while being related to Apolipoprotein E ( ApoE ) polymorphism. However, it is unclear how these clinical illnesses and genetic factors modify the dementia risk.
Methods
We enrolled 600 dementia cases and 6000 matched non-dementia controls, with identified ApoE genotype (ε4/ε4, ε4/ε3, and ε3/ε3). Eight comorbidities were selected by medical records, and counted if occurring within 3 years of enrollment.
Results
The dementia group had a higher ratio of carrying ε4 allele and prevalence of comorbidities than the non-dementia group. Homozygous ε4 carriers presented the broken line of dementia risk with the peak age at 65–75 years and odds ratio (OR) up to 6.6. The risk only emerged after 65 years of age in ε3/ε4 subjects with OR around 1.6–2.4 when aged > 75 years. Cerebrovascular accident (CVA) is the commonest comorbidity (14.6%). CVA, sleep disorder, and functional gastrointestinal disorders remained as significant risk comorbidities for dementia throughout all age groups (OR = 1.7–5.0). When functional gastrointestinal disorder and ε4 allele both occurred, the dementia risk exceeded the summation of individual risks (OR = 3.7 and 1.9 individually, OR = 6.0 for the combination). Comorbidities could also be predictors of dementia.
Conclusion
Combining the genetic and clinical information, we detected cognitive decline and optimize interventions early when the patients present a specific illness in a particular age and carry a specific ApoE allele. Of comorbidities, functional gastrointestinal disorder is the strongest predicting factor for dementia in ε4 allele carriers.
Background
Dementia is an urgent public health problem worldwide, and the determination of the contribution of pain to cognitive decline or dementia is significant for the prevention of dementia.
Objective
To comprehensively explore the contribution of pain to subsequent cognitive decline or dementia and analyze possible influencing factors.
Design
Systematic review and meta-analysis of cohort studies.
Methods
We systematically searched MEDLINE, EMBASE, PsycINFO, CINAHL, Cochrane Library, China National Knowledge Internet, WANFANG DATA and VIP for cohort studies from database inception to January 21, 2022. Random-effects meta-analysis was used to pool odds ratios (ORs) and 95% confidence intervals (CIs) of incident cognitive decline or dementia among patients with pain. Subgroup analyses and meta-regression were used to explore the sources of heterogeneity.
Results
A total of 35 cohort studies containing 1,122,503 participants were included. As a whole, pain (OR = 1.24; 95% CI = 1.17–1.31) was a risk factor for subsequent cognitive decline or dementia; headache, migraine, tension-type headache, widespread pain, and irritable bowel syndrome, but not burning mouth syndrome, were also risk factors. Pain increased the risk of all-cause dementia (OR = 1.26; 95% CI = 1.18–1.35), Alzheimer's disease (OR = 1.28; 95% CI = 1.12–1.47), and vascular dementia (OR = 1.31; 95% CI = 1.06–1.62). Pain interference (OR = 1.42; 95% CI = 1.16–1.74) was associated with an increased risk of cognitive decline or dementia, while pain intensity was not. Pooled results from studies with sample sizes less than 2000 or with relatively low quality showed that pain did not increase the risk of cognitive decline or dementia. There was no statistically significant increase in the risk of cognitive decline or dementia in people with pain aged ≥ 75 years.
Conclusions
Our results demonstrated that pain increased the risk of subsequent cognitive decline or dementia. Sample size, study methodological quality, types of pain, pain severity (pain interference), and age composition of the study population may affect the relationship between pain and cognitive decline or dementia.
Registration
PROSPERO (CRD42022316406).
Objective
Multimorbidity and non-cancer chronic pain conditions (NCPC) are independently linked to elevated risk for cognitive impairment and incident Alzheimer’s Disease and Related Dementias (ADRD)-both - We present the study of potential joint and interactive effects of these conditions on the risk of incident ADRD in older population.
Methods
This retrospective-cohort study drew baseline and 2-year follow-up data from linked Medicare claims and Medicare Current Beneficiary Survey (MCBS). Baseline multimorbidity and NCPC were ascertained using claims data. ADRD was ascertained at baseline and follow-up.
Results
NCPC accompanied by multimorbidity (vs. absence of NCPC or multimorbidity) had a significant and upward association with incident ADRD (adjusted odds ratio (AOR): 1.72, 95% CI 1.38, 2.13, p< 0.0001). Secondary analysis by number of comorbid conditions suggested that the joint effects of NCPC and multimorbidity on ADRD risk may increase with rising number contributing chronic conditions. Interaction analyses indicated significantly elevated excess risk for incident ADRD.
Pain is inversely associated with cognitive function in older adults, but the effects of pain on cognitive decline are not fully clear. This study examined the associations of baseline pain, pain persistence, and incident pain with changes in cognition across 10 years in a sample of healthy community-dwelling older adults (n = 688; Mage = 74, SD = 6.05) from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) trial. While ACTIVE was a four-arm single-blind cognitive training randomized controlled trial, the present study includes only participants from the no-contact control group. Pain was examined using the Medical Outcomes Survey SF-36-Item (MOS SF-36) and cognitive tests examined simple processing speed, complex processing speed, divided and selective attention, memory, reasoning, and cognitive status. Multilevel models tested the associations of baseline pain, incident pain, and pain persistence on cognitive function and cognitive decline, adjusted for baseline age, time (years after follow-up), race, gender, education, marital status, and depressive symptoms at baseline and over time. Thirty-one percent reported pain at baseline which was related to worse baseline memory and accelerated decline in processing speed. Forty-two percent of older adults reported incident pain had accelerated decline in complex processing speed, divided attention, memory, reasoning, and cognitive status. On average, older adults reported a mean of two waves of pain persistence related to accelerated decline in memory. In sum, pain is common in community-dwelling older adults and is related to accelerated cognitive decline, especially when the incident.
Background
The histamine type 1 receptor antagonist (H1RA) has been commonly used. This study aimed to examine the association between the usage of H1RA and the risk of dementia.
Methods
A total of 8,986 H1RA users aged ≥50 and 26,958 controls matched a ratio of 1:3 for age, sex, and comorbidity, were selected between January 1, and December 31, 2000, from Taiwan’s National Health Insurance Research Database. Fine and Gray’s survival analysis (competing with mortality) was used to compare the risk of developing dementia during a 15-year follow-up period (2000–2015).
Results
In general, the H1RA usage was not significantly associated with dementia (adjusted subdistribution hazard ratio [SHR] = 1.025, 95% confidence interval [CI] = 0.883–1.297, p = 0.274) for the H1RA cohort. However, a differential risk was found among the groups at risk. The patients with the usage of H1RA aged ≥65 years (adjusted SHR: 1.782, 95% CI = 1.368–2.168, p < 0.001) were associated with a higher risk of dementia, in comparison to the control groups. Furthermore, the patients with the usage of H1RA that were male, or had more comorbidities, were also associated with an increased risk of dementia.
Conclusion
The usage of H1RA was associated with the risk of developing dementia in the patients aged ≥ 65 years.
Background and objective
Chronic pain may be an early indicator of cognitive decline, but previous studies have not systematically examined the population-level associations between widespread pain and adverse cognitive outcomes and stroke. This study was designed to determine the association between widespread pain, a common subtype of chronic pain, and subsequent dementia, Alzheimer’s disease dementia and stroke.
Methods
This retrospective cohort study used data from the US community-based Framingham Heart Study. Pain status was assessed at a single time point between 1990 and 1994. Widespread pain was determined based on the Framingham Heart Study pain homunculus. Dementia follow-up occurred across a median of 10 years (IQR, 6–13 years) for persons who were dementia free at baseline. Proportional hazard models examined associations between widespread pain and incident dementia, Alzheimer’s disease dementia and stroke.
Results
A total of 347 (14.1%) subjects fulfilled the criteria for widespread pain, whereas 2117 (85.9%) subjects did not. Of 188 cases of incident all-cause dementia, 128 were Alzheimer’s disease dementia. In addition, 139 patients suffered stroke during the follow-up period. After multivariate adjustment including age and sex, widespread pain was associated with 43% increase in all-cause dementia risk (HR: 1.43; 95% CI 1.06 to 1.92), 47% increase in Alzheimer’s disease dementia risk (HR: 1.47; 95% CI 1.13 to 2.20) and 29% increase in stroke risk (HR: 1.29; 95% CI 1.08 to 2.54). Comparable results were shown in the subgroup of individuals over 65 years old.
Conclusion
Widespread pain was associated with an increased incidence of all-cause dementia, Alzheimer’s disease dementia and stroke.
Trial registration number
NCT00005121 .
Patients with chronic neuropathic pain (NP) have a significantly increased risk of central nervous degeneration. Trigeminal neuralgia (TN) is a typical NP, and this manifestation is more obvious. In addition to severe pain, patients with TN are often accompanied by cognitive dysfunction and have a higher risk of central nervous system degeneration, but the mechanism is not clear. The NLRP3 inflammasome assembles inside of microglia on activation, which plays an important role in neurodegeneration such as Alzheimer disease. MCC950 is a specific blocker of NLRP3 inflammasome, which can improve the performance of degenerative diseases. Although NLRP3 inflammasome assembles inside of microglia on activation has been shown to be essential for the development and progression of amyloid pathology, its whether it mediates the neurodegeneration caused by NP is currently unclear. By constructing a rat model of chronic TN, we found that as the course of the disease progresses, TN rats have obvious cognitive and memory deficit. In addition, Tau hyperphosphorylation and Aβ expression increase in the cortex and hippocampus of the brain. At the same time, we found that NLRP3 expression increased significantly in model rats. Interestingly, NLRP3 specific blocker MCC950 can alleviate the neurodegeneration of trigeminal neuralgia rats to a certain extent. It is suggested that our NLRP3 inflammasome plays an important role in the neurodegeneration of trigeminal neuralgia rats. And it is related to the activation of central nervous system inflammation.
Fibromyalgia (FM) is a condition of chronic widespread pain (CWP) that can occur throughout the life cycle and is likely underrecognized in older patients. FM is associated with considerable suffering and reduction in quality of life and may occur as a unique condition, but in older patients is most likely to be associated with another medical illness. Understood mechanistically to be a sensitization of the nervous system, recently identified as nociplastic pain, FM is accepted as a valid medical illness that requires a positive diagnosis and directed treatments. The cornerstone of treatments for FM are nonpharmacologic interventions, with the understanding that medications provide only modest benefit for most patients, and with particular concern about adverse effects in older patients. If FM is not recognized, treatments may be misdirected to the other medical condition, with failure to address FM symptoms, leading to overall poor outcome. In contrast, new complaints in older patients should not immediately be attributed to FM, and physicians should be vigilant to ensure that onset of a new illness is not ignored. As FM is most often a lifelong condition, patients should be encouraged to identify their own personal strategies that can attenuate symptoms, especially when symptoms flare. Continued life participation should be the outcome goal.
This study examined whether pain is associated with subjective memory problems or cognition in Puerto Rican older adults. Participants came from the Puerto Rican Elderly Health Conditions (PREHCO) study, aged 60 and over (n = 2,144). Analyses examined concurrent and longitudinal associations of pain with subjective memory problems and cognition using a cognitive screener. Overall, participants with pain were more likely to report concurrent subjective memory problems than those without pain. Older adults with pain also exhibited slightly lower concurrent cognition. Novel pain was associated with cognitive decline and greater likelihood of incident subjective memory problems at follow-up. Persistent pain was only related to incident subjective memory problems at follow-up. Pain is associated with cognitive decline and subjective memory problems in older Puerto Ricans. Future studies should implement more in-depth neuropsychological assessments and examine the potential role of barriers to pain management in this population.
Objective
Fibromyalgia (FM) is a chronic widespread pain syndrome. Although its mechanism remains relatively unknown, accelerated neurodegeneration in the brain has been reported in patients with FM. Sleep disturbance can increase the risk of neurocognitive disorders, which are associated with tau and beta-amyloid (Aβ) protein accumulation. We hypothesize neurodegeneration in patients with FM may be associated with sleep disturbance.
Methods
In this case-control study, we analyzed serum tau and Aβ levels and their association with symptom profiles for patients with FM, by recruiting 22 patients with FM and 22 age-matched healthy participants. The visual analog scale, Fibromyalgia Impact Questionnaire, pressure pain threshold test, Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory-II, Beck Anxiety Inventory, and serum tau and beta-amyloid-42 (Aβ-42) levels were recorded. The Mann–Whitney test was conducted to compare questionnaire and protein level results between the groups. Pearson correlation test was conducted to investigate the correlation of questionnaire scores with tau and Aβ-42 levels in patients with FM. The significance level was set at P < .05.
Results
Serum tau and Aβ-42 levels were significantly higher in patients with FM than in controls. A positive correlation between serum tau levels and PSQI scores was observed in patients with FM ( r = 0.476, P = .025). We found that only sleep disturbance in patients with FM was significantly associated with higher serum tau levels among all symptom scores.
Conclusions
We suggest sleep disturbance may play a vital role in the pathomechanism of accelerated neurodegeneration in FM.
Genital warts are a common sexually transmitted disease caused by human papillomavirus (HPV) infections. The prevalence of dementia is 4–8% in those aged 65 years or older in Taiwanese community studies, with a high social and economic burden for patients, family caregivers, the community and society. Previous studies have shown that viral infections such as herpes simplex and herpes zoster were associated with dementia. This study aimed to investigate the association between dementia and HPV infections. A population‐based cohort study using data from Taiwan’s National Health Insurance Research Database was conducted. Fine and Grays’s survival analysis was employed to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for the association between genital warts and dementia. From all of the potential participants aged 50 years or more, a total of 16 116 patients were enrolled, including 4029 genital warts‐infected patients, with 12 087 sex‐, age‐ and indexed date‐matched controls (1:3). The cumulative incidences of dementia were 10.72 per 103 person‐years and 6.43 per 103 person‐years in the genital warts and control group, respectively. There were 475 dementia cases from the genital warts cohort during the follow‐up period of 15 years. The adjusted HR for dementia was 1.485 (95% CI, 1.321–1.668; P < 0.001) for genital warts patients after adjusting for all of the covariates. Our study indicates that genital warts infection may increase the risk of dementia.
This study aims to investigate the association between pulmonary embolism (PE) and the risk of psychiatric disorders. A total of 21,916 patients aged ≥20 years with PE between January 1, 2000, and December 31, 2015, were selected from the National Health Insurance Research Database of Taiwan, along with 65,748 (1:3) controls matched for sex and age. Cox regression model revealed the crude HR was 1.539 (95% CI 1.481 to 1.599; p<0.001), and after adjusting all the covariates, the adjusted HR was 1.704 (95% CI 1.435 to 1.991, p<0.001), for the risk of psychiatric disorders in the PE cohort. PE was associated with the overall psychiatric disorders, dementia, anxiety, depression, and sleep disorders, after the exclusion of the psychiatric diagnoses in the first year. PE was associated with the overall psychiatric disorders, dementia, anxiety, and depression, after the exclusion of the psychiatric diagnoses in the first 5 years. The patients with PE were associated with psychiatric disorders. This finding could serve as a reminder to the physicians to be more watchful and aware in the long-term follow-up of patients with PE for their care and potential mental health problems.
This study aimed to investigate the association between males with psychosexual disorders (PSDs) and the risk of developing psychiatric disorders. A total of 34,972 enrolled patients, with 8,743 subjects who had suffered from PSD and 26,229 controls (1:3) matched for age and index year, from Taiwan’s Longitudinal Health Insurance Database (LHID) from 2000 to 2015, selected from the National Health Insurance Research Database (NHIRD). After adjusting all the confounding factors, the multivariate Cox regression model was used to compare the risk of developing psychiatric disorders, between the PSD and non-PSD groups, during the 15 years of follow-up. Of the all enrollees, 1,113 in the PSD cohort and 2,611 in the non-PSD cohort (1,180.96 vs. 954.68 per 100,000 person-year) developed psychiatric disorders. Multivariate Cox regression model survival analysis revealed that, after adjusting for gender, age, monthly income, urbanization level, geographic region, and comorbidities, the adjusted hazard ratio (HR) was 2.448 (95% CI [2.227, 2.633], p < .001). PSD has been associated with the increased risk in anxiety disorders, depressive disorders, bipolar disorders, sleep disorders, and psychotic disorders, respectively. Sexual dysfunctions, paraphilia, and gender identity disorders were associated with the overall psychiatric disorders with adjusted HRs as 1.990 (p < .001), 11.622 (p < .001), and 5.472 (p < .001), respectively. Male patients who suffered from PSD have a higher risk of developing psychiatric disorders, and this finding should be considered as a timely reminder for the clinicians to provide much more attention for these patients because of their mental health issues.
Fibromyalgia (FM) and other chronic pain syndromes are associated with cognitive dysfunction and attentional deficits, but the neural basis of such alterations is poorly understood. Dyscognition may be related to high levels of neural noise, understood as increased random electrical fluctuations that impair neural communication; however, this hypothesis has not yet been tested in any chronic pain condition. Here we compared electroencephalographic activity (EEG) in 18 FM patients-with high self-reported levels of cognitive dysfunction-and 22 controls during a cognitive control task. We considered the slope of the Power Spectrum Density (PSD) as an indicator of neural noise. As the PSD slope is flatter in noisier systems, we expected to see shallower slopes in the EEG of FM patients. Higher levels of neural noise should be accompanied by reduced power modulation and reduced synchronization between distant brain locations after stimulus presentation. As expected, FM patients showed flatter PSD slopes. After applying a Laplacian spatial filter, we found reduced theta and alpha power modulation and reduced midfrontal-posterior theta phase synchronization. Results suggest higher neural noise and impaired local and distant neural coordination in the patients and support the neural noise hypothesis to explain dyscognition in FM.
Neurodegeneration elicits neuroinflammatory responses to kill pathogens, clear debris and support tissue repair. Neuroinflammation is a dynamic biological response characterized by the recruitment of innate and adaptive immune system cells in the site of tissue damage. Resident microglia and infiltrating immune cells partake in the restoration of central nervous system homeostasis. Nevertheless, their activation may shift to chronic and aggressive responses, which jeopardize neuron survival and may contribute to the disease process itself. Positron Emission Tomography (PET) molecular imaging represents a unique tool contributing to in vivo investigating of neuroinflammatory processes in patients. In the present review, we first provide an overview on the molecular basis of neuroinflammation in neurodegenerative diseases with emphasis on microglia activation, astrocytosis and the molecular targets for PET imaging. Then, we review the state-of-the-art of in vivo PET imaging for neuroinflammation in dementia conditions associated with different proteinopathies, such as Alzheimer’s disease, frontotemporal lobar degeneration and Parkinsonian spectrum.
Introduction: Rheumatoid arthritis (RA) is one of the most common chronic inflammatory diseases. The goal of this study was to analyze the risk of depression in patients diagnosed with RA and treated by general practitioners in the UK.
Methods: The present study included patients first diagnosed with RA between 2000 and 2014 (index date). Individuals were excluded if they had also been diagnosed with depression or if they had received therapy for depression at or prior to the index date. The primary outcome measure was the rate of patients with depression (ICD 10: F32, 33) within 5 years of the RA diagnosis. Demographic data included gender and age. Furthermore, a revised version of the Charlson comorbidity index was used as a generic marker of comorbidity.
Results: A total of 4187 patients were included in the study. After 5 years of follow-up, 23.7% of men and 36.5% of women had developed depression (log rank p value <0.001). Women were more likely to develop depression than men (HR 1.61, 95% CI 1.42–1.84). Age and Charlson comorbidity score had no significant impact on the risk of being diagnosed with this psychiatric disorder.
Conclusion: Around 30% of RA patients developed depression within 5 years of the RA diagnosis. The depression risk was higher in women than in men. The current findings also indicate that improved detection and treatment of patients with both RA and depression are important.
In addition to central hyperexcitability and impaired top–down modulation, chronic inflammation probably plays a role in the pathophysiology of fibromyalgia (FM). Indeed, on the basis of both animal experiments and human studies involving the analysis of cytokines and other inflammation-related proteins in different body fluids, neuroinflammatory mechanisms are considered to be central to the pathophysiology of many chronic pain conditions. However, concerning FM, previous human plasma/serum and/or cerebrospinal fluid (CSF) cytokine studies have looked only at a few predetermined cytokine candidates. Instead of analyzing only a few substances at a time, we used a new multiplex protein panel enabling simultaneous analysis of 92 inflammation-related proteins. Hence, we investigated the CSF and plasma inflammatory profiles of 40 FM patients compared with CSF from healthy controls (n=10) and plasma from blood donor controls (n=46). Using multivariate data analysis by projection, we found evidence of both neuroinflammation (as assessed in CSF) and chronic systemic inflammation (as assessed in plasma). Two groups of proteins (one for CSF and one for plasma) highly discriminating between patients and controls are presented. Notably, we found high levels of CSF chemokine CX3CL1 (also known as fractalkine). In addition, previous findings concerning IL-8 in FM were replicated, in both CSF and plasma. This is the first time that such an extensive inflammatory profile has been described for FM patients. Hence, FM seems to be characterized by objective biochemical alterations, and the lingering characterization of its mechanisms as essentially idiopathic or even psychogenic should be seen as definitively outdated.
An increased risk of suicide ideation and death has been reported in patients with fibromyalgia. This study aimed to evaluate the risk of a suicide event in patients with primary fibromyalgia and in fibromyalgia patients with comorbidities. We used the Longitudinal Health Insurance Database, a subset of the national insurance claim dataset, which enrolled 1 million Taiwanese people from 2000 to 2005, to identify 95,150 patients with incident fibromyalgia (ICD-9-CM 729.0-729.1) and 190,299 reference subjects matched by sex, age, and index date of diagnosis, with a mean of 8.46±2.37 years of follow-up until 2011. The risk of a suicide event (ICD-9-CM, External-Cause Codes 950-959) was analyzed with a Cox proportional hazards model. Stratification analysis was performed by separating fibromyalgia patients and reference subjects with respect to each comorbidity to determine the risk of suicide in fibromyalgia patients with or without comorbidity relative to subjects who had neither fibromyalgia nor comorbidity. In this Taiwanese dataset, there were 347 suicide events in patients with fibromyalgia (4.16 per 104 person-years) and 424 in matched reference subjects (2.63 per 104 person-years) with a significant crude hazard ratio (HR) of 1.58 (95% confidence interval [CI] 1.38-1.83) and an adjusted HR of 1.38 (95% CI 1.17-1.71) for fibromyalgia patients relative to the matched reference subjects. According to the 2-2 stratification analysis, we found that fibromyalgia patients without comorbidity had an independent but mild risk of a suicide event with adjusted HRs ranging from 1.33 to 1.69 relative to subjects with neither fibromyalgia nor comorbidity. Meanwhile, fibromyalgia patients with comorbidity led to a markedly enhanced risk of a suicide event relative to the matched reference subjects, with adjusted HRs ranging from 1.51 to 8.23. Our analysis confirmed a mild-to-moderate risk of a suicide event in patients with primary fibromyalgia. Attention should be paid to the prevention of suicide in fibromyalgia patients with concomitant comorbidities. Copyright © 2016 the Author(s). Published by Wolters Kluwer Health, Inc. All rights reserved.
Objectives:
To determine whether periodontitis is a modifiable risk factor for dementia.
Design:
Prospective cohort study.
Setting:
National Health Insurance Research Database in Taiwan.
Participants:
Individuals aged 65 and older with periodontitis (n = 3,028) and an age- and sex-matched control group (n = 3,028).
Measurements:
Individuals with periodontitis were compared age- and sex-matched controls with for incidence density and hazard ratio (HR) of new-onset dementia. Periodontitis was defined according to International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes 523.3-5 diagnosed by dentists. To ensure diagnostic validity, only those who had concurrently received antibiotic therapies, periodontal treatment other than scaling, or scaling more than twice per year performed by certified dentists were included. Dementia was defined according to ICD-9-CM codes 290.0-290.4, 294.1, 331.0-331.2.
Results:
After adjustment for confounding factors, the risk of developing dementia was calculated to be higher for participants with periodontitis (HR = 1.16, 95% confidence interval = 1.01-1.32, P = .03) than for those without.
Conclusion:
Periodontitis is associated with greater risk of developing dementia. Periodontal infection is treatable, so it might be a modifiable risk factor for dementia. Clinicians must devote greater attention to this potential association in an effort to develop new preventive and therapeutic strategies for dementia.
Alzheimer’s disease (AD) is an age-related neurodegenerative disorder for which there are no effective strategies to prevent or slow its progression. Because AD is multifactorial, recent research has focused on understanding interactions among the numerous risk factors and mechanisms underlying the disease. One mechanism through which several risk factors may be acting is inflammation. AD is characterized by chronic inflammation that is observed before clinical onset of dementia. Several genetic and environmental risk factors for AD increase inflammation, including apolipoprotein E4, obesity, and air pollution. Additionally, sex steroid hormones appear to contribute to AD risk, with age-related losses of estrogens in women and androgens in men associated with increased risk. Importantly, sex steroid hormones have anti-inflammatory actions and can interact with several other AD risk factors. This review examines the individual and interactive roles of inflammation and sex steroid hormones in AD, as well as their relationships with the AD risk factors apolipoprotein E4, obesity, and air pollution.
Neuropsychiatric diseases might enhance stroke development, possibly through inflammation and atherosclerosis. Approximately 25% to 40% of patients with stroke, largely younger patients, are not associated with any conventional stroke risk factors. In this research, we explored whether fibromyalgia (FM), a neuropsychosomatic disorder, increases stroke risk.
From a claims dataset with one million enrollees sourced of the Taiwan National Health Insurance database, we selected 47,279 patients with FM and randomly selected 189,112 age- and sex-matched controls within a 3-year period from January 1, 2000 to December 31, 2002. Stroke risk was assessed using Cox proportional hazards regression.
Comorbidities associated with increased stroke risk, such as hypertension, diabetes, hyperlipidemia, coronary heart disease, irritable bowel syndrome, and interstitial cystitis, were more prevalent in patients with FM and high stroke risk than in the controls. The overall stroke risk was 1.25-fold (95% confidence interval [CI]: 1.21–1.30) higher in the FM group than in the non-FM group. Even without comorbidities, stroke risk was higher in patients with FM than in the controls (adjusted hazard ratio [aHR] = 1.44, 95% CI: 1.35–1.53, P < 0.001). The relative risk of stroke was 2.26-fold between FM and non-FM groups in younger patients (age <35 years, 95% CI: 1.86–2.75).
This is the first investigation associating FM with an increased risk of stroke development. The outcomes imply that FM is a significant risk factor for stroke and that patients with FM, particularly younger patients, require close attention and rigorous measures for preventing stroke.
Background:
The successful prevention and treatment of coronary heart disease (CHD) and stroke has resulted in a substantial increase in longevity, with subsequent growth in the population of older people at risk for dementia.
Objectives:
The authors evaluated the relationship of coronary and other peripheral atherosclerosis to risk of death, dementia, and CHD in the very elderly. Because the extent of vascular disease differs substantially between men and women, sex- and race-specific analyses were included, with a specific focus on women with low coronary artery calcium (CAC) Agatston scores.
Methods:
We evaluated the relationship between measures of subclinical cardiovascular disease (CAC, carotid intimal medial thickness, stenosis, and ankle brachial index) and risk of dementia, CHD, and total mortality in 532 participants of the Cardiovascular Health Study-Cognition Study from 1998/1999 (mean age, 80 years) to 2012/2013 (mean age, 93 years).
Results:
Thirty-six percent of participants had CAC scores >400. Women and African-Americans had lower CAC scores. Few men had low CAC scores. CAC score and number of coronary calcifications were directly related to age-adjusted total mortality and CHD. The age-specific incidence of dementia was higher than for CHD. Only about 25% of deaths were caused by CHD and 16% by dementia. Approximately 64% of those who died had a prior diagnosis of dementia. White women with low CAC scores had a significantly decreased incidence of dementia.
Conclusions:
In subjects 80+ years of age, there is a greater incidence of dementia than of CHD. CAC, as a marker of atherosclerosis, is a determinant of mortality, and risk of CHD and myocardial infarction. White women with low CAC scores had a significantly decreased risk of dementia. A very important unanswered question, especially in the very elderly, is whether prevention of atherosclerosis and its complications is associated with less Alzheimer disease pathology and dementia. (Cardiovascular Health Study [CHS]; NCT00005133).
Abstract: Neuropsychiatric diseases might enhance stroke development,
possibly through inflammation and atherosclerosis. Approximately
25% to 40% of patients with stroke, largely younger patients,
are not associated with any conventional stroke risk factors. In this
research, we explored whether fibromyalgia (FM), a neuropsychosomatic
disorder, increases stroke risk.
From a claims dataset with one million enrollees sourced of the
Taiwan National Health Insurance database, we selected 47,279 patients
with FM and randomly selected 189,112 age- and sex-matched controls
within a 3-year period from January 1, 2000 to December 31, 2002.
Stroke risk was assessed using Cox proportional hazards regression.
Comorbidities associated with increased stroke risk, such as hypertension,
diabetes, hyperlipidemia, coronary heart disease, irritable
bowel syndrome, and interstitial cystitis, were more prevalent in patients
with FM and high stroke risk than in the controls. The overall stroke risk
was 1.25-fold (95% confidence interval [CI]: 1.21–1.30) higher in the
FM group than in the non-FM group. Even without comorbidities, stroke
risk was higher in patients with FM than in the controls (adjusted hazard
ratio [aHR]¼1.44, 95% CI: 1.35–1.53, P<0.001). The relative risk of
stroke was 2.26-fold between FM and non-FM groups in younger
patients (age <35 years, 95% CI: 1.86–2.75).
This is the first investigation associating FMwith an increased risk of
stroke development. The outcomes imply that FM is a significant risk
factor for stroke and that patients with FM, particularly younger patients,
require close attention and rigorous measures for preventing stroke.
Background: The aim of the present study was to determine the prevalence, profile, and severity of dementia and the relative impact of these factors on caregiver burden in a selected population of persons with dementia and their caregivers. Methods: A convenience sample of 100 outpatients and their family caregivers dyads who presented to a memory clinic in one medical center during one consecutive year were recruited. The diagnosis and severity of dementia were determined according to the Diagnostic and Statistical Manual of Mental Disorders, Version IV, Text Revision. The clinical dementia rating scale, mini-mental status examination, and Clinical Global Impression of severity were also administered. The caregiver strain index was used to assess caregiver burden. Results: Caregiver burden is related to the severity of dementia, impairment of cognitive function, and severity of neuropsychiatric symptoms. The caregivers who were younger, nonspousal family members, had a poor relationship with the dementia patient, and psychosomatic symptoms after caring for the patient, or provided longer hours of care-giving, experienced greater strains. Hiring foreign helpers was not associated with a lower caregiver burden. Conclusions: Greater caregiver burden is associated with several factors related to persons with dementia and their caregivers. A possible over-burden on caregivers should be of concern in Taiwan. Hiring foreign helpers was not associated with a lower caregiver burden.
Background
Elderly patients with type 2 diabetes mellitus and hypertension are at high risk for developing dementia. In addition to comorbid disease conditions (Dx), prescription drugs (Rx) are important risk factors for dementia.
Objective
Develop and validate the RxDx-Dementia risk index by combining diagnosis and prescription information in a single risk index to predict incident dementia, and compare its performance with diagnosis-based Charlson comorbidity score (CCS) and prescription-based chronic disease score (CDS).
Methods
Elderly patients diagnosed with type 2 diabetes mellitus and hypertension, and without prior dementia were identified from the Clinical Practice Research Datalink (2003–2012). A Cox proportional hazard model was constructed to model the time to dementia by incorporating age, gender, and 31 RxDx disease conditions as independent variables. Points were assigned to risk factors to obtain summary risk score. Discrimination and calibration of the risk index were evaluated. Different risk indices were compared against RxDx-Dementia risk index using c-statistic, net reclassification improvement (NRI) and integrated discrimination improvement (IDI).
Results
Of 133,176 patients with type 2 diabetes mellitus and hypertension, 3.42% patients developed dementia.The c-statistics value for RxDx-Dementia risk index was 0.806 (95% CI, 0.799–0.812). Based on the c-statistics, NRI and IDI values, the RxDx-Dementia risk index performed better compared to CCS, CDS, and their combinations.
Conclusion
The RxDx-Dementia risk index can be a useful tool to identify hypertensive and diabetic patients who are at high risk of developing dementia. This has implications for clinical management of patients with multiple comorbid conditions as well as risk adjustment for database studies.
Objective:
Patients with late-onset depression (LOD) have been reported to run a higher risk of subsequent dementia. The present study was conducted to assess whether statins can reduce the risk of dementia in these patients.
Methods:
We used the data from National Health Insurance of Taiwan during 1996-2009. Standardized Incidence Ratios (SIRs) were calculated for LOD and subsequent dementia. The criteria for LOD diagnoses included age ≥65 years, diagnosis of depression after 65 years of age, at least three service claims, and treatment with antidepressants. The time-dependent Cox proportional hazards model was applied for multivariate analyses. Propensity scores with the one-to-one nearest-neighbor matching model were used to select matching patients for validation studies. Kaplan-Meier curve estimate was used to measure the group of patients with dementia living after diagnosis of LOD.
Results:
Totally 45,973 patients aged ≥65 years were enrolled. The prevalence of LOD was 12.9% (5,952/45,973). Patients with LOD showed to have a higher incidence of subsequent dementia compared with those without LOD (Odds Ratio: 2.785; 95% CI 2.619-2.958). Among patients with LOD, lipid lowering agent (LLA) users (for at least 3 months) had lower incidence of subsequent dementia than non-users (Hazard Ratio = 0.781, 95% CI 0.685-0.891). Nevertheless, only statins users showed to have reduced risk of dementia (Hazard Ratio = 0.674, 95% CI 0.547-0.832) while other LLAs did not, which was further validated by Kaplan-Meier estimates after we used the propensity scores with the one-to-one nearest-neighbor matching model to control the confounding factors.
Conclusions:
Statins may reduce the risk of subsequent dementia in patients with LOD.
Objectives:
Fibromyalgia has seldom been associated with coronary heart disease (CHD). The aim of this study was to evaluate the risk of CHD in patients with fibromyalgia.
Methods:
We used a dataset of one million participants, systemically scrambled from the Taiwanese national insurance beneficiaries, to identify 61,612 patients with incident fibromyalgia (ICD-9-CM 729.0-729.1) and 184,834 reference subjects matched by sex, age and index date of diagnosis in a 1:3 ratio from 2000 to 2005, with a mean 8.86 ± 2.68 years of follow-up until 2011. Risk of CHD was analyzed by Cox proportional hazard modeling.
Results:
Patients with fibromyalgia had a mean age of 44.1 ± 16.5 years. CHD events developed in fibromyalgia patients (n = 8,280; 15.2 per 103 person-years) and reference subjects (n = 15,162; 9.26 per 103 person-years) with a significant incidence rate ratio of 1.64 (95% confidence interval: 1.61-1.68). The adjusted hazard ratio for CHD in fibromyalgia patients relative to reference subjects was 1.47 (1.43-1.51), after adjusting for age, gender, occupation, monthly income, traditional cardiovascular comorbidities, depression and anxiety. We noted that fibromyalgia and cardiovascular comorbidities had a significant interaction effect on CHD risk (p for interaction <0.01), which was markedly enhanced in fibromyalgia patients with concomitant comorbidities relative to patients with primary fibromyalgia and reference subjects (no fibromyalgia, no comorbidity).
Conclusions:
Our report shows that fibromyalgia patients have an independent risk for CHD development. Fibromyalgia patients with concomitant comorbidities have markedly increased CHD risk relative to those with primary fibromyalgia.
Various studies have shown that irritable bowel syndrome (IBS) is highly associated with other pathologies, including fibromyalgia (FM). The objective of this study was to analyze the differences among risk factors associated with IBS following FM in a nationwide prospective cohort study.
We propose that a relationship exists between FM and IBS. This article presents evidence obtained from a cohort study in which we used data from the Taiwan National Health Insurance Research Database to clarify the relationship between FM and IBS. The follow-up period ran from the start of FM diagnosis to the date of the IBS event, censoring, or December 31, 2011. We analyzed the risk of IBS using Cox proportional hazard regression models, including sex, age, and comorbidities.
During the follow-up period, from 2000 to 2011, the overall incidence of IBS was higher in FM patients than in non-FM patients (7.47 vs 4.42 per 1000 person-years), with a crude hazard ratio = 1.69 (95% confidence interval [CI] 1.45–1.63). After adjustment for age, sex, and comorbidities, FM was associated with a 1.54-fold increased risk for IBS.
Mutually risk factors may influence the relationship between FM and IBS. We recommend that physiologists conduct annual examinations of FM patients to reduce the incidence of IBS progression.
The purpose of this study was to relate central inflammation to autonomic activity (heart rate variability (HRV)) in patients with rheumatoid arthritis (RA) and fibromyalgia (FM). RA patients had reduced parasympathetic activity and FM patients had increased sympathetic activity compared to healthy controls. Comparisons between RA and FM showed higher cerebrospinal fluid (CSF) interleukin (IL)-1β inversely correlated to parasympathetic activity in RA. The FM patients had higher concentrations of CSF IL-8, IL-1Ra, IL-4 and IL-10, but none of these cytokines correlated with HRV. In conclusion, we found different profiles of central cytokines, i.e., elevated IL-1β in inflammatory pain (RA) and elevated IL-8 in dysfunctional pain (FM).
Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
Background:
Stroke is a major cause of disability in the elderly and considerably increases the risk of dementia, which is another important source of disability. This population-based study aimed to examine the risk of dementia in patients with stroke compared with non-stroke cases with similar comorbidities.
Methods:
Using the Taiwan National Health Insurance databank covering the period 2001-2007, this retrospective cohort study evaluated the risk of dementia in 10,884 patients with first stroke who had no history of dementia. In this study, we performed a 1:5 case-control matched analysis, in which cases were matched to controls based on their estimated propensity scores, which were estimated with demographics and associated risk factors. This approach reduced selection bias. Cox proportional hazards regression analysis was then used to estimate the risk of dementia in stroke patients.
Results:
During the 5-year follow-up period, 1,487 (13.74%) stroke and 1,402 (2.59%) non-stroke patients suffered dementia. Stroke was independently associated with a 6.09 (95% confidence interval [CI], 5.66 to 6.55) times greater risk of dementia 5 years after stroke. Older age was associated with a higher incidence of dementia after stroke. Each stroke type had different impacts on the occurrence of dementia. The hazard ratio of dementia among hemorrhagic stroke patients was much higher than those of ischemic stroke and controls.
Conclusion:
The findings of this study suggest that stroke confers an increased risk of dementia, especially in the elderly and in patients with hemorrhagic stroke. We advocate the need for close observation and enhanced health education programs to benefit patients with stroke.
Objective
Fibromyalgia patients frequently report cognitive abnormalities. As the hippocampus plays an important role in learning and memory, we determined whether individuals with fibromyalgia had smaller hippocampal volume compared with healthy control participants.
Methods
T1-weighted structural magnetic resonance imaging (MRI) scans were acquired from 40 female participants with fibromyalgia and 22 female healthy controls. The volume of the hippocampus was estimated using the software FreeSurfer. An analysis of covariance model controlling for potentially confounding factors of age, whole brain size, MRI signal quality, and Beck Depression Inventory scores were used to determine significant group differences.
Results
Fibromyalgia participants had significantly smaller hippocampi in both left (F[1,56]=4.55, P=0.037, η²p=0.08) and right hemispheres (F[1,56]=5.89, P=0.019, η²p=0.10). No significant effect of depression was observed in either left or right hemisphere hippocampal volume (P=0.813 and P=0.811, respectively).
Discussion
Potential mechanisms for reduced hippocampal volume in fibromyalgia include abnormal glutamate excitatory neurotransmission and glucocorticoid dysfunction; these factors can lead to neuronal atrophy, through excitotoxicity, and disrupt neurogenesis in the hippocampus. Hippocampal atrophy may play a role in memory and cognitive complaints among fibromyalgia patients.
An increasing population of dementia patients produces substantial societal impacts. We assessed the prevalence of mild cognitive impairment (MCI) and all-cause dementia, including very mild dementia (VMD), in Taiwan. In a nationwide population-based cross-sectional survey, participants were selected by computerized random sampling from all 19 Taiwan counties and were enrolled between December 2011 and March 2013. Cases were identified through in-person interviews based on the National Institute on Aging-Alzheimer's Association clinical criteria. Demographic data and histories involving mental status and function in daily living were collected. The principal objective assessments were the Taiwanese Mental Status Examination and Clinical Dementia Rating. In all, 10,432 people aged 65 years or older (mean age 76.2±6.7, 52.3% women) were interviewed. The age-adjusted prevalence of all-cause dementia was 8.04% (95% CI 7.47-8.61), including a 3.25% (95% CI 2.89-3.61) prevalence of VMD; that of MCI was 18.76% (95% CI 17.91-19.61). Women had a higher prevalence than men of both all-cause dementia (9.71% vs. 6.36%) and MCI (21.63% vs. 15.57%). MCI affects a considerable portion of the population aged 65 and above in Taiwan. The inclusion of VMD yields dementia prevalence rates higher than those previously reported from Taiwan. Old age, female gender, and a low educational level are significant associated factors.
Femoral neck fracture is common in the elderly, and its impact has increased in aging societies. Comorbidities, poor levels of activity and pain may contribute to the development of depression, but these factors have not been well addressed. This study aims to investigate the frequency and risk of major depression after a femoral neck fracture using a nationwide population-based study. The Taiwan Longitudinal Health Insurance Database was used in this study. A total of 4,547 patients who were hospitalized for femoral neck fracture within 2003 to 2007 were recruited as a study group; 13,641 matched non-fracture participants were enrolled as a comparison group. Each patient was prospectively followed for 3 years to monitor the occurrence of major depression. Cox proportional-hazards models were used to compute the risk of major depression between members of the study and comparison group after adjusting for residence and socio-demographic characteristics. The most common physical comorbidities that were present after the fracture were also analyzed. The incidences of major depression were 1.2% (n = 55) and 0.7% (n = 95) in the study and comparison groups, respectively. The stratified Cox proportional analysis showed a covariate-adjusted hazard ratio of major depression among patients with femoral neck fracture that was 1.82 times greater (95% CI, 1.30-2.53) than that of the comparison group. Most major depressive episodes (34.5%) presented within the first 200 days following the fracture. In conclusion, patients with a femoral neck fracture are at an increased risk of subsequent major depression. Most importantly, major depressive episodes mainly occurred within the first 200 days following the fracture.
Cognitive and behavioral impairments are core manifestations of fibromyalgia and may be more disabling than pain itself. Involvement of the central nervous system is ascertained by the fact that frontoparietal and limbic cortices are often functionally and structurally affected along the course of this disease. Even though neuroimaging has brought some experimental evidence to support such network disruption, there are currently no clinically effective biomarkers that detect and quantify cognitive and behavioral disturbances in fibromyalgia; thus, traditional scales and tests of neuropsychiatric assessment remain the most important diagnostic tools. This review addresses the most common cognitive and behavioral impairments in people with fibromyalgia, while explaining their pathophysiological basis and currently available therapeutic options.
Fibromyalgia syndrome is mainly characterized by pain, fatigue, and sleep disruption. The etiology of fibromyalgia is still unclear: if central sensitization is considered to be the main mechanism involved, then many other factors, genetic, immunological, and hormonal, may play an important role. The diagnosis is typically clinical (there are no laboratory abnormalities) and the physician must concentrate on pain and on its features. Additional symptoms (e.g., Raynaud's phenomenon, irritable bowel disease, and heat and cold intolerance) can be associated with this condition. A careful differential diagnosis is mandatory: fibromyalgia is not a diagnosis of exclusion. Since 1990, diagnosis has been principally based on the two major diagnostic criteria defined by the ACR. Recently, new criteria have been proposed. The main goals of the treatment are to alleviate pain, increase restorative sleep, and improve physical function. A multidisciplinary approach is optimal. While most nonsteroidal anti-inflammatory drugs and opioids have limited benefit, an important role is played by antidepressants and neuromodulating antiepileptics: currently duloxetine (NNT for a 30% pain reduction 7.2), milnacipran (NNT 19), and pregabalin (NNT 8.6) are the only drugs approved by the US Food and Drug Administration for the treatment of fibromyalgia. In addition, nonpharmacological treatments should be associated with drug therapy.
Times are changing. Taiwan is one of the richest countries in the Asia Pacific region. It enacted its single-payer national health insurance program in 1995: in all estimates, it has been very successful. It has a strong healthcare system and the universal health insurance ensures that all citizens have grown to expect a high level of care. Healthcare systems are designed to meet the healthcare needs of target populations. There are a wide variety of healthcare systems around the world. In some countries, healthcare system planning is distributed among market participants, whereas in others planning is made more centrally among governments, trade unions, charities, religions, or other co-ordinated bodies to deliver planned healthcare services targeted to the populations they serve. However, healthcare planning has often been evolutionary rather than revolutionary. In healthcare all work carried out must be at the highest quality, and a much higher proportion of resources must be invested in quality in healthcare. The aim of this report is to give an overview of the healthcare service provision in Taiwan.
The aim of this study was to estimate the prevalence of fibromyalgia, as well as to assess the major symptoms of this syndrome in an adult, low socioeconomic status population assisted by the primary health care system in a city in Brazil.
We cross-sectionally sampled individuals assisted by the public primary health care system (n = 768, 35-60 years old). Participants were interviewed by phone and screened about pain. They were then invited to be clinically assessed (304 accepted). Pain was estimated using a Visual Analogue Scale (VAS). Fibromyalgia was assessed using the Fibromyalgia Impact Questionnaire (FIQ), as well as screening for tender points using dolorimetry. Statistical analyses included Bayesian Statistics and the Kruskal-Wallis Anova test (significance level = 5%).
From the phone-interview screening, we divided participants (n = 768) in three groups: No Pain (NP) (n = 185); Regional Pain (RP) (n = 388) and Widespread Pain (WP) (n = 106). Among those participating in the clinical assessments, (304 subjects), the prevalence of fibromyalgia was 4.4% (95% confidence interval [2.6%; 6.3%]). Symptoms of pain (VAS and FIQ), feeling well, job ability, fatigue, morning tiredness, stiffness, anxiety and depression were statically different among the groups. In multivariate analyses we found that individuals with FM and WP had significantly higher impairment than those with RP and NP. FM and WP were similarly disabling. Similarly, RP was no significantly different than NP.
Fibromyalgia is prevalent in the low socioeconomic status population assisted by the public primary health care system. Prevalence was similar to other studies (4.4%) in a more diverse socioeconomic population. Individuals with FM and WP have significant impact in their well being.
Background:
Primary headaches include migraines, tension-type headaches and other primary headache syndromes. Migraines and tension-type headaches are associated with patient discomfort and other diseases. This study aimed to investigate the association between primary headaches and the risk of developing dementia, and to clarify the association between different types of headaches and dementia.
Materials and methods:
We conducted a nationwide matched cohort population-based study. A total of 3,620 patients with newly diagnosed primary headaches, including migraines and tension-type headaches, between January 1 and December 31, 2000 were selected from the National Health Insurance Research Database of Taiwan, along with 10,860 controls matched for sex and age. After adjusting for confounding factors, Fine and Gray׳s competing risk analysis was used to compare the risk of developing dementia during 10 years of follow-up.
Results:
Of the study subjects, 170 (4.70 %) developed dementia compared with 433 (3.99%) of the controls. Fine and Gray׳s competing risk analysis revealed that the study subjects were more likely to develop dementia (hazard ratio = 2.057; 95% CI: 1.718-2.462; P < 0.001). After adjusting for sex, age, monthly income, urbanization level, geographic region of residence and comorbidities, the hazard ratio for dementia was 2.048 (95% CI: 1.705-2.461, P < 0.001). Migraines and tension-type headaches were associated with nonvascular dementia but not vascular dementia.
Conclusions:
The patients with headaches had a 105% increased risk of dementia. Further studies are needed to elucidate the underlying mechanisms.
Chronic inflammation, which changes the neurotransmitter metabolism and kindles neuroendocrine system dysfunction in the central nervous system, might cause fibromyalgia (FM) formation. In FM patients without traditional FM risk factors, such as hypertension, hyperlipidemia, diabetes, sleep disorder, depression, and anxiety, the chronic inflammatory process is a possible risk factor for FM. Thus, we investigated whether chronic osteomyelitis (COM), a disease characterized by chronic inflammation, increases FM risk. Including data for 1 million enrollees, the Longitudinal Health Insurance Database was used, and 1,244 COM patients without FM history and 4,976 randomly selected sex- and age-matched control subjects without COM or FM history were extracted. The development of FM over a 13-year follow-up period from 1999 to 2011 was evaluated, and FM risk was estimated using the Cox proportional regression model. The aforementioned FM risk factors were more common in COM patients, who had a significantly greater FM risk than did the control subjects. Compared with those who had no associated risk factors, patients with COM had a greater FM risk than did the control subjects (adjusted hazard ratio [aHR] = 1.32, 95% confidence interval [CI], .99-1.75). Younger people had an even greater risk (age younger than 35 years: aHR = 1.58, 95% CI, 1.03-2.44; age 60 years or older: aHR = 1.03, 95% CI, .78-1.36). To our knowledge, this is the first study to link COM to an enhanced risk of FM development. The results imply that COM is a predictor of FM, suggesting that close follow-up for patients with COM is required to prevent FM, especially in younger populations.
Perspective:
COM is associated with the augmented risk of developing FM, and rigorous treatments for COM patients might decrease the future risk of FM formation, especially in those with relatively younger ages.
Background:
Chronic periodontitis and gingivitis are associated with various diseases; however, their impact on dementia is yet to be elucidated. This study is aimed at investigating the association between chronic periodontitis and gingivitis, and the risk of developing dementia.
Methods:
A total of 2,207 patients, with newly diagnosed chronic periodontitis and gingivitis between January 1, 2000 and December 31, 2000, were selected from the National Health Insurance Research Database of Taiwan, along with 6,621 controls matched for sex and age. After adjusting for confounding factors, Cox proportional hazards analysis was used to compare the risk of developing dementia during the 10-year follow-up period.
Results:
Of the study subjects, 25 (1.13%) developed dementia compared to 61 (0.92%) in the control group. Cox proportional hazards regression analysis revealed that the study subjects were more likely to develop dementia (hazard ratio (HR) 2.085, 95% CI 1.552-4.156, p < 0.001). After adjusting for sex, age, monthly income, urbanization level, geographic region, and comorbidities, the HR for dementia was 2.54 (95% CI 1.297-3.352, p = 0.002).
Conclusions:
Patients with chronic periodontitis and gingivitis have a higher risk of developing dementia. However, further studies on other large or national data sets are required to support the current findings.
Aims:
The association between heart failure and dementia remains unclear. We assessed the risk of dementia among patients with heart failure and members of a general population comparison cohort.
Methods and results:
Individual-level data from Danish medical registries were linked in this nationwide population-based cohort study comparing patients with a first-time hospitalization for heart failure between 1980 and 2012 and a year of birth-, sex-, and calendar year-matched comparison cohort from the general population. Stratified Cox regression analysis was used to compute 1-35-year hazard ratios (HRs) for the risk of all-cause dementia and, secondarily, Alzheimer's disease, vascular dementia, and other dementias. Analyses included 324 418 heart failure patients and 1 622 079 individuals from the general population (median age 77 years, 52% male). Compared with the general population cohort, risk of all-cause dementia was increased among heart failure patients [adjusted HR 1.21, 95% confidence interval (CI) 1.18-1.24]. The associations were stronger in men and in heart failure patients under age 70. Heart failure patients had higher risks of vascular dementia (adjusted HR 1.49, 95% CI 1.40-1.59) and other dementias (adjusted HR 1.30, 95% CI 1.26-1.34) than members of the general population cohort. Heart failure was not associated with Alzheimer's disease (adjusted HR 1.00, 95% CI 0.96-1.04).
Conclusion:
Heart failure was associated with an increased risk of all-cause dementia. Heart failure may represent a risk factor for dementia, but not necessarily for Alzheimer's disease.
Background:
Previous studies have stated that atrial fibrillation (AF) is associated with a higher risk of dementia. However, none have examined the competition between death and incident dementia in patients with AF. We evaluated the risk of incident dementia in patients with AF in comparison to people without this arrhythmia, considering of the competing risk of death.
Methods:
AF and non-AF cohorts were identified using the large administrative database of the Lombardy Region and followed for ten years. Patients with incident dementia were identified if they had an ICD 9 code referring to dementia at hospital discharge or a prescription for any anti-dementia drug. The association of AF with dementia or death was assessed with the multivariable Cox proportional-regression model, sensitivity analysis with a 1:1 propensity score matching and competing-risk analysis.
Results:
In 2003 a total of 27,431 patients were hospitalized for AF in the Lombardy Region, while the cohort of non-AF counted 1,600,200 people. AF was associated with a higher risk of dementia (17%) and death (51%) at multivariable Cox analysis. These results were confirmed by the model fitted after propensity score matching. However, competing risk analysis found the association between AF and incident dementia was no longer significant (HR 0.99; 95% CI 0.94-1.04).
Conclusions:
In this real-world population the association between AF and dementia was no longer statistically significant when death was considered a competing risk.
Method:
Members of the Fibromyalgia Support Network of Western Australia were invited to undertake an anonymous online survey. Information was gathered regarding demographics, symptom onset, the timing of diagnosis, employment status and changes in the ability to work.
Results:
287 responses were analysed. 90.6% of respondents were female, mean age 51.1 ± 10.6 years and had experienced symptoms between 2 to 20 years. 52.8% were diagnosed less than 5 years previously. 54.2% were working full-time and 21.5% working part time at symptom onset, however only 15.6% were currently working full time, with 44.8% not currently working at all. 24.3% stopped and 32.6% reduced paid work directly because of fibromyalgia within 5 years of symptom development, with 15.3% ceasing and an additional 17.4% reducing work because of symptoms before diagnosis. 35.1% currently received financial support because they were unable to work due to FM symptoms. 24.3% reported fibromyalgia medication increased their ability to work, while 20.8% reported it reduced their ability to work.
Conclusion:
A community pilot survey of Australians with fibromyalgia indicates a high impact on work ability. This occurs from symptom onset and often before diagnosis. Early diagnosis and intervention may provide a window of opportunity to prevent work disability in fibromyalgia.
Objective:
To examine the association between the risks of depression and vascular dementia (VaD) based on Taiwan's National Health Insurance Research Database.
Methods:
This retrospective longitudinal matched-cohort study used National Health Insurance Research Database data from 49,955 participants (9,991 with new onset depression, 39,964 controls). A Cox regression analysis was performed on the whole sample and the subgroup of patients with depression. We further excluded patients who developed VaD within 3 or 5 years after enrollment to evaluate depression as an independent risk factor for or a prodrome of VaD.
Results:
During the 10-year follow-up period, the incidence rate ratio of VaD between patients with depression and controls was 4.24 [95% confidence interval (CI) 2.90-6.21, P < 0.001]. After adjustment for covariates, the hazard ratio (HR) of VaD in patients with depression was 3.10 (95% CI 2.13-4.52, P < 0.001). In the whole sample, risk factors for VaD besides depression were aged ≥60 years (HR = 20.08), hypertension (HR = 1.70), diabetes (HR = 1.61), coronary artery disease (HR = 2.26), head injury (HR = 2.20), and cerebrovascular disease (HR = 3.02). In patients with depression, aged ≥60 years (HR = 32.16), coronary artery disease (HR = 2.82), head injury (HR = 2.06), and cerebrovascular disease (HR = 2.37) remained risk factors for VaD. After excluding those who developed VaD within 3 or 5 years, HRs remained high (3.28, 95% CI 2.03-5.31, P < 0.001; 2.12, 95% CI 1.05-4.25, P = 0.035, respectively).
Conclusions:
Our findings suggest that depression is an independent risk factor for subsequent VaD. Older age, cerebrovascular disease, head injury, and coronary artery disease might increase the risk of VaD among patients with depression.
Alzheimer’s disease (AD) is the most common underlying cause of dementia, and novel drugs for its treatment are needed. Of the different theories explaining the development and progression of AD, “amyloid hypothesis” is the most supported by experimental data. This hypothesis states that the cleavage of amyloid precursor protein (APP) leads to the formation of amyloid beta (Aβ) peptides that congregate with formation and deposition of Aβ plaques in the frontal cortex and hippocampus. Risk factors including neurotransmitter modulation, chronic inflammation, metal-induced oxidative stress and elevated cholesterol levels are key contributors to the disease progress. Current therapeutic strategies abating AD progression are primarily based on anti-acetylcholinesterase (AChE) inhibitors as cognitive enhancers. The AChE inhibitor, donepezil, is proven to strengthen cognitive functions and appears effective in treating moderate to severe AD patients. N-Methyl-D-aspartate receptor antagonist, memantine, is also useful, and its combination with donepezil demonstrated a strong stabilizing effect in clinical studies on AD. Nonsteroidal anti-inflammatory drugs delayed the onset and progression of AD and attenuated cognitive dysfunction. Based upon epidemiological evidence and animal studies, antioxidants emerged as potential AD preventive agents; however, clinical trials revealed inconsistencies. Pharmacokinetic and pharmacodynamic profiling demonstrated pleiotropic functions of the hypolipidemic class of drugs, statins, potentially contributing towards the prevention of AD. In addition, targeting the APP processing pathways, stimulating neuroprotective signaling mechanisms, using the amyloid anti-aggregants and Aβ immunotherapy surfaced as well-tested strategies in reducing the AD-like pathology. Overall, this review covers mechanism of inducing the Aβ formation, key risk factors and major therapeutics prevalent in the AD treatment nowadays. It also delineates the need for novel screening approaches towards identifying drugs that may prevent or at least limit the progression of this devastating disease.
Activated microglia, the resident macrophages of the brain, are a feature of Alzheimer's disease. Animal models suggest that when activated microglia are further activated by a subsequent systemic infection this results in significantly raised levels of interleukin 1beta within the CNS, which may in turn potentiate neurodegeneration. This prospective pilot study in Alzheimer's disease subjects showed that cognitive function can be impaired for at least two months after the resolution of a systemic infection and that cognitive impairment is preceded by raised serum levels of interleukin 1beta. These relations were not confounded by the presence of any subsequent systemic infection or by baseline cognitive scores. Further research is needed to determine whether recurrent systemic infections drive cognitive decline in Alzheimer's disease subjects through a cytokine mediated pathway.
Unlabelled:
Milnacipran, a serotonin/norepinephrine reuptake inhibitor, has been approved by the US Food and Drug Administration for the treatment of fibromyalgia (FM). This report presents the results of a randomized, double-blind, placebo-controlled trial of milnacipran conducted to test the hypotheses that a) similar to patients with chronic fatigue syndrome, patients with FM have increased ventricular lactate levels at baseline; b) 8 weeks of treatment with milnacipran will lower ventricular lactate levels compared with baseline levels and with ventricular lactate levels after placebo; and c) treatment with milnacipran will improve attention and executive function in the Attention Network Test compared with placebo. In addition, we examined the results for potential associations between ventricular lactate and pain. Baseline ventricular lactate measured by proton magnetic resonance spectroscopic imaging was found to be higher in patients with FM than in healthy controls (F1,37 = 22.11, P < .0001, partial η(2) = .37). Milnacipran reduced pain in patients with FM relative to placebo but had no effect on cognitive processing. At the end of the study, ventricular lactate levels in the milnacipran-treated group had decreased significantly compared with baseline and after placebo (F1,18 = 8.18, P = .01, partial η(2) = .31). A significantly larger proportion of patients treated with milnacipran showed decreases in both ventricular lactate and pain than those treated with placebo (P = .03). These results suggest that proton magnetic resonance spectroscopic imaging measurements of lactate may serve as a potential biomarker for a therapeutic response in FM and that milnacipran may act, at least in part, by targeting the brain response to glial activation and neuroinflammation.
Perspective:
Patients treated with milnacipran showed decreases in both pain and ventricular lactate levels compared with those treated with placebo, but, even after treatment, levels of ventricular lactate remained higher than in controls. The hypothesized mechanism for these decreases is via drug-induced reductions of a central inflammatory state.
Several cross-sectional studies have reported a common comorbidity between depression and fibromyalgia syndrome (FMS). However, a bidirectional temporal association between these two distinct diseases has rarely been investigated. Using the Taiwan National Health Insurance Research Database, 25,969 patients with FMS and without any psychiatric disorder and 17,142 patients with depression and without FMS between 2000 and 2008 were enrolled and separately compared with age- and sex-matched (1:4) control groups. Patients with FMS who developed a new-onset depression and those with depression who developed a new-onset FMS were identified during the follow-up (to the end of 2011). The conditional Cox regression analyses, after adjustment for demographic data and medical comorbidities, showed that the patients with FMS were associated with an increased risk (hazard ratio [HR] = 7.46, 95% confidence interval [CI] = 6.77-8.22) of subsequent depression, and that those with depression were associated with an increased risk (HR = 6.28, 95% CI = 5.67-6.96) of subsequent FMS. Our results supported a bidirectional temporal association between depression and FMS. Each disease occurring first may increase the risk of the other subsequently. Further study may be necessary to determine the underlying mechanism between depression and FMS, and to clarify whether a prompt intervention for depression or FMS may decrease the risk of the other later in life.
Our study supported a bidirectional temporal association between depression and FMS that each disease occurring first may increase the risk of the other subsequently. This result may imply a shared pathophysiology between FMS and depression, but it needs the further investigation.
Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.
Although depression and type 2 diabetes mellitus (DM) may independently increase the risk for dementia, no studies have examined whether the risk for dementia among people with comorbid depression and DM is higher than the sum of each exposure individually.
To examine the risk for all-cause dementia among persons with depression, DM, or both compared with persons with neither exposure.
We performed a national population-based cohort study of 2 454 532 adults, including 477 133 (19.4%) with depression, 223 174 (9.1%) with DM, and 95 691 (3.9%) with both. We included all living Danish citizens 50 years or older who were free of dementia from January 1, 2007, through December 31, 2013 (followed up through December 31, 2013). Dementia was ascertained by physician diagnosis from the Danish National Patient Register or the Danish Psychiatric Central Register and/or by prescription of a cholinesterase inhibitor or memantine hydrochloride from the Danish National Prescription Registry. Depression was ascertained by psychiatrist diagnosis from the Danish Psychiatric Central Research Register or by prescription of an antidepressant from the Danish National Prescription Registry. Diabetes mellitus was identified using the National Diabetes Register.
We estimated the risk for all-cause dementia associated with DM, depression, or both using Cox proportional hazards regression models that adjusted for potential confounding factors (eg, demographics) and potential intermediates (eg, medical comorbidities).
During 13 834 645 person-years of follow-up, 59 663 participants (2.4%) developed dementia; of these, 6466 (10.8%) had DM, 15 729 (26.4%) had depression, and 4022 (6.7%) had both. The adjusted hazard ratio for developing all-cause dementia was 1.83 (95% CI, 1.80-1.87) for persons with depression, 1.20 (95% CI, 1.17-1.23) for persons with DM, and 2.17 (95% CI, 2.10-2.24) for those with both compared with persons who had neither exposure. The excess risk for all-cause dementia observed for individuals with comorbid depression and DM surpassed the summed risk associated with each exposure individually, especially for persons younger than 65 years (hazard ratio, 4.84 [95% CI, 4.21-5.55]). The corresponding attributable proportion due to the interaction of comorbid depression and DM was 0.25 (95% CI, 0.13-0.36; P < .001) for those younger than 65 years and 0.06 (95% CI, 0.02-0.10; P = .001) for those 65 years or older.
Depression and DM were independently associated with a greater risk for dementia, and the combined association of both exposures with the risk for all-cause dementia was stronger than the additive association.
Cognitive dysfunction is a signature feature of fibromyalgia. Many who develop cognitive problems in their middle years are concerned that it is prodromal to Alzheimer's disease.
To determine if deficits in episodic memory and progressive cognitive decline, hallmarks of Alzheimer's disease, are prominent in the cognitive makeup of fibromyalgia patients.
In a cross-sectional study, performance on 15 neurocognitive (NC) measures was evaluated in 2 cohorts of fibromyalgia subjects. The first cohort contained 94 subjects with a short duration of cognitive problems (≤12 months). The second cohort contained 55 subjects with a long duration of cognitive problems (≥84 months).
The 2 groups were similar in education (14.9 ± 2.3 vs 14.9 ± 2.4), vocabulary scale score (11.2 ± 2.3 vs 11.6 ± 2.7), and depression (17.9 ± 9.8 vs 17.7 ± 9.4). The mean durations of cognitive problems in the short- and long-term group were 7.3 ± 3.9 months and 13.3 ± 7.1 years, respectively. There was no evidence of decline on 14 of 15 measures in the fibromyalgia group with an additional 12.6 years of cognitive dysfunction. Normality of function was in evidence on 4 measures of episodic memory in both cohorts.
Fibromyalgia patients' fear of developing Alzheimer's disease was not borne out by the data. The cognitive pattern of fibromyalgia appears distinct from that of Alzheimer's disease. Fibrofog is not associated with either episodic memory loss on standard tests of episodic memory or progressive cognitive decline. Patients with fibrofog remember personally experienced events termed episodic memory at a normal rate in quiet, distraction-free conditions. Patients with Alzheimer's disease do not. They forget the essential elements of short stories just read to them in environments free of distractions. In Alzheimer's disease, the brain mechanisms responsible for encoding personally experienced events into memory are irreversibly impaired. In fibrofog, the encoding mechanisms are intact. At the heart of memory loss in fibromyalgia is the inability to appropriately filter out relevant distractions. Encoding mechanisms that otherwise operate normally in forming episodic memories for everyday events in fibromyalgia appear to malfunction when 2 streams of information operate concurrently (relevant information and a source of distraction overlap). The findings should allay the worries of many with fibromyalgia who fear that fibrofog is the start of a dementing process.
Chronic hypertension, particularly midlife high blood pressure, has been associated with an increased risk for cognitive decline and dementia. In this context, antihypertensive drugs might have a preventive effect, but the association remains poorly understood.
The aim of this systematic review was to examine all published findings that investigated this relationship and discuss the mechanisms underlying the potential benefits of antihypertensive medication use.
A literature search was conducted using MEDLINE, Embase, and the Cochrane Library for publications from 1990 onwards mentioning hypertension, antihypertensive drugs, cognitive decline, and dementia.
A total of 38 relevant publications, corresponding to 18 longitudinal studies, 11 randomized controlled trials, and nine meta-analyses were identified from the 10,251 articles retrieved in the literature search. In total, 1,346,176 subjects were included in these studies; the average age was 74 years. In the seven longitudinal studies assessing the effect of antihypertensive medication on cognitive impairment or cognitive decline, antihypertensive drugs appeared to be beneficial. Of the 11 longitudinal studies that assessed the effect of antihypertensive medication on incidence of dementia, only three did not find a significant protective effect. Antihypertensive medication could decrease the risk of not only vascular dementia but also Alzheimer's disease. Four randomized controlled trials showed a potentially preventive effect of antihypertensive drugs on the incidence of dementia or cognitive decline: SYST-EUR (Systolic Hypertension in Europe Study) I and II, with a 55 % reduction in dementia risk (3.3 vs. 7.4 cases per 1,000 patient years; p < 0.001); HOPE (Heart Outcomes Prevention Evaluation), with a 41 % reduction in cognitive decline associated with stroke (95 % confidence interval [CI] 6-63); and PROGRESS (Perindopril Protection against Recurrent Stroke Study), with a 19 % reduction in cognitive decline (95 % CI 4-32; p = 0.01). Meta-analyses have sometimes produced conflicting results, but this may be due to methodological considerations. The lack of homogeneity across study designs, patient populations, exposition, outcomes, and duration of follow-up are the most important methodological limitations that might explain the discrepancies between some of these studies.
Antihypertensive drugs, particularly calcium channel blockers and renin-angiotensin system blockers, may be beneficial in preventing cognitive decline and dementia. However, further randomized controlled trials with longer periods of follow-up and cognition as the primary outcome are needed to confirm these findings.
Objective:
Although persons with lower socioeconomic status (SES) generally have poorer health status for many medical conditions, the association of SES with symptom severity in fibromyalgia (FM) is unknown. The subjective symptoms of FM may be influenced by personal perceptions, and environmental and psychosocial factors. Therefore SES may influence symptom expression and severity.
Methods:
Data for this cross-sectional analysis were obtained from a real-life prospective cohort of 246 patients with FM categorized according to level of education: high school graduates or less (Group 1; n = 99), college graduates (Group 2; n = 84), and university graduates (Group 3; n = 63). The association between level of education, a well-validated measure of SES, and disease severity, functional status, and quality of life were examined.
Results:
Lower education was significantly associated with older age (p = 0.039), current unemployment (p < 0.001), and more severe disease, as measured by patient global assessment disease activity (p = 0.019), McGill Pain Questionnaire (p = 0.026), Pain Disability Index (p = 0.031), Pain Catastrophizing Scale (p = 0.015), Health Assessment Questionnaire (p = 0.001), and Fibromyalgia Impact Questionnaire (p = 0.002), but not pain level, anxiety, or depression. These associations remained significant even upon adjusting for age and sex differences.
Conclusion:
Patients with FM and lower SES, as assessed by education level, reported greater symptom severity and functional impairment, despite reporting similar levels of pain, depression, and anxiety. Although FM spans all socioeconomic groups, factors other than specific disease characteristics or mental status, appear to play an important role in patients' perception of illness.
Headache has not been established as a risk factor for dementia. The aim of this study was to determine whether any headache was associated with subsequent development of vascular dementia (VaD), Alzheimer's disease (AD) or other types of dementia.
This prospective population-based cohort study used baseline data from the Nord-Trøndelag Health Study (HUNT 2) performed during 1995-1997 and, from the same Norwegian county, a register of cases diagnosed with dementia during 1997-2010. Participants aged ≥20 years who responded to headache questions in HUNT 2 were categorized (headache free; with any headache; with migraine; with nonmigrainous headache). Hazard ratios (HRs) for later inclusion in the dementia register were estimated using Cox regression analysis.
Of 51,383 participants providing headache data in HUNT 2, 378 appeared in the dementia register during the follow-up period. Compared to those who were headache free, participants with any headache had increased risk of VaD ( N = 63) (multivariate-adjusted HR = 2.3, 95% CI 1.4-3.8, P = 0.002) and of mixed dementia (VaD and AD ( N = 52)) (adjusted HR = 2.0, 95% CI 1.1-3.5, P = 0.018). There was no association between any headache and later development of AD ( N = 180).
In this prospective population-based cohort study, any headache was a risk factor for development of VaD.
The incidence of Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) with associated serious complications continues to grow rapidly especially in developed countries. Emerging evidence indicates that AD and T2DM share some common risk factors with comparable pathological features including insulin resistance, amyloidogenesis, glucocorticoid imbalance, inflammation, mitochondrial function and oxidative stress. T2DM has been identified as a risk factor for AD. It has even been hypothesized that AD might be "type 3 diabetes". In addition to amyloid precursor protein processing and tau phosphorylation, commonalities between T2DM and AD in molecular mechanisms provide clues to the identification of novel therapeutic targets such as glucagon-like peptide 1, butyrylcholinesterase, and receptor for advanced glycosylation end products. Although several classes of anti-diabetic drugs are available, achieving long-term glycaemic control without side effects is often challenging. This review summarizes recent evidence for the pathological links, common therapeutic targets, currently FDA-approved and potential future therapies, giving special attention to ongoing clinical trials of antidiabetic drugs in AD patients and common therapeutic strategies in the management of both AD and T2DM.
Objectives:
To describe and understand varieties and characteristics of sensitization contributing to hyperalgesia in participants with chronic pain conditions.
Methods:
Thermal stimulation was delivered to the face, forearm, and calf of pain-free participants and individuals with irritable bowel syndrome, temporomandibular pain disorder (TMD), and fibromyalgia syndrome (FM). Three-second contacts by a preheated thermode occurred at 30-second intervals in ascending and then in descending series (0.7°C steps).
Results:
Thermal pain ratings during ascending series were greater at each site in individuals diagnosed with chronic pain. Intense pain at the time of testing further enhanced the ratings at all sites, but mild or moderate clinical pain did not have this effect. Thermal pain in all participants was greater during descending series compared with the ascending series of arm and leg stimulation. The hypersensitivity during the descending series was comparable in pain-free, FM and TMD participants but was increased in duration for arm or leg stimulation of FM participants.
Discussion:
The widespread sensitization for irritable bowel syndrome and TMD participants does not rely on mechanisms of spatial and temporal summation often invoked to explain widespread hyperalgesia associated with chronic pain. Increased sensitivity during descending series of stimulation of an arm or leg but not the face indicates a propensity for sensitization of nociceptive input to the spinal cord. Abnormally prolonged sensitization for FM participants reveals a unique influence of widespread chronic pain referred to deep somatic tissues.
Objective:
The temporal relationship between Tourette syndrome (TS) and depression is unclear. This cohort study evaluates the relationship between TS and depression in Taiwan.
Methods:
Claims data from the Taiwan National Health Insurance database were used to conduct retrospective cohort analyses. The study cohort contained 1337 TS patients who were frequency matched by sex, age, urbanization of residence area, parental occupation, and baseline year with 10 individuals without TS. Cox's proportional hazard regression analysis was conducted to estimate the effects of TS on depression risk.
Results:
In patients with TS, the risk of developing depression was significantly higher than in patients without TS (p value for log-rank test < .0001). After adjusting for potential confounding, the TS cohort was 4.85 times more likely to develop depression than the control cohort (HR = 4.85, 95% CI = 3.46-6.79).
Conclusions:
In Taiwan, patients with TS have a higher risk of developing depression. The findings of this study are compatible with studies from other countries. This study could provide an evidence to inform the prognosis for a child with TS. The mechanism between TS and increased depression risk requires further investigation.
Objective
To estimate and compare the prevalence of fibromyalgia by 2 different methods in Olmsted County, Minnesota.Methods
The first method was a retrospective review of medical records of potential cases of fibromyalgia in Olmsted County using the Rochester Epidemiology Project (from January 1, 2005, to December 31, 2009) to estimate the prevalence of diagnosed fibromyalgia in clinical practice. The second method was a random survey of adults in Olmsted County using the fibromyalgia research survey criteria to estimate the percentage of responders who met the fibromyalgia research survey criteria.ResultsOf the 3,410 potential patients identified by the first method, 1,115 had a fibromyalgia diagnosis documented in the medical record by a health care provider. The age- and sex-adjusted prevalence of diagnosed fibromyalgia by this method was 1.1%. By the second method, of the 2,994 people who received the survey by mail, 830 (27.6%) responded and 44 (5.3%) met the fibromyalgia research survey criteria. The age- and sex-adjusted prevalence of fibromyalgia in the general population of Olmsted County by this method was estimated at 6.4%.Conclusion
To the best of our knowledge, this is the first report of the rate at which fibromyalgia is being diagnosed in a community. This is also the first report of prevalence as assessed by the fibromyalgia research survey criteria. Our results suggest that patients, particularly men, who meet the fibromyalgia research survey criteria are unlikely to have been given a diagnosis of fibromyalgia.
Objective
The aim of the study was to conduct a meta-analysis of epidemiological and case control studies to determine whether arterial hypertension is specifically associated with an increased risk of vascular dementia (VaD).DesignLongitudinal and cross-sectional prospective studies using operationalised criteria to define VaD and hypertension, with a normal control comparison group were systematically reviewed. Cochrane Library, Embase, Medline, and PsycInfo data sources were searched along with reference lists of included articles and reviews. Original, prevalence or incidence studies were included if operationalised criteria for hypertension and VaD as well as number of cases with and without hypertension in VaD and non-demented groups were provided. Intervention studies and post-stroke and CADASIL studies were excluded.ResultsEleven studies recruiting either volunteers or clinical patients, or which were population-based, examined a total of 768 people with VaD and 9857 control cases. A meta-analysis of the six longitudinal studies showed that hypertension was significantly associated with increased risk of incident VaD (odds ratio, OR: 1.59, CI: 1.29–1.95, p < 0.0001). A similar association between hypertension and the risk of prevalent VaD was found in the five cross-sectional studies (OR: 4.84, CI: 3.52–6.67, p < 0.00001).Conclusions
Hypertension significantly increases the risk of vascular dementia. The current meta-analysis highlights the potential importance of rigorous treatment of hypertension as a key measure to help prevent the development of VaD. Copyright © 2010 John Wiley & Sons, Ltd.
This article reviews the biologic, genetic, and environmental factors that may contribute to the pathophysiology of fibromyalgia. As an affective spectrum disorder, fibromyalgia may share these causal factors with a number of related and co-occurring pain conditions, such as irritable bowel syndrome or temporomandibular disorder. There is strong evidence that cardinal pain symptoms of fibromyalgia may be due to alterations in central processing of sensory input, along with aberrations in the endogenous inhibition of pain. Genetic research has shown familial aggregation of fibromyalgia and other related disorders such as major depressive disorder. Exposure to physical or psychosocial stressors, as well as abnormal biologic responses in the autonomic nervous system and neuroendocrine responses, may also contribute to dysfunctional pain processing. As fibromyalgia research continues to progress, it is expected that the pathophysiology of this disorder will be further elucidated, leading to more rational and targeted strategies for the treatment of patients with this condition.
Clinical and laboratory evidence confirm that dyscognition is a real and troubling symptom in fibromyalgia (FM), and that the cognitive mechanisms most affected in FM are working memory, episodic memory, and semantic memory. Recent evidence provides further convergence on specific difficulty with attentional control. Dyscognition in FM cannot be attributed solely to concomitant psychiatric conditions such as depression and poor sleep, but does seem to be related to the level of pain. This article presents recent contributions regarding the etiology of the cognitive dysfunction, its impact on patients, and highlights the need for further research on this facet of FM.
To determine the incidence of self-reported depression (SRD) in rheumatoid arthritis and to identify and rank clinically useful predictors of depression.
We assessed 22,131 patients for SRD between 1999 and 2008. We collected demographic, clinical and treatment data, household income, employment and work disability status, comorbidity, scales for function, pain, global, and fatigue, the Regional Pain Scale (RPS), the Symptom Intensity (SI) scale (a linear combination of the RPS and the fatigue scales) and linear combinations of the Health Assessment Questionnaire, pain and global severity. We used logistic regression analyses with multivariable fractional polynomial predictors, and Random Forest analysis to determine the importance of the predictors.
The cross-sectional prevalence of self-reported depression was 15.2% (95% confidence interval [95% CI] 14.7-15.7%) and the incidence rate was 5.5 (95% CI 5.3-5.7) per 100 patient years of observation. The cumulative risk of SRD after 9 years was 38.3% (95% CI 36.6-40.1%). Almost all variables were significant predictors in logistic models. In Random Forest analyses, the SI scale, followed by comorbidity, best predicted self-reported depression, and no other variable or combination of variables improved prediction compared with the SI scale.
Pain extent and fatigue (SI scale) are the dominant predictors of SRD. These variables, also of central importance in the symptomatology of fibromyalgia, are powerful markers of distress. A strong case can be made for the inclusion of these assessments in routine rheumatology practice. In addition, actual knowledge of comorbidity provides important insights into the patient's global health and associated perceptions.
This study aims to determine to what extent the reporting of pain in adulthood varies by adult socioeconomic status, whether there are additional long-term effects of socioeconomic status in childhood and whether any such relationships are mediated through adult psychological ill health.
A prospective cohort study (the 1958 British Birth Cohort Study) was conducted. Participants were recruited, at birth, in 1958 and were followed-up throughout childhood and adulthood, most recently at 45 years when information was collected on regional and widespread pain, and various potential mediating factors.
The prevalence of shoulder, forearm, low back, knee and chronic widespread pain at 45 years generally increased with lower adult social class. Persons in the lowest social class (compared to the highest) experienced nearly a threefold increase in the risk of chronic widespread pain: relative risk: 2.9 (95% CI 1.8 to 4.6). The strength of association varied between 1.5 and 2.0 for regional pains. Childhood social class also demonstrated a relationship with most regional pains and chronic widespread pain. With the exception of forearm pain, the magnitude of effect of childhood social status on reporting of pain in adulthood was less than that of adult social status. On multivariable analysis these relationships were partly explained by poor adult mental health, psychological distress, adverse life events and lifestyle factors.
These results emphasise the importance and potential impact of measures to reduce social adversity, which will have the effect of improving musculoskeletal health in adult life and other major causes of morbidity.