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Dementia prevention, intervention, and care
Abstract
Acting now on dementia prevention, intervention, and care will vastly improve living and dying for individuals with dementia and their families, and in doing so, will transform the future for society. Dementia is the greatest global challenge for health and social care in the 21st century. It occurs mainly in people older than 65 years, so increases in numbers and costs are driven, worldwide, by increased longevity resulting from the welcome reduction in people dying prematurely. The Lancet Commission on Dementia Prevention, Intervention, and Care met to consolidate the huge strides that have been made and the emerging knowledge as to what we should do to prevent and manage dementia. Globally, about 47 million people were living with dementia in 2015, and this number is projected to triple by 2050. Dementia affects the individuals with the condition, who gradually lose their abilities, as well as their relatives and other supporters, who have to cope with seeing a family member or friend become ill and decline, while responding to their needs, such as increasing dependency and changes in behaviour. Additionally, it affects the wider society because people with dementia also require health and social care. The 2015 global cost of dementia was estimated to be US$818 billion, and this figure will continue to increase as the number of people with dementia rises. Nearly 85% of costs are related to family and social, rather than medical, care. It might be that new medical care in the future, including public health measures, could replace and possibly reduce some of this cost.
... 7 Physical inactivity, smoking, depression, social isolation, hearing loss, hypertension, obesity, diabetes, and low educational attainment are well established, potentially modifiable risk factors for dementia. [8][9][10][11] The prevalence of hearing loss in the normal population according to The Global Burden of Disease study, which incorporated mild and unilateral hearing loss, estimated that the population with hearing loss rose from 30.7 million (30.0%) in 2010 to 62.0 million (33.1%) in 2021. 12,13 Hearing loss was associated with a higher chance of having dementia. ...
... We collected demographic data on modifiable risk factors for dementia (Table 1). 9 Cognitive severity test and aphasia screening test All patients were assessed cognitive tests using the Thai Mental State Examination (TMSE), a standard cognitive test in Thailand. 20 The severity of dementia, as classified by TMSE scores, is defined as follows: 0-12 (severe), 13-18 (moderate), and 19-30 (mild). ...
... Diabetes affects insulin and the metabolic system, the brain must decrease insulin production, resulting in increased sugar in the bloodstream, causing impaired cognitive function. 9 In this study, we found a smoking prevalence of 31.4%, which is comparable to the 2017 Lancet Commissions report, where 27.4% of individuals over 65 years old were smokers, making it the third highest risk factor. 12 Smoking is known to increase the risk of vascular complications, including cardiovascular pathology, and exposure to cigarette smoke introduces neurotoxins that contribute to stroke, silent infarction, oxidative stress, atherosclerosis, and inflammation. ...
Introduction
Dementia and hearing loss pose a substantial global health challenge, and understanding their association is crucial. This study aims to determine the prevalence of hearing loss in dementia patients and investigate the risk factors for dementia severity including hearing loss.
Methods
This study was a cross-sectional study. Patients with dementia diagnosed by a psychiatrist or neurologist were invited to participate in this study. Audiometry and tympanometry were performed for hearing investigation. The severity of dementia was determined by the Thai Mental State Examination questionnaire, and the SD-SLP-01 aphasia screening questionnaire and associate factors were collected.
Results
A total of 88 participants were included in the study. Two participants withdrew because they were unable to complete hearing tests. The prevalence of hearing loss in this study was 94.2%. The prevalence of aphasia was 25.6%. The most common type of hearing loss is sensorineural hearing loss. Twenty-five percent of participants had moderate to severe hearing loss. A statistically significant difference was observed in the mean Thai Mental State Examination scores across different degrees of hearing loss (p = 0.040). The factors that contributed to the severity of dementia included aphasia (OR: 14.40, 95% CI: 4.53–45.73, p < 0.001) and severe hearing loss (OR: 55.00, 95% CI: 0.83–3,650.97, p = 0.014).
Conclusions
Our findings revealed an extremely high prevalence of hearing loss in the dementia population. Furthermore, a statistically significant association was observed between severe hearing loss and dementia.
... Older adults meeting physical activity (PA) recommendations have a reduced risk of non-communicable diseases such as cardiovascular disease [1,2] and diabetes [3]. Sufficient PA has been associated with reduced risk of cognitive decline and dementia, particularly Alzheimer's disease (AD) [4,5]. Older adults are the most sedentary age group [6]. ...
... Older adults are the most sedentary age group [6]. Furthermore, as ageing is associated with a higher risk for cognitive decline and other health-related challenges [5,7], it is crucial to investigate potential barriers to participation in lifestyle intervention programs including maintaining a physically active lifestyle. Sleep problems, depressive symptoms, and pain are common complaints in late life [8][9][10][11], often co-occurring [12][13][14], impacting negatively on PA. ...
... Multidomain lifestyle interventions including exercise are increasingly recognised as a promising dementia risk reduction strategy [5,31]. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was the first large-scale longterm randomized controlled trial to show that a 2-year multidomain lifestyle intervention -combining exercise, diet, cognitive training and vascular risk factor management could improve or maintain cognition in older adults at risk for dementia [31]. ...
Background
Physical activity (PA) and exercise interventions offer health benefits can reduce dementia risk. However, there might be barriers to engage in PA, such as sleep problems, depressive symptoms and pain, which are common complaints with older adults. We investigated sleep duration, sleep quality, depressive symptoms, and pain at baseline as potential determinants of: (i) adherence to the exercise intervention component of a 2-year multidomain lifestyle intervention; (ii) intervention’s effect on PA after 2 years; and (iii) overall PA after 2 years (exploratory analyses).
Methods
The FINGER trial included 1259 individuals at risk for dementia, aged 60–77 years who were randomized (1:1) to a multidomain lifestyle intervention (exercise, diet, cognitive training, vascular risk factor management) or a control (regular health advice) group. Logistic regression analyses were used with exercise adherence (adherent: ≥66% participation) or self-reported PA (active: ≥2 times/week) as outcomes, adjusted for relevant baseline characteristics. Data on PA at baseline and at 2-years were available for 1100 participants.
Results
Adherence to the exercise intervention was less likely with sleep duration < 6 h or ≥ 9 h per night compared with 7–8 h. OR (95% CI) were 0.46 (0.21–0.99) and 0.38 (0.20–0.74), respectively. The intervention group was more likely to be physically active than the control group at two years (OR 1.87, 95% CI 1.36–2.55). This intervention benefit did not significantly vary by baseline sleep duration, depressive symptoms, or pain (p > 0.3 for all interactions). Regardless of randomization group, those sleeping < 6 h were less likely to be physically active at two years, compared with participants sleeping 7–8 h (OR 0.36, 95% CI 0.18–0.72). Depressive symptoms or pain were not related to PA at two years.
Conclusions
Older adults with sleep problems, depressive symptoms, or pain may benefit from lifestyle interventions. However, both short and long sleep duration can pose barriers to engaging in exercise intervention and should be carefully considered when designing strategies to promote PA among older populations at risk for dementia.
Trial registration
The FINGER trial was registered at ClinicalTrials.gov with identifier NCT01041989 on 04/01/2010.
... Dementia is the fifth leading cause of death globally, accounting for 2.4 million deaths worldwide each year 3 . Furthermore, dementia places substantial financial and emotional burdens on patients, caregivers and society as a whole 4 . ...
... In the absence of curative treatments, the primary prevention of dementia through the reduction of risk factors has become a public health priority 4 . Observational epidemiology studies have identified several risk factors for dementia, including hypertension 5 . ...
Dementia is a leading cause of death and disability worldwide. Here we tested the effectiveness of blood pressure (BP) reduction on the risk of all-cause dementia among 33,995 individuals aged ≥40 years with uncontrolled hypertension in rural China. We randomly assigned 163 villages to a non-physician community healthcare provider-led intervention and 163 villages to usual care. In the intervention group, trained non-physician community healthcare providers initiated and titrated antihypertensive medications according to a simple stepped-care protocol to achieve a systolic BP goal of <130 mm Hg and a diastolic BP goal of <80 mm Hg, with supervision from primary care physicians. Over 48 months, the net reduction in systolic BP was 22.0 mm Hg (95% confidence interval (CI) 20.6 to 23.4; P < 0.0001) and that in diastolic BP was 9.3 mm Hg (95% CI 8.7 to 10.0; P < 0.0001) in the intervention group compared to usual care. The primary outcome of all-cause dementia was significantly lower in the intervention group than in the usual care group (risk ratio: 0.85; 95% CI 0.76 to 0.95; P = 0.0035). Additionally, serious adverse events occurred less frequently in the intervention group (risk ratio: 0.94; 95% CI 0.91 to 0.98; P = 0.0006). This cluster-randomized trial indicates that intensive BP reduction is effective in lowering the risk of all-cause dementia in patients with hypertension. ClinicalTrials.gov: NCT03527719.
... The problems facing older adults with dementia are complex because they exhibit symptoms in many domains 1 . The two core symptoms of dementia are cognitive impairment and neuropsychiatric behaviors, which are common and often considered to be the greatest challenge in dementia care 1,4,[8][9][10] . Behavioral and psychological symptoms of dementia (BPSD)-also known as neuropsychiatric behaviors-include apathy, agitation, aberrant ADL 2.44 (0.122) 13.43 (< 0.001) 0.8 (0.451) CBI 7.16 (0.009) 57.51 (< 0.001) 22.94 (< 0.001) Table 3. Linear mixed-effects regression model. ...
... Fulfilling these physical and psychological needs in a timely manner can significantly reduce the occurrence of such behaviors. Intervening during the moderate and early stages of dementia is crucial 1 . Unlike pharmacological treatments, non-pharmacological interventionsrecommended as a first-line treatment-have demonstrated effectiveness in improving the quality of life and slowing disease progression in patients with dementia. ...
This study aims to evaluate the effects of a creative expressive art-based storytelling accompanied by caregivers (CrEAS-AC) program on reducing behavioral and psychological symptoms of dementia (BPSD) in older adults with dementia and caregiver burden compared to a general social contact (SC) control group. In this two-arm randomized controlled trial, dyads comprising participants with dementia and their caregivers were randomly assigned to the CrEAS-AC (n = 39) and SC groups (n = 39). Interventions were applied twice per week for 12 weeks. The primary outcomes were BPSD (NPI and AES-I) and caregiver distress, while secondary outcomes included communication ability (SFACS-S and SFACS-C), caregiver burden (CBI), and other health-related outcomes (activities of daily living and QOL-AD). All variables were measured at baseline, 12-week follow-up, and 24-week follow-up. Linear mixed model analyses indicated that participants in the CrEAS-AC group showed significantly lower scores on NPI, AES-I, caregiver distress, and CBI post-intervention at the 12-week follow-up, compared with the SC group. They also showed higher scores on QOL-AD, SFACS-S, and SFACS-C. Baseline characteristics did not modify the effects of the interventions, which were maintained until at least 24-week follow-up. The CrEAS-AC program, as an art-based intervention, is therefore potentially effective in reducing behavioral and psychological symptoms of dementia and improving communication ability and quality of life in older adults with dementia, as well as reducing caregivers’ distress and burden.
Trial registration: The study was registered in the Chinese Clinical Trials Registry (ID: ChiCTR2200064838) on 19/10/2022.
... 16 Timely treatment of hearing loss can reduce new dementia cases by 9.1%, the largest reduction among all known modifiable risk factors. 17 It was seen that 37.9% of the participants in our study had hypertension and were under medication, where the duration of hypertension was from 2 years to 43 years. A study done in India and USA showed hypertension prevalence to be 55.3% and 66% respectively. ...
... Exercise is associated with a reduced risk of dementia. 17 Aerobic exercise was seen to be better than resistance exercise and 30 minutes per day for 5 days in a week of moderate to vigorous exercise decreases the risk of dementia. 41,42 These modifiable risk factors account for about 40% of worldwide dementias, which could theoretically be prevented or delayed. ...
Dementia is attributable to 12 known risk factors in 40% cases. This study aimed to assess the prevalence of defined risk factors among people living with dementia. 174 patients with dementia and caregivers were interviewed using semi-structured pro forma, risk factors provided by the Lancet Commission on Dementia (2020), and Dementia Severity Rating Scale (DSRS). The prevalence of 11 known risk factors and associations between the risk factors and dementia severity were assessed. The mean age of the participants was 73.9 years (SD = 8.34 years). The education below intermediate level was 83.3%, 17.8% had hearing loss, 37.9% had hypertension, 24.1% had diabetes, 25.9% and 55.2% had alcohol and nicotine harmful use respectively and 8% had a history of traumatic brain injury and obesity each. There is a substantial prevalence of risk factors among people living with dementia in Nepal but no associations between any of the risk factors and dementia severity.
... However, despite significant advancements in understanding AD pathophysiology, more than half of the overall risk remains unexplained, underscoring the critical need to identify additional AD risk factors that can be targeted during the preclinical stage. 2 One promising line of investigation centers on cortisol, a steroid hormone essential for cellular homeostasis and the stress response. ...
INTRODUCTION
This study investigates whether midlife cortisol levels predict Alzheimer's disease (AD) biomarker burden 15 years later, with particular attention to sex differences and menopausal status.
METHODS
We analyzed data from 305 cognitively unimpaired Framingham Heart Study participants (48.5% female; mean age: 39.6 ± 8.1 years). Serum cortisol was categorized into tertiles, with amyloid ([¹¹C]PiB) and tau ([¹⁸F]Flortaucipir) positron emission tomography (PET) imaging conducted 15 years later. We performed multivariable regression analyses adjusted for confounders including, apolipoprotein E4 (APOE4) status.
RESULTS
Elevated midlife cortisol correlated with increased amyloid deposition, specifically in post‐menopausal women, predominantly in posterior cingulate, precuneus, and frontal‐lateral regions (p < 0.05). No significant associations were observed with tau burden or in males.
DISCUSSION
These findings reveal post‐menopausal women with high midlife cortisol are at increased risk of AD. Results highlight the importance of identifying early risk factors when biomarkers are detectable but cognitive impairment is absent.
Highlights
High midlife cortisol is linked to increased amyloid deposition in post‐menopausal women.
Cortisol showed no association with tau pathology.
Post‐menopausal hormone changes may amplify cortisol's effects on amyloid.
... AD is characterized by a progressive decline of cognitive functions (e.g., memory, language, executive function, and visuospatial skill) that are accompanied by widespread disruptions in functional connectivity within crucial neural networks (Chou et al., 2022). Despite decades of research, pharmacological interventions remain largely ineffective in mitigating disease progression, offering only symptomatic relief with minimal impact on underlying neurodegenerative mechanisms (Canter et al., 2016;Livingston et al., 2017). This therapeutic gap highlights the urgent need to explore and develop alternative, more effective treatment strategies. ...
Background
Repetitive transcranial magnetic stimulation (rTMS) is emerging as a promising non-invasive intervention for Alzheimer’s disease (AD), yet therapeutic outcomes remain inconsistent across studies. This meta-analysis aimed to evaluate the cognitive benefits of rTMS in AD patients, with a specific focus on stimulation targets and protocols variations.
Methods
A systematic literature search was conducted in PubMed, Web of Science, Embase, and Cochrane Library for relevant English-language studies published up to 31 May 2024. Cognitive outcomes were assessed using the Mini-Mental State Examination (MMSE) and Alzheimer’s Disease Assessment Scale-Cognitive Section (ADAS-Cog). Data were pooled using a random-effects model, with standardized mean difference (SMD) or mean differences (MD) and 95% confidence intervals (CI) calculated. Subgroup analyses were performed to examine the effects of stimulation targets, protocol variations and population demographics on rTMS efficacy.
Results
Twenty-two studies involving 874 participants were included in this meta-analysis. Overall, rTMS significantly improved cognitive function (SMD = 0.27; 95% CI = 0.14–0.41; p < 0.0001), showing that the efficacy of rTMS varied by stimulation target and protocol. Stimulation of the dorsolateral prefrontal cortex (DLPFC) led to significant cognitive improvement (SMD = 0.49, 95% CI = −0.26 to 0.73; p < 0.0001), whereas bilateral DLPFC stimulation showed no significant improvement (SMD = 0.13; 95% CI = −0.40 to 0.66; p = 0.62). Stimulating the parietal lobe or associated regions produced moderate cognitive benefits (SMD = 0.29; 95% CI = 0.03–0.55; p = 0.03). Notably, multi-target stimulation over the bilateral DLPFC, parietal lobes, Wernicke’s area, and Broca’s area also showed substantial cognitive improvement (MD = 2.85; 95% CI = 1.69–4.00; p < 0.00001). Additionally, subgroup analysis based on geographical background revealed greater effects in studies conducted in Asia (SMD = 0.40, 95% CI = 0.14–0.65; p < 0.003).
Conclusion
rTMS is an effective intervention for cognitive enhancement in AD, with its efficacy significantly influenced by stimulation target and protocol. Notably, the greater cognitive benefits observed in Asian populations suggest a potential role of genetic and demographic factors that warrant further investigation. These findings contribute to the development of optimized, personalized rTMS protocols for AD treatment.
Systematic review registration
https://www.crd.york.ac.uk/PROSPERO/recorddashboard , CRD42023434084.
... Modifiable lifestyle factors are amongst the most promising avenues of promoting brain health during later stages in life (Livingston et al. 2017;Gottesman and Seshadri 2022;Song et al. 2020). Positive factors like increasing physical activity, for example, have promoted neurogenesis in the hippocampus (Erickson et al. 2011;Sahay et al. 2011;Villemure et al. 2015). ...
Age-related hippocampal alterations often accompany cognitive decline, a significant risk factor for dementias. Modifiable lifestyle factors may help preserve hippocampal neural tissue and slow neurodegeneration and potentially promote cognition in old age. Here, we sought to identify the relationship between lifestyle and cognition in the context of the hippocampal microstructure across the lifespan. We used data from 494 subjects (36–100 years old) without cognitive impairment from the Human Connectome Project-Ageing study. We estimated hippocampal microstructure using myelin-sensitive (T1w/T2w ratio), inflammation-sensitive (MD) and fibre-sensitive (FA) MRI markers. We identified microstructural-lifestyle/-cognition using non-negative matrix factorization to integrate MRI measures into a multivariate spatial signature of hippocampal microstructure covariance followed by partial least squares analysis. Our results reveal that the preservation of axon density and myelin in regions corresponding to subicular regions and CA1 to CA3 regions are negatively associated with age, and is associated with improved performance in executive function tasks, however, this is also associated with a decreased performance in memory tasks. We also show that microstructure is preserved across the hippocampus when there is normal hearing levels, physical fitness and insulin levels and this is negatively associated with age in the presence of cardiovascular risk factors like high body mass index, blood pressure, triglycerides and blood glucose that are in turn associated with hippocampal neurodegeneration. Taken together, our results suggest that lifestyle factors like normal hearing, physical fitness and normal insulin levels may help preserve hippocampal microstructure which may be useful in maintaining optimum performance on executive function tasks and potentially other modes of cognition.
... Thus, the burden of hearing loss remains high, exacerbated by the lack of widespread public health interventions and limited availability of hearing aids and other assistive devices. It underscores the importance of early intervention and access to health interventions and hearing aids to mitigate cognitive decline and improve overall quality of life (34)(35)(36). To address these challenges, innovative approaches are needed, such as telemedicine, community-based education, and the development of affordable, low-cost hearing aids tailored for low-resource settings (37,38). ...
Background
Complete hearing loss, especially the age-related type, poses a significant public health challenge globally. This study aims to assess the global burden on the prevalence of complete hearing loss from 1992 to 2021 and forecast trends up to 2036.
Methods
Using data from the Global Burden of Disease (GBD) Study 2021, we assessed the global burden of complete hearing loss across 204 countries and territories. We analyzed temporal trends in ASPR using Joinpoint regression, evaluated the contributions of age, period, and cohort effects through Age-Period-Cohort modeling, and performed decomposition analysis to determine the impact of demographic and epidemiological changes on prevalence trends. Predictions of future ASPR trends were made using Bayesian Age-Period-Cohort (BAPC) and Autoregressive Integrated Moving Average (ARIMA) models.
Results
By 2021, the global prevalence of complete hearing loss had reached 9.9 million cases, with the ASPR declining from 134.35 to 117.79 per 100,000. The overall Estimated Annual Percentage Change (EAPC) was−0.45. The most significant reductions were observed in low-SDI regions, particularly Sub-Saharan Africa (EAPC: −0.74). In contrast, high-SDI regions, including North America and Western Europe, showed more modest declines (EAPC: −0.18). Notably, East Asia exhibited a 62.3% increase in prevalence, with high-income Asia Pacific showing the highest relative rise at 83.97%. Age-related hearing loss remained the dominant cause, especially among individuals aged 60 and above. Males were more affected than females. Population aging and growth were the major drivers of the increased prevalence in high-SDI regions, while population growth was the primary factor in low-SDI areas.
Conclusion
The burden of complete hearing loss remains high in prevalence, particularly in aging populations within high-SDI regions, despite overall reductions in ASPR. Significant regional disparities remain, highlighting the need for targeted interventions to improve access to hearing care and affordable technologies in low-SDI regions.
... Currently, approximately 6.9 million Americans aged 65 and older live with dementia, a number expected to reach 13.8 million by 2060 (2024). This trend imposes severe psychological and financial burdens on patients and their families while presenting significant challenges to healthcare systems and economies (Livingston et al. 2017). Given the lack of effective treatments for cognitive impairment and dementia, identifying and addressing modifiable risk factors has become a pressing priority. ...
Background
Cognitive impairment is a growing concern worldwide, driven by an aging population. Emerging evidence suggests that micronutrients may play critical roles in maintaining cognitive health and preventing neurodegeneration. However, the causal relationships between specific micronutrients and cognitive function remain unclear.
Methods
This study employed a two‐sample Mendelian randomization (MR) approach to investigate the causal effects of 16 circulating micronutrients on cognitive function. Genetic variants associated with micronutrient levels were used as instrumental variables (IVs), and cognitive outcomes, including reaction time, cognitive performance, prospective memory, and fluid intelligence, were assessed using publicly available genome‐wide association study (GWAS) datasets. Sensitivity analyses were conducted to evaluate heterogeneity, pleiotropy, and robustness of the findings.
Results
MR analysis revealed potential positive effects of β‐carotene and phosphorus on reaction time, reflecting faster cognitive responses. Vitamin E was positively associated with cognitive performance, while vitamin B6 had a negative effect. Selenium was positively correlated with fluid intelligence, whereas elevated vitamin A1 levels were associated with reduced fluid intelligence. No significant associations were observed for other micronutrients across the cognitive domains assessed.
Conclusion
This study highlights the roles of specific micronutrients, like β‐carotene, phosphorus, selenium, and vitamin E, in cognitive health, while excessive vitamin A1 and B6 may be harmful, warranting further investigation.
... At the same time, we also acknowledge that the majority of dementia patients are unable to receive treatment with new drugs due to high prices and blocked purchasing channels. Therefore, prioritizing early prevention and control strategies focused on the modifiable risk factors could hold greater significance [24][25][26][27] . ...
To explore the knowledge, attitude, and practice (KAP) on dementia and cognitive impairment among medical specialists with expertise unrelated to dementia. This study enrolled medical specialists with expertise unrelated to dementia from 318 medical institutions in China, between March and April 2023. A self-designed questionnaire was used for data collection and KAP assessment. A total of 1288 valid questionnaires were collected, 62.58% from female participants. The KAP scores were 11.02 ± 2.11 (range: 0–13), 22.16 ± 3.40 (range: 0–24), and 29.48 ± 6.92 (range: 0–32), respectively. The structural equation model showed that knowledge was positively associated with attitude (path coefficient = 0.503, P < 0.001), while both knowledge (path coefficient = 0.713, P < 0.001) and attitude (path coefficient = 0.797, P < 0.001) were positively associated with practice. Type of institution (path coefficient = 0.184, P = 0.035) and professional title (path coefficient = 0.133, P = 0.026) were positively associated with knowledge score. The mediation analysis revealed the significant total effects for professional title on knowledge, knowledge and professional title on attitude, and knowledge, attitude, and education on practice. Medical specialists in China with expertise unrelated to dementia might have good knowledge, a positive attitude, and proactive practice toward dementia and cognitive impairment. Tailored educational interventions should be specifically designed for individuals with lower professional titles and those working outside public tertiary hospitals.
... [10][11][12][13] Previous studies show that weight loss may be an early sign of AD. [14][15][16][17][18] Prior to the onset of dementia, alterations in nutritional status, 19 metabolism, and neurodegeneration [20][21][22] may influence body mass index (BMI). However, determining the earliest age at which weight loss potentially results from emergent AD pathophysiology poses challenges because higher midlife BMI is associated with a higher risk of AD. 21,[23][24][25][26] Due to this bidirectional relationship between AD and weight loss, weight loss resulting from AD progression may not be easily identifiable. Observational studies evaluating BMI in mid to late life present conflicting estimates regarding the age at which lower BMI is associated with AD, ranging from 8 to 20 years before AD diagnosis. ...
INTRODUCTION
Decreases in body mass index (BMI) may be early consequences of Alzheimer's disease (AD) pathophysiological changes. Previous research in the UK Biobank estimated that AD‐related genes began affecting BMI around age 47. We assessed whether this result could be replicated using longitudinal data in an independent cohort.
METHODS
Using All of Us (AOU) (N = 197,619, aged 30+) data, we estimated linear mixed models for associations of Z‐scored AD‐Genetic Risk Score (AD‐GRS) with BMI, stratified by decade of age. We calculated the earliest age at which AD‐GRS was associated with differences in BMI using cross‐validated models adjusted for demographics.
RESULTS
Higher AD‐GRS was statistically associated with lower BMI in participants aged 60–70 (b = −0.060 [−0.113, −0.007]). Best fitting models suggested the inverse association of AD‐GRS and BMI emerged beginning at ages 47–54.
DISCUSSION
AD genes accelerate age‐related weight loss starting in middle age.
Highlights
Understanding when physiological changes from amyloid pathology begin is key for AD prevention.
Our findings indicate that AD‐associated genes accelerate midlife weight loss, starting between 47 and 54 years.
AD prevention research should consider that disease pathology likely begins by middle age.
... With the further development of global aging and increasing life expectancy, dementia imposes a heavy disease and economic burden on older adults. AD is the most common type of dementia and a major global public health issue (44). The treatment costs for AD and related dementia are high (45,46). ...
Background
Research indicates that mild cognitive impairment (MCI) in older adults is linked to physical activity; however, the relationship between varying levels of physical activity (PAL) and the risk of MCI needs further exploration.
Objective
This study explores the association and dose–response relationship between different levels of physical activity and MCI in older adults.
Methods
Using data from the 2020 China Health and Retirement Longitudinal Study (CHARLS), this cross-sectional analysis included 5,373 older adults aged 60 and above. Binary logistic regression models and restricted cubic spline (RCS) methods were employed to examine the association and dose–response relationship between different PAL levels and the risk of MCI in the overall population and subgroups. Sensitivity analyses were conducted to validate the robustness of the results.
Results
In the overall study population, compared to the lowest PAL quartile, participants in the second PAL quartile had a significantly reduced risk of MCI by 21.3% (p < 0.05). Given that the second PAL quartile had the lowest risk of MCI, a logistic regression model was constructed using the second quartile as the reference group. The results showed that, compared to the second PAL quartile, participants in the first and fourth PAL quartiles had significantly increased risks of MCI by 27.1% (p < 0.05) and 38.2% (p < 0.05), respectively. In subgroup analyses, compared to the second PAL quartile, female participants in the third and fourth PAL quartiles had significantly increased risks of MCI by 50.1% (p < 0.05) and 89.0% (p < 0.05), respectively; participants aged 60–74 in the first and fourth PAL quartiles had significantly increased risks of MCI by 29.4% (p < 0.05) and 42.2% (p < 0.05), respectively; and rural residents in the fourth PAL quartile had a significantly increased risk of MCI by 33.5% (p < 0.05). In the Chinese older adult population, a dose–response relationship was observed between physical activity and the risk of MCI. The RCS curve showed that as physical activity increased, the risk of MCI gradually decreased, reaching a beneficial point at 900 MET-min/week, with the lowest risk at approximately 1,600 MET-min/week. Beyond 1,600 MET-min/week, the risk of MCI began to rise, reaching a significant increase at 2,100 MET-min/week. Sensitivity analyses confirmed the robustness of the findings.
Conclusion
Physical activity levels between 900 and 2,100 MET-min/week are associated with a reduced risk of MCI in the Chinese older adult population. Using physical activity to predict the risk of MCI in this population is feasible, and moderate physical activity may be an effective strategy for preventing and managing MCI.
... The manifestation of symptoms is dependent upon the affected brain regions that undergo neuronal loss 8 . Treatments for neurodegenerative disease are rather limited and mostly include (i) pharmacological agents to slow down the degenerative process or compensate for the neuronal loss; and (ii) non-pharmacological interventions to improve quality of life 9,10 . Therefore, therapeutic approaches to replace the lost neuronal and non-neuronal cells may prove to be more effective. ...
Incidence of neurodegenerative diseases such as Alzheimer′s, Parkinson′s, Huntington′s, and amyotrophic lateral sclerosis have increased dramatically as life expectancy at birth has risen year-over-year and the population ages. Neurological changes within the central nervous system, specifically the brain, include cell loss and deterioration that impact motor function, memory, executive function, and mood. Available treatments are limited and often only address symptomatic manifestations of the disease rather than disease progression. Cell transplantation therapy has shown promise for treating neurodegenerative diseases, but a source of autologous cells is required. Blastocyst complementation provides an innovative method for generating those autologous neural cells. By injecting mouse induced pluripotent stem cells (iPSCs) into a wild type (WT) mouse blastocyst, we generated a chimeric mouse brain derived of both donor and host neuronal and non-neuronal cells. An embryonic day 12.5 (E12.5), automated image analysis of mouse-mouse chimeric brains showed the presence of GFP-labeled donor-derived dopaminergic and serotonergic neuronal precursors. GFP-labeled donor-derived cholinergic precursor neurons and non-neuronal microglia-like and macrophage-like cells were also observed using more conventional imaging analysis software. This work demonstrates that the generation of mouse-mouse chimeric neural cells is possible; and that characterization of early neuronal and non-neuronal precursors provides a first step towards utilizing these cells for cell transplantation therapies for neurodegenerative diseases.
... Cognitive decline, the hallmark of dementia, profoundly impacts daily functioning and diminishes patients' quality of life. Additionally, sensory impairments, particularly hearing loss, are recognized as significant risk factors that exacerbate cognitive deterioration in older adults with dementia [1][2][3]. ...
Background: Dementia patients often experience a decline in both their cognitive and sensory functions, particularly hearing, which significantly impacts their quality of life. This study evaluates the effectiveness of a combined Digital Cognitive Stimulation Therapy (DKST) and online hearing training intervention in enhancing the quality of life of individuals with dementia. Methods: Twenty-three patients participated in a six-month program integrating cognitive exercises and hearing rehabilitation, facilitated by trained co-therapists. Quality of life was assessed using the Quality of Life (QoL) Questionnaire, while the Mini-Mental State Examination (MMSE) was employed to categorize participants based on their cognitive status. Results: The results revealed significant improvements in the overall quality of life. Conclusions: This study demonstrates that combining DKST with hearing training effectively addresses sensory and cognitive challenges, supporting improved quality of life and highlighting the potential of digital interventions in demen-tia care.
... According to the World Health Organization, over 55 million people globally are living with dementia, a number projected to double every 20 years as populations age [1]. Early detection and intervention in cognitive decline are critical for improving patient outcomes and managing the social and economic burdens associated with these conditions [2,3]. Traditional diagnostic methods, such as the Mini-Mental State Examination (MMSE) [4][5][6], are widely used but can be time-consuming and resource-intensive, particularly when applied to large populations [7][8][9]. ...
... Prior research suggests that physical activity (PA) promotes successful aging in older adults, effectively reducing the risk of chronic diseases [2] and risk of functional loss [3], improving self-rated health [4] and enhancing cognition [5]. PA is also known to have significant antidepressant effects [6], which delay dementia [7], prevent cognitive deterioration [8], and positively ameliorate depressive symptoms (DS) in older adults [3]. DS and cognition are essential factors affecting the ability to perform daily activities in older adult participants [9]. ...
Introduction
The present study aimed to explore the effect of different levels of physical activity on depression, instrumental activities of daily living (IADLs), and activities of daily living (ADLs) among older adults over the age of 60.
Methods
Data on older adults’ health were obtained from the China Longitudinal Aging Social Survey (CLASS) conducted in 2021. A questionnaire was used to survey older adults aged 60 years and older in 28 regions of China. The International Physical Activity Questionnaire (IPAQ) was used to evaluate physical activity, and participants were categorized into groups based on their physical activity levels: vigorous (5.38%), moderate (16.33%), light (74.58%), and no physical activity (control group). The CES-D9 scale was used to assess the level of depression, and both the activities of daily living (ADLs) scale and the instrumental activities of daily living (IADLs) scale were used to evaluate self-care ability. Propensity score matching was used to determine the intensity of physical activity that affected depression, instrumental daily activity ability (IADLs), and activities of daily living (ADLs) among the participants.
Results
The participation rates of vigorous, moderate, and light physical activities among the older adult Chinese participants were 5.38%, 16.33%, and 74.58%, respectively. Propensity score matching (PSM) showed moderate and light physical activity decreased depression by -0.367 and − 0.409 units, respectively. Moderate and light physical activity increased instrumental activities of daily living (IADLs) by 0.165 and 0.607 units, respectively. Light physical activity increased the level of activities of daily living (ADLs) by 0.265 units.
Conclusion
Moderate and light physical activity in older adults alleviates depression and improves instrumental activities of daily living (IADLs), and light physical activity improves the level of activities of daily living (ADLs).
... Globally, the number of people living with dementia is projected to increase from approximately 57 million cases in 2019 to 153 million in 2050, largely owing to population growth and aging (4). Accumulating evidence suggests that the onset of neurodegenerative diseases may be prevented or delayed by addressing modifiable risk factors, for example through lifestyle changes and other interventions-many of which are subject to ongoing investigations (1,(5)(6)(7). ...
Age-related neurodegenerative disorders, including dementia, are a major global health concern. This article describes the first comprehensive, data-driven molecular model of the neuro-glia-vascular system to explore the complex relationships between the aging brain, energy metabolism, blood flow, and neuronal activity. Comprising 16,800 interaction pathways, the model includes all key enzymes, transporters, metabolites, and circulatory factors vital for neuronal electrical activity. We found significant alterations in metabolite concentrations and differential effects on adenosine triphosphate (ATP) supply in neurons and astrocytes and within subcellular compartments in aged brains and identified reduced sodium/potassium adenosine triphosphatase (Na⁺/K⁺-ATPase) activity as the leading cause of impaired neuronal action potentials. The model predicts that the metabolic pathways cluster more closely in the aged brain, suggesting a loss of robustness and adaptability. Additionally, the aged metabolic system displays reduced flexibility, undermining its capacity to efficiently respond to stimuli and recover from damage. Through transcription factor analysis, the estrogen-related receptor alpha (ESRRA) emerged as a central target connected to these aging-related changes. An unguided optimization search pinpointed potential interventions capable of restoring the brain’s metabolic flexibility and action potential generation. These strategies include increasing the nicotinamide adenine dinucleotide (NADH) cytosol-mitochondria shuttle, NAD⁺ pool, the ketone β-hydroxybutyrate, lactate, and Na⁺/K⁺-ATPase, while reducing blood glucose levels. The model is open sourced to help guide further research into brain metabolism.
... 1 High levels of physical inactivity adversely affect physical, psychological and social components of successful ageing 2 and are an important modifiable risk factor for dementia in older adults. 3 While increasing physical activity in older adults is an important public health strategy, uncertainty exists around the best way to achieve this. Structured exercise programmes have long been known to improve morbidity and mortality in older patients with cardiovascular disease, 4 impaired glucose metabolism 5 and a range of other disorders. ...
Objectives
Physical activity is important for health, but the influence of structured, supervised aerobic exercise sessions on habitual physical activity in healthy older adults is unclear.
Methods
We evaluated habitual physical activity in the Hertfordshire Physical Activity Trial, where healthy older adults were randomised to 36 supervised 1-hour gymnasium sessions on a cycle ergometer at moderate intensity over 12 weeks or to a control group with no intervention. We estimated physical activity energy expenditure (PAEE) and time spent in sedentary behaviour and light and moderate or vigorous physical activity over 7 days at three time points (before, during and immediately after the intervention) with individually calibrated combined heart rate and movement sensing.
Results
Of 100 randomised participants (44% female, aged 67–76 years), 96% completed follow-up. Midway through the intervention, neither overall PAEE nor time spent at different intensities were different between groups. However, on the 3 days of the week that the structured exercise sessions occurred (Monday, Wednesday, Friday), the exercise group had a 9.1 kJ kg⁻¹ day⁻¹ ((2.5, 15.7), p=0.007) increase in PAEE, a reduction in sedentary time and increased time spent at light and moderate or vigorous physical activity, compared with the control group.
Conclusions
Three 1-hour bouts per week of structured aerobic exercise increased daily physical activity on the days they occurred, but not overall physical activity across the whole week. Population-wide strategies such as better cycling and walking infrastructure may increase physical activity in healthy older adults more effectively than treatment with structured exercise programmes.
Trial registration number
ISRCTN60986572.
... Dado que no existe un tratamiento curativo o ralentizador del deterioro global asociado a la demencia, su manejo se centra en la generación de planes de cuidado integral que permitan a la persona y su entorno vivir con la mejor calidad de vida posible a pesar de tener demencia y en el contexto de los déficits presentes, reduciendo riesgos y protegiendo la salud del cuidador (42,43) . Por ende, en la detección de necesidades de cuidado, y en especial en los cuidados postdiagnóstico, la valoración del autoestigma puede ser una herramienta pertinente y útil, permitiendo a los equipos de salud disponer con otra dimensión de evaluación para elaborar los planes de cuidado de las personas con demencia y sus familias. ...
INTRODUCCIÓN. En salud, el autoestigma es un tipo de estigma en que el paciente internaliza la percepción negativa de su condición, afectando su bienestar y restringiendo la búsqueda de cuidados. La demencia es un problema de salud estigmatizado. El autoestigma en demencia ha recibido limitada atención y los instrumentos disponibles para su evaluación no se ajustan a este problema de salud. OBJETIVO. Desarrollar un cuestionario para la evaluación de autoestigma en personas con diagnóstico de demencia tipo Alzheimer en etapa inicial. METODOLOGÍA. Estudio mixto de desarrollo con dos fases. Primero, se realizó un estudio cualitativo con entrevistas a once personas con el diagnóstico de Alzheimer en etapa leve, produciendo información sobre manifestaciones del autoestigma. Considerando esta información, se realizó la abstracción conceptual y operacional para dimensiones e ítems. Mediante consulta a expertos (n:3) y a personas con demencia en etapa leve (n:3) se evaluó la validez aparente y de contenido de las dimensiones y sus ítems, y se indagó en consideraciones para aceptabilidad y utilidad. RESULTADOS. Se generó una primera versión del cuestionario para evaluar manifestaciones cognitivas y conductuales-afectivas del autoestigma en demencia, compuesto de cuatro dimensiones y 22 ítems medibles a través de escala de Likert en cuatro niveles. CONCLUSIÓN. Se presenta el cuestionario y consideraciones para su utilización. Próximos estudios debiesen examinar en la validez de criterio mediante evaluación psicométrica. Disponer de una evaluación del autoestigma es relevante en la detección de necesidades de las personas con demencia y la elaboración de planes de cuidado integral.
... The phrase "alcohol-related dementia" refers to a type of dementia caused by the direct effects of persistent alcohol use on the brain. Dementia is a clinical condition defined by a gradual decline in cognitive ability and the ability to live and function independently [157]. Dementia impairs memory, reasoning, behavior, and the capacity to do daily tasks [158], and it is a significant cause of impairment in elderly individuals. ...
Alcohol use disorder (AUD) is a medical condition that impairs a person's ability to stop or manage their drinking in the face of negative social, occupational, or health consequences. AUD is defined by the National Institute on Alcohol Abuse and Alcoholism as a "severe problem". The central nervous system is the primary target of alcohol's adverse effects. It is crucial to identify various neurological disorders associated with AUD, including alcohol withdrawal syndrome, Wernicke-Korsakoff syndrome, Marchiafava-Bignami disease, dementia, and neuropathy. To gain a better understanding of the neurological environment of alcoholism and to shed light on the role of various neurotransmitters in the phenomenon of alcoholism. A comprehensive search of online databases, including PubMed, EMBASE, Web of Science, and Google Scholar, was conducted to identify relevant articles. Several neurotransmitters (dopamine, gamma-aminobutyric acid, serotonin, and glutamate) have been linked to alcoholism due to a brain imbalance. Alcoholism appears to be a complex genetic disorder, with variations in many genes influencing risk. Some of these genes have been identified, including two alcohol metabolism genes, alcohol dehydrogenase 1B gene and aldehyde dehydrogenase 2 gene , which have the most potent known effects on the risk of alcoholism. Neuronal degeneration and demyelination in people with AUD may be caused by neuronal damage, nutrient deficiencies, and blood brain barrier dysfunction; however, the underlying mechanism is unknown. This review will provide a detailed overview of the neurobiology of alcohol addiction, followed by recent studies published in the genetics of alcohol addiction, molecular mechanism and detailed information on the various acute and chronic neurological manifestations of alcoholism for the Future research.
Background and aim
Long-term adherence to the Mediterranean Diet has been shown to improve cognitive function in patients. However, there is a lack of evidence regarding the impact of the Mediterranean diet and cognitive impairment on long-term mortality outcomes. This study aims to explore whether there is an interaction between the degree of adherence to the Mediterranean diet and cognitive impairment on long-term mortality outcomes.
Methods
The study included 2,520 participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2014. The adherence to the Mediterranean diet was assessed using the 9-point alternative Mediterranean diet index (aMED index). Cognitive function was assessed using the Consortium to Establish a Registry for Alzheimer’s disease (CERAD), the Animal Fluency Test (AFT), and the Digital Symbol Substitution Test (DSST). By accessing public records from the National Death Index (NDI), NHANES participants’ information was linked to death certificate records to determine mortality and causes of death during the follow-up period, up to December 31, 2019, with causes specified according to ICD-10. Participants were categorized based on the median aMED score into low adherence (scores 0–3), moderate adherence (score 4), and high adherence (scores 5–9) groups. Cognitive impairment was assessed by calculating the arithmetic mean of standardized scores (Z-scores) for each cognitive test. Participants with scores below the first quartile of the arithmetic mean were considered to have cognitive impairment. Cox proportional hazards regression models were used to assess the relationship between cognitive impairment, aMED, and all-cause and cardiovascular mortality outcomes. Additionally, the interaction between cognitive impairment and aMED on these outcomes was evaluated.
Results
The study included 2,520 participants, with 481 deaths during the follow-up period, of which 129 (26.8%) were cardiovascular-related. The median aMED score in the population was 4, and 632 individuals (25.1%) were considered to have cognitive impairment. A higher aMED score was associated with a reduced risk of long-term all-cause mortality and cardiovascular-related mortality (HR, 0.65; 95% CI, 0.52–0.81, p < 0.001; HR, 0.73; 95% CI, 0.47–0.91, p = 0.039). Cognitive impairment was associated with an increased risk of long-term all-cause mortality and cardiovascular mortality (HR, 1.78; 95% CI, 1.46–2.18, p < 0.001; HR, 1.80; 95% CI, 1.22–2.64, p = 0.003). Individuals with both lower aMED scores and cognitive impairment had higher risks of all-cause and cardiovascular mortality. Subgroup analysis indicates that only in the cognitive impairment subgroup is a higher Mediterranean diet score associated with a reduced risk of cardiovascular mortality. There is an interaction between lower aMED scores and cognitive impairment in increasing cardiovascular-related mortality (p for interaction = 0.028).
Conclusion
There is an interaction between adherence to the Mediterranean diet and cognitive impairment concerning cardiovascular-related mortality, but not all-cause mortality. Among individuals with cognitive impairment, adherence to the Mediterranean diet has a more significant impact on cardiovascular-related mortality.
INTRODUCTION
Dementia progression is heterogeneous and predicting who will decline quickly remains an open problem. Most work in this area has focused on volunteer‐based cohorts, which are subject to recruitment biases. Instead, we examine predictors of rate of cognitive decline in cognitive assessment scores using electronic health record (EHR) data from a US memory clinic.
METHODS
Data include patients with their first memory clinic visit (baseline) between January 1, 2014 and May 31, 2024. We used a discrete‐time model to identify significant predictors of baseline and 6 month change in Mini‐Mental State Examination (MMSE) scores (Montreal Cognitive Assessment scores were converted to MMSE equivalents for analysis). Inverse probability weighting was used to account for selection and censoring biases and p values were adjusted for multiple comparisons.
RESULTS
The cohort included 9583 patients, of which 7113 had a baseline cognitive assessment. Average MMSE at baseline was 23.2. Variables associated with lower baseline MMSE included female sex, non‐White race, Medicaid enrollment, baseline dementia diagnosis, and cholinesterase inhibitor prescription, while higher scores were associated with prior diagnoses of chronic pain or fatigue. Quicker post‐baseline decline was associated with older age, dementia diagnoses, and cholinesterase inhibitor prescription, while slower decline was associated with a higher number of total prescriptions, distance from home to clinic, and Social Deprivation Index. Notably, rate of decline was not associated with mild cognitive impairment, other non‐dementia cognitive impairment, or any of the comorbidities considered.
DISCUSSION
While several significant predictors were identified, the lack of associations with broad categories of comorbidities and social determinants of health suggest that finer grained predictors may be needed. Additionally, the finding that cholinesterase inhibitor prescriptions predicted quicker decline merits additional investigation in real‐world samples. The model developed in this work may serve as a first step toward an EHR‐based progression risk tool.
Highlights
In a memory clinic setting, faster decline in Mini‐Mental State Examination scores was associated with age, dementia diagnosis, and cholinesterase inhibitor or memantine prescription.
Slower decline was associated with the patient's total number of prescriptions.
Neither race nor ethnicity were associated with rate of decline, nor were baseline mild cognitive impairment, other non‐dementia cognitive impairment, diabetes, hypertension, obesity, depression, anxiety, chronic pain/fatigue, or hearing loss.
Background
People from minoritised ethnic groups are more likely to be impacted by dementia. In the general population, dementia may be prevented or delayed by up to 40% by reducing risk in 12 modifiable risk factors (MRF). However, minoritised ethnic groups are not systematically included.
Objectives
We conducted a scoping review following Joanna Briggs Institute guidance to map: (1) which minoritised ethnic groups have been included in UK research on dementia MRF, (2) for which MRF and (3) using which research methods.
Eligibility criteria
Eligible studies analysed one or more of the 12 MRFs among minoritised ethnic groups.
Evidence sources
Medline, Embase Classic+Embase, PsycInfo, Web of Science, CINAHL and grey literature were searched.
Charting methods
Patient and public involvement with minoritised ethnic groups and professionals informed the data extraction tool. We use frequencies and graphs in data description.
Results
We screened 7748 records, assessed 122 full text records and included 14 studies, which mostly used broad ethnic groups. Hypertension, diabetes and depression were studied as predictors of dementia in 10, eight and six studies, respectively, compared with low social contact and air pollution in just two each. Measures of MRF lacked consistency, and data per ethnic group were not reported in several studies. Research examining interactions in combinations of MRFs was lacking.
Conclusions
More research is needed with specific ethnic groups, consistent measures and focusing on discrimination and MRF interaction and severity. This will be key to personalised risk reduction with diverse communities.
China’s aging population and the rising public health burden from cognitive impairment are pressing concerns. Using mixed-effects models, we analyzed the association between particulate matter and its components with cognitive function using 20,115 observations from 123 Chinese cities and assessed economic costs under various socioeconomic scenarios. The single-pollutant model showed cognitive scores decrease with higher pollutant concentrations: PM1 (-0.53 points/0.1 µg/m³), PM2.5 (-0.30), PM10 (-0.14), organic matter (-1.44), ammonium (-1.55), sulfate (-1.70), and black carbon (-7.23). Nitrate showed no statistical association. In the multi-pollutant model, PM₁, PM₂.₅, organic matter, sulfate, and black carbon exhibited a statistically negative association with cognitive scores. Sustainable strategies reducing particulate matter levels could mitigate aging impacts and lower economic costs by $19.35 billion by 2050, offering significant health and financial benefits.
With an increase in the aging population, successful aging has become a worldwide requirement. Healthy cognitive functioning is an essential element of successful aging. Therefore, the present study intended to examine the influence of perceived social support and life purpose on cognitive functioning. The present study has employed a correlational research design. The sample comprised 140 middle-aged adults (ages 35 to 55 years) who were recruited through the purposive sampling technique. Montreal Cognitive Assessment (MoCA), Purpose in Life scale and Multidimensional Scale of Perceived Social Support (MSPSS) were used as assessment measures. Findings indicated that cognitive functioning has a significant positive relationship with life purpose and perceived social support. Furthermore, purpose in life and family and friends support found to explain the significant amount of variance in cognitive functioning even after controlling for the effects of age and education of the participants. To conclude, a higher sense of purpose in life and perceived social support tend to protect cognitive functioning in middle age. Therefore, the present study findings have implicated a practical way for healthcare providers for the prevention of cognitive impairment and promotion of successful aging.
Introduction
Cognitive assessment is essential to detect early cognitive decline and guide interventions. Self-administered computerized assessment is a promising option for periodic cognitive screening in the general population. One of the most critical challenges to implementing cognitive screening in at risk populations is participants’ adherence. However, there is insufficient evidence to determine which factors are essential for adherence to long-term digital cognitive screening.
Aims
This study aims to investigate potential sociodemographic and health predictors of adherence to a self-administered web-based cognitive monitoring, the Brain on Track (BoT), in the general population.
Methods
Participants (n = 347) were recruited from the general community. The participants were asked to perform one BoT test every 3 months for cognitive screening and were followed at two time points, namely, 1-year and 3- to 6-year follow-up. Regression models were used to investigate sociodemographic and health predictors of adherence to BoT use at 1 year and up to 6 years.
Results
Being older positively affects adherence to periodic cognitive screening for both follow-up periods. Being a female, having more years of formal education, presenting more BoT baseline correct answers and fewer BoT baseline incorrect answers, and reporting memory complaints positively affect adherence to periodic screening at 3 to 6 years of follow-up but not at 1-year follow-up.
Discussion
The identified determinants of adherence can be considered when planning long-term cognitive screening protocols to increase adherence. Specific strategies could be helpful to improve the adherence of participants who adhere less.
Importance
Although diabetes is a risk factor for dementia, the effect of glucose-lowering therapy for prevention of incident dementia is uncertain.
Objective
To determine whether cardioprotective glucose-lowering therapy (sodium-glucose cotransporter-2 inhibitors [SGLT2is], glucagon-like peptide-1 receptor agonists [GLP-1RAs], metformin, and pioglitazone), compared with controls, was associated with a reduction in risk of dementia or cognitive impairment, and among primary dementia subtypes.
Data Sources
The PubMed and Embase databases were searched for studies published from inception of the database to July 11, 2024.
Study Selection
Randomized clinical trials comparing cardioprotective glucose-lowering therapy with controls that reported dementia or change in cognitive scores. Cardioprotective glucose-lowering therapies were defined as drug classes recommended by guidelines for reduction of cardiovascular events, based on evidence from phase III randomized clinical trials. Inclusion criteria were assessed independently and inconsistencies were resolved by consensus.
Data Extraction and Synthesis
Data were screened and extracted independently by 2 authors adhering to the PRISMA guidelines in August 2024. Random-effects meta-analysis models were used to estimate a pooled treatment effect.
Main Outcomes and Measures
The primary outcome measure was dementia or cognitive impairment. The secondary outcomes were primary dementia subtypes, including vascular and Alzheimer dementia, and change in cognitive scores.
Results
Twenty-six randomized clinical trials were eligible for inclusion (N = 164 531 participants), of which 23 trials (n = 160 191 participants) reported the incidence of dementia or cognitive impairment, including 12 trials evaluating SGLT2is, 10 trials evaluating GLP-1RAs, and 1 trial evaluating pioglitazone (no trials of metformin were identified). The mean (SD) age of trial participants was 64.4 (3.5) years and 57 470 (34.9%) were women. Overall, cardioprotective glucose-lowering therapy was not significantly associated with a reduction in cognitive impairment or dementia (odds ratio [OR], 0.83 [95% CI, 0.60-1.14]). Among drug classes, GLP-1RAs were associated with a statistically significant reduction in dementia (OR, 0.55 [95% CI, 0.35-0.86]), but not SGLT2is (OR, 1.20 [95% CI, 0.67-2.17]; P value for heterogeneity = .04).
Conclusions and Relevance
While cardioprotective glucose-lowering therapies were not associated with an overall reduction in all-cause dementia, this meta-analysis of randomized clinical trials found that glucose lowering with GLP-1RAs was associated with a statistically significant reduction in all-cause dementia.
Background: Sex differences in the association of cognitive function and imaging measures with dementia have not been fully investigated. Understanding sex differences in the dementia-related socioeconomic, cognitive, and imaging measurements is crucial for uncovering sex-related pathways to dementia and facilitating early diagnosis, family planning, and cost control. Methods: We selected data from the Open Access Series of Imaging Studies, with longitudinal measurements of brain volumes, on 150 individuals aged 60 to 96 years. Dementia status was determined using the Clinical Dementia Rating (CDR) scale, and Alzheimer’s disease was diagnosed as a CDR of ≥0.5. Generalized estimating equation models were used to estimate the associations of socioeconomic, cognitive, and imaging factors with dementia in men and women. Results: The study sample consisted of 88 women (58.7%) and 62 men (41.3%), and the average age of the subjects was 75.4 years at the initial visit. A lower socioeconomic status was associated with a reduced estimated total intracranial volume in men, but not in women. Ageing and lower MMSE scores were associated with a reduced nWBV in both men and women. Lower education affected dementia more in women than in men. Age, education, Mini-Mental State Examination (MMSE), and normalized whole-brain volume (nWBV) were associated with dementia in women, while only MMSE and nWBV were associated with dementia in men. Conclusions: The association between education and the prevalence of dementia differs in men and women. Women may have more risk factors for dementia than men.
Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is marked by the abnormal production of amyloid-beta (Aβ) fibrils, a key biomarker for diagnosis and illness monitoring. Advanced microfluidic devices, such as brain-on-a-chip (BoC), are innovative preclinical tools with the potential to revolutionize AD early diagnosis and treatment. However, existing BoCs face limitations, including challenges in biosensing integration, limited sensitivity, and automation. In this study, we demonstrate the feasibility of integrating fluorescence-based detection of Aβ fibrils within microfluidic platforms, improving efficiency and precision in biomarker analysis, while also reducing sample volume requirements, with potential application in BoC. The fluorescent probe CRANAD-2, known for its in vivo specificity and strong fluorescence response to Aβ fibrils, was first characterized in a macroscale system to establish baseline performance. These results were used to guide subsequence microfluidic experiments, reducing sample volume while maintaining analytical reliability. The study revealed consistent fluorescence responses and a strong linear relationship between Aβ concentration and fluorescence intensity in both setups. This proof-of-concept study shows, for the first time, the potential of integrating optical biosensing into microfluidic devices for Aβ detection, offering a new technological tool for advancing AD studies.
Background The deposition of toxic aggregated amyloid-β (Aβ) is a key pathogenic event in Alzheimer's disease (AD), resulted from the continuous cleavage of amyloid precursor protein (APP) by BACE1 (β-site APP cleaving enzyme 1) and γ-secretase. Small interfering RNA (siRNA) has shown great potential for disease treatment by specifically silencing target gene. However, the poor brain delivery efficiency of siRNA limits its therapeutic efficacy against AD. Methods Herein, this study designed a simplified while effective BACE1 siRNA (siBACE1) delivery system, namely dendritic polyamidoamine modified with the neurotropic virus-derived peptide RVG29 and polyethylene glycol (PPR@siBACE1). Results PPR@siBACE1 could cross the blood brain barrier efficiently and enter brain parenchyma in large amount, with subsequent neurotropism and potential microglia-targeting ability. Both in vitro and in vivo studies validated the effective brain delivery of siBACE1 and strong BACE1 silencing efficiency. Treatment with PPR@siBACE1 not only curtails the production of Aβ but also potentiates the phagocytosis of Aβ by microglia, with much improvement of the memory deficit and reduced neuroinflammatory response in AD mice. Conclusions In summary, this study provides a reliable delivery platform for the gene therapy of AD.
The objective of this review study is to examine the combined antidepressant effects of exercise and polyphenol supplementation, with a focus on specific polyphenolic compounds such as crocin, curcumin, and quercetin, as well as different forms of physical exercise, including aerobic and resistance training. The research examines how these interventions influence depressive-like behaviors, cognitive function, and neurochemical markers in animal models and human participants. The findings demonstrate that both exercise and polyphenols independently contribute to mood enhancement, reduced anxiety, and improved cognitive function through mechanisms such as neurogenesis, neurotransmitter modulation, and anti-inflammatory effects. Notably, the combined interventions showed a synergistic effect, providing more significant benefits in reducing symptoms of depression and anxiety, enhancing cognitive performance, and supporting overall mental well-being. These results suggest that integrating exercise and polyphenol supplementation could be a promising non-pharmacological approach to managing depression and related disorders.
Recovery from COVID-19 can be accompanied by persistent symptoms and complications, collectively termed post-COVID syndrome or ‘long COVID’. This study explores the prevalence and nature of long-term physical and psychological complications among recovered COVID-19 patients in Dhaka, six months post-discharge.
A cross-sectional study was conducted with 384 patients from COVID-dedicated hospitals in Dhaka. Data on psychological and physical outcomes, including fatigue, insomnia, and dementia, were collected using validated tools. Confidence intervals (CIs) were used to examine associations and determine statistical significance.
Among the participants, the most common symptoms at hospital admission were cough (93.9%), fever (87.2%), and dyspnea (66.9%). Post-discharge, 74% of respondents reported health issues, with general weakness (58.5%) being the most common. Older participants (≥ 50) had a higher likelihood of longer hospital stays, with only 35.9% hospitalized for ≤ 7 days (CI: 45%–55% in < 50). They also exhibited higher comorbidity rates, including hypertension (57.1%; CI: 38%–45%) and diabetes (53.7%; CI: 22%–28%). Older participants were more likely to experience complications, with 93.1% reporting at least one (CI: 65%–75%). Insomnia was prevalent in both age groups (82.0%; CI: 78%–85%), with dementia more common in older participants (34.6%; CI: 25%–35%).
While older adults exhibited higher rates of dementia and longer hospital stays, the high prevalence of psychological complications across all groups emphasizes the need for comprehensive post-COVID care strategies, particularly for older patients.
Māori are the indigenous people of Aotearoa New Zealand. Cognitive Stimulation Therapy (CST) was initially developed in the UK, lacking in Māori cultural content and values. Cultural adaptation is needed to ensure Māori with dementia can benefit from this evidence-based treatment. This paper reports the outcome of a project aimed to adapt CST for Māori. We followed the five phases of international guidelines using the formative method for adapting CST to other cultures, including a critical cultural examination of the 18 CST principles. We piloted two CST-Māori programmes and collected pre- and post-outcome measures using the RUDAS and the World Health Organization Quality of Life (WHOQOL-BREF) questionnaire. Written qualitative feedback was sought from participants and their family at the end of the CST-Māori programme. A total of 15 Māori (female: 53.3%) participated in the two programmes. Their mean age was 75.9 years (SD = 6.6) and mean baseline RUDAS scores was 17.7 (SD = 2.3). There was a statistically significant improvement in cognition (RUDAS: pre = 17.7, post = 19.4, p = 0.003) and in the WHOQOL subscales of physical (pre = 75.9, post = 88.5, p = 0.003), psychological (pre = 72.7, post = 81.3, p = 0.024) and environment (pre-80.6, post = 88.0, p = 0.006). Written feedback confirmed the acceptability of this culturally adapted programme by Māori living with dementia and their whanau (families). CST was successfully adapted for Māori with dementia. It is a culturally acceptable cognitive intervention and preliminary data confirmed the effectiveness of CST-Māori in improving cognition and quality of life.
Clinical guidelines «Cognitive disorders in the elderly and senile persons».
Background
Hearing loss has been related to impaired cognition among older adults. The cost effectiveness of existing hearing support tools is controversial. Other potential modifying strategies that could effectively intervene in this prevalent and far-reaching association between hearing loss and cognitive decline remain unclear. This study aimed to narratively and quantitatively synthesize the mediators and moderators involved in the link between hearing loss and cognitive impairment from a psycho-social and physical point of view.
Method
We searched 6 databases for articles exploring mediating or moderating associations of hearing loss-cognition association from inception to March, 2024. Data were synthesized narratively and quantitatively by meta-analytic approaches.
Results
The search yielded 63 included studies. Social (social engagement, social support, age, sex, ethnicity, cognitive reserve)-psycho (depression, anxiety, loneliness, resilience)-physical (cardiovascular diseases and risk factors, perceived health, disability, APOE carrier, vision impairment, gait speed) variables mediated or moderated the relationship between hearing loss and cognitive impairment to varying degrees. Subgroup analyses identified susceptible populations at greater risk for cognitive decline, including women, younger elders with hearing loss, and older adults with dual sensory loss.
Conclusion
Combined interventions targeting these modifiable variables across psycho-social and physical dimensions may be more cost-effective for intervening in the ensemble of hearing loss-cognitive impairment in older adults.
Alzheimer’s disease (AD) represents a significant challenge among neurodegenerative disorders, as effective treatments and therapies remain largely undeveloped. Despite extensive research efforts employing various methodologies and diverse genetic models focused on amyloid-β (Aβ) pathology, the research for effective therapeutic strategies remains inconclusive. The key pathological features of AD include Aβ senile plaques, neurofibrillary tangles (NFTs), and the activation of neuroinflammatory pathways. Presently, investigations into AD and assessing potential treatments predominantly utilize Aβ transgenic models. Conversely, non-transgenic models may provide valuable insights into the multifaceted pathological states associated with AD. Thus, these models may serve as practical complementary tools for evaluating therapeutic and intervention strategies, since the primary AD risk factors are most frequently modeled. This review aims to critically assess the existing literature on AD non-transgenic models induced by streptozotocin, scopolamine, aging, mechanical stress, metals, and dietary patterns to enhance their application in AD research.
Aim:
To develop and validate a model to predict cognitive decline within 12 months for home care clients without a diagnosis of dementia.
Design:
We included all adults aged ≥ 18 years who had at least two interRAI Home Care assessments within 12 months, no diagnosis of dementia and a baseline Cognitive Performance Scale score ≤ 1. The sample was randomly split into a derivation cohort (75%) and a validation cohort (25%). Significant cognitive decline was defined as an increase (deterioration) in Cognitive Performance Scale scores from '0' or '1' at baseline to a score of ≥ 2 at the follow-up assessment.
Methods:
Using the derivation cohort, a multivariable logistic regression model was used to predict cognitive decline within 12 months. Covariates included demographics, disease diagnoses, sensory and communication impairments, health conditions, physical and social functioning, service utilisation, informal caregiver status and eight interRAI-derived health index scales. The predicted probability of cognitive decline was calculated for each person in the validation cohort. The c-statistic was used to assess the model's discriminative ability. This study followed the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) reporting guidelines.
Results:
A total of 6796 individuals (median age: 82; female: 60.4%) were split into a derivation cohort (n = 5098) and a validation cohort (n = 1698). Logistic regression models using the derivation cohort resulted in a c-statistic of 0.70 (95% CI 0.70, 0.73). The final regression model (including 21 main effects and 8 significant interaction terms) was applied to the validation cohort, resulting in a c-statistic of 0.69 (95% CI 0.66, 0.72).
Conclusion:
interRAI data can be used to develop a model for identifying individuals at risk of cognitive decline. Identifying this group enables proactive clinical interventions and care planning, potentially improving their outcomes. While these results are promising, the model's moderate discriminative ability highlights opportunities for improvement.
Background
Cognitive impairment (CI) is a major public health concern among the geriatric population and affects around 50 million people worldwide. The prevalence of CI ranges from 5.1% to 41%, and it is considered an initial stage for conditions like acute dementia, Alzheimer’s disease, and schizophrenia. However, diagnosing CI is controversial due to the absence of clear clinical criteria, leading to memory complaints and retained cognitive abilities being used as indicators. While several studies have examined gender differences in cognition and memory, most of these studies have focused on developed countries, leaving a gap in knowledge for other populations.
Methodology
407 participants (115 CI individuals and 292 no-CI individuals) in the age range of 36–85 years were recruited in this study. Rowland Universal Dementia Assessment Scale (RUDAS) was implemented for cognitive assessment, and the Post Graduate Institute Memory Scale (PGIMS) was administered for memory assessment. Data generated in the present study have been analyzed in IBM SPSS version 22.
Results
CI individuals have a significantly higher average age. Females were more cognitively impaired in the studied population. Further, a significantly low PGIMS score among CI individuals has been observed in the present study. Moreover, illiteracy and unemployment were significantly higher, and the PGIMS score was significantly lower among females, both in the case and control groups independently. Most importantly, a significant difference of 9 out of 10 memory domains between males and females in the control category reduced to 5 out of 10 domains in the CI category.
Conclusion
The present study differentiates gender differences among the CI individuals. Females were more impaired in terms of CI and memory performance. Further, the present study would be clinically beneficial with gender-specific diagnosis and pharmaceutical implications.
Background
A disease of unknown aetiology, Alzheimer's disease (AD) is the most common type of dementia. As the elderly population grows worldwide, the number of patients with AD also increases rapidly. The aim of this meta-analysis is to evaluate the prevalence and incidence of AD in Europe.
Methodology
We conducted a literature search on Medline, Scopus, and CINAHL Complete using the keywords “Alzheimer”, “Alzheimer's disease”, and “AD” combined with “prevalence”, “incidence”, and “epidemiology”. A Bayesian random effects model with 95% credible intervals was used. The I² statistic was applied to assess heterogeneity.
Results
The prevalence of Alzheimer's disease in Europe was estimated at 5.05% (95% CI, 4.73-5.39). The prevalence in men was 3.31% (95% CI, 2.85-3.80) and in women, 7.13% (95% CI, 6.56-7.72), and increased with age.
The incidence of Alzheimer's disease in Europe was 11.08 per 1000 person-years (95% CI, 10.30-11.89). Broken down by sex, it was 7.02 per 1000 person-years (95% CI, 6.06-8.05) in men and 13.25 per 1000 person-years (95% CI, 12.05-14.51) in women; again these rates increased with age.
Conclusions
The results of our meta-analysis allow a better grasp of the impact of this disease in Europe.
The British Association for Psychopharmacology coordinated a meeting of experts to review and revise its previous 2011 guidelines for clinical practice with anti-dementia drugs. As before, levels of evidence were rated using accepted standards which were then translated into grades of recommendation A-D, with A having the strongest evidence base (from randomised controlled trials) and D the weakest (case studies or expert opinion). Current clinical diagnostic criteria for dementia have sufficient accuracy to be applied in clinical practice (B) and both structural (computed tomography and magnetic resonance imaging) and functional (positron emission tomography and single photon emission computerised tomography) brain imaging can improve diagnostic accuracy in particular situations (B). Cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) are effective for cognition in mild to moderate Alzheimer's disease (A), memantine for moderate to severe Alzheimer's disease (A) and combination therapy (cholinesterase inhibitors and memantine) may be beneficial (B). Drugs should not be stopped just because dementia severity increases (A). Until further evidence is available other drugs, including statins, anti-inflammatory drugs, vitamin E, nutritional supplements and , cannot be recommended either for the treatment or prevention of Alzheimer's disease (A). Neither cholinesterase inhibitors nor memantine are effective in those with mild cognitive impairment (A). Cholinesterase inhibitors are not effective in frontotemporal dementia and may cause agitation (A), though selective serotonin reuptake inhibitors may help behavioural (but not cognitive) features (B). Cholinesterase inhibitors should be used for the treatment of people with Lewy body dementias (both Parkinson's disease dementia and dementia with Lewy bodies), and memantine may be helpful (A). No drugs are clearly effective in vascular dementia, though cholinesterase inhibitors are beneficial in mixed dementia (B). Early evidence suggests multifactorial interventions may have potential to prevent or delay the onset of dementia (B). Though the consensus statement focuses on medication, psychological interventions can be effective in addition to pharmacotherapy, both for cognitive and non-cognitive symptoms. Many novel pharmacological approaches involving strategies to reduce amyloid and/or tau deposition in those with or at high risk of Alzheimer's disease are in progress. Though results of pivotal studies in early (prodromal/mild) Alzheimer's disease are awaited, results to date in more established (mild to moderate) Alzheimer's disease have been equivocal and no disease modifying agents are either licensed or can be currently recommended for clinical use.
Background: Bilingualism may contribute to cognitive reserve, protect against cognitive decline, and delay the onset of dementia.
Objective: We systematically reviewed evidence about the effect of bilingualism on subsequent cognitive decline or dementia.
Methods: We searched electronic databases and references for longitudinal studies comparing cognitive decline in people who were bilingual with those who were monolingual and evaluated study quality. We conducted meta-analyses using random effects models to calculate pooled odds ratio of incident dementia.
Results: We included 13/1,156 eligible articles. Meta-analysis of prospective studies of the effects of bilingualism on future dementia gave a combined Odds Ratio of dementia of 0.96 (95% CI 0.74–1.23) in bilingual participants (n = 5,527) compared to monolinguals. Most retrospective studies found that bilingual people were reported to develop symptoms of cognitive decline at a later age than monolingual participants.
Conclusion: We did not find that bilingualism protects from cognitive decline or dementia from prospective studies. Retrospective studies are more prone to confounding by education, or cultural differences in presentation to dementia services and are therefore not suited to establishing causative links between risk factors and outcomes.
Background
Variation in the clinical manifestation of dementia has been associated with differences in cognitive reserve, although less is known about the cumulative effects of exposure to cognitive reserve factors over the life course. We examined the association of cognitive reserve-related factors over the lifespan with the risk of dementia in a community-based cohort of older adults.
Methods and findings
Information on early-life education, socioeconomic status, work complexity at age 20, midlife occupation attainment, and late-life leisure activities was collected in a cohort of dementia-free community dwellers aged 75+ y residing in the Kungsholmen district of Stockholm, Sweden, in 1987–1989. The cohort was followed up to 9 y (until 1996) to detect incident dementia cases. To exclude preclinical phases of disease, participants who developed dementia at the first follow-up examination 3 y after the baseline were excluded (n = 602 after exclusions). Structural equation modelling was used to generate latent factors of cognitive reserve from three periods over the life course: early (before 20 y), adulthood (around 30–55 y), and late life (75 y and older). The correlation between early- and adult-life latent factors was strong (γ = 0.9), whereas early–late (γ = 0.27) and adult–late (γ = 0.16) latent factor correlations were weak. One hundred forty-eight participants developed dementia during follow-up, and 454 remained dementia-free. The relative risk (RR) of dementia was estimated using Cox models with life-course cognitive reserve-enhancing factors modelled separately and simultaneously to assess direct and indirect effects. The analysis was repeated among carriers and noncarriers of the apolipoprotein E (APOE) ε4 allele. A reduced risk of dementia was associated with early- (RR 0.57; 95% CI 0.36–0.90), adult- (RR 0.60; 95% CI 0.42–0.87), and late-life (RR 0.52; 95% CI 0.37–0.73) reserve-enhancing latent factors in separate multivariable Cox models. In a mutually adjusted model, which may have been imprecisely estimated because of strong correlation between early- and adult-life factors, the late-life factor preserved its association (RR 0.65; 95% CI 0.45–0.94), whereas the effect of midlife (RR 0.73; 95% CI 0.50–1.06) and early-life factors (RR 0.76; 95% CI 0.47–1.23) on the risk of dementia was attenuated. The risk declined progressively with cumulative exposure to reserve-enhancing latent factors, and having high scores on cognitive reserve-enhancing composite factors in all three periods over the life course was associated with the lowest risk of dementia (RR 0.40; 95% CI 0.20–0.81). Similar associations were detected among APOE ε4 allele carriers and noncarriers. Limitations include measurement error and nonresponse, with both biases likely favouring the null. Strong correlation between early- and adult-life latent factors may have led to a loss in precision when estimating mutually adjusted effects of all periods.
Conclusions
In this study, cumulative exposure to reserve-enhancing factors over the lifespan was associated with reduced risk of dementia in late life, even among individuals with genetic predisposition.
Background
Most people with dementia do not receive timely diagnosis, preventing them from making informed plans about their future and accessing services. Many countries have a policy to increase timely diagnosis, but trials aimed at changing general practitioner (GP) practice have been unsuccessful. We aimed to assess whether a GP’s personal letter, with an evidence-based leaflet about overcoming barriers to accessing help for memory problems—aimed at empowering patients and families—increases timely dementia diagnosis and patient presentation to general practice.
Methods and finding
Multicentre, cluster-randomised controlled trial with raters masked to an online computer-generated randomisation system assessing 1 y outcome. We recruited 22 general practices (August 2013–September 2014) and 13 corresponding secondary care memory services in London, Hertfordshire, and Essex, United Kingdom. Eligible patients were aged ≥70 y, without a known diagnosis of dementia, living in their own homes. There were 6,387 such patients in 11 intervention practices and 8,171 in the control practices. The primary outcome was cognitive severity on Mini Mental State Examination (MMSE). Main secondary outcomes were proportion of patients consulting their GP with suspected memory disorders and proportion of those referred to memory clinics. There was no between-group difference in cognitive severity at diagnosis (99 intervention, mean MMSE = 22.04, 95% confidence intervals (CIs) = 20.95 to 23.13; 124 control, mean MMSE = 22.59, 95% CI = 21.58 to 23.6; p = 0.48). GP consultations with patients with suspected memory disorders increased in intervention versus control group (odds ratio = 1.41; 95% CI = 1.28, 1.54). There was no between-group difference in the proportions of patients referred to memory clinics (166, 2.5%; 220, 2.7%; p = .077 respectively). The study was limited as we do not know whether the additional patients presenting to GPs had objective as well as subjective memory problems and therefore should have been referred. In addition, we aimed to empower patients but did not do anything to change GP practice.
Conclusions
Our intervention to access timely dementia diagnosis resulted in more patients presenting to GPs with memory problems, but no diagnoses increase. We are uncertain as to the reason for this and do not know whether empowering the public and targeting GPs would have resulted in a successful intervention. Future interventions should be targeted at both patients and GPs.
Trial registration
Current Controlled Trials ISRCTN19216873
Objectives
This review aims to understand what elements of psychosocial interventions are associated with improved outcomes for people with dementia to inform implementation in care homes.
Design
A systematic review of qualitative and quantitative intervention studies was undertaken.
Eligibility criteria for included studies
We included primary research studies evaluating psychosocial interventions that trained care home staff to deliver a specific intervention or that sought to change how staff delivered care to residents with dementia and reported staff and resident qualitative or quantitative outcomes.
Methods
We searched MEDLINE, PsychINFO and EMBASE electronic databases and hand-searched references up to May 2016. Quality of included papers was rated independently by 2 authors, using operationalised checklists derived from standard criteria. We discussed discrepancies and reached consensus. We conducted a narrative synthesis of quantitative and a thematic synthesis of qualitative findings to find what was effective immediately and in sustaining change.
Results
We identified 49 papers fulfilling predetermined criteria. We found a lack of higher quality quantitative evidence that effects could be sustained after psychosocial interventions finished with no evidence that interventions continued to work after 6 months. Qualitative findings suggest that staff valued interventions focusing on getting to know, understand and connect with residents with dementia. Successful elements of interventions included interactive training, post-training support, aiming to train most staff, retaining written materials afterwards and building interventions into routine care.
Conclusions
Psychosocial interventions can improve outcomes for staff and residents with dementia in care homes; however, many trial results are limited. Synthesis of qualitative findings highlight core components of interventions that staff value and feel improve care. These findings provide useful evidence to inform the development of sustainable, effective psychosocial interventions in care homes.
Trial registration number
CRD42015017621.
Family carers report high levels of decisional conflict when deciding whether their relative with dementia can continue to be cared for in their own home. We tested, in a feasibility randomised controlled trial, the first decision aid (the DECIDE manual) aiming to reduce such conflict. Twenty family carers received the DECIDE intervention, and 21 received usual treatment. The intervention group had reduced decisional conflict compared with controls (mean difference −11.96, 95% confidence interval −20.10 to −3.83, P=0.005). All carers receiving the intervention completed and valued it, despite some still reporting difficulties with family conflict and problems negotiating services.
Declaration of interest
None.
Copyright and usage
© The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.
Exposure to particulate matter (PM) in the ambient air and its interactions with APOE alleles may contribute to the acceleration of brain aging and the pathogenesis of Alzheimer’s disease (AD). Neurodegenerative effects of particulate air pollutants were examined in a US-wide cohort of older women from the Women’s Health Initiative Memory Study (WHIMS) and in experimental mouse models. Residing in places with fine PM exceeding EPA standards increased the risks for global cognitive decline and all-cause dementia respectively by 81 and 92%, with stronger adverse effects in APOE ε4/4 carriers. Female EFAD transgenic mice (5xFAD+/−/human APOE ε3 or ε4+/+) with 225 h exposure to urban nanosized PM (nPM) over 15 weeks showed increased cerebral β-amyloid by thioflavin S for fibrillary amyloid and by immunocytochemistry for Aβ deposits, both exacerbated by APOE ε4. Moreover, nPM exposure increased Aβ oligomers, caused selective atrophy of hippocampal CA1 neurites, and decreased the glutamate GluR1 subunit. Wildtype C57BL/6 female mice also showed nPM-induced CA1 atrophy and GluR1 decrease. In vitro nPM exposure of neuroblastoma cells (N2a-APP/swe) increased the pro-amyloidogenic processing of the amyloid precursor protein (APP). We suggest that airborne PM exposure promotes pathological brain aging in older women, with potentially a greater impact in ε4 carriers. The underlying mechanisms may involve increased cerebral Aβ production and selective changes in hippocampal CA1 neurons and glutamate receptor subunits.
Purpose
To understand activity in dementia care, we examine relationships of disease stage with types and characteristics of meaningful activities (cueing needs, help with initiation, and recommended engagement time) provided in a home-based intervention trial designed to reduce behavioral symptoms.
Design and Methods
Data involved 158 activity prescriptions or written documents detailing prescribed activities, cueing needs, and engagement goals designed by occupational therapists for 56 families. Activities were categorized as arts and crafts, exercise/physical, cognitive, music/entertainment, manipulation/sensory/sorting, family/social/ reminiscence, and domestic/homemaking. Bivariate correlations examined relationships of activity categories and characteristics with disease stage (mild, moderate, or severe). Kruskal–Wallis H tests examined differences among disease stages and frequency of type of activities prescribed, recommended cues, and engagement time. For significant Kruskal–Wallis tests, pairwise comparisons utilized the Mann–Whitney U test.
Results
Activity categories and instructions for set up were significantly related to cognitive and functional levels. Persons with mild dementia were most often prescribed complex arts and crafts and cognitive activities. Persons with moderate dementia were most often prescribed music/entertainment. Persons with severe dementia were most often prescribed simple physical exercises and manipulation/sensory/sorting activities. Average time prescribed for activities was less for those in severe (15min) versus moderate (24min) and mild (28min) stages. The severe group required more assistance with activity initiation and cueing/redirection.
Implications
Type of activity, recommended cueing, and engagement time differed by dementia stage. Findings provide guidance as to how to use and set up activities across the dementia trajectory.
Purpose of the Study
Age-related hearing loss negatively affects health outcomes, yet disparities in hearing care, such as hearing aid use, exist based on race/ethnicity and socioeconomic position. Recent national efforts highlight reduction of hearing care disparities as a public health imperative. This study a) describes a community engagement approach to addressing disparities, b) reports preliminary outcomes of a novel intervention, and c) discusses implementation processes and potential for wide-scale testing and use.
Design and Methods
This was a prospective, randomized control pilot, with a 3-month delayed treatment group as a waitlist control, that assessed feasibility, acceptability, and preliminary efficacy of a community-delivered, affordable, and accessible intervention for older adults with hearing loss. Outcomes were assessed at 3 months, comparing immediate and delayed groups, and pooled to compare the cohort’s pre- and 3-month post-intervention results.
Results
All participants completed the study (n = 15). The program was highly acceptable: 93% benefited, 100% would recommend the program, and 67% wanted to serve as future program trainers. At 3 months, the treated group (n = 8) experienced fewer social and emotional effects of hearing loss and fewer depressive symptoms as compared to the delayed treatment group (n = 7). Pooling 3-month post-intervention scores (n = 15), participants reported fewer negative hearing-related effects (effect size = −0.96) and reduced depressive symptoms (effect size = −0.43).
Implications
The HEARS (Hearing Equality through Accessible Research & Solutions) intervention is feasible, acceptable, low risk, and demonstrates preliminary efficacy. HEARS offers a novel, low-cost, and readily scalable solution to reduce hearing care disparities and highlights how a community-engaged approach to intervention development can address disparities.
Background More information about the pattern of behavioural and psychological symptoms of dementia (BPSD) in the course of dementia is needed to inform patients and clinicians and to design future interventions. Aims To determine the persistence and incidence of BPSD and their relation to cognitive function, in individuals with dementia or in cohorts investigated for dementia onset.Method A systematic literature review analysed the baseline prevalence, persistence and incidence of 11 symptoms. The review was conducted according to established guidelines with the exception that we could not exclude the possibilities of bias in the studies examined. Results The 59 included studies showed considerable heterogeneity in their objectives and methods. The symptoms hyperactivity and apathy showed high persistence and incidence; depression and anxiety low or moderate persistence and moderate incidence; and psychotic symptoms low persistence with moderate or low incidence. Conclusions Despite heterogeneity across studies in terms of setting, focus and length of follow-up, there were clinically relevant differences in the longitudinal courses of different BPSD. Apathy was the only symptom with high baseline prevalence, persistence and incidence during the course of dementia. Declaration of interest None.This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY) licence.
Early diagnosis and intervention for people with dementia is increasingly considered a priority, but practitioners are concerned with the effects of earlier diagnosis and interventions on patients and caregivers. This systematic review evaluates the qualitative evidence about how people accommodate and adapt to the diagnosis of dementia and its immediate consequences, to guide practice.
Dramatic global increases in future numbers of people with dementia have been predicted. No multicentre population-based study powered to detect changes over time has reported dementia incidence. MRC Cognitive Function and Ageing Study (CFAS) undertook baseline interviews in populations aged 65 þ years in England and Wales (1989–1994). Three areas (CFAS I) were selected for new sampling two decades later (2008–2011) with same geographical boundaries, sampling and approach methods (CFAS II). At 2 years CFAS I interviewed 5,156 (76% response) with 5,288 interviewed in CFAS II (74% response). Here we report a 20% drop in incidence (95% CI: 0–40%), driven by a reduction in men across all ages above 65. In the UK we estimate 209,600 new dementia cases per year. This study was uniquely designed to test for differences across geography and time. A reduction of age-specific incidence means that the numbers of people estimated to develop dementia in any year has remained relatively stable.
Background
Interventions that improve cognitive function in Alzheimer's disease are urgently required.
Aims
To assess whether a novel cognitive training paradigm based on ‘chunking’ improves working memory and general cognitive function, and is associated with reorganisation of functional activity in prefrontal and parietal cortices (trial registration: ISRCTN43007027).
Method
Thirty patients with mild Alzheimer's disease were randomly allocated to receive 18 sessions of 30 min of either adaptive chunking training or an active control intervention over approximately 8 weeks. Pre- and post-intervention functional magnetic resonance imaging (fMRI) scans were also conducted.
Results
Adaptive chunking training led to significant improvements in verbal working memory and untrained clinical measures of general cognitive function. Further, fMRI revealed a bilateral reduction in task-related lateral prefrontal and parietal cortex activation in the training group compared with controls.
Conclusions
Chunking-based cognitive training is a simple and potentially scalable intervention to improve cognitive function in early Alzheimer's disease.
Objective: To identify common difficult decisions made by family carers on behalf of people with dementia, and facilitators of and barriers to such decisions, in order to produce information for family carers about overcoming barriers. / Design: Qualitative study to delineate decision areas through focus groups and complexity of decision making in individual interviews. / Setting: Community settings in London. / Participants: 43 family carers of people with dementia in focus groups and 46 carers who had already made such decisions in individual interviews. / Results: Family carers identified five core problematic areas of decision making: accessing dementia related health and social services; care homes; legal-financial matters; non-dementia related health care; and making plans for the person with dementia if the carer became too ill to care for them. They highlighted the difficulties in making proxy decisions, especially against active resistance, and their altered role of patient manager while still a family member. Families devised strategies to gain agreement in order to ensure that the person with dementia retained dignity. / Conclusions: The following strategies helped with implementation of decisions: introducing change slowly; organising legal changes for the carer as well as the patient; involving a professional to persuade the patient to accept services; and emphasising that services optimised, not impeded, independence. To access services, carers made patients’ general practice appointments, accompanied them to the surgery, pointed out symptoms, gained permission to receive confidential information, asked for referral to specialist services, and used professionals’ authority to gain patients’ agreement. End of life decisions were particularly difficult. They were helped by knowledge of the person with dementia’s previous views, clear prognostic information, and family support. Information sheets to help carers to overcome barriers to proxy decision making have been developed; their impact in practice has yet to be evaluated.
Background: Genetic heterogeneity in amnestic mild cognitively impaired (aMCI) subjects could lead to variations in progression rates and response to cholinomimetic agents. Together with the apolipoprotein E4 (APOE-ɛ4) gene, butyrylcholinesterase (BCHE) has become recently one of the few Alzheimer’s disease (AD) susceptibility genes with distinct pharmacogenomic properties.
Objective: To validate candidate genes (APOE/BCHE) which display associations with age of onset of AD and donepezil efficacy in aMCI subjects.
Methods: Using the Petersen et al. (2005) study on vitamin E and donepezil efficacy in aMCI, we contrasted the effects of BCHE and APOE variants on donepezil drug response using the Alzheimer’s Disease Assessment Score-Cognition (ADAS-Cog) scale. Independently, we assessed the effects of APOE/BCHE genotypes on age of onset and cortical choline acetyltransferase activity in autopsy-confirmed AD and age-matched control subjects.
Results: Statistical analyses revealed a significant earlier age of onset in AD for APOE-ɛ4, BCHE-K*, and APOE-ɛ4/BCHE-K* carriers. Among the carriers of APOE-ɛ4 and BCHE-K*, the benefit of donepezil was evident at the end of the three-year follow-up. The responder’s pharmacogenomic profile is consistent with reduced brain cholinergic activity measured in APOE-ɛ4 and BCHE-K* positive subjects.
Conclusions: APOE-ɛ4 and BCHE-K* positive subjects display an earlier age of onset of AD, an accelerated cognitive decline and a greater cognitive benefits to donepezil therapy. These results clearly emphasize the necessity of monitoring potential pharmacogenomic effects in this population of subjects, and suggest enrichment strategies for secondary prevention trials involving prodromal AD subjects.
CFAS II has been supported by the UK Medical Research Council (Research Grant: G06010220) and received additional support from the National Institute for Health Research (NIHR), comprehensive clinical research networks in West Anglia, Nottingham City and Nottinghamshire County NHS Primary Care trusts and the dementias and neurodegenerative disease research Network (DeNDRoN) in Newcastle. MRC CFAS I was funded by the MRC (Research Grant: G9901400) and the National Health Service (NHS). F.E.M. is supported by the MRC (Research Grant: U105292687). This research was done within the UK National Institute of Health Research collaboration for leadership in applied health research and care for Cambridgeshire and Peterborough (CLAHRC EoE), the Biomedical Research Centre infrastructures at Cambridge and Newcastle upon Tyne. We thank the participants, their families, the general practitioners and their staff, the primary care trusts and CCGs for their cooperation and support. We thank the CFAS II fieldwork interviewers at Cambridge, Nottingham and Newcastle for their valuable contribution. Funding was given by UK Medical Research Council.
Objective
The objective of this study was to evaluate peer support and reminiscence therapy, separately and together, in comparison with usual care for people with dementia and their family carers.
Design
Factorial pragmatic randomised trial, analysed by treatment allocated, was used for this study.
Setting
The trial ran in Community settings in England.
Participants
People with dementia and their family carers were the participants.
Interventions
Treatment as usual (TAU) plus one of the following: one-to-one peer support to family carers from experienced carers (Carer Supporter Programme; CSP), group reminiscence therapy (Remembering Yesterday, Caring Today; RYCT) for people with dementia and carers, both or neither.
Main outcome measures
Primary outcomes included health-related quality of life (SF-12) for carers and quality of life (QoL-AD) for people with dementia; secondary outcomes included quality of relationship for carers and people with dementia; both were collected by blinded assessors at baseline, 5 and 12 months (primary end point).
Results
Of 291 pairs recruited, we randomised 145 (50%) to CSP (71% uptake) and 194 (67%) to RYCT (61% uptake). CSP and RYCT, separately or together, were not effective in improving primary outcomes or most secondary outcomes. For CSP versus ‘no CSP’, adjusted difference in means was 0.52 points on the SF-12 (95% CI −1.28 to 2.32) and −0.08 points on the QoL-AD (95% CI −1.70 to 1.56). For RYCT versus ‘no RYCT’, the difference was 0.10 points on the SF-12 (95% CI −1.72 to 1.93) and 0.51 points on the QoL-AD (95% CI −1.17 to 2.08). However, carers reported better relationships with the people with dementia (difference 1.11, 95% CI 0.00 to 2.21, p=0.05). Comparison of combined intervention with TAU, and of intervention received, suggested differential impacts for carers and persons with dementia.
Conclusions
There is no evidence from the trial that either peer support or reminiscence is effective in improving the quality of life.
Trial registration number
ISRCTN37956201; Results.
Background:
Cardiovascular risk factors are associated with an increased risk of dementia. We assessed whether a multidomain intervention targeting these factors can prevent dementia in a population of community-dwelling older people.
Methods:
In this open-label, cluster-randomised controlled trial, we recruited individuals aged 70-78 years through participating general practices in the Netherlands. General practices within each health-care centre were randomly assigned (1:1), via a computer-generated randomisation sequence, to either a 6-year nurse-led, multidomain cardiovascular intervention or control (usual care). The primary outcomes were cumulative incidence of dementia and disability score (Academic Medical Center Linear Disability Score [ALDS]) at 6 years of follow-up. The main secondary outcomes were incident cardiovascular disease and mortality. Outcome assessors were masked to group assignment. Analyses included all participants with available outcome data. This trial is registered with ISRCTN, number ISRCTN29711771.
Findings:
Between June 7, 2006, and March 12, 2009, 116 general practices (3526 participants) within 26 health-care centres were recruited and randomly assigned: 63 (1890 participants) were assigned to the intervention group and 53 (1636 participants) to the control group. Primary outcome data were obtained for 3454 (98%) participants; median follow-up was 6·7 years (21 341 person-years). Dementia developed in 121 (7%) of 1853 participants in the intervention group and in 112 (7%) of 1601 participants in the control group (hazard ratio [HR] 0·92, 95% CI 0·71-1·19; p=0·54). Mean ALDS scores measured during follow-up did not differ between groups (85·7 [SD 6·8] in the intervention group and 85·7 [7·1] in the control group; adjusted mean difference -0·02, 95% CI -0·38 to 0·42; p=0·93). 309 (16%) of 1885 participants died in the intervention group, compared with 269 (16%) of 1634 participants in the control group (HR 0·98, 95% CI 0·80-1·18; p=0·81). Incident cardiovascular disease did not differ between groups (273 [19%] of 1469 participants in the intervention group and 228 [17%] of 1307 participants in the control group; HR 1·06, 95% CI 0·86-1·31; p=0·57).
Interpretation:
A nurse-led, multidomain intervention did not result in a reduced incidence of all-cause dementia in an unselected population of older people. This absence of effect might have been caused by modest baseline cardiovascular risks and high standards of usual care. Future studies should assess the efficacy of such interventions in selected populations.
Funding:
Dutch Ministry of Health, Welfare and Sport; Dutch Innovation Fund of Collaborative Health Insurances; and Netherlands Organisation for Health Research and Development.
Key messages ‐ For people with mild‐to‐moderate dementia, cognitive stimulation probably leads to small benefits in cognition (the general ability to think and remember). ‐ We found a range of other probable benefits, including improved well‐being, mood and day‐to‐day abilities, but benefits were generally slight and, especially for cognition and well‐being, varied greatly between studies. ‐ Most studies evaluated group cognitive stimulation. Future studies should try to clarify the effects of individual cognitive stimulation, assess how often group sessions should take place to have the best effect, and identify who benefits most from cognitive stimulation. What is dementia? Dementia is an umbrella term for numerous brain disorders. Alzheimer’s disease is the most common of these. People of all ages can develop dementia, but most often it occurs in later life. People with dementia typically experience a decline in their cognitive abilities, which can impair memory, thinking, language and practical skills. These problems usually worsen over time and can lead to isolation, upset and distress for the person with dementia and those providing care and support. Cognitive stimulation Cognitive stimulation (CS) is a form of 'mental exercise' developed specifically to help people with dementia. It involves a wide range of activities aiming to stimulate thinking and memory generally, including discussion of past and present events and topics of interest, word games, puzzles, music and creative practical activities. Usually delivered by trained staff working with a small group of people with dementia for around 45 minutes twice‐weekly, it can also be provided on a one‐to‐one basis. Some programmes have trained family carers to provide CS to their relative. What did we want to find out? We wanted to find out if CS was better for people living with dementia than usual care or unstructured social activities to improve: ‐ cognitive abilities (including memory, thinking and language skills) ‐ well‐being and mood ‐ day‐to‐day abilities ‐ distress and upset for the person with dementia and/or carers We also wanted to find out if family carers experienced any changes associated with the person with dementia receiving CS or if there were any unwanted effects. What did we do?We searched for studies that looked at group or individual CS compared with usual care or unstructured social activity in people living with dementia. We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes. What did we find? We found 37 studies involving 2766 participants with mild or moderate dementia and an average age of 79 years. The biggest study involved 356 participants, the smallest 13. The studies were conducted in 17 countries from five continents, with most in Europe. Fewer than half (16) included participants living in care homes or hospitals. The length of the trials varied from four weeks to two years. Sessions per week varied from one to six. The overall number of sessions varied from eight to 520. Most studies lasted for around 10 weeks, with around 20 sessions. Most studies offered CS in groups, with just eight examining individual CS. Main results No negative effects were reported. We found that CS probably results in a small benefit to cognition at the end of the course of sessions compared with usual care/unstructured activities. This benefit equates roughly to a six‐month delay in the cognitive decline usually expected in mild‐to‐moderate dementia. We found preliminary evidence suggesting that cognition benefited more when group sessions occurred twice weekly or more (rather than once weekly) and that benefits were greater in studies where participants’ dementia at the outset was of mild severity. We also found that participants improved on measures of communication and social interaction and showed slight benefits in day‐to‐day activities and in their own ratings of their mood. There is probably also a slight improvement in participants’ well‐being and in experiences that are upsetting and distressing for people with dementia and carers. We found CS probably made little or no difference to carers' mood or anxiety. What are the limitations of the evidence? Our confidence in the evidence is only moderate because of concerns about differences in results between studies. We cannot be certain of the exact reasons for these differences, but we noted that studies varied in: • the way CS was delivered (individually, in groups, using an app) and the programme of activities included • who delivered the programme (trained professionals, care workers, family carers) • the frequency of sessions (1 per week to 5 per week) • the duration of the programme (from 4 weeks to 1 or 2 years) • the type(s) of dementia with which participants were diagnosed and the severity of the dementia • whether participants lived in care homes and hospitals or in their own homes We were unable to examine as many of these sources of potential difference as would have been desirable because of the relatively small number of studies reflecting each aspect. How up‐to‐date is this evidence? This review updates our previous review from 2012, with evidence up‐to‐date to March 2022.
Dementia is an increasing focus for policymakers, civil organizations and multidisciplinary researchers. The most recent descriptive epidemiological research into dementia is enabling investigation into how the prevalence and incidence are changing over time. To establish clear trends, such comparisons need to be founded on population-based studies that use similar diagnostic and research methods consistently over time. This narrative Review synthesizes the findings from 14 studies that investigated trends in dementia prevalence (nine studies) and incidence (five studies) from Sweden, Spain, the UK, the Netherlands, France, the USA, Japan and Nigeria. Besides the Japanese study, these studies indicate stable or declining prevalence and incidence of dementia, and some provide evidence of sex-specific changes. No single risk or protective factor has been identified that fully explains the observed trends, but major societal changes and improvements in living conditions, education and healthcare might have favourably influenced physical, mental and cognitive health throughout an individual's life course, and could be responsible for a reduced risk of dementia in later life. Analytical epidemiological approaches combined with translational neuroscientific research could provide a unique opportunity to explore the neuropathology that underlies changing occurrence of dementia in the general population.
Objective: To determine the relationship between hearing loss and cognitive function as assessed with a standardized neurocognitive battery. We hypothesized a priori that greater hearing loss is associated with lower cognitive test scores on tests of memory and executive function. Method: A cross-sectional cohort of 347 participants ≥55 years in the Baltimore Longitudinal Study of Aging without mild cognitive impairment or dementia had audiometric and cognitive testing performed in 1990–1994. Hearing loss was defined by an average of hearing thresholds at 0.5, 1, 2, and 4 kHz in the better-hearing ear. Cognitive testing consisted of a standardized neurocognitive battery incorporating tests of mental status, memory, executive function, processing speed, and verbal function. Regression models were used to examine the association between hearing loss and cognition while adjusting for confounders. Results: Greater hearing loss was significantly associated with lower scores on measures of mental status (Mini-Mental State Exam), memory (Free Recall), and executive function (Stroop Mixed, Trail Making B). These results were robust to analyses accounting for potential confounders, nonlinear effects of age, and exclusion of individuals with severe hearing loss. The reduction in cognitive performance associated with a 25 dB hearing loss was equivalent to the reduction associated with an age difference of 6.8 years. Conclusion: Hearing loss is independently associated with lower scores on tests of memory and executive function. Further research examining the longitudinal association of hearing loss with cognitive functioning is needed to confirm these cross-sectional findings.
This is the protocol for a review and there is no abstract. The objectives are as follows: The objectives of this review are to evaluate: The efficacy of cholinesterase inhibitors for the treatment of cognitive impairment or dementia in neurological conditions associated with rarer dementias; The adverse effects of cholinesterase inhibitors in these conditions.
This is the protocol for a review and there is no abstract. The objectives are as follows: This review has two primary objectives. Objective A: To estimate the accuracy of DAT imaging for the diagnosis of dementia with Lewy bodies (DLB) in patients with dementia in secondary care.Objective B: To assess the value of DAT imaging in clinical practice by estimating the accuracy of DAT imaging for the diagnosis of DLB in secondary care patients with a pre-existing suspicion of DLB on the basis of a clinical work-up. The secondary objective is to use subgroup analyses to investigate the following potential sources of heterogeneity. (a) Age of participants. (b) Severity of dementia. The performance of the index test itself may vary with dementia severity. For objective B, since the performance of the clinical criteria may also depend on the severity of dementia, the 'added value' to be obtained from the index test may vary significantly. (c) For objective B, diagnostic status at inclusion (possible or probable DLB, or both). (d) DAT imaging method (SPECT or PET, ligand).
The aging of the US population is expected to lead to a large increase in the number of adults with dementia, but some recent studies in the US and other high-income countries suggest that the age-specific risk of dementia may have declined over the last 25 years. Clarifying current and future population trends in dementia prevalence and risk has important societal implications.
We used data from the Health and Retirement Study (HRS), a nationally representative population-based longitudinal survey of US adults to compare the prevalence of dementia in the US in 2000 and 2012. Our sample included individuals aged 65 or older from the 2000 (N = 10,675) and 2012 (N = 10,627) waves of the HRS. Dementia was identified in each year using HRS cognitive measures and validated diagnostic classifications.
Dementia prevalence decreased from 11.7% in 2000 to 9.0% (P < .001). More years of education was associated with a lower risk for dementia, and average years of education increased significantly (from 11.7 to 12.7 years; P < .001) between 2000 and 2012. The decline in dementia prevalence occurred even though there was a significant age- and sex-adjusted increase between years in the cardiovascular risk profile among older US adults.
The prevalence of dementia in the US declined significantly between 2000 and 2012. An increase in educational attainment among older adults was associated with some of the decline in dementia prevalence, but the full set of social, behavioral, and medical factors contributing to the decline is still uncertain.
Importance:
Neuropsychiatric symptoms, depressive symptoms in particular, are common in patients with dementia but whether depressive symptoms in adulthood increases the risk for dementia remains the subject of debate.
Objective:
To characterize the trajectory of depressive symptoms over 28 years prior to dementia diagnosis to determine whether depressive symptoms carry risk for dementia.
Design, setting, and participants:
Up to 10 308 persons, aged 35 to 55 years, were recruited to the Whitehall II cohort study in 1985, with the end of follow-up in 2015. Data analysis for this study in a UK general community was conducted from October to December 2016.
Exposures:
Depressive symptoms assessed on 9 occasions between 1985 and 2012 using the General Health Questionnaire.
Main outcomes and measures:
Incidence of dementia (n = 322) between 1985 and 2015.
Results:
Of the 10 189 persons included in the study, 6838 were men (67%) and 3351 were women (33%). Those reporting depressive symptoms in 1985 (mean follow-up, 27 years) did not have significantly increased risk for dementia (hazard ratio [HR], 1.21; 95% CI, 0.95-1.54) in Cox regression adjusted for sociodemographic covariates, health behaviors, and chronic conditions. However, those with depressive symptoms in 2003 (mean follow-up, 11 years) had an increased risk (HR, 1.72; 95% CI, 1.21-2.44). Those with chronic/recurring depressive symptoms (≥2 of 3 occasions) in the early study phase (mean follow-up, 22 years) did not have excess risk (HR, 1.02; 95% CI, 0.72-1.44) but those with chronic/recurring symptoms in the late phase (mean follow-up, 11 years) did have higher risk for dementia (HR, 1.67; 95% CI, 1.11-2.49). Analysis of retrospective depressive trajectories over 28 years, using mixed models and a backward time scale, shows that in those with dementia, differences in depressive symptoms compared with those without dementia became apparent 11 years (difference, 0.61; 95% CI, 0.09-1.13; P = .02) before dementia diagnosis and became more than 9 times larger at the year of diagnosis (difference, 5.81; 95% CI, 4.81-6.81; P < .001).
Conclusions and relevance:
Depressive symptoms in the early phase of the study corresponding to midlife, even when chronic/recurring, do not increase the risk for dementia. Along with our analysis of depressive trajectories over 28 years, these results suggest that depressive symptoms are a prodromal feature of dementia or that the 2 share common causes. The findings do not support the hypothesis that depressive symptoms increase the risk for dementia.
Background/aims:
The aims of this study were to validate the newly developed version of the Addenbrooke's Cognitive Examination (ACE-III) against standardised neuropsychological tests and its predecessor (ACE-R) in early dementia.
Methods:
A total of 61 patients with dementia (frontotemporal dementia, FTD, n = 33, and Alzheimer's disease, AD, n = 28) and 25 controls were included in the study.
Results:
ACE-III cognitive domains correlated significantly with standardised neuropsychological tests used in the assessment of attention, language, verbal memory and visuospatial function. The ACE-III also compared very favourably with its predecessor, the ACE-R, with similar levels of sensitivity and specificity.
Conclusion:
The results of this study provide objective validation of the ACE-III as a screening tool for cognitive deficits in FTD and AD.
Dementia is an increasing focus for policymakers, civil organizations and multidisciplinary researchers. The most recent descriptive epidemiological research into dementia is enabling investigation into how the prevalence and incidence are changing over time. To establish clear trends, such comparisons need to be founded on population-based studies that use similar diagnostic and research methods consistently over time. This narrative Review synthesizes the findings from 14 studies that investigated trends in dementia prevalence (nine studies) and incidence (five studies) from Sweden, Spain, the UK, the Netherlands, France, the USA, Japan and Nigeria. Besides the Japanese study, these studies indicate stable or declining prevalence and incidence of dementia, and some provide evidence of sex-specific changes. No single risk or protective factor has been identified that fully explains the observed trends, but major societal changes and improvements in living conditions, education and healthcare might have favourably influenced physical, mental and cognitive health throughout an individual's life course, and could be responsible for a reduced risk of dementia in later life. Analytical epidemiological approaches combined with translational neuroscientific research could provide a unique opportunity to explore the neuropathology that underlies changing occurrence of dementia in the general population.
Background:
No large trials have been done to investigate the efficacy of an intervention combining a specific compound and several lifestyle interventions compared with placebo for the prevention of cognitive decline. We tested the effect of omega 3 polyunsaturated fatty acid supplementation and a multidomain intervention (physical activity, cognitive training, and nutritional advice), alone or in combination, compared with placebo, on cognitive decline.
Methods:
The Multidomain Alzheimer Preventive Trial was a 3-year, multicentre, randomised, placebo-controlled superiority trial with four parallel groups at 13 memory centres in France and Monaco. Participants were non-demented, aged 70 years or older, and community-dwelling, and had either relayed a spontaneous memory complaint to their physician, limitations in one instrumental activity of daily living, or slow gait speed. They were randomly assigned (1:1:1:1) to either the multidomain intervention (43 group sessions integrating cognitive training, physical activity, and nutrition, and three preventive consultations) plus omega 3 polyunsaturated fatty acids (ie, two capsules a day providing a total daily dose of 800 mg docosahexaenoic acid and 225 mg eicosapentaenoic acid), the multidomain intervention plus placebo, omega 3 polyunsaturated fatty acids alone, or placebo alone. A computer-generated randomisation procedure was used to stratify patients by centre. All participants and study staff were blinded to polyunsaturated fatty acid or placebo assignment, but were unblinded to the multidomain intervention component. Assessment of cognitive outcomes was done by independent neuropsychologists blinded to group assignment. The primary outcome was change from baseline to 36 months on a composite Z score combining four cognitive tests (free and total recall of the Free and Cued Selective Reminding test, ten Mini-Mental State Examination orientation items, Digit Symbol Substitution Test, and Category Naming Test) in the modified intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT00672685).
Findings:
1680 participants were enrolled and randomly allocated between May 30, 2008, and Feb 24, 2011. In the modified intention-to-treat population (n=1525), there were no significant differences in 3-year cognitive decline between any of the three intervention groups and the placebo group. Between-group differences compared with placebo were 0?093 (95% CI 0?001 to 0?184; adjusted p=0?142) for the combined intervention group, 0?079 (-0?012 to 0?170; 0?179) for the multidomain intervention plus placebo group, and 0?011 (-0?081 to 0?103; 0?812) for the omega 3 polyunsaturated fatty acids group. 146 (36%) participants in the multidomain plus polyunsaturated fatty acids group, 142 (34%) in the multidomain plus placebo group, 134 (33%) in the polyunsaturated fatty acids group, and 133 (32%) in the placebo group had at least one serious emerging adverse event. Four treatment-related deaths were recorded (two in the multidomain plus placebo group and two in the placebo group). The interventions did not raise any safety concerns and there were no differences between groups in serious or other adverse events.
Interpretation:
The multidomain intervention and polyunsaturated fatty acids, either alone or in combination, had no significant effects on cognitive decline over 3 years in elderly people with memory complaints. An effective multidomain intervention strategy to prevent or delay cognitive impairment and the target population remain to be determined, particularly in real-world settings.
Funding:
French Ministry of Health, Pierre Fabre Research Institute, Gerontopole, Exhonit Therapeutics, Avid Radiopharmaceuticals.
The British Association for Psychopharmacology coordinated a meeting of experts to review and revise its previous 2011 guidelines for clinical practice with anti-dementia drugs. As before, levels of evidence were rated using accepted standards which were then translated into grades of recommendation A–D, with A having the strongest evidence base (from randomised controlled trials) and D the weakest (case studies or expert opinion).
Current clinical diagnostic criteria for dementia have sufficient accuracy to be applied in clinical practice (B) and both structural (computed tomography and magnetic resonance imaging) and functional (positron emission tomography and single photon emission computerised tomography) brain imaging can improve diagnostic accuracy in particular situations (B). Cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) are effective for cognition in mild to moderate Alzheimer’s disease (A), memantine for moderate to severe Alzheimer’s disease (A) and combination therapy (cholinesterase inhibitors and memantine) may be beneficial (B). Drugs should not be stopped just because dementia severity increases (A). Until further evidence is available other drugs, including statins, anti-inflammatory drugs, vitamin E, nutritional supplements and Ginkgo biloba, cannot be recommended either for the treatment or prevention of Alzheimer’s disease (A). Neither cholinesterase inhibitors nor memantine are effective in those with mild cognitive impairment (A). Cholinesterase inhibitors are not effective in frontotemporal dementia and may cause agitation (A), though selective serotonin reuptake inhibitors may help behavioural (but not cognitive) features (B). Cholinesterase inhibitors should be used for the treatment of people with Lewy body dementias (both Parkinson’s disease dementia and dementia with Lewy bodies), and memantine may be helpful (A). No drugs are clearly effective in vascular dementia, though cholinesterase inhibitors are beneficial in mixed dementia (B). Early evidence suggests multifactorial interventions may have potential to prevent or delay the onset of dementia (B). Though the consensus statement focuses on medication, psychological interventions can be effective in addition to pharmacotherapy, both for cognitive and non-cognitive symptoms. Many novel pharmacological approaches involving strategies to reduce amyloid and/or tau deposition in those with or at high risk of Alzheimer’s disease are in progress. Though results of pivotal studies in early (prodromal/mild) Alzheimer’s disease are awaited, results to date in more established (mild to moderate) Alzheimer’s disease have been equivocal and no disease modifying agents are either licensed or can be currently recommended for clinical use.<br/
Background:
Emerging evidence suggests that living near major roads might adversely affect cognition. However, little is known about its relationship with the incidence of dementia, Parkinson's disease, and multiple sclerosis. We aimed to investigate the association between residential proximity to major roadways and the incidence of these three neurological diseases in Ontario, Canada.
Methods:
In this population-based cohort study, we assembled two population-based cohorts including all adults aged 20-50 years (about 4·4 million; multiple sclerosis cohort) and all adults aged 55-85 years (about 2·2 million; dementia or Parkinson's disease cohort) who resided in Ontario, Canada on April 1, 2001. Eligible patients were free of these neurological diseases, Ontario residents for 5 years or longer, and Canadian-born. We ascertained the individual's proximity to major roadways based on their residential postal-code address in 1996, 5 years before cohort inception. Incident diagnoses of dementia, Parkinson's disease, and multiple sclerosis were ascertained from provincial health administrative databases with validated algorithms. We assessed the associations between traffic proximity and incident dementia, Parkinson's disease, and multiple sclerosis using Cox proportional hazards models, adjusting for individual and contextual factors such as diabetes, brain injury, and neighbourhood income. We did various sensitivity analyses, such as adjusting for access to neurologists and exposure to selected air pollutants, and restricting to never movers and urban dwellers.
Findings:
Between 2001, and 2012, we identified 243 611 incident cases of dementia, 31 577 cases of Parkinson's disease, and 9247 cases of multiple sclerosis. The adjusted hazard ratio (HR) of incident dementia was 1·07 for people living less than 50 m from a major traffic road (95% CI 1·06-1·08), 1·04 (1·02-1·05) for 50-100 m, 1·02 (1·01-1·03) for 101-200 m, and 1·00 (0·99-1·01) for 201-300 m versus further than 300 m (p for trend=0·0349). The associations were robust to sensitivity analyses and seemed stronger among urban residents, especially those who lived in major cities (HR 1·12, 95% CI 1·10-1·14 for people living <50 m from a major traffic road), and who never moved (1·12, 1·10-1·14 for people living <50 m from a major traffic road). No association was found with Parkinson's disease or multiple sclerosis.
Interpretation:
In this large population-based cohort, living close to heavy traffic was associated with a higher incidence of dementia, but not with Parkinson's disease or multiple sclerosis.
Funding:
Health Canada (MOA-4500314182).
BACKGROUND: Use of antipsychotics to treat behavioural symptoms of dementia has been associated with increased risks of mortality and stroke. Little is known about individual patient characteristics that might be associated with bad or good outcomes. AIMS: We examined the risperidone clinical trial data to look for individual patient characteristics associated with these adverse outcomes. METHOD: Data from all double-blind randomised controlled trials of risperidone in dementia patients (risperidone n = 1009, placebo n = 712) were included. Associations between characteristics and outcome were analysed based on crude incidences and exposure-adjusted incidence rates, and by time-to-event analyses using Cox proportional hazards regression. Interactions between treatment (risperidone or placebo) and characteristic were analysed with a Cox proportional hazards regression model with main effects for treatment and characteristic in addition to the interaction term. RESULTS: Baseline complications of depression (treatment by risk factor interaction on cerebrovascular adverse event (CVAE) hazard ratio (HR): P = 0.025) and delusions (P = 0.043) were associated with a lower relative risk of CVAE in risperidone-treated patients (HR = 1.47 and 0.54, respectively) compared to not having the complication (HR = 5.88 and 4.16). For mortality, the only significant baseline predictor in patients treated with risperidone was depression, which was associated with a lower relative risk (P<0.001). The relative risk of mortality was increased in risperidone patients treated with anti-inflammatory medications (P = 0.021). CONCLUSIONS: Only anti-inflammatory medications increased mortality risk with risperidone. The reduced risks of CVAE in patients with comorbid depression and delusions, and of mortality with depression, may have clinical implications when weighing the benefits and risks of treatment with risperidone in patients with dementia.
Importance:
The aging of the US population is expected to lead to a large increase in the number of adults with dementia, but some recent studies in the United States and other high-income countries suggest that the age-specific risk of dementia may have declined over the past 25 years. Clarifying current and future population trends in dementia prevalence and risk has important implications for patients, families, and government programs.
Objective:
To compare the prevalence of dementia in the United States in 2000 and 2012.
Design, setting, and participants:
We used data from the Health and Retirement Study (HRS), a nationally representative, population-based longitudinal survey of individuals in the United States 65 years or older from the 2000 (n = 10 546) and 2012 (n = 10 511) waves of the HRS.
Main outcomes and measures:
Dementia was identified in each year using HRS cognitive measures and validated methods for classifying self-respondents, as well as those represented by a proxy. Logistic regression was used to identify socioeconomic and health variables associated with change in dementia prevalence between 2000 and 2012.
Results:
The study cohorts had an average age of 75.0 years (95% CI, 74.8-75.2 years) in 2000 and 74.8 years (95% CI, 74.5-75.1 years) in 2012 (P = .24); 58.4% (95% CI, 57.3%-59.4%) of the 2000 cohort was female compared with 56.3% (95% CI, 55.5%-57.0%) of the 2012 cohort (P < .001). Dementia prevalence among those 65 years or older decreased from 11.6% (95% CI, 10.7%-12.7%) in 2000 to 8.8% (95% CI, 8.2%-9.4%) (8.6% with age- and sex-standardization) in 2012 (P < .001). More years of education was associated with a lower risk for dementia, and average years of education increased significantly (from 11.8 years [95% CI, 11.6-11.9 years] to 12.7 years [95% CI, 12.6-12.9 years]; P < .001) between 2000 and 2012. The decline in dementia prevalence occurred even though there was a significant age- and sex-adjusted increase between years in the cardiovascular risk profile (eg, prevalence of hypertension, diabetes, and obesity) among older US adults.
Conclusions and relevance:
The prevalence of dementia in the United States declined significantly between 2000 and 2012. An increase in educational attainment was associated with some of the decline in dementia prevalence, but the full set of social, behavioral, and medical factors contributing to the decline is still uncertain. Continued monitoring of trends in dementia incidence and prevalence will be important for better gauging the full future societal impact of dementia as the number of older adults increases in the decades ahead.
Aim and objectives:
The objective of the study was to evaluate the impact of the Dementia ABC educational programme on the participants' competence in person-centred care and on their level of job satisfaction.
Background:
The development of person-centred care for people with dementia is highly recommended, and staff training that enhances such an approach may positively influence job satisfaction and the possibility of recruiting and retaining competent care staff.
Design:
The study is a longitudinal survey, following participants over a period of 24 months with a 6-month follow-up after completion of the programme.
Methods:
A total of 1,795 participants from 90 municipalities in Norway are included, and 580 from 52 municipalities completed all measurements. The person-centred care assessment tool (P-CAT) is used to evaluate person-centredness. The psychosocial workplace environment and job satisfaction questionnaire is used to investigate job satisfaction. Measurements are made at baseline, and after 12, 24 and 30 months.
Results:
A statistically significant increase in the mean P-CAT subscore of person-centred practice and the P-CAT total score is found at 12, 24 and 30 months compared to baseline. A statistically significant decrease in scores in the P-CAT subscore for organisational support is found at all points of measurement compared to baseline. Statistically significant increases in satisfaction with workload, personal and professional development, demands balanced with qualifications and variation in job tasks as elements of job satisfaction are reported.
Conclusion:
The evaluation of the Dementia ABC educational programme identifies statistically significant increases in scores of person-centredness and job satisfaction, indicating that the training has a positive impact.
Implications for practice:
The results indicate that a multicomponent training programme including written material, multidisciplinary reflection groups and workshops has a positive impact on the development of person-centred care practice and the job satisfaction of care staff.
OBJECTIVE: The objective of this study was to evaluate peer support and reminiscence therapy, separately and together, in comparison with usual care for people with dementia and their family carers. DESIGN: Factorial pragmatic randomised trial, analysed by treatment allocated, was used for this study. SETTING: The trial ran in Community settings in England. PARTICIPANTS: People with dementia and their family carers were the participants. INTERVENTIONS: Treatment as usual (TAU) plus one of the following: one-to-one peer support to family carers from experienced carers (Carer Supporter Programme; CSP), group reminiscence therapy (Remembering Yesterday, Caring Today; RYCT) for people with dementia and carers, both or neither. MAIN OUTCOME MEASURES: Primary outcomes included health-related quality of life (SF-12) for carers and quality of life (QoL-AD) for people with dementia; secondary outcomes included quality of relationship for carers and people with dementia; both were collected by blinded assessors at baseline, 5 and 12 months (primary end point). RESULTS: Of 291 pairs recruited, we randomised 145 (50%) to CSP (71% uptake) and 194 (67%) to RYCT (61% uptake). CSP and RYCT, separately or together, were not effective in improving primary outcomes or most secondary outcomes. For CSP versus 'no CSP', adjusted difference in means was 0.52 points on the SF-12 (95% CI -1.28 to 2.32) and -0.08 points on the QoL-AD (95% CI -1.70 to 1.56). For RYCT versus 'no RYCT', the difference was 0.10 points on the SF-12 (95% CI -1.72 to 1.93) and 0.51 points on the QoL-AD (95% CI -1.17 to 2.08). However, carers reported better relationships with the people with dementia (difference 1.11, 95% CI 0.00 to 2.21, p=0.05). Comparison of combined intervention with TAU, and of intervention received, suggested differential impacts for carers and persons with dementia. CONCLUSIONS: There is no evidence from the trial that either peer support or reminiscence is effective in improving the quality of life. TRIAL REGISTRATION NUMBER: ISRCTN37956201; Results.
To assess whether a manual based coping strategy compared with treatment as usual reduces depression and anxiety symptoms in carers of family members with dementia.
Objective To assess whether the START (STrAtegies for RelatTives) intervention added to treatment as usual is cost effective compared with usual treatment alone. Design Cost effectiveness analysis nested within a pragmatic randomised controlled trial. Setting Three mental health and one neurological outpatient dementia service in London and Essex, UK. Participants Family carers of people with dementia. Intervention Eight session, manual based, coping intervention delivered by supervised psychology graduates to family carers of people with dementia added to usual treatment, compared with usual treatment alone. Primary outcome measures Costs measured from a health and social care perspective were analysed alongside the Hospital Anxiety and Depression Scale total score (HADS-T) of affective symptoms and quality adjusted life years (QALYs) in cost effectiveness analyses over eight months from baseline. Results Of the 260 participants recruited to the study, 173 were randomised to the START intervention, and 87 to usual treatment alone. Mean HADS-T scores were lower in the intervention group than the usual treatment group over the 8 month evaluation period (mean difference −1.79 (95% CI −3.32 to −0.33)), indicating better outcomes associated with the START intervention. There was a small improvement in health related quality of life as measured by QALYs (0.03 (−0.01 to 0.08)). Costs were no different between the intervention and usual treatment groups (£252 (−28 to 565) higher for START group). The cost effectiveness calculations suggested that START had a greater than 99% chance of being cost effective compared with usual treatment alone at a willingness to pay threshold of £30 000 per QALY gained, and a high probability of cost effectiveness on the HADS-T measure. Conclusions The manual based coping intervention START, when added to treatment as usual, was cost effective compared with treatment as usual alone by reference to both outcome measures (affective symptoms for family carers, and carer based QALYs). Trial Registration ISCTRN 70017938
Objectives:
Antidepressants are commonly used in dementia. Depression is a frequent and important co-morbidity in dementia, and antidepressants are often used to treat depression and more widely. However, there are questions about their utility in depression in dementia and other behavioural and psychological symptoms of dementia. The aim of this narrative review is to summarize the evidence on whether there is therapeutic value in prescribing antidepressants to people with dementia.
Methods:
A PubMed search was performed to identify randomized controlled trials that prescribed antidepressants to people with dementia, either in the treatment of behavioural and psychological symptoms of dementia (depression, anxiety, agitation/aggression, psychosis and apathy) or for secondary outcomes (quality of life, carer burden, activities of daily living, cognition, clinical severity and adverse events).
Results:
Thirty-six randomized controlled trials were identified (participant n = 3386). A consistent finding in well-designed blinded placebo controlled trials in dementia is the lack of positive effect of antidepressants on outcomes of interest, including depression. One large well-designed study has reported a significant reduction in agitation in people with dementia, but at the expense of clinically significant adverse events. Otherwise, change observed in open trials is also seen in the placebo group, suggesting that any effect is not attributable to the prescription of antidepressants.
Conclusions:
It is striking how few data there are on indications other than depression. We should question the use of antidepressants in dementia. Definitive trials of clinical effectiveness of specific indications such as anxiety and agitation in dementia and discontinuation of antidepressants in dementia are needed. Copyright © 2016 John Wiley & Sons, Ltd.
Alzheimer's disease (AD) is characterized by deposition of amyloid-β (Aβ) plaques and neurofibrillary tangles in the brain, accompanied by synaptic dysfunction and neurodegeneration. Antibody-based immunotherapy against Aβ to trigger its clearance or mitigate its neurotoxicity has so far been unsuccessful. Here we report the generation of aducanumab, a human monoclonal antibody that selectively targets aggregated Aβ. In a transgenic mouse model of AD, aducanumab is shown to enter the brain, bind parenchymal Aβ, and reduce soluble and insoluble Aβ in a dose-dependent manner. In patients with prodromal or mild AD, one year of monthly intravenous infusions of aducanumab reduces brain Aβ in a dose- and time-dependent manner. This is accompanied by a slowing of clinical decline measured by Clinical Dementia Rating - Sum of Boxes and Mini Mental State Examination scores. The main safety and tolerability findings are amyloid-related imaging abnormalities. These results justify further development of aducanumab for the treatment of AD. Should the slowing of clinical decline be confirmed in ongoing phase 3 clinical trials, it would provide compelling support for the amyloid hypothesis.
Importance
Poor continuity of care may contribute to high health care spending and adverse patient outcomes in dementia.
Objective
To examine the association between medical clinician continuity and health care utilization, testing, and spending in older adults with dementia.
Design, Setting, and Participants
This was a study of an observational retrospective cohort from the 2012 national sample in fee-for-service Medicare, conducted from July to December 2015, using inverse probability weighted analysis. A total of 1 416 369 continuously enrolled, community-dwelling, fee-for-service Medicare beneficiaries 65 years or older with a claims-based dementia diagnosis and at least 4 ambulatory visits in 2012 were included.
Exposures
Continuity of care score measured on patient visits across physicians over 12 months. A higher continuity score is assigned to visit patterns in which a larger share of the patient’s total visits are with fewer clinicians. Score range from 0 to 1 was examined in low-, medium-, and high-continuity tertiles.
Main Outcomes and Measures
Outcomes include all-cause hospitalization, ambulatory care sensitive condition hospitalization, emergency department visit, imaging, and laboratory testing (computed tomographic [CT] scan of the head, chest radiography, urinalysis, and urine culture), and health care spending (overall, hospital and skilled nursing facility, and physician).
Results
Beneficiaries with dementia who had lower levels of continuity of care were younger, had a higher income, and had more comorbid medical conditions. Almost 50% of patients had at least 1 hospitalization and emergency department visit during the year. Utilization was lower with increasing level of continuity. Specifically comparing the highest- vs lowest-continuity groups, annual rates per beneficiary of hospitalization (0.83 vs 0.88), emergency department visits (0.84 vs 0.99), CT scan of the head (0.71 vs 0.83), urinalysis (0.72 vs 1.09), and health care spending (total spending, 24 371) were higher with lower continuity even after accounting for sociodemographic factors and comorbidity burden (P < .001 for all comparisons). The rate of ambulatory care sensitive condition hospitalization was similar across continuity groups.
Conclusions and Relevance
Among older fee-for-service Medicare beneficiaries with a dementia diagnosis, lower continuity of care is associated with higher rates of hospitalization, emergency department visits, testing, and health care spending. Further research into these relationships, including potentially relevant clinical, clinician, and systems factors, can inform whether improving continuity of care in this population may benefit patients and the wider health system.
