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The symptom of low mood in the prodromal stage of mild cognitive impairment and dementia: A cohort study of a community dwelling elderly population
Abstract
To investigate the symptom of low mood as a predictor of mild cognitive impairment (MCI) and its progression to dementia, taking into account: (i) MCI severity, (ii) time of assessment and (iii) interaction with other factors.
764 cognitively healthy elderly subjects living in the community, from the Kungsholmen Project. Participants were assessed by direct interview to detect low mood. Subjects were then followed for 6 years to identify those who developed MCI. People with incident MCI were followed for a further 3 years to assess progression to dementia.
People with low mood at baseline had a 2.7-fold (95% CI 1.9 to 3.7) increased risk of developing MCI at follow-up. The association was stronger for amnestic MCI (aMCI: HR 5.8; 95% CI 3.1 to 10.9) compared with global cognitive impairment (other cognitive impairment no dementia, oCIND: HR 2.2; 95% CI 1.5 to 3.3). ApoE-ε4 interacted with low mood in a synergistic fashion, increasing the risk of aMCI, while no interaction with psychiatric, vascular, frailty related or psychosocial factors was observed. Low mood at baseline, as opposed to low mood co-occurring with MCI, was associated with a 5.3-fold (95% CI 1.2 to 23.3) increased risk of progression to dementia in aMCI. In contrast, no association was found in oCIND.
Low mood was more strongly associated with aMCI than with global cognitive impairment. Progression towards dementia was predicted only by low mood manifest in the prodromal stage of MCI. These findings indicate that low mood is particularly prominent in the very early stages of cognitive decline.
... Our finding that depression or depressive symptoms at baseline were associated with incident MCI after adjusting for potential confounders is in accordance with prior communitybased studies on this topic with longitudinal design which have also shown that baseline depressive disorder [10,52] or depressive symptomatology [11,44,[53][54][55][56][57][58][59] are significant predictors of incident MCI. For instance, a study by Steenland et al. [52] found that depression, based on clinical judgment, significantly predicted incident MCI in 5,607 individuals with a mean age of 73 years. ...
... Finally, depression could lead to cognitive impairment only when certain susceptibility factors are present. For example, Geda et al. [10] , and Caracciolo et al. [55] observed that the joint effect of depression and APOE genotype was significantly higher than the independent effect of depression for the development of MCI. ...
... Our study found that there were no significant differences in the association between baseline depression and both MCI subtypes. Although not totally comparable due to differences in the methods of assessment for depression or MCI, Caracciolo et al. [55] reported a significant association between baseline low mood, defined as the presence of perceived sadness, and the risk of developing both aMCI (HR = 5.8, 95% CI = 3.1, 10.90) and other cognitive impairments but no dementia (HR = 2.2, 95% CI = 1.5, 3.3) in 764 elders. In a study by Geda et al. [56] , baseline depression predicted aMCI (HR = 1.74, 95% CI = 1.22, ...
Background/aims:
In the absence of effective treatments for dementia, major efforts are being directed towards identifying the risk factors of the prodromal phase of the disease. We report the incidence rates of mild cognitive impairment (MCI) in a Spanish population sample and assess the effect of depression at baseline on incident MCI (or MCI subtypes) at a 3-year follow-up.
Methods:
A total of 1,642 participants (age ≥50 years) were examined as part of a Spanish nationally representative longitudinal study. MCI was defined as the presence of cognitive concerns, objective evidence of impairment in one or more cognitive domains, preservation of independence in functional abilities, and no dementia. Depression was assessed through an adaptation of the Composite International Diagnostic Interview (CIDI 3.0). Binary and multinomial logistic regression analyses were carried out to assess the associations.
Results:
The overall MCI incidence rate was 33.19 (95% CI = 26.02, 43.04) per 1,000 person-years. Depression at baseline predicted the onset of MCI at follow-up after controlling for sociodemographics, cognitive functioning, and other physical health conditions (OR = 2.79; 95% CI = 1.70, 4.59). The effect of baseline depression on incident MCI subtypes was as follows: amnestic MCI, OR = 3.81 (95% CI = 1.96, 7.43); nonamnestic MCI, OR = 2.03 (95% CI = 0.98, 4.21).
Conclusion:
Depression significantly increases the risk for MCI. Targeting depression among those at risk for dementia may help delay or even prevent the onset of dementia.
... 5 The other core symptom of depression is low mood. 5 The presence of low mood only has been shown to be particularly prominent in the early stages of cognitive decline, 6 and to better predict the progression from mild cognitive impairment to Alzheimer Disease (AD) than a composite score from a depression rating scale. 7 Taken together, low mood may be a better predictor of incipient dementia than a diagnosis of depression or depressive symptoms according to a rating scale. ...
... A dichotomized variable was created, in which having low mood was coded as 1 and not having low mood as 0. In SNAC-K, low mood at baseline was assessed by two low mood items: sadness (subjective) and apparent sadness (objective) that are included in the Comprehensive Psychopathological Rating Scale. 30 The presence of low mood was indicated by a cutoff of ≥1 on the sadness item 6 and ≥2 on the apparent sadness item. 30 A dichotomized variable was created, in which fulfilling the criteria for low mood in either of the two items was coded as 1, and not fulfilling the criteria in any of the items as 0. ...
Objective:
This study aims to explore whether low mood is related to an increased dementia risk in two cohorts of older adults of different generations, and whether marital status and living situation modify this association.
Methods:
Participants (≥70 years), free from dementia and living at home, were identified from two population-based studies: the Kungsholmen Project (KP; n = 1,197) and the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K; n = 1,402). Low mood was obtained by self-report (KP and SNAC-K) at baseline in 1987-89 (KP) and 2001-04 (SNAC-K). Incident dementia cases were ascertained over 9 years, using the same diagnostic procedures and comparable criteria for the two cohorts (DSM-III-R in KP and DSM-IV-TR in SNAC-K). Hazard ratios (HR) were derived from Cox proportional hazards models.
Results:
Those having low mood at baseline were at higher risk of dementia in both cohorts combined (HR: 1.2, 95% confidence interval (CI): 1.0-1.4) than those without low mood. However, an increased risk was detected only in those who did not have a partner (HR: 1.5, 95% CI: 1.2-1.9), or lived alone (HR: 1.5, 95% CI: 1.2-1.9), but not among those who had a partner or lived with someone (HR: 0.8, 95% CI: 0.5-1.2).
Conclusion:
Marital status and living situation have the potential to buffer the detrimental effects of low mood on dementia onset. Thus, specific attention from health care should target individuals having low mood and who do not have a partner or live alone.
... A study by van der Mussele et al. [66] indicated that participants with MCI showed the same percentage of depressive symptoms (16%) regardless of MCI subtype. In concordance, we found the same prevalence rates of depressive symptoms and increased PRRs for both MCI subtypes, Table 2 Association between currently elevated depressive symptoms (CES-D ≥18) and MCI for the total regression sample and stratified by gender [67]. Amnestic MCI reflects most likely the prodromal AD stage [17]. ...
... when currently elevated symptoms are not considered. Similar results were obtained by Caracciolo et al. [67] with data from the Kungsholmen Project. Low mood three years prior to the MCI diagnosis was associated with naMCI (hazard ratio = 2.2 (1.3-3.2)) and even more pronounced with aMCI (5.8 (3.1-10.9)). ...
Background:
The literature suggests an association between depression and mild cognitive impairment (MCI) and dementia, but not all studies have examined this association with regard to MCI subtypes reflecting different dementia etiologies.
Objective:
To examine if there is a cross-sectional relationship of depression and MCI and to examine if the relationship differs depending on the type of depression (currently elevated depressive symptoms or a positive history of lifetime depression or both) and on the MCI subtype (amnestic versus non-amnestic MCI (aMCI/naMCI)).
Methods:
From the second examination of the population-based Heinz Nixdorf Recall study (50% men, 50-80 years), 583 participants with MCI (aMCI n = 304; naMCI n = 279) and 1,446 cognitively normal participants were included in the analyses. Currently elevated depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D; score ≥18). Furthermore, participants were asked if they have ever received a previous diagnosis of depression. Log-Poisson regression models (adjusted for sociodemographic/cardiovascular risk factors) were calculated to determine the association of MCI and its subtypes with all depression variables.
Results:
The fully adjusted prevalence rate ratios for MCI, aMCI, and naMCI in depressed versus non-depressed participants were 2.06 (95% confidence interval, 1.60-2.64), 3.06 (2.21-4.23), and 1.93 (1.46-2.57). A positive history of lifetime depression without current depressive symptoms was solely associated with naMCI (1.31 (0.99-1.73)).
Conclusion:
These results suggest that the relationship of depression/depressive symptoms and MCI might differ depending on the timing of depression and on the MCI subtype. Our longitudinal follow-up will allow us to further elucidate this relationship.
... 55 One study used a self-report rating of perceived sadness. 56 Several measures were used to assess anxiety, such as the State-Trait Anxiety Inventory (STAI) 30 and the Goldberg Anxiety Scale (GAS). 51 One study used both the Geriatric Anxiety Inventory (GAI) and the Anxiety Status Inventory (ASI). ...
... Those with low mood were 2.5 times more likely to progress to a classification of MCI over 6 years. 56 Two studies concluded that a diagnosis of depression was associated with a greater incidence of MCI. 18,59 Taking medication for symptoms of anxiety or depression was found to be significantly predictive of a progression from not cognitively impaired to MCI over 4 years. ...
This systematic review, with meta-analyses conducted where data were available, aimed to investigate the prevalence of symptoms of depression and anxiety in mild cognitive impairment (MCI), and to establish how symptoms of depression and anxiety relate to the progression from no cognitive impairment to MCI, and from MCI to dementia. Sixty studies were included in the review. Meta-analyses indicated that symptoms of depression and anxiety were more prevalent in people with MCI than in people with normal cognitive function, and increased the risk of progression from no cognitive impairment to MCI. There were mixed results regarding the effect of such symptoms on progression from MCI to dementia. The findings highlight the need for more research in this area, which can inform attempts to slow or halt the progression of cognitive impairment in later life, with resulting benefits for quality of life.
... The prevalence of NPS is higher in MCI than in the general population, but lower than in dementia [4][5][6]. Since there are multiple outcomes of MCI [7], an association between NPS and cognitive decline may be useful in distinguishing individuals at most risk of converting to dementia from those more likely to remain stable [8,9]. ...
... Additionally, little is known about their effect on cognitively healthy people and risk for incident MCI or dementia. There is some evidence from prospective studies for depression as a risk factor for incident MCI [8], incident dementia [9], and incident cognitive impairment [21]. Rosenberg and colleagues [21] showed that baseline depression was predictive of incident cognitive impairment across a number of cognitive domains. ...
Neuropsychiatric symptoms (NPS) are non-cognitive disturbances such as depression. Rates of NPS have been shown to increase as cognitive ability declines and may be useful in predicting transition from mild cognitive impairment (MCI) to dementia. This community-based study reports the association between NPS and cognitive decline over two years. Participants included 873 community dwelling adults aged 70-90 years enrolled in the Sydney Memory and Ageing Study. NPS were assessed by the Neuropsychiatric Inventory (NPI). Cognitive impairment was defined by diagnosis (MCI or incident dementia) or neuropsychological test performance across five cognitive domains. Cognitive decline was defined by progression to dementia or worse neuropsychological performance. Total NPS at baseline did not differ between those without cognitive impairment (26.2%) and those with MCI (28.8%), but agitation and apathy were associated with MCI. Only baseline depression was associated with dementia at follow-up. Total NPS at baseline was cross-sectionally associated with cognitive impairment in executive function, attention, and global cognition, but did not predict cognitive decline. Depression, anxiety, agitation, anxiety, and apathy were all associated with impairment in at least one cognitive domain, but only anxiety and agitation were significantly associated with cognitive decline. Sensitivity analyses applied more stringent criteria for NPS and cognitive impairment in MCI but did not alter interpretation of results from the main analysis. Overall rates of NPS at baseline were not associated with MCI, dementia, or cognitive decline over two years. Additional follow-up is needed to further examine this association over a longer time course.
... The relationship between depression and cognitive impairment is influenced by various neurobiological factors often described by genetic, neuroimaging, and neurotrophin alterations [31]. For example, the epsilon 4 allele of the apolipoprotein E epsilon 4 gene (APOE-e4) is a known genetic risk factor for Alzheimer's disease (AD) and has been linked to depression, with studies suggesting an additive risk for cognitive impairment and a synergistic effect in increasing the incidence of dementia and mild cognitive impairment [32][33][34][35][36][37][38]. Additionally, dysregulation of the hypothalamic-pituitary-adrenal axis in individuals with depression can result in elevated cortisol levels and consequent hippocampal atrophy, which is also seen in AD [39][40][41]. ...
Accumulating research has described cognitive impairment in adults with depression, however, few studies have focused on this relationship during older adulthood. Our cross-sectional study investigated the association between cognitive function performance and clinically significant depression symptoms in older adults. We analysed the data from the 2011 to 2014 National Health and Nutrition Examination Survey on older (aged 60 years and above) US adults. Cognitive function was assessed as a composite score and on a test-by-test basis based on the Consortium to Establish a Registry for Alzheimer's Disease Word List Learning Test, the Word List Recall Test, and Intrusion Word Count Test, the Animal Fluency Test, and the Digit Symbol Substitution Test (DSST). Depression was defined as clinically significant depression symptoms based on the standard cutoff point of the Patient Health Questionnaire-9 (PHQ-9) score of 10 or greater. Adjusted-logistic regression analysis was employed using survey weights to examine the former relationships. Sociodemographic factors, in addition to medical history and status in terms of self-reported chronic illness and the incidence of stroke or memory-cognitive function loss, were considered as covariates. Among 1622 participants of a survey-weighted 860,400 US older adults, cognitive performance was associated with clinically significant depression symptoms (p = 0.003) after adjustment. Most prominently, older adults with significant cognitive deficits had approximately two and a half times (OR: 2.457 [1.219-4.953]) higher odds for a PHQ-9 score above threshold compared to those with the highest performance. Particularly, those with lowest DSST score had increased odds of almost four times (OR: 3.824 [1.069-13.678]). Efforts to decipher the underlying aetiology of these negative disparities may help create opportunities and interventions that could alleviate the risks from depression, cognitive impairment, and associated consequences in older adults at a population level.
... While some studies found motivational-related symptoms (i.e. loss of interest, psychomotor slowing, and concentration problems) to be associated with increased risk of dementia (Berger et al., 1999;Bartolini et al., 2005;Mossaheb et al., 2012), other studies have reported that particularly symptoms of low mood were associated with cognitive outcomes (Devanand et al., 1996;Caracciolo et al., 2011;Richard et al., 2013). It has been proposed that motivational symptoms (i.e. ...
Depression has been found to be associated with cognitive decline. This study evaluated the association of general depressive symptoms and motivational-related symptoms with cognitive impairment 6 years later and to explore the role of potential underlying mechanisms. In 2690 cognitively healthy persons aged ≥60 from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) depressive symptoms were derived from the Montgomery Åsberg Depression Rating Scale (MADRS). Cognitive performance was assessed at baseline and 6 years later in 1810 persons with the Mini Mental State Examination (global cognition), Digit Span Forward (short-term memory), Digit Span Backward (working memory), Clock-test (visuospatial construction), and the 5-item test (immediate and delayed recall). Bi-factor analysis on the MADRS yielded a General Depression factor and an unrelated Motivational factor. After adjusting for demographics, the General Depression factor was only associated with 6-year impairment in delayed recall (OR (95% CI): 1.18 (1.04–1.34)). This association was no longer significant after adjusting for demographics, cardiovascular risk, lifestyle factors and medication use. The Motivational factor was not significantly associated with future cognitive impairments after adjusting for demographics. Concluding, almost all associations of general depressive symptoms and motivational-related symptoms with future cognitive impairments appeared to be confounded by demographics. Only the association of general depressive symptoms with future memory impairments appeared to be explained by a combination of demographics, cardiovascular risk, lifestyle and medication use.
... Signs of depression are often expressed as an emotional feeling of sadness or "low mood". Johnson et al (2013) found that MCI participants with depression experienced greater deficits in cognitive functioning than their non-depressed counterparts, and "low mood" were shown by Caracciolo et al. (2011) to be particularly prominent in the very early stages of cognitive decline and strongly associated with amnestic mild cognitive impairment (aMCI), i.e. the predementia stage of Alzheimer's, than with global cognitive impairment. Different emotions are accompanied by various adaptive responses in the autonomic and somatic nervous systems (Johnstone & Scherer, 2000). ...
Cognitive and mental deterioration, such as difficulties with memory and language, are some of the typical phenotypes for most neurodegenerative diseases including Alzheimer's disease and other dementia forms. This paper describes the first phases of a project that aims at collecting various types of cognitive data, acquired from human subjects in order to study relationships among linguistic and extra-linguistic observations. The project's aim is to identify, extract, process, correlate, evaluate, and disseminate various linguistic phenotypes and measurements and thus contribute with complementary knowledge in early diagnosis, monitor progression, or predict individuals at risk. In the near future, automatic analysis of these data will be used to extract various types of features for training, testing and evaluating automatic classifiers that could be used to differentiate individuals with mild symptoms of cognitive impairment from healthy, age-matched controls and identify possible indicators for the early detection of mild forms of cognitive impairment. Features will be extracted from audio recordings (speech signal), the transcription of the audio signals (text) and the raw eye-tracking data.
... Losing weight could be a consequence of progressive cognitive deterioration, which involves ability to purchase food, as well as that of cooking meals [32] or the tendency to forget to eat. Cognitive decline and maybe concomitant depressed mood [33] could therefore be associated with a reduced food intake leading to involuntary weight loss. It has been found that apathy has a strong association with loss of weight in nursing home residents with dementia [34]. ...
Background:
Weight loss is common in people with Alzheimer's disease (AD) and it could be a marker of impending AD in Mild Cognitive Impairment (MCI) and improve prognostic accuracy, if accelerated progression to AD would be shown.
Aims:
To assess weight loss as a predictor of dementia and AD in MCI.
Methods:
One hundred twenty-five subjects with MCI (age 73.8 ± 7.1 years) were followed for an average of 4 years. Two weight measurements were carried out at a minimum time interval of one year. Dementia was defined according to DSM-IV criteria and AD according to NINCDS-ADRDA criteria. Weight loss was defined as a ≥4% decrease in baseline weight.
Results:
Fifty-three (42.4%) MCI progressed to dementia, which was of the AD-type in half of the cases. Weight loss was associated with a 3.4-fold increased risk of dementia (95% CI = 1.5-6.9) and a 3.2-fold increased risk of AD (95% CI = 1.4-8.3). In terms of years lived without disease, weight loss was associated to a 2.3 and 2.5 years earlier onset of dementia and AD.
Conclusions:
Accelerated progression towards dementia and AD is expected when weight loss is observed in MCI patients. Weight should be closely monitored in elderly with mild cognitive impairment.
... 14 Depression in elderly individuals have more elements of cognitive impairment which may be misidentified as dementia, similarly prodromal phase of dementia frequently presents as depression. [15][16][17] Dementia often masks the symptoms of depression. Compromised cognitive functioning in dementia adversely affects individual's ability in expressing the emotional and cognitive elements of depression (sadness, anhedonia, hopelessness, worthlessness and helplessness). ...
Dementia is one of the common mental health morbidities of the elderly population. Depression is commonly associated with dementia which further increases the burden of care, compromises the quality of life and functioning in this vulnerable group. Depression in dementia can be explained through several biopsychosocial mechanisms. There are several neurobiologic risk factors of depression and dementia, while some of them are unique to either of them, many of these factors are common to both, which suggests the possibility of overlap of the mechanisms of genesis of these two disorders. Understanding the common risk factors that attribute to depression and dementia, and addressing the modifiable common risk factors may be an effective preventive strategy for these entities. This review focuses on the risk factors of depression in dementia and their biological correlates.
... Symptoms of depression at follow-up were only associated with a change from not cognitively impaired to a classification of MCI. This contradicts previous research which has found that anxiety and depression are risk factors for cognitive decline (Caracciolo, Backman, Monastero, Winblad, & Fratiglioni, 2011;Geda et al., 2006;Goveas, Espeland, Woods, Wassertheil-Smoller, & Kotchen, 2011) but supports other research which has found that anxiety and depression may not be risk factors for progression from MCI to dementia (Gallagher et al., 2011;Vicini Chilovi et al., 2009). ...
Objectives: Subjective memory complaints (SMC) are common in older people and previous research has shown an association with mood problems such as depression and anxiety. SMC form part of the criteria for many definitions of mild cognitive impairment (MCI), but there is controversy over whether they should be included as they may be related more strongly to mood than to objective cognitive impairment. This study aimed to clarify the relationship between mood and SMC in people with MCI.
Method: This paper reports an analysis of data from the Medical Research Council Cognitive Function and Ageing study. Structured interviews were conducted with community-dwelling older people to assess a range of aspects of cognitive functioning and mood. Data from two time points approximately 24 months apart were used in this analysis. At baseline, participants without dementia or severe cognitive impairment were categorised into three groups according to cognitive status. Mood was investigated by assessing symptoms of anxiety and depression which were defined using a diagnostic algorithm. Associations were tested using logistic regression and chi square analyses.
Results: A clear association was shown between SMC and mood, both cross-sectionally and over time. The relationship between our two competing definitions of MCI suggested that mood problems were more strongly related to the presence of SMC than objective cognitive impairment.
Conclusion: SMC may be a function of anxiety and depression rather than being related to objective cognitive function. This questions whether SMC should be included in definitions of MCI.
... However, in Alzheimer's disease (AD), there are strong arguments to consider that depression and apathy are independent clinical dimensions (Aalten et al., 2007;Aalten et al., 2008). Depression is a well-characterized mental disorder with validated clinical diagnostic criteria and specific validated clinical rating scales (Gelenberg, 2010;Nutt, 2011), but there is still inconsistent evidence that depression increases the conversion rate to dementia in MCI (Panza et al., 2008;Caracciolo et al., 2011;Chan et al., 2011) (reviewed in the work of Enache et al. (2011)). Conversely, apathy remains an ill-defined entity and whether it can exist as an independent psychiatric condition remains an open question (Starkstein and Leentjens, 2008;Drijgers et al., 2010). ...
Objective
The goal of this study is to evaluate brain metabolism in mild cognitive impairment (MCI) patients with and without apathy (as determined by the Neuropsychiatric Inventory Questionnaire).Methods
Baseline data from 65 MCI participants (11 with apathy and 54 without) from the Alzheimer's Disease (AD) Neuroimaging Initiative study were analyzed. All participants underwent a comprehensive cognitive and neuropsychiatric assessment, volumetric MRI and measures of cerebral glucose metabolism applying 18F-fluorodeoxyglucose positron emission tomography at baseline. The presence of apathy at baseline was determined by the Neuropsychiatric Inventory Questionnaire.ResultsThere was no difference between apathy and apathy-free MCI patients regarding cognitive assessment and neuropsychiatric measures when apathy-specific items were removed. Cerebrovascular disease load and cerebral atrophy were equivalent in both groups. Compared with the apathy-free MCI patients, MCI patients with apathy had significantly decreased metabolism in the posterior cingulate cortex.Conclusion
The presence of apathy in MCI patients is associated with AD-specific pattern of brain metabolic defect. These results could suggest that apathy belongs to the spectrum of prodromal AD symptoms. Copyright © 2014 John Wiley & Sons, Ltd.
... Sleep problems, constipation, psychological distress, low mood, low energy, and obesity-related disorders, such as diabetes and metabolic syndrome, are common in the elderly, with varying impact on physical and psychological function. [1][2][3][4] The world's population is aging so rapidly that the population aged 60 years and older has nearly doubled during the past two decades and is projected to reach 2 billion by 2050. 5 Therefore, the growing number of elderly people highlights a need to identify interventions and strategies to maintain and enhance their health. ...
Background
The aim of this study was to explore the potential benefits of the Dejian mind–body intervention (DMBI) for psychological and physical health in older Chinese adults.
Methods
After confirmation of eligibility, the subjects were invited to receive DMBI once a week for 12 weeks. The intervention involved components of learning self-awareness and self-control, practicing mind–body exercises, and adopting a special vegetarian diet. Intervention-related changes were measured using the Perceived Stress Scale, Geriatric Depression Scale, Pittsburgh Sleep Quality Index, Chinese Constipation Questionnaire, and self-report ratings of health. Indicators of metabolic syndrome and walking speed were also measured.
Results
Of the 44 subjects recruited, 42 (54.8% men) completed the study, giving an adherence rate of 95%. There was a significant reduction in perceived stress (P<0.05). A significant improvement was also found in systolic blood pressure among those who had abnormally high blood pressure at baseline (P<0.05). Physical fitness as reflected by walking speed was also significantly increased after the intervention (P<0.05). Sleep disturbances were reduced (P<0.01). Self-rated health was significantly enhanced, with the percentage rating very good health increasing from 14.3% at baseline to 42.8% after the intervention (P<0.001). No intervention effect was found for waist circumference, lipids and fasting blood glucose levels, Pittsburgh Sleep Quality Index global score, and constipation measures.
Conclusion
The DMBI was feasible and acceptable, and subjects showed some improvements in psychological and physical health. A larger controlled trial is needed to confirm these promising preliminary results.
... Sleep problems, constipation, psychological distress, low mood, low energy, and obesity-related disorders, such as diabetes and metabolic syndrome, are common in the elderly, with varying impact on physical and psychological function. [1][2][3][4] The world's population is aging so rapidly that the population aged 60 years and older has nearly doubled during the past two decades and is projected to reach 2 billion by 2050. 5 Therefore, the growing number of elderly people highlights a need to identify interventions and strategies to maintain and enhance their health. ...
Dovepress 727 O r I g I n A l r e s e A r C h open access to scientific and medical research Open Access Full Text Article http://dx.doi.org/10.2147/CIA.S59985 A Chinese Chan-based mind–body intervention improves psychological well-being and physical health of community-dwelling elderly: a pilot study
... hy. Ellison et al. reported that the most frequently reported neuropsychiatric symptom in their MCI population under study was depression/dysphoria (63.3%), then apathy (60.5%), followed by anxiety, irritability/lability and nighttime behaviors. [38] Low mood has been found to be particularly prominent in the very early stages of cognitive decline. [43,44] Also depression and apathy appear to be most useful for identifying MCI subjects at highest risk of developing dementia. [25] Detection of depression and its differentiation from apathy in MCI patients is needed because both will require differentiated treatment approaches. Depression has been found to have a complex relationship wit ...
development of clinically evident AD, by many years, perhaps even decades. [2] Hence the field of ageing and dementia is now focusing on the characterization of the earliest stages of cognitive impairment. Research has identified a transitional state between the cognitive changes that occur in normal ageing and AD known as mild cognitive impairment (MCI). [3] Clinically, MCI can be defined as impairment in one or more cognitive domains-typically memory, or an overall mild decline across all cognitive abilities that is greater than would
... hy. Ellison et al. reported that the most frequently reported neuropsychiatric symptom in their MCI population under study was depression/dysphoria (63.3%), then apathy (60.5%), followed by anxiety, irritability/lability and nighttime behaviors. [38] Low mood has been found to be particularly prominent in the very early stages of cognitive decline. [43,44] Also depression and apathy appear to be most useful for identifying MCI subjects at highest risk of developing dementia. [25] Detection of depression and its differentiation from apathy in MCI patients is needed because both will require differentiated treatment approaches. Depression has been found to have a complex relationship wit ...
Abstract
0Background: Neuropsychiatric impairments play a significant role throughout the course of cognitive decline. Many psychological and behavioral symptoms are present in patients of mild cognitive impairment (MCI) similar to that seen in individuals with dementia.
Aims and Objectives: To study the relevance of neuropsychiatric symptoms of MCI and the impact it has on caregivers of these patients.
Materials and Methods: This cross-sectional study was done on 90 patients (30 MCI, 30 dementia and 30 controls) above the age of 50 years. The scales used were Hindi-Mental Status Examination, Global deterioration scale and Neuropsychiatric inventory (NPI). Statistical analysis was done using SPSS 16 software.
Results: 73.33% (22) of the subjects in MCI group, 90% (27) of subjects in dementia group and 53.33% (16) of subjects having normal cognition had neuropsychiatric complaints. 73.33% (22) relatives of subjects in the MCI group, 90% (27) relatives of subjects in dementia group and 46.67% (14) relatives of subjects in the normal group (i.e. control group) experienced some distress. The differences in the mean NPI severity, frequency, distress and total scores of the three groups were statistically significant. Severity and frequency of neuropsychiatric symptoms significantly predicted the caregiver's distress.
Conclusions: Neuropsychiatric symptoms increase both in frequency and severity with increasing cognitive decline, and they cause distress both to the patient as well as the caregiver; and hence their early recognition is a must. The NPI appears to be a useful tool in that regard.
Keywords: Behavioral symptoms, caregivers, mild cognitive impairment
How to cite this article:
Trivedi SC, Subramanyam AA, Pinto C, Gambhire DD. Neuropsychiatric symptoms in mild cognitive impairment: An analysis and its impact on caregiving. Indian J Psychiatry 2013;55:154-60
... hy. Ellison et al. reported that the most frequently reported neuropsychiatric symptom in their MCI population under study was depression/dysphoria (63.3%), then apathy (60.5%), followed by anxiety, irritability/lability and nighttime behaviors. [38] Low mood has been found to be particularly prominent in the very early stages of cognitive decline. [43,44] Also depression and apathy appear to be most useful for identifying MCI subjects at highest risk of developing dementia. [25] Detection of depression and its differentiation from apathy in MCI patients is needed because both will require differentiated treatment approaches. Depression has been found to have a complex relationship wit ...
development of clinically evident AD, by many years, perhaps even decades. [2] Hence the field of ageing and dementia is now focusing on the characterization of the earliest stages of cognitive impairment. Research has identified a transitional state between the cognitive changes that occur in normal ageing and AD known as mild cognitive impairment (MCI). [3] Clinically, MCI can be defined as impairment in one or more cognitive domains-typically memory, or an overall mild decline across all cognitive abilities that is greater than would
... A cohort study of Korean community dwelling individuals found a synergistic interaction between depressive symptoms and the APOE-e4 allele in increasing the incidence of dementia [39]. These two factors also had a synergistic effect in increased incidence of amnestic MCI [40]. ...
Depression and cognitive disorders, including dementia and mild cognitive impairment, are common in the elderly. Depression is also a common feature of cognitive impairment although the symptoms of depression in cognitive impairment differ from depression without cognitive impairment. Pre-morbid depression approximately doubles the risk of subsequent dementia. There are two predominant, though not mutually exclusive, constructs linking pre-morbid depression to subsequent cognitive impairment: Alzheimer's pathology and the vascular depression hypothesis. When evaluating a patient with depression and cognitive impairment, it is important to obtain caregiver input and to evaluate for alternative etiologies for depressive symptoms such as delirium. We recommend a sequential approach to the treatment of depression in dementia patients: (1) a period of watchful waiting for milder symptoms, (2) psychosocial treatment program, (3) a medication trial for more severe symptoms or failure of psychosocial interventions, and (4) possible ECT for refractory symptoms.
... [38] Low mood has been found to be particularly prominent in the very early stages of cognitive decline. [43,44] Also depression and apathy appear to be most useful for identifying MCI subjects at highest risk of developing dementia. [25] Detection of depression and its differentiation from apathy in MCI patients is needed because both will require differentiated treatment approaches. ...
Neuropsychiatric impairments play a significant role throughout the course of cognitive decline. Many psychological and behavioral symptoms are present in patients of mild cognitive impairment (MCI) similar to that seen in individuals with dementia.
To study the relevance of neuropsychiatric symptoms of MCI and the impact it has on caregivers of these patients.
This cross-sectional study was done on 90 patients (30 MCI, 30 dementia and 30 controls) above the age of 50 years. The scales used were Hindi-Mental Status Examination, Global deterioration scale and Neuropsychiatric inventory (NPI). Statistical analysis was done using SPSS 16 software.
73.33% (22) of the subjects in MCI group, 90% (27) of subjects in dementia group and 53.33% (16) of subjects having normal cognition had neuropsychiatric complaints. 73.33% (22) relatives of subjects in the MCI group, 90% (27) relatives of subjects in dementia group and 46.67% (14) relatives of subjects in the normal group (i.e. control group) experienced some distress. The differences in the mean NPI severity, frequency, distress and total scores of the three groups were statistically significant. Severity and frequency of neuropsychiatric symptoms significantly predicted the caregiver's distress.
Neuropsychiatric symptoms increase both in frequency and severity with increasing cognitive decline, and they cause distress both to the patient as well as the caregiver; and hence their early recognition is a must. The NPI appears to be a useful tool in that regard.
... [38] Low mood has been found to be particularly prominent in the very early stages of cognitive decline. [43,44] Also depression and apathy appear to be most useful for identifying MCI subjects at highest risk of developing dementia. [25] Detection of depression and its differentiation from apathy in MCI patients is needed because both will require differentiated treatment approaches. ...
Although numerous studies have investigated modifiable risk factors for mild cognitive impairment (MCI) among community-dwelling seniors, no meta-analysis has summarized these findings. Five databases were searched from January 1, 2000, to December 30, 2023. The protocol was registered with PROSPERO. Data were extracted and reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Relevant meta-analyses of modifiable risk factors were performed. The evidence of each factor was assessed by the GRADE for cohort studies. Of 16,651 citations, 87 studies involving 225,584 community-dwelling seniors were included. Fourteen meta-analyses involving 20 studies with 44,199 participants were performed. The analyses revealed low-to-moderate-quality evidence supporting that diabetes, 2 or more comorbidities, anxiety, apathy, depressive symptoms, and physical frailty were risk factors for incident MCI in older adults. Conversely, hypertension, agitation, and irritability might not be risk factors. Additionally, moderate-quality evidence supports the protective effect of engaging in cognitive-demanding activities on the onset of MCI. Collectively, this study constitutes the first extensive compilation of evidence regarding the various risk factors for the development of MCI in older adults. Our findings hold significant potential to guide the formulation of prevention and management strategies to either prevent or potentially reverse the onset of MCI.
The elderly have an elevated risk of clinical depression because of isolation from family and friends and a reticence to report their emotional states. The present study explored whether data from a commercial neuroscience platform could predict low mood and low energy in members of a retirement community. Neurophysiologic data were collected continuously for three weeks at 1Hz and averaged into hourly and daily measures, while mood and energy were captured with self-reports. Two neurophysiologic measures averaged over a day predicted low mood and low energy with 68% and 75% accuracy. Principal components analysis showed that neurologic variables were statistically associated with mood and energy two days in advance. Applying machine learning to hourly data classified low mood and low energy with 99% and 98% accuracy. Two-day lagged hourly neurophysiologic data predicted low mood and low energy with 98% and 96% accuracy. This study demonstrates that continuous measurement of neurophysiologic variables may be an effective way to reduce the incidence of mood disorders in vulnerable people by identifying when interventions are needed.
Noncognitive psychopathological symptoms (NPS) in elderly patients are increasingly attracting the attention of researchers in the field of neurodegenerative diseases. The question is raised whether these symptoms are risk factors or initial manifestations of the neurodegeneration process. This article provides information on the prevalence of late-onset NPS together with mild cognitive impairment (MCI), combination of which reflects the risk of developing dementia. The characteristic of mild behavioral impairment syndrome, which is currently used along with the concept of MCI, is given. The authors summarized data of the studies published over the past 10 years on the effect of NPS on the progression of cognitive impairment. Topics related to the differential diagnosis of these disorders, as well as existing approaches to treatment, are considered.
Background
: Although several neuropsychiatric symptoms (NPSs) have been demonstrated to have value in the prediction of the progression of mild cognitive impairment (MCI) to dementia, these symptoms are less studied for the prediction of the transition from normal cognition (NC) to MCI.
Methods
: Prospective cohort studies were included if they reported on at least one NPS at baseline and had MCI as the outcome.
Results
: We obtained 13 cohort studies with a total population of 33,066. Depression was the most common neuropsychiatric symptom and could significantly predict transition to MCI (RR = 1.49, 95% CI: 1.13–1.86). However, depression was more capable of predicting amnestic MCI (RR=1.43, 95% CI: 1.04-1.83) than non-aMCI (RR= 0.96, 95% CI 95% CI: 0.60-1.33). Subgroup analysis suggested that the association between depression and MCI changed with depression severity, depression criteria, apolipoprotein-E-adjusted status, age, the percentage of females, and follow-up times, but some data were too sparse for a reliable estimate. Regarding other NPSs, there were insufficient data to assess their effect on the development of MCI. However, apathy, anxiety, sleep disturbances, irritability, and agitation might be risk factors for the prediction of NC-MCI transition with strong predictive value.
Conclusions
: Depression was associated with an approximately 1.5-fold sincreased risk of the progression to MCI in the population with normal cognition. Other NPSs with underlying predictive value deserve more attention.
Background:
Affective symptoms are considered a risk factor or prodromal symptom for dementia. Recent reviews indicate that depressive symptoms predict progression from mild cognitive impairment (MCI) to dementia, but results need to be further explored.
Objective:
To investigate the effect of depressive symptoms on the development of dementia in people with MCI, and explore potential sources of between-study variability, including study setting by a systematic review and meta-analysis.
Methods:
Databases were searched for prospective studies defining people with MCI at baseline, investigating dementia at follow-up and giving information about depressive symptoms. Two authors independently extracted data from the studies and rated the methodological quality. Meta-analyses were conducted using random-effect models to yield pooled risk ratios (RR). Meta-regression analyses tested differences between clinical and community-based studies and other sources of heterogeneity.
Results:
Thirty-five studies, representing 14,158 individuals with MCI, were included in the meta-analysis. Depressive symptoms in MCI predicted dementia in 15 community-based studies (RR = 1.69, 95% CI 1.49-1.93, I2 = 0.0%), but not in 20 clinical studies (RR = 1.02, 95% CI 0.92-1.14, I2 = 73.0%). Further investigation of this effect showed that the mean age of community-based studies was significantly higher than of clinical studies but neither this nor other study characteristics explained variability in study outcomes.
Conclusions:
Depressive symptoms are associated with an increased risk of conversion from MCI to dementia in community-based studies. In contrast, evidence in clinical populations was insufficient with high heterogeneity.
Mild cognitive impairment remains a clinical diagnosis, aided by history, neurologic examination, screening mental status examination, and secondary testing. It can be difficult to distinguish from normal aging without understanding a patient's prior level of intellectual function and new complaint. Geriatricians encounter patients with mild cognitive impairment in all long-term care settings. Making the diagnosis allows patients and their families to understand limits and develop strategies to maximize function. Etiologies associated with mild cognitive impairment include degenerative and vascular processes, psychiatric causes, and comorbid medical conditions. Treatable medical conditions may also present as mild cognitive impairment and have reversible outcomes.
Neuropsychiatric symptoms (NPS) are non-cognitive disturbances such as depression. Rates of NPS have been shown to increase as cognitive ability declines and may be useful in predicting transition from mild cognitive impairment (MCI) to dementia. This community-based study reports the association between NPS and cognitive decline over two years. Participants included 873 community dwelling adults aged 70–90 years enrolled in the Sydney Memory and Ageing Study. NPS were assessed by the Neuropsychiatric Inventory (NPI). Cognitive impairment was defined by diagnosis (MCI or incident dementia) or neuropsychological test performance across five cognitive domains. Cognitive decline was defined by progression to dementia or worse neuropsychological performance. Total NPS at baseline did not differ between those without cognitive impairment (26.2%) and those with MCI (28.8%), but agitation and apathy were associated with MCI. Only baseline depression was associated with dementia at follow-up. Total NPS at baseline was cross-sectionally associated with cognitive impairment in executive function, attention, and global cognition, but did not predict cognitive decline. Depression, anxiety, agitation, anxiety, and apathy were all associated with impairment in at least one cognitive domain, but only anxiety and agitation were significantly associated with cognitive decline. Sensitivity analyses applied more stringent criteria for NPS and cognitive impairment in MCI but did not alter interpretation of results from the main analysis. Overall rates of NPS at baseline were not associated with MCI, dementia, or cognitive decline over two years. Additional follow-up is needed to further examine this association over a longer time course.
Objective:
Public health campaigns encouraging early help seeking have increased rates of mild cognitive impairment (MCI) diagnosis in Western countries, but we know little about how to treat or predict dementia outcomes in persons with the condition.
Method:
The authors searched electronic databases and references for longitudinal studies reporting potentially modifiable risk factors for incident dementia after MCI. Two authors independently evaluated study quality using a checklist. Meta-analyses were conducted of three or more studies.
Results:
There were 76 eligible articles. Diabetes and prediabetes increased risk of conversion from amnestic MCI to Alzheimer's dementia; risk in treated versus untreated diabetes was lower in one study. Diabetes was also associated with increased risk of conversion from any-type or nonamnestic MCI to all-cause dementia. Metabolic syndrome and prediabetes predicted all-cause dementia in people with amnestic and any-type MCI, respectively. Mediterranean diet decreased the risk of conversion to Alzheimer's dementia. The presence of neuropsychiatric symptoms or lower serum folate levels predicted conversion from any-type MCI to all-cause dementia, but less formal education did not. Depressive symptoms predicted conversion from any-type MCI to all-cause dementia in epidemiological but not clinical studies.
Conclusions:
Diabetes increased the risk of conversion to dementia. Other prognostic factors that are potentially manageable are prediabetes and the metabolic syndrome, neuropsychiatric symptoms, and low dietary folate. Dietary interventions and interventions to reduce neuropsychiatric symptoms, including depression, that increase risk of conversion to dementia may decrease new incidence of dementia.
Objective:
To establish whether, in a cohort with normal cognition, severity of depressive symptoms at baseline was related to the time taken for conversion to mild cognitive impairment (MCI) and whether this interacted with other potential risk factors, including APOE ε4 status and demographic and cognitive variables.
Methods:
In a population-based cohort study, 126 cognitively normal subjects were assessed for depressive symptoms at baseline using the Geriatric Depression Scale (GDS) and were then followed over 20 years with regular cognitive assessments. The interval-censored accelerated failure time model was used to establish whether GDS and other factors, including APOE ε4 status, predicted the median time to development of MCI.
Results:
Fifty subjects developed MCI. In APOE ε4 noncarriers, the degree of depressive symptoms at baseline predicted the time to development of MCI: An increase in GDS of 1 standard deviation (3.85) was associated with shortening of the median time to conversion to MCI by 25.4% (p = 0.0024, z = -5.6). This relationship remained statistically significant after controlling for cognitive and other confounding variables. The relationship was not significant in APOE ε4 carriers.
Conclusion:
Depressive symptoms (measured by GDS) predict time to conversion to MCI in cognitively normal people who do not carry the APOE ε4 allele. This may explain conflicting results of previous studies where APOE ε4 status was not taken into account when exploring the relationship between depression and MCI. It may also have a clinical application in helping to identify people at greater risk of developing MCI.
We investigated the relation of subjective cognitive impairment (SCI) and cognitive impairment no dementia (CIND) to common chronic diseases of the elderly and multimorbidity, and assessed the contribution of genetic background and shared familial environment to these associations. Subjects were 11,379 dementia-free twin individuals aged ≥ 65 from the Swedish Twin Registry. SCI was defined as subjective complaint of cognitive change without objective cognitive impairment and CIND was defined according to current criteria. In unmatched, fully-adjusted regression models, mental, musculoskeletal, respiratory, and urological diseases were all significantly associated with increased odds ratios (ORs) of SCI and CIND. Circulatory and gastrointestinal diseases were related to SCI only, while endocrine diseases were associated with CIND. The adjusted ORs of multimorbidity were 2.1 [95% confidence intervals (95% CI): 1.8-2.3] for SCI and 1.5 for CIND (95% CI: 1.3-1.8). A dose-dependent relationship was observed between number of chronic diseases and ORs for SCI but not for CIND. In co-twin control analyses, the chronic diseases-SCI association was largely unchanged. On the other hand, the chronic diseases-CIND association was no longer statistically significant, except for cancer, where an increased OR was observed. In conclusion, chronic morbidity is associated with both SCI and CIND but disease profiles do not always overlap between the two cognitive syndromes. The association is stronger when diseases co-occur, especially for SCI. Genetic and early-life environmental factors may partially explain the association of CIND but not that of SCI with chronic diseases.
The aim of this study was to explore the relationship between cerebrospinal fluid Alzheimer's disease (AD) markers and depression in elderly people.
We included subjects with AD as well as persons with subjective cognitive impairment and normal cognition. Depression was assessed with the Cornell Scale for Depression in Dementia, and a cut-off score of >6 was used to define depression. Cerebrospinal fluid was analyzed using commercially available assays for β-amyloid 1-42, total tau, and phosphorylated tau 181.
A total of 183 participants (66.7% female) were included (92 with AD and 91 with subjective cognitive impairment), with a mean age (±SD) of 67.6 ± 7.4 years, a Mini-Mental State Examination score of 26.0 ± 4.0, and a median Cornell Scale for Depression in Dementia score of 5 (range 0-19). Depression scores were not associated with higher phosphorylated tau 181 and total tau or reduced β-amyloid 1-42 in AD or non-demented subjects.
These results suggest that AD pathology does not contribute to depression, indicating that other factors may be more important. Further studies of the aetiology of depression in elderly people with and without AD are warranted.
Depression in people with dementia has important implications, such as reduced quality of life of patients and carers, and is associated with increased costs and reduced cognition. Here, we review recent studies of the epidemiology, course, mechanisms and treatment of depression in people with dementia.
Depression is both a risk factor and a prodrome of Alzheimer's disease. Depression is a common occurrence in all types of dementias and at all disease stages, including in mild cognitive impairment (MCI). Many studies have explored whether depression in MCI increased the conversion rate to dementia, but findings are inconsistent. Studies of the mechanisms are relatively few and findings inconsistent, but inflammatory, trophic and cerebrovascular factors may contribute, in addition to monoamine deficiency and severity of plaques and tangle pathology. Studies of antidepressants for depression in dementia are inconclusive, with several negative findings reported in recent large studies, suggesting that antidepressant may not confer benefit over placebo.
Depression is a common risk factor, prodrome, and accompanying symptom of people with Alzheimer's dementia. The mechanisms are unknown, and there is little evidence of effective therapies.
Several studies have found reduced hippocampal volume in patients with unipolar depression, but discrepancies exist. The authors performed a systematic review and meta-analysis of volumetric studies of the hippocampus in patients with mood disorders.
Studies of hippocampal volume in unipolar and bipolar patients were identified. A meta-analysis of the 12 studies of unipolar depression fulfilling specific criteria was performed. The sample comprised 351 patients and 279 healthy subjects.
The studies were highly heterogeneous regarding age and gender distribution, age at onset of the disorder, average number of episodes, and responsiveness to treatment, but the pooled effect size of depression was significant in both hemispheres for the unipolar patients. The weighted average showed a reduction of hippocampal volume of 8% on the left side and 10% on the right side. The causes of the heterogeneity were analyzed, and a meta-regression showed that the total number of depressive episodes was significantly correlated to right but not left hippocampal volume reduction.
Hippocampal volume is reduced in patients with unipolar depression, maybe as a consequence of repeated periods of major depressive disorder. Bipolar patients did not seem to show a reduction in hippocampal volume, but this has been much less investigated.
Affective symptoms are common in subjects with mild cognitive impairment (MCI), but there is disagreement whether these symptoms are predictive for Alzheimer's disease (AD). We investigated the predictive accuracy of affective symptoms for AD during a follow-up study in subjects with MCI, and whether the predictive accuracy was modified by age, the presence of amnestic MCI or the length of follow-up.
Newly referred subjects (n=263) with MCI older than 55 years were selected from a memory clinic and followed up after 2, 5 and 10 years. Predictors investigated were: symptoms of depression, anxiety, apathy and sleeping problems.
Affective symptoms were present in 50-70% of the subjects. The average follow-up period was 5.4 years and 79 subjects (29%) developed AD. Sleeping problems were associated with a decreased risk for AD [odds ratio (OR) 0.35, p<0.001]. Symptoms of depression (OR 0.61, p=0.059) and anxiety (OR 0.58, p=0.051) showed a trend in the same direction. The OR of apathy for AD was 0.67 (p=0.14). Depression was associated with a decreased risk for AD only in subjects without amnestic MCI, but not in subjects with amnestic MCI. Moreover, anxiety was related to the risk for AD differently between subjects diagnosed with AD at the 5-year follow-up (OR 0.23) and subjects diagnosed with AD at the 10-year follow-up (OR 1.7).
Affective symptoms are associated with a decreased risk for AD. The risk may be dependent on MCI subtype or length of follow-up, but it does not depend on age.
Objective:
To examine risk factors for mild cognitive impairment (MCI) and progression to dementia in a prospective community-based study of subjects aged 65 years and over.
Methods:
6892 participants who were over 65 and without dementia were recruited from a population-based cohort in three French cities. Cognitive performance, clinical diagnosis of dementia, and clinical and environmental risk factors were evaluated at baseline and 2-year and 4-year follow-ups.
Results:
42% of the population were classified as having MCI at baseline. After adjustment for confounding with logistic regression models, men and women classified as having MCI were more likely to have depressive symptomatology and to be taking anticholinergic drugs. Men were also more likely to have a higher body mass index, diabetes and stroke, whereas women were more likely to have poor subjective health, to be disabled, to be socially isolated, and to suffer from insomnia. The principal adjusted risk factors for men for progression from MCI to dementia in descending order were ApoE4 allele (OR = 3.2, 95% CI 1.7 to 5.7), stroke (OR = 2.8, 95% CI 1.2 to 6.9), low level of education (OR = 2.3, 95% CI 1.3 to 4.1), loss of Instrumental Activities of Daily Living (IADL) (OR = 2.2, 95% CI 1.1 to 4.5) and age (OR = 1.2, 95% CI 1.1 to 1.2). In women, progression is best predicted by IADL loss (OR = 3.5, 95% CI 2.1 to 5.9), ApoE4 allele (OR = 2.3, 95% CI 1.4 to 4.0), low level of education (OR = 2.2, 95% CI 1.3 to 3.6), subclinical depression (OR = 2.0, 95% CI 1.1 to 3.6), use of anticholinergic drugs (OR = 1.8, 95% CI 1.0 to 3.0) and age (OR = 1.1, 95% CI 1.1 to 1.2).
Conclusions:
Men and women have different risk profiles for both MCI and progression to dementia. Intervention programmes should focus principally on risk of stroke in men and depressive symptomatology and use of anticholinergic medication in women.
Little is known about the population-based prevalence of neuropsychiatric symptoms in mild cognitive impairment (MCI).
To estimate the prevalence of neuropsychiatric symptoms in MCI and normal cognitive aging in a defined population.
Cross-sectional study derived from an ongoing population-based prospective cohort study.
The Mayo Clinic Study of Aging.
We studied a random sample of 1969 individuals without dementia from the target population of 9965 elderly persons residing in Olmsted County (Minnesota) on the prevalence date (October 1, 2004). Neuropsychiatric data were available for 319 of 329 subjects with MCI (97.0%) and 1590 of 1640 subjects with normal cognition (97.0%). Neurologic, cognitive, and neuropsychiatric data were obtained from the study participants. A classification of MCI, dementia, and normal cognitive aging was adjudicated by an expert consensus panel. Accordingly, 329 subjects were classified as having MCI and the remaining 1640 subjects were classified as having normal cognition.
Neuropsychiatric Inventory Questionnaire score.
Multivariate logistic regression analyses were conducted after adjusting for age, sex, and educational status. By considering both the odds ratio (OR) and the frequency of a symptom, the most distinguishing features between the 2 groups were apathy (OR, 4.53; 95% confidence interval [CI], 3.11-6.60; P < .001), agitation (3.60; 2.18-5.92; P < .001), anxiety (3.00; 2.01-4.48; P < .001), irritability 2.99; 2.11-4.22; P < .001), and depression (2.78; 2.06-3.76; P < .001). The OR was highest for delusion (8.12; 95% CI, 2.92-22.60; P < .001); however, it was rare in both subjects with MCI (11 of 319 [3.4%]) and those with normal cognition (6 of 1590 [0.4%]). Thus, the population attributable risk for delusion was only 2.62% compared with 14.60% for apathy.
Nonpsychotic symptoms affected approximately 50% of subjects with MCI and 25% of subjects with normal cognition. In contrast, psychotic symptoms were rare.
Mild cognitive impairment has been regarded as a precursor to dementia of Alzheimer type, but not all patients with mild cognitive impairment develop dementia.
To determine whether depression may increase the risk of developing dementia.
The outpatient clinics of a community general hospital.
Prospective cohort study.
A cohort of 114 patients with amnestic mild cognitive impairment was followed up for a mean period of 3 years. At baseline, the patients underwent memory tests, the Spanish version of the Mini-Mental State Examination, a verbal fluency test, the Geriatric Depression Scale, and the Clinical Dementia Rating Scale for staging purposes. Psychiatric examination for depression was based on structured interview and Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition criteria. We also carried out either computed tomography or magnetic resonance imaging of the brain.
We carried out periodic evaluations based on the Mini-Mental State Examination, verbal fluency test, Geriatric Depression Scale, Blessed Dementia Rating Scale, and Clinical Dementia Rating Scale. The end point was the development of probable Alzheimer disease according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association.
Depression was observed in 41 patients (36%) at baseline. After a mean period of 3 years, 59 patients (51.7%) developed dementia of Alzheimer type, and 6 died. Of the depressed patients, 35 (85%) developed dementia in comparison with 24 (32%) of the nondepressed patients (relative risk, 2.6; 95% confidence interval, 1.8-3.6). The survival analysis also showed that depressed patients developed dementia earlier than the nondepressed. Most patients with depression at baseline exhibited a poor response to antidepressants.
We conclude that patients with mild cognitive impairment and depression are at more than twice the risk of developing dementia of Alzheimer type as those without depression. Patients with a poor response to antidepressants are at an especially increased risk of developing dementia.
In this study, the relations between cognitive status and neuropsychiatric impairments in nondemented older adults in cross section and over time is examined. Using data from the Canadian Study of Health and Aging (CSHA), a longitudinal, nation-wide study in which data were collected 3 times (ie, CSHA-1, CSHA-2, CSHA-3) at 5-year intervals, individuals were classified with (n = 240) and without (n = 386) cognitive impairment at CSHA-2. Loss of interest, changes in personality and mood, and depression were reported by a knowledgeable informant (ie, family or friends) more frequently for those with cognitive impairment than for those without cognitive impairment. After controlling for initial cognitive status, loss of interest and depression contributed significantly to the prediction of mild cognitive impairment, dementia, and Alzheimer's disease over time. These findings suggest that these neuropsychiatric impairments play significant roles throughout the course of cognitive decline and should be taken into consideration even before cognitive impairment is evident.
A high ratio of plasma amyloid-beta peptide 40 (Abeta(40)) to Abeta(42), determined by both high Abeta(40) and low Abeta(42) levels, increases the risk of Alzheimer disease. In a previous study, we reported that depression is also associated with low plasma Abeta(42) levels in the elderly population.
To characterize plasma Abeta(40):Abeta(42) ratio and cognitive function in elderly individuals with and without depression.
Cross-sectional study.
Homecare agencies.
A total of 995 homebound elderly individuals of whom 348 were defined as depressed by a Center for Epidemiological Studies Depression score of 16 or greater.
Cognitive domains of memory, language, executive, and visuospatial functions according to levels of plasma Abeta(40) and Abeta(42) peptides.
Subjects with depression had lower plasma Abeta(42) levels (median, 14.1 vs 19.2 pg/mL; P = .006) and a higher plasma Abeta(40):Abeta(42) ratio (median, 8.9 vs 6.4; P < .001) than did those without depression in the absence of cardiovascular disease and antidepressant use. The interaction between depression and plasma Abeta(40):Abeta(42) ratio was associated with lower memory score (beta = -1.9, SE = 0.7, P = .006) after adjusting for potentially confounders. Relative to those without depression, "amyloid-associated depression," defined by presence of depression and a high plasma Abeta(40):Abeta(42) ratio, was associated with greater impairment in memory, visuospatial ability, and executive function; in contrast, nonamyloid depression was not associated with memory impairment but with other cognitive disabilities.
Amyloid-associated depression may define a subtype of depression representing a prodromal manifestation of Alzheimer disease.
Objective: To examine preclinical depressive symptoms 3 years before the diagnosis of AD. Methods: The authors compared incident AD patients and nondemented individuals in terms of baseline mood- and motivation-related symptoms of depression, and assessed whether depressive symptoms in preclinical AD are related to self-perceived memory problems. Participants came from a population-based longitudinal study on aging and dementia in Stockholm, Sweden. The sample consisted of 222 persons older than 74 years who were followed for a 3-year interval. Thirty-four individuals had developed AD at follow-up, whereas 188 remained nondemented. Dementia diagnosis was made according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised. Depressive symptoms were assessed by the Comprehensive Psychopathological Rating Scale. Results: The incident AD patients had more depressive symptoms than the nondemented persons at baseline. There was a dominance of motivation-related symptoms of depression (e.g., lack of interest, loss of energy, concentration difficulties) in preclinical AD. This association remained when adjusting for subjective memory complaints. Conclusions: Depressive symptoms are elevated preclinically in AD, and this elevation is not merely a by-product of self-perceived cognitive difficulties. Thus, depressive symptoms may be part of the preclinical phase in AD.
Background
Subjects with a mild cognitive impairment (MCI) have a memory impairment beyond that expected for age and education yet are not demented. These subjects are becoming the focus of many prediction studies and early intervention trials.Objective
To characterize clinically subjects with MCI cross-sectionally and longitudinally.Design
A prospective, longitudinal inception cohort.Setting
General community clinic.Participants
A sample of 76 consecutively evaluated subjects with MCI were compared with 234 healthy control subjects and 106 patients with mild Alzheimer disease (AD), all from a community setting as part of the Mayo Clinic Alzheimer's Disease Center/Alzheimer's Disease Patient Registry, Rochester, Minn.Main Outcome Measures
The 3 groups of individuals were compared on demographic factors and measures of cognitive function including the Mini-Mental State Examination, Wechsler Adult Intelligence Scale–Revised, Wechsler Memory Scale–Revised, Dementia Rating Scale, Free and Cued Selective Reminding Test, and Auditory Verbal Learning Test. Clinical classifications of dementia and AD were determined according to the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association criteria, respectively.Results
The primary distinction between control subjects and subjects with MCI was in the area of memory, while other cognitive functions were comparable. However, when the subjects with MCI were compared with the patients with very mild AD, memory performance was similar, but patients with AD were more impaired in other cognitive domains as well. Longitudinal performance demonstrated that the subjects with MCI declined at a rate greater than that of the controls but less rapidly than the patients with mild AD.Conclusions
Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD. They appear to constitute a clinical entity that can be characterized for treatment interventions.
To examine the risk factors for mild cognitive impairment (MCI) in a longitudinal population study-the Cardiovascular Health Study Cognition Study.
We examined the factors that in the period 1991 through 1994 predicted the development of MCI in all participants of the Cardiovascular Health Study Cognition Study. Further examination was conducted in the Pittsburgh, Pa, cohort (n = 927), where participants with MCI were classified as having either the MCI amnestic-type or the MCI multiple cognitive deficits-type.
Multicenter population study.
This study includes all participants of the Cardiovascular Health Study Cognition Study (n = 3608) who had a magnetic resonance imaging (MRI) scan of the brain between 1991 and 1994, and detailed neuropsychological, neurological, and medical evaluations to identify the presence of MCI or dementia in the period 1998 to 1999. The mean time between the closest clinical examination to the MRI and the diagnostic evaluation for cognitive disorders was 5.8 years for the Cardiovascular Health Study Cognition Study cohort and 6.0 years for the Pittsburgh cohort.
Risk factors for MCI at the time of the MRI were identified using logistic regression, controlling for age, race, educational level, baseline Modified Mini-Mental State Examination and Digit Symbol Test scores, measurements of depression, MRI findings (atrophy, ventricular volume, white matter lesions, and infarcts), the presence of the apolipoprotein E (APOE) epsilon4 allele, hypertension, diabetes mellitus, and heart disease.
Mild cognitive impairment (n = 577) was associated with race (African American), low educational level, low Modified Mini-Mental State Examination and Digit Symbol Test scores, cortical atrophy, MRI-identified infarcts, and measurements of depression. The MCI amnestic-type was associated with MRI-identified infarcts, the presence of the APOE epsilon4 allele, and low Modified Mini-Mental State Examination scores. The MCI multiple cognitive deficits-type was associated with low Modified Mini-Mental State Examination and Digit Symbol Test scores.
The development of MCI is associated with measurements of cognition and depression, racial and constitutional factors, and cerebrovascular disease. Early cognitive deficits seem to be a common denominator for the 2 forms of MCI; the presence of cerebrovascular disease and the APOE epsilon4 allele is associated with the amnestic type of MCI.
To evaluate the prognostic utility of the presence, persistence, and patterns of depression in subjects with amnestic Mild Cognitive Impairment (MCI).
Sixty amnestic MCI patients were assessed cognitively and for presence of depression using the 30 item Geriatric Depression Scale (GDS). They were followed annually for an average period of 4.3 years.
Simple presence or absence of depression at referral did not predict progression of MCI to AD. Positive answers to specific GDS questions referring to "melancholic" affect as well as the persistence of depression over two to three years significantly predicted cognitive deterioration leading to AD.
The affective characteristics of depression at referral and the persistence of depression were better predictors of conversion to AD than the simple presence or absence of depression measured at referral time.
Introduction General Conditions for the Randomization-Validity of Infinite-m Repeated-Imputation Inferences Examples of Proper and Improper Imputation Methods in a Simple Case with Ignorable Nonresponse Further Discussion of Proper Imputation Methods The Asymptotic Distribution of (Q̄m, Ūm, Bm) for Proper Imputation Methods Evaluations of Finite-m Inferences with Scalar Estimands Evaluation of Significance Levels from the Moment-Based Statistics Dm and Δm with Multicomponent Estimands Evaluation of Significance Levels Based on Repeated Significance Levels
There is an increasing evidence that depressive symptoms are associated with the development of cognitive impairment and dementia in late life. The authors sought to examine whether depression increased the risk of incident cognitive impairment in a longitudinal study of older women.
Observational study, up to six examinations spanning up to 9 years.
University-based Division of Geriatric Medicine.
Community-based sample of 436 older, nondemented women.
Participants were followed up with regular medical and neuropsychiatric evaluations. Cognitive assessment included episodic immediate and delayed memory, psychomotor speed, and executive functioning. Participants were characterized as having incident impairment on a cognitive test when scores fell below the 10th percentile on age-adjusted norms. Baseline depressive symptoms were measured using the Geriatric Depression Scale (GDS) (30-item). Discrete-time Cox proportional hazards regression with generalized linear models were used to determine whether baseline risk factors predicted incident impairment on each cognitive test, defined as performance below the tenth percentile on age-adjusted norms.
Baseline GDS was highly associated with incident impairment on all cognitive tests (p <0.03). These associations were unaffected by vascular conditions except diabetes, which was associated with incident impairment in delayed recall and psychomotor speed.
These data suggest that depression may be the risk factors for cognitive decline, and thus a potential target for diagnostic and therapeutic interventions.
The epsilon4 allele of apolipoprotein E (APOE) is the major genetic risk factor for Alzheimer's disease (AD). Although there have been numerous studies attempting to elucidate the underlying mechanism for this increased risk, how apoE4 influences AD onset and progression has yet to be proven. However, prevailing evidence suggests that the differential effects of apoE isoforms on Abeta aggregation and clearance play the major role in AD pathogenesis. Other potential mechanisms, such as the differential modulation of neurotoxicity and tau phosphorylation by apoE isoforms as well as its role in synaptic plasticity and neuroinflammation, have not been ruled out. Inconsistent results among studies have made it difficult to define whether the APOE epsilon4 allele represents a gain of toxic function, a loss of neuroprotective function, or both. Therapeutic strategies based on apoE propose to reduce the toxic effects of apoE4 or to restore the physiological, protective functions of apoE.
Mild cognitive impairment (MCI) is a clinical concept proposed as an intermediate state between normal aging and dementia. This condition has multiple heterogeneous sources, including clinical presentation, etiology, and prognosis. Recently, the prevalence and associated features of neuropsychiatric symptoms (NPS) in MCI have been described. We systematically searched the PubMed database (last accessed on August 31, 2008) for articles on NPS in MCI. Included articles used strict selection criteria, and outcome variables were extracted in duplicate; of the 27 articles included, 14 (52%) used prospective cohorts. The global prevalence of NPS in MCI ranged from 35% to 85%. The most common behavioral symptoms were depression, anxiety, and irritability. Hospital-based samples reported a higher global prevalence of NPS than population-based studies; this discrepancy probably reflected differences in demographics, study setting, MCI diagnostic criteria, and behavioral instruments used. Prospective studies showed that NPS, particularly depression, may represent risk factors for MCI or predictors for the conversion of MCI to Alzheimer's disease (AD). NPS are very prevalent in subjects with MCI, displaying a similar pattern of symptoms compared to dementia and AD. Large cohort studies using standardized MCI criteria and behavioral instruments are required to evaluate the prognostic role of NPS in MCI.
Late-life depression (LLD) is associated with persistent cognitive impairment in a subset of individuals. The purpose of this study was to 1) examine the frequency and characteristics of cognitive diagnoses (Mild Cognitive Impairment [MCI], dementia) among remitted elderly depressed subjects and 2) to compare the prevalence rate and correlates of cognitive diagnoses with those of comparison subjects.
Crosssectional.
Outpatient geriatric mental health clinic.
The authors examined cognitive diagnoses among 109 subjects age 65 and older, after depression treatment response and 65 never-depressed, age- and education-equated comparison subjects.
Cognitive diagnoses were independently established by the University of Pittsburgh's Alzheimer's Disease Research Center. Bivariate and multivariate analyses were conducted to examine the role of specific risk factors for cognitive diagnosis among depressed subjects.
Relative to comparison subjects, nearly twice as many depressed subjects were diagnosed with MCI or dementia (48% versus 28%). Of the 109 depressed subjects, 38% were diagnosed with MCI (63% amnestic, 37% nonamnestic). The majority of amnestic MCI subjects (85%) had the multiple domain subtype. Age, but not age of onset or lifetime depression duration, predicted cognitive diagnosis.
Despite adequate depression treatment response, 48% of remitted depressed subjects had a cognitive diagnosis. Of the 38% diagnosed with MCI, there was high representation among both the amnestic and the nonamnestic subtypes, suggesting heterogeneity in cognitive course and outcomes in LLD.
It was a pleasure reading the article of Wilson et al1 dealing with changes of depressive symptoms in the prodromal phase of Alzheimer disease (AD) in a large cohort of elderly subjects. They tested the reverse causality hypothesis, arguing that depression would be a consequence of the disease rather than a risk factor. The hypothesis is plausible from a biological standpoint and worthy of consideration since there is a continuum between normality, mild cognitive impairment, and AD. The follow-up period was long enough to detect an increase of depressive symptoms in the early phases of the disease. However, Wilson et al were unable to verify their hypothesis as no increases in depressive symptoms were detected before the diagnosis of AD was made. Aside from the possibility of low sensitivity of the self-reported instrument used to measure depressive symptoms in AD, increases in depressive symptoms were not observed in determined subgroups according to determined variables (perceived memory dysfunction, personality traits, and vascular disease).
1. The CPRS (the Comprehensive Psychopathological Rating Scale) is a recently constructed rating instrument consisting of 65 scaled items, covering a wide range of psychiatric symptoms. Explicit definitions in a non-technical language are provided for items as well as scale steps. 2. The CPRS is mainly intended for evaluation of treatment effects, but due to the explicit descriptions, it has also been found useful for teaching purposes. It can be used in full, or as an item pool for which subscales for different psychiatric syndromes can be designed. Subscales exist, inter al., for depression, schizophrenia, obsessive-compulsive disorder, neurasthenic syndromes and mental distress in connection with severe physical illness. 3. The CPRS is available in parallel Swedish and English versions. It has been translated into all Scandinavian languages, and into German, Italian and Spanish. French and Russian versions are in preparation. 4. The rating is based on an interview which will require less than an hour in most cases if the scale is used in full. Due to the non-technical language used, raters without formal training in psychiatry (i.e. nurses, psychologists, general practitioners) can use the scale without reduction in reliability.
The Kungsholmen Project is a study on elderly people living in a parish of Stockholm, Sweden. The study uses a longitudinal approach with the principal purpose of determining the natural history of Alzheimer's disease and other dementias. The study population consists of all 2,368 inhabitants of the Kungsholmen area in Stockholm, aged 75 years and above in October, 1987. The study design consists of three phases. Phase I consists of a screening test used in order to identify the 'possible' dementia cases; phase II is a complete clinical examination carried out in order to reach a final diagnosis of dementia; in phase III the whole population is reexamined in order to ascertain new cases of dementia. DSM-IIIR criteria for dementia and different types of dementia are used. The final diagnosis is based on a consensus using two preliminary diagnoses, made separately by different physicians.
The aging of the population of the United States and a concern for the well-being of older people have hastened the emergence of measures of functional health. Among these, measures of basic activities of daily living, mobility, and instrumental activities of daily living have been particularly useful and are now widely available. Many are defined in similar terms and are built into available comprehensive instruments. Although studies of reliability and validity continue to be needed, especially of predictive validity, there is documented evidence that these measures of self-maintaining function can be reliably used in clinical evaluations as well as in program evaluations and in planning. Current scientific evidence indicates that evaluation by these measures helps to identify problems that require treatment or care. Such evaluation also produces useful information about prognosis and is important in monitoring the health and illness of elderly people.
This study addressed the effects of study time on episodic recall and recognition of words in a community-based sample of healthy older adults ranging from 75 to 96 years of age (N = 221). Results indicated a slight but reliable age-related deterioration of free-recall performance that was attributable to age deficits in secondary memory. The size of the age-related impairment in recognition was reduced relative to that in recall. As well, for all age groups, recall and recognition were higher when items were slowly as opposed to rapidly presented, indicating proficient utilization of study time in very old age. Finally, multiple regression analyses indicated that, although a variety of demographic (i.e., age and education), psychometric (i.e., Mini-Mental State Exam [MMSE] and Block Design scores), and biological (i.e., thyroid-stimulating hormone) variables were related to free-recall performance, only Block Design and MMSE scores made independent contributions to recognition performance.
We investigated apolipoprotein E polymorphism stroke risk in a population sample of 1810 persons aged 75 years or more in Stockholm (the Kungsholmen Project). Information on cognition at cohort inception (from 1987 to 1989) and on stroke occurrence (from 1969 to 1994) is available for the cohort. In the cohort, cognitive impairment is associated with the epsilon 4 allele, and longer survival in subjects aged > or = 85 years with good cognition is associated with the epsilon 2 allele and the absence of epsilon 4.
We compared stroke incidence in the 1077 of 1124 genotyped subjects who carried epsilon 2/3, epsilon 3/3, or epsilon 3/4 and estimated the proportion of cognitive impairment attributable to stroke.
Risk of stroke did not vary with apolipoprotein E polymorphism (P = .82): 24% of 87 incident stroke patients during follow-up compared with 25% of 827 subjects with normal cognition and no stroke diagnosis at baseline carried the epsilon 3/4 genotype. An estimated 9% of cognitive impairment was attributable to stroke. Notably, a reduced epsilon 3/4 frequency of 20% was found in subjects who survived a prior stroke and were included in the cohort, and risk of hemorrhagic stroke tended to be associated with the presence of the epsilon 3/4 genotype and the absence of epsilon 2/3.
This population-based study indicates that apolipoprotein E polymorphism is not a risk factor for ischemic stroke in subjects aged > or = 75 years (although it might possibly influence survival after stroke occurrence and be a risk factor for infrequent hemorrhagic stroke) and that approximately 10% of cognitive impairment in this age group is attributable to stroke.
To determine the incidence of different types of dementia in the very old, and to explore the relation with age and gender.
A dementia-free cohort was followed for an average of three years in Stockholm, Sweden. At the end of the follow-up, the subjects were interviewed by nurses, clinically examined by physicians, and cognitively assessed by psychologists. Deceased cohort members were studied using death certificates, hospital clinical records, and discharge diagnoses. Dementia diagnoses were made according to the DSM-III-R criteria independently by two physicians.
The cohort consisted of 1,473 subjects (75+ years old), of which 987 were clinically examined at follow-up, 314 died before the examination, and 172 refused to participate.
During the follow-up, 148 subjects developed dementia. In the age-group 75 to 79, the incidence rates for dementia were 19.6 for women and 12.4 for men per 1,000 person-years, whereas for 90+ year-old subjects the corresponding figures were 86.7 and 15.0 per 1,000 person-years. A similar pattern of distribution by age and gender was seen for Alzheimer's disease. In each age stratum, the incidence rates of dementia and Alzheimer's disease were higher for women than for men. The age-adjusted odds ratio for women was 1.9 for dementia and 3.1 for Alzheimer's disease.
(1) The incidence of dementia increases with age, even in the oldest age groups; (2) women have a higher risk of developing dementia than men, especially at very old ages; (3) this pattern is mainly due to the age and gender distribution of Alzheimer's disease, rather than vascular dementia.
To examine preclinical depressive symptoms 3 years before the diagnosis of AD.
The authors compared incident AD patients and nondemented individuals in terms of baseline mood- and motivation-related symptoms of depression, and assessed whether depressive symptoms in preclinical AD are related to self-perceived memory problems. Participants came from a population-based longitudinal study on aging and dementia in Stockholm, Sweden. The sample consisted of 222 persons older than 74 years who were followed for a 3-year interval. Thirty-four individuals had developed AD at follow-up, whereas 188 remained nondemented. Dementia diagnosis was made according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised. Depressive symptoms were assessed by the Comprehensive Psychopathological Rating Scale.
The incident AD patients had more depressive symptoms than the nondemented persons at baseline. There was a dominance of motivation-related symptoms of depression (e.g., lack of interest, loss of energy, concentration difficulties) in preclinical AD. This association remained when adjusting for subjective memory complaints.
Depressive symptoms are elevated preclinically in AD, and this elevation is not merely a by-product of self-perceived cognitive difficulties. Thus, depressive symptoms may be part of the preclinical phase in AD.
Few data are available on the effect of social ties on dementia development. This study explored whether single social network components and different degrees of the social connections affect dementia incidence.
A community-based cohort of 1203 non-demented people, living at home in the Kungsholmen district of Stockholm, Sweden, and who had good cognition, was followed for an average period of 3 years. On the basis of medical and psychological data, 176 patients were diagnosed with dementia according to the criteria of the third edition revision of the Diagnostic and Statistical Manual of Mental Disorders. Information on social network was obtained by personal interview by trained nurses at baseline. The covariates included in the analysis were age, sex, education, cognitive and functional status, depressive symptoms, and vascular diseases.
Those individuals living alone, and those without any close social ties, both had an adjusted relative risk for developing dementia of 1.5 (95% CI 1.0-2.1 and 1.0-2.4, respectively). Compared with married people living with someone, single people and those living alone had an adjusted relative risk of 1.9 (95% CI 1.2-3.1). Infrequent contacts with network resources did not increase the risk of the disease if such contacts were experienced as satisfying. When all components were combined in an index, a poor or limited social network increased the risk of dementia by 60% (95% CI 1.2-2.1), and a significant gradient was found for the four degrees of social connections (p=0.0009).
An extensive social network seems to protect against dementia. Confirmation of this finding and further investigation to clarify the mechanisms are worthwhile due to the implications for prevention.
To estimate the age-specific incidence rate of mild cognitive impairment (MCI) according to sex and educational level and to explore the course of MCI, particularly its progression to AD, in a population-based cohort.
A community-based cohort of nondemented elderly people (Personnes Agées QUID [PAQUID]) was followed longitudinally for 5 years. MCI was defined as memory complaints with objective memory impairment, without dementia, impairment of general cognitive functioning, or disability in activities of daily living. Incidence rates were calculated using the person-years method. A descriptive analysis at the different follow-up times was performed to study the course of MCI.
At baseline, there were 58 prevalent cases of MCI (2.8% of the sample). During a 5-year follow-up, 40 incident cases of MCI occurred in 1,265 subjects at risk. The global incidence rate of MCI was 9.9/1,000 person-years. MCI was a good predictor of AD with an annual conversion rate of 8.3% and a good specificity, but it was very unstable over time: Within 2 to 3 years, only 6% of the subjects continued to have MCI, whereas >40% reverted to normal.
Conventionally defined MCI has reasonable predictive value and specificity for AD. However, MCI was very unstable across time in this study. Furthermore, the definition of MCI seems to be too restrictive and should probably be extended to other categories of individuals also at high risk of developing AD.
The main genetic risk factor for rheumatoid arthritis (RA) is the shared epitope (SE) of HLA-DR, while smoking is an important environmental risk factor. We studied a potential gene-environment interaction between SE genes and smoking in the etiology of the 2 major subgroups of RA: rheumatoid factor (RF)-seropositive and RF-seronegative disease.
A population-based case-control study involving incident cases of RF-seropositive and RF-seronegative RA (858 cases and 1,048 controls) was performed in Sweden. Cases and controls were classified according to their cigarette smoking status and HLA-DRB1 genotypes. The relative risk of developing RA was calculated for different gene/smoking combinations and was compared with the relative risk in never smokers without SE genes.
The relative risk of RF-seropositive RA was 2.8 (95% confidence interval [95% CI] 1.6-4.8) in never smokers with SE genes, 2.4 (95% CI 1.3-4.6) in current smokers without SE genes, and 7.5 (95% CI 4.2-13.1) in current smokers with SE genes. Smokers carrying double SE genes displayed a relative risk of RF-seropositive RA of 15.7 (95% CI 7.2-34.2). The interaction between smoking and SE genes was significant, as measured by the attributable proportion due to interaction, which was 0.4 (95% CI 0.2-0.7) for smoking and any SE, and 0.6 (95% CI 0.4-0.9) for smoking and a double SE. Neither smoking nor SE genes nor the combination of these factors increased the risk of developing RF-seronegative RA.
The disease risk of RF-seropositive RA associated with one of the classic genetic risk factors for immune-mediated diseases (the SE of HLA-DR) is strongly influenced by the presence of an environmental factor (smoking) in the population at risk.
Research on diabetes mellitus as a risk factor for dementia and its main subtypes has produced conflicting results. The authors investigated the relationship between diabetes mellitus and risk of dementia, Alzheimer disease (AD), and vascular dementia (VaD).
A dementia-free cohort of 1,301 community dwellers aged 75 years and older in Stockholm, Sweden, was longitudinally examined twice over 6 years to detect dementia cases (Diagnostic and Statistical Manual of Mental Disorders-III-R diagnostic criteria). Cox proportional hazards models were used to analyze the data with adjustment for several potential confounders.
During the 5,584 person-years of follow-up, 350 subjects developed dementia, including 260 AD and 49 VaD cases. Diabetes mellitus was associated with hazard ratios (HR) of 1.5 (95% CI 1.0 to 2.1, p = 0.04) for dementia, 2.6 (95% CI 1.2 to 6.1) for VaD, and 1.3 (95% CI 0.9 to 2.1) for AD. Patients who were treated with oral antidiabetic medications had HRs of 1.7 (95% CI 1.0 to 2.8, p = 0.04) for dementia and 3.6 (95% CI 1.3 to 9.5) for VaD. There were significant interactions of diabetes with severe systolic hypertension (> or =180 mm Hg) on dementia and its main subtypes, and of diabetes with heart disease on VaD.
Diabetes mellitus increases the risk of dementia, and VaD in particular, in very old people. The risk for dementia and VaD is especially high when diabetes mellitus occurs together with severe systolic hypertension or heart disease.
Mild cognitive impairment is an evolving construct. While appropriate questions have been raised concerning its definition, outcome, and potential treatments, considerable progress has been made. We agree with Gauthier and Touchon4 that MCI is heterogeneous. The heterogeneity reflects a refinement of the entity rather than a weakness. Just as the construct of dementia has been refined over the years to reflect increasing sophistication in diagnostic skill, so has the characterization of MCI been refined. If the approach to classifying the syndrome of MCI into multiple subtypes is combined with the presumed etiology, much of the variability in the literature can be resolved. The construct is useful both for clinical as well as research purposes. If used in a systematic fashion, it can help characterize the prodromal states of several types of dementia. If specific criteria are used including etiology, it can predict clinically probable AD with high specificity, and this provides physicians and investigators an opportunity to recognize, counsel, and ultimately treat the condition before it advances to fully expressed dementia. In essence, we have to be able to move the diagnostic threshold for these disorders back to earlier stages of impairment with the anticipation of developing appropriate therapies to intervene at these stages. Ideally, we would like to develop markers that predict the future development of dementia and intervene with safe and effective therapies to truly prevent AD and the other dementing disorders.
Depressive symptoms are common in patients with dementia and may be associated with increased risk of developing dementia. It has been hypothesized that depressive symptoms and dementia may be attributable to underlying vascular disease in some older persons.
To test the hypotheses (1) that depressive symptoms are associated with increased risk of developing mild cognitive impairment (MCI), a preclinical state that often precedes dementia, and (2) that the association between depressive symptoms and MCI is attributable to underlying vascular disease.
Prospective, population-based, longitudinal study.
Random sample of adults 65 years or older recruited from 4 US communities.
Subjects were 2220 participants in the Cardiovascular Health Study Cognition Study with high cognitive function at baseline. Depressive symptoms were measured at baseline using the 10-item Center for Epidemiological Studies Depression Scale and were classified as none (0-2 points), low (3-7 points), and moderate or high (>/=8 points). Vascular disease measures at baseline included confirmed history of stroke, transient ischemic attack, diabetes mellitus, or hypertension; carotid artery stenosis; ankle-arm blood pressure index; and small or large infarcts or white matter disease on cerebral magnetic resonance imaging. Mild cognitive impairment was diagnosed after 6 years of follow-up based on the consensus of a team of dementia experts using standard clinical criteria.
Diagnosis of MCI.
Depressive symptoms at baseline were associated with increased risk of MCI (10.0%, 13.3%, and 19.7% for those with no, low, and moderate or high depressive symptoms, respectively). This association was diminished only slightly by adjustment for vascular disease measures and demographics. Vascular disease measures also were associated with increased risk of MCI, and these associations were not diminished by adjustment for depressive symptoms or demographics.
Depressive symptoms were associated with increased risk of MCI, and this association was independent of underlying vascular disease.
It remains unknown whether depression and apolipoprotein E genotype are risk factors for incident mild cognitive impairment (MCI).
To determine whether elderly individuals with depression (measured by the short Geriatric Depression Scale) are at increased risk of developing incident MCI.
Prospective cohort study.
Primary care clinic.
A cohort of 840 cognitively normal elderly subjects without depression at recruitment who were followed up prospectively for a median of 3.5 years (range, 0.4-12.8 years). Subjects who developed depression (score of >/=6 on the short Geriatric Depression Scale; depression cohort) were compared with all remaining subjects (referent cohort).
Incidence of MCI (primary outcome) and incidence of MCI or dementia (composite secondary outcome).
Individuals in the depression cohort were at significantly increased risk of subsequent incident MCI (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.2-4.1) after adjusting for age (time scale), sex, and education, and considering dementia as a competing outcome. The association was stronger in men but did not vary by severity of depression. We observed a synergistic interaction between apolipoprotein E genotype (epsilon3/epsilon4 or epsilon4/epsilon4) and depression (joint effect HR, 5.1; 95% CI, 1.9-13.6; test for additive interaction, P = .03). We found a similar association between depression and the subsequent composite outcome of incident MCI or dementia (HR, 2.6; 95% CI, 1.6-4.3).
Cognitively normal elderly individuals who develop depression are at increased risk of subsequent MCI. We found a synergistic interaction between depression and apolipoprotein E genotype.
Mild cognitive impairment (MCI) is a condition referring to the persons with cognitive deficits measurable in some form or another, but not meeting criteria for dementia, and who have an increased risk of becoming demented.
To establish the rate of progression to dementia in MCI, to investigate the risk of conversion for amnestic vs multiple-domains subtypes, and to identify the predictors of progression.
MCI (n = 105) individuals enrolled in a longitudinal study received annual clinical and psychometric examinations for up to a mean of 3 years. The diagnosis of MCI according to Mayo Clinic Petersen's Criteria was conducted by a panel of specialists.
After 3 years of follow-up, 23 of 105 subjects with MCI were diagnosed with dementia. 40 showed cognitive decline not dementia, 34 were stable and showed no cognitive decline or improvement, while eight showed cognitive improvement.
We conclude that conversion rate from MCI to DSM-IIIR dementia was 21.9% over a period of 3 years. The occurrence of depressive symptoms may constitute a predictor for those who are more likely to progress to dementia. The risk of conversion to dementia was higher among the subjects with an evidence of impairment extending beyond memory than with those who suffered only from memory deficits, and the subjects who converted to dementia in this subtype had significantly higher baseline plasma total homocysteine levels than non-converters.
The objectives of this study were to investigate the relation of vascular, neuropsychiatric, social, and frailty-related factors with "Cognitive impairment, no dementia" (CIND) and to verify their effect independently of future progression to Alzheimer disease (AD).
Seven hundred eighteen subjects aged 75+ years who attended baseline, 3- and 6-year follow-up examinations of the Kungsholmen Project, a Swedish prospective cohort study, were studied. CIND was defined according to the performance on the Mini-Mental State Examination. Potential risk factors were collected at baseline and clustered according to four research hypotheses (frailty, vascular, neuropsychiatric, and social hypothesis), each representing a possible pathophysiological mechanism of CIND independently of subsequent development of AD.
Over a mean 3.4 years of follow up, 82 participants (11.4%) developed CIND. When the population was subsequently followed for a mean of 2.7 years, subjects with CIND had a threefold increased risk to progress to AD. After multiple adjustments, including adjustment for the development of AD at the 6-year follow up, risk factors for CIND were hip fracture, polypharmacy, and psychoses.
The results suggest that not only the AD-type neurodegenerative process, but also neuropsychiatric- and frailty-related factors may induce cognitive impairment in nondemented elderly. These findings may have relevant preventive and therapeutic implications.
To determine the occurrence of neuropsychiatric symptomatology and the relation to future development of Alzheimer disease (AD) in persons with and without mild cognitive impairment (MCI).
We followed 185 persons with no cognitive impairment and 47 with MCI (amnestic and multidomain), ages 75 to 95, from the population-based Kungsholmen Project, Stockholm, Sweden, for 3 years. Three types of neuropsychiatric symptoms were assessed at baseline: mood-related depressive symptoms, motivation-related depressive symptoms, and anxiety-related symptomatology. AD at 3-year follow-up was diagnosed according to Diagnostic and Statistical Manual for Mental Disorders-III-R criteria.
Psychiatric symptoms occurred more frequently in persons with MCI (36.2% mood, 36.2% motivation, and 46.8% anxiety symptoms) than in cognitively intact elderly individuals (18.4% mood, 13.0% motivation, and 24.9% anxiety). Of persons with both MCI and anxiety symptoms, 83.3% developed AD over follow-up vs 6.1% of cognitively intact persons and 40.9% persons who had MCI without anxiety. Among persons with MCI, the 3-year risk of progressing to AD almost doubled with each anxiety symptom (relative risk [RR] = 1.8 [1.2 to 2.7] per symptom). Conversely, among cognitively intact subjects, only symptoms of depressive mood were related to AD development (RR = 1.9 [1.0 to 3.6] per symptom).
The predictive validity of mild cognitive impairment (MCI) for identifying future Alzheimer disease (AD) cases is improved in the presence of anxiety symptoms. Mood-related depressive symptoms (dysphoria, suicidal ideation, etc.) in preclinical AD might be related to the neuropathologic mechanism, as they appear preclinically in persons both with and without MCI.
To determine incidence rates of non-dementia cognitive impairment, to examine the impact of attrition due to death on the observed incidence estimates, and to compare the observed and corrected estimates of non-dementia cognitive impairment with dementia incidence rates.
A total of 1,435 persons without dementia aged 75+ from the Kungsholmen Project were evaluated for occurrence of dementia over 9 years. A total of 1,070 cognitively unimpaired subjects were also followed using amnestic mild cognitive impairment (aMCI) and other cognitive impairment, no dementia (OCIND) definitions. To correct the observed incidence rates for attrition due to death, cognitive status for subjects lost due to death was imputed using information on previous cognitive and health status. Observed and corrected incidence rates (IR) and 95% CIs were calculated with the person-years method, using Poisson distribution.
Incidence rates per 1,000 person-years were as follows: dementia IR = 70.4 (64.0 to 77.4); aMCI observed IR = 11.4 (8.6 to 15.1), corrected IR = 13.7 (10.3 to 18.2); OCIND observed IR = 33.8 (28.7 to 39.8), corrected IR = 42.1 (36.5 to 48.6). Both aMCI and OCIND incidence increased with advancing age. Observed incidence of aMCI and OCIND together was similar to that of dementia at age 75 to 79 but lower at more advanced ages. However, the cognitive impairment incidence after age 79 increased substantially when the estimates were corrected for attrition due to death during follow-up.
Non-dementia cognitive impairment is common and often underestimated in population studies that do not adjust for attrition.
Mild cognitive impairment (MCI) is often a prodromal of dementia and depressive symptoms have been suggested as risk factor for dementing disorders. We evaluated the possible impact of depressive symptoms on the rate of progression to dementia in MCI patients after a 3.5-year follow-up; and the interaction between depressive symptoms and vascular risk factors for conversion to dementia.
A total of 2,963 individuals from a sample of 5,632 65-84 year old subjects were evaluated at the first (1992-1993), and second survey (1995-1996) of the Italian Longitudinal Study on Aging (ILSA), a prospective cohort study. MCI and dementia were classified using current clinical criteria. Depressive symptoms were measured with the Geriatric Depression Scale.
Among the 2,963 participants, 139 prevalent MCI patients were diagnosed at the first survey. During the 3.5-year follow-up, 14 MCI patients progressed to dementia, and we did not find any significant relationship between depressive symptoms and rate of progression to dementia (RR 1.42, 95% CI, 0.48-4.23, chi2 0.40, p < 0.53). No socio-demographic variables or vascular risk factors modified the association between depressive symptoms and conversion to dementia.
In our population, depressive symptoms were not associated with the rate of progression to dementia in MCI patients. Our findings did not support a role of socio-demographic variables or vascular risk factors in the association of depressive symptoms and conversion to dementia.
Prospective studies have established an association between depressive symptoms and risk of dementia, but how depressive symptoms change during the evolution of dementia is uncertain.
To test the hypothesis that depressive symptoms increase during the prodromal phase of Alzheimer disease (AD).
Prospective cohort study.
For up to 13 years, 917 older Catholic nuns, priests, and monks without dementia at study onset completed annual clinical evaluations that included administration of the 10-item Center for Epidemiologic Studies Depression Scale and clinical classification of mild cognitive impairment and AD.
Change in depressive symptoms reported on the Center for Epidemiologic Studies Depression Scale.
At baseline, participants reported a mean (SD) of 1.0 (1.5) depressive symptoms. Those who developed AD (n = 190) showed no increase in depressive symptoms before the diagnosis was made, and this finding was not modified by age, sex, education, memory complaints, vascular burden, or personality. There was no systematic change in depressive symptoms after the AD diagnosis, although symptoms tended to decrease in women relative to men and in those with a higher premorbid level of openness and a lower premorbid level of agreeableness. Among those without cognitive impairment at baseline, depressive symptoms did not increase in those who subsequently developed mild cognitive impairment.
We found no evidence of an increase in depressive symptoms during the prodromal phase of AD.
Depression, apolipoprotein E genotype, and the incidence of mild cognitive impairment: a prospective cohort study
- Geda Ye
- Knopman Ds
- Mrazek
- Da
Geda YE, Knopman DS, Mrazek DA, et al. Depression, apolipoprotein E genotype, and the incidence of mild cognitive impairment: a prospective cohort study. Arch Neurol 2006;63:435e40.
Depressive symptoms, vascular disease, and mild cognitive impairment: findings from the Cardiovascular Health Study
- Alexopoulos Gs Lopez
- Ol
Barnes DE, Alexopoulos GS, Lopez OL, et al. Depressive symptoms, vascular disease, and mild cognitive impairment: findings from the Cardiovascular Health Study. Arch Gen Psychiatry 2006;63:273e9.
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