Association of amyloid-beta with depression or depressive symptoms in older adults without dementia: a systematic review and meta-analysis.
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ABSTRACT:
SUBMITTER: Twait EL
PROVIDER: S-EPMC10789765 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Association of amyloid-beta with depression or depressive symptoms in older adults without dementia: a systematic review and meta-analysis.
Twait Emma L EL Wu Jen-Hao JH Kamarioti Maria M Basten Maartje M van der Flier Wiesje M WM Gerritsen Lotte L Geerlings Mirjam I MI
Translational psychiatry 20240115 1
Several lines of evidence have indicated that depression might be a prodromal symptom of Alzheimer's disease (AD). This systematic review and meta-analysis investigated the cross-sectional association between amyloid-beta, one of the key pathologies defining AD, and depression or depressive symptoms in older adults without dementia. A systematic search in PubMed yielded 689 peer-reviewed articles. After full-text screening, nine CSF studies, 11 PET studies, and five plasma studies were included. ...[more]
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Project description:ObjectiveTo understand the role of depressive symptoms in preclinical Alzheimer's disease, it is essential to define their temporal relationship to Alzheimer's proteinopathies in cognitively normal older adults. The study objective was to examine associations of brain amyloid beta and longitudinal measures of depression and depressive symptom clusters in a cognitively normal sample of older adults.MethodA total of 270 community-dwelling, cognitively normal elderly individuals underwent baseline Pittsburgh compound B (PiB) positron emission tomography (PET) measures of cortical aggregate amyloid beta and annual assessments with the 30-item Geriatric Depression Scale (GDS). The authors evaluated continuous PiB binding as a predictor of GDS score or GDS cluster, calculated as total scores and mean scores for three GDS item clusters (apathy-anhedonia, dysphoria, and anxiety-concentration), across time (1-5 years; mean=3.8 years) in separate mixed-effects models with backward elimination. Initial predictors included PiB binding, age, sex, Hollingshead score, American National Adult Reading Test (AMNART) score, apolipoprotein E ε4 status, depression history, and their interactions with time.ResultsHigher PiB binding predicted accelerated rates of increase in GDS score over time, adjusting for depression history. Higher PiB binding also predicted steeper rates of increase for anxiety-concentration scores, adjusting for depression history and the AMNART score-by-time interaction. In a post hoc model estimating anxiety scores without concentration disturbance items, the PiB binding-by-time interaction remained significant.ConclusionsHigher amyloid beta burden was associated with increasing anxious-depressive symptoms over time in cognitively normal older individuals. Prior depression history was related to higher but not worsening symptom ratings. These results suggest a direct or indirect association of elevated amyloid beta levels with worsening anxious-depressive symptoms and support the hypothesis that emerging neuropsychiatric symptoms represent an early manifestation of preclinical Alzheimer's disease.
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Project description:ObjectiveTo clarify associations between APOE ε4 allele and age on longitudinal rates of β-amyloid (Aβ) accumulation within Aβ+ and Aβ- older individuals without dementia.MethodsWe analyzed 595 older adults without dementia classified cross-sectionally as Aβ- (n = 325) and Aβ+ (n = 270) using longitudinal florbetapir PET. The influence of age and APOE genotype on longitudinal accumulation of Aβ was examined with linear mixed models.ResultsAPOE ε4 and older age were associated with higher risk of being classified as Aβ+ at baseline. The annual rate of Aβ accumulation was significantly greater than zero for Aβ- ε3 (0.0021 ± 0.0007 standardized uptake value ratio [SUVR] units) and Aβ- ε4 (0.0044 ± 0.0010 SUVR units), as well as Aβ+ ε3 (0.0141 ± 0.0019 SUVR units) and Aβ+ ε4 (0.0126 ± 0.0018 SUVR units). Aβ accumulation was significantly faster in Aβ- ε4 compared to Aβ- ε3 and Aβ- ε2. Rates of Aβ accumulation did not differ significantly between Aβ+ APOE groups. Older age was associated with higher rates of Aβ accumulation in the Aβ- group.ConclusionsAPOE ε4 carriage and older age were predictors of longitudinal Aβ accumulation within the Aβ- group but not the Aβ+ group. APOE ε2 carriage was protective against longitudinal Aβ accumulation within the Aβ- group. APOE genotype in conjunction with chronologic age may aid in participant selection for primary prevention trials aimed at halting Aβ accumulation before abnormal levels are reached.
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Project description:ImportanceDepression has been identified as a risk factor for dementia. However, most studies have measured depressive symptoms at only one time point, and older adults may show different patterns of depressive symptoms over time.ObjectiveTo investigate the association between trajectories of depressive symptoms and risk of dementia in older adults.Design, setting, and participantsThis was a prospective cohort investigation of black and white community-dwelling older adults in the Health, Aging, and Body Composition study. Participants were enrolled between May 1997 and June 1998 and followed up through 2001-2002. The dates of this analysis were September 2014 to December 2015. The setting was community research centers in Memphis, Tennessee, and Pittsburgh, Pennsylvania. Trajectories of depressive symptoms were assessed from baseline to year 5. Symptoms were measured with the Center for Epidemiologic Studies Depression Scale Short Form, and trajectories were calculated using latent class growth curve analysis.Main outcomes and measuresIncident dementia through year 11, determined by dementia medication use, hospital records, or significant cognitive decline (≥1.5 SD race-specific decline on the Modified Mini-Mental State Examination). We examined the association between depressive symptom trajectories and dementia incidence using Cox proportional hazards regression models adjusted for demographics, health factors that differed between groups, and cognition during the depressive symptom assessment period (baseline to year 5).ResultsThe analytic cohort included 2488 black and white older adults with repeated depressive symptom assessments from baseline to year 5 who were free of dementia throughout that period. Their mean (SD) age at baseline was 74.0 (2.8) years, and 53.1% (n = 1322) were female. The following 3 depressive symptom trajectories were identified: consistently minimal symptoms (62.0% [n = 1542] of participants), moderate and increasing symptoms (32.2% [n = 801] of participants), and high and increasing symptoms (5.8% [n = 145] of participants). Compared with the consistently minimal trajectory, having a high and increasing depressive symptom trajectory was associated with significantly increased risk of dementia (fully adjusted hazard ratio, 1.94; 95% CI, 1.30-2.90), while the moderate and increasing trajectory was not associated with risk of dementia after full adjustment. Sensitivity analyses indicated that the high and increasing trajectory was associated with dementia incidence, while depressive symptoms at individual time points were not.Conclusions and relevanceOlder adults with a longitudinal pattern of high and increasing depressive symptoms are at high risk for dementia. Individuals' trajectory of depressive symptoms may inform dementia risk more accurately than one-time assessment of depressive symptoms.
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Project description:Ageing and depression are associated with disability and have significant consequences for health systems in many other developing countries. Depression prevalence figures among the elderly are scarce in developing countries.To estimate the prevalence of depressive symptoms and their cross-sectional association with selected covariates in a community sample of Mexico City older adults affiliated to the main healthcare provider.Cross-sectional, multistage community survey.A total of 7,449 persons aged 60 years and older.Depression was assessed using the 30-item Geriatric Depression Scale (GDS); cognitive impairment, using the Mini-Mental State Examination; and health-related quality of life with the SF-36 questionnaire.The prevalence of significant depressive symptoms was estimated to be 21.7%, and 25.3% in those aged 80 and older. After correcting for GDS sensitivity and specificity, major depression prevalence was estimated at 13.2%. Comparisons that follow are adjusted for age, sex, education and stressful life events. The prevalence of cognitive impairment was estimated to be 18.9% in depressed elderly and 13.7% in non-depressed. SF-36 overall scores were 48.0 in depressed participants and 68.2 in non-depressed (adjusted mean difference = -20.2, 95% CI = -21.3, -19.1). Compared to non-depressed elderly, the odds of healthcare utilization were higher among those depressed, both for any health problem (aOR 1.4, 95% CI = 1.1, 1.7) and for emotional problems (aOR 2.7, 95% CI = 2.2, 3.2).According to GDS estimates, one of every eight Mexican older adults had major depressive symptoms. Detection and management of older patients with depression should be a high priority in developing countries.
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Project description:ImportanceDepressive symptoms in older adults may be a harbinger of Alzheimer disease (AD), even in preclinical stages. It is unclear whether worsening depressive symptoms are manifestations of regional distributions of core AD pathology (amyloid) and whether cognitive changes affect this relationship.ObjectiveTo evaluate whether increasing depressive symptoms are associated with amyloid accumulation in brain regions important for emotional regulation and whether those associations vary by cognitive performance.Design, setting, and participantsParticipants from the Harvard Aging Brain Study, a longitudinal cohort study, underwent annual assessments of depressive symptoms and cognition alongside cortical amyloid positron emission tomography (PET) imaging at baseline and every 2 to 3 years thereafter (mean [SD] follow-up, 8.6 [2.2] years). Data collection was conducted from September 2010 to October 2022 in a convenience sample of community-dwelling older adults who were cognitively unimpaired with, at most, mild baseline depression. Data were analyzed from October 2022 to December 2023.Main outcomes and measuresDepression (Geriatric Depression Scale [GDS]-30-item), cognition (Preclinical Alzheimer Cognitive Composite-5 [PACC]), and a continuous measure of cerebral amyloid (Pittsburgh compound B [PiB] PET) examined in a priori-defined regions (medial orbitofrontal cortex [mOFC], lateral orbitofrontal cortex, middle frontal cortex [MFC], superior frontal cortex, anterior cingulate cortex, isthmus cingulate cortex [IC], posterior cingulate cortex, and amygdala). Associations between longitudinal GDS scores, regional amyloid slopes, and PACC slopes were assessed using linear mixed-effects models.ResultsIn this sample of 154 individuals (94 [61%] female; mean [SD] age, 72.6 [6.4] years; mean (SD) education, 15.9 [3.1] years), increasing PiB slopes in the bilateral mOFC, IC, and MFC were associated with increasing GDS scores (mOFC: β = 11.07 [95% CI, 5.26-16.87]; t = 3.74 [SE, 2.96]; P = .004; IC: β = 12.83 [95% CI, 5.68-19.98]; t = 3.51 [SE, 3.65]; P = .004; MFC: β = 9.22 [95% CI, 2.25-16.20]; t = 2.59 [SE, 3.56]; P = .03). Even with PACC slope as an additional covariate, associations remained significant in these regions.Conclusions and relevanceIn this cohort study of cognitively unimpaired older adults with, at most, mild baseline depressive symptoms, greater depressive symptoms over time were associated with amyloid accumulation in regions associated with emotional control. Furthermore, these associations persisted in most regions independent of cognitive changes. These results shed light on the neurobiology of depressive symptoms in older individuals and underscore the importance of monitoring for elevated mood symptoms early in AD.
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Project description:BackgroundPrevious studies have explored the application of non-invasive biomarkers of language dysfunction for the early detection of Alzheimer's disease (AD). However, language dysfunction over time may be quite heterogeneous within different diagnostic groups.MethodPatient demographics and clinical data were retrieved from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database for the participants without dementia who had measures of cerebrospinal fluid (CSF) biomarkers and language dysfunction. We analyzed the effect of longitudinal neuropathological and clinical correlates in the pathological process of semantic fluency and confrontation naming. The mediation effects of AD biomarkers were also explored by the mediation analysis.ResultThere were 272 subjects without dementia included in this analysis. Higher rates of decline in semantic fluency and confrontation naming were associated with a higher risk of progression to MCI or AD, and a greater decline in cognitive abilities. Moreover, the rate of change in semantic fluency was significantly associated with Aβ deposition, while confrontation naming was significantly associated with both amyloidosis and tau burden. Mediation analyses revealed that both confrontation naming and semantic fluency were partially mediated by the Aβ aggregation.ConclusionIn conclusion, the changes in language dysfunction may partly stem from the Aβ deposition, while confrontation naming can also partly originate from the increase in tau burden. Therefore, this study sheds light on how language dysfunction is partly constitutive of mild cognitive impairment and dementia and therefore is an important clinical predictor.
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Project description:ImportanceDepressive symptoms are prevalent among older adults and may be early manifestations of Alzheimer disease (AD) before onset of mild cognitive impairment. However, it remains unclear whether worsening depressive symptoms in the presence of AD pathology are associated with cognitive decline in older adults.ObjectiveTo determine the longitudinal association between depressive symptoms, cognition, and cortical amyloid in community-dwelling older adults.Design, setting, and participantsParticipants from the Harvard Aging Brain Study, a cohort study, underwent annual assessments of depression and cognition and baseline cortical amyloid measurement (mean, 4.42 years; range, 2-7 years). Data collection was from September 2010 to August 2017 in a convenience sample of community-dwelling adults (276 participants, all cognitively unimpaired) with at most mild depression at entry.Main outcomes and measuresDepression (Geriatric Depression Scale [GDS]), cognition (Preclinical Alzheimer Cognitive Composite [PACC]), and a continuous measure of cortical amyloid (Pittsburgh Compound-B positron emission tomography imaging). Change in GDS and baseline amyloid were examined as interactive predictors of PACC decline in a linear mixed model with backward elimination, adjusting for age, sex, and education.ResultsParticipants were 164 women and 112 men (mean [SD] age, 73.5 [6.0] years). At baseline, the mean (SD) GDS score was 3.0 (2.8) (range, 0-12), the mean (SD) PACC score was -0.004 (0.67) (range, -2.32 to 1.88), and the mean (SD) amyloid positron emission tomography distribution volume ratio was 1.16 (0.20) (range, 0.92-1.94). At last follow-up, the mean (SD) GDS score was 3.9 (2.9) (range, 0-12), and the mean (SD) PACC score was -0.09 (1.27) (range, -5.66 to 1.67). The interaction between cortical amyloid and increasing GDS was associated with declining cognition (β = -0.19; 95% CI, -0.27 to -0.12; P < .001).Conclusions and relevanceIn this study, cortical amyloid moderated the association between worsening depressive symptoms and declining cognition in older adults. While future work is needed to better understand causal associations, these findings may enhance early detection and prevention of AD clinical symptoms.
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Project description:The relationship between mild behavioral impairment (MBI) and Alzheimer's disease (AD) is intricate and still not well investigated. The purpose of the study is to examine the roles of the AD imaging pathologies in modulating the associations of MBI with cognitive impairments. We analyzed 1129 participants (563 [49.86%] female), who had measures of Neuropsychiatric Inventory Questionnaire (NPI-Q), cognition, and amyloid PET AD biomarkers from the Alzheimer's disease Neuroimaging Initiative (ADNI). We assess the longitudinal neuropathological and clinical correlates of baseline MBI via linear mixed effects and Cox proportional hazard models. The mediation analyses were used to test the mediation effects of AD pathologies on cognition. We found that MBI was associated with worse global cognition as represented by Mini-Mental State Examination (MMSE) (p < 0.001), and higher β-amyloid burden (p < 0.001). β-amyloid partially mediated the effects of MBI on cognition with the mediation percentage varied from 14.67 to 40.86% for general cognition, memory, executive, and language functions for non-dementia individuals. However, no significant associations were discovered between MBI and tau burden or neurodegeneration. Furthermore, longitudinal analyses revealed that individuals with MBI had a faster increase in brain amyloid burden (p < 0.001) and a higher risk of clinical conversion (HR = 2.42, 95% CI = 1.45 to 4.01 p < 0.001). In conclusion, MBI could be an imperative prediction indicator of clinical and pathological progression. In addition, amyloid pathologies might partially mediate the influences of MBI on cognitive impairments and AD risk.
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