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Depressive Symptoms and Biomarkers of Alzheimer's Disease in Cognitively Normal Older Adults.

ABSTRACT: Even low levels of depressive symptoms are associated with an increased risk of cognitive decline in older adults without overt cognitive impairment (CN). Our objective was to examine whether very low, "subthreshold symptoms of depression" are associated with Alzheimer's disease (AD) biomarkers of neurodegeneration in CN adults and whether these associations are specific to particular depressive symptoms. We analyzed data from 248 community-dwelling CN older adults, including measurements of cortical amyloid burden, neurodegeneration markers of hippocampal volume (HV) and cerebral 18F-fluorodeoxyglucose (FDG) metabolism in a composite of AD-related regions and the 30-item Geriatric Depression Scale (GDS). Participants with GDS >10 were excluded. General linear regression models evaluated the cross-sectional relations of GDS to HV or FDG in separate backward elimination models. Predictors included GDS total score, age, gender, premorbid intelligence, a binary amyloid variable and its interaction with GDS. Principal component analyses of GDS item scores revealed three factors (the Dysphoria, Apathy-Anhedonia, and Anxiety-Concentration Factors). In secondary analyses, GDS total score was replaced with the three factor scores in repeated models. Higher GDS score (p?=?0.03) was significantly associated with lower HV and was marginally related (p?=?0.06) to FDG hypometabolism. In secondary models, higher Dysphoria (p?=?0.02) and Apathy-Anhedonia (p?=?0.05) were related to lower HV while higher Apathy-Anhedonia (p?=?0.003) was the sole factor related to FDG hypometabolism. Amyloid was not a significant predictor in any model. In conclusion, very low-level dysphoria, apathy and anhedonia may point to neurodegeneration in AD-related regions but this association appears to be independent of amyloid burden.

SUBMITTER: Donovan NJ

PROVIDER: S-EPMC4544638 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Depressive Symptoms and Biomarkers of Alzheimer's Disease in Cognitively Normal Older Adults.

Donovan Nancy J NJ Hsu David C DC Dagley Alexander S AS Schultz Aaron P AP Amariglio Rebecca E RE Mormino Elizabeth C EC Okereke Olivia I OI Rentz Dorene M DM Johnson Keith A KA Sperling Reisa A RA Marshall Gad A GA

Journal of Alzheimer's disease : JAD 20150101 1

Even low levels of depressive symptoms are associated with an increased risk of cognitive decline in older adults without overt cognitive impairment (CN). Our objective was to examine whether very low, "subthreshold symptoms of depression" are associated with Alzheimer's disease (AD) biomarkers of neurodegeneration in CN adults and whether these associations are specific to particular depressive symptoms. We analyzed data from 248 community-dwelling CN older adults, including measurements of cor ...[more]

PMID: 25697700

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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.

Project description:BackgroundNeuropsychiatric symptoms (NPS) have been reported to be useful in predicting incident dementia among cognitively normal older persons. However, the literature has not been conclusive on the differential utilities of the various NPS in predicting the subtypes of dementia. This study compared the risks of Alzheimer's and non-Alzheimer's dementia associated with the various NPS, among cognitively normal older persons.MethodsThis cohort study included 12,452 participants from the Alzheimer's Disease Centers across USA, who were ≥ 60 years and had normal cognition at baseline. Participants completed the Neuropsychiatric Inventory-Questionnaire at baseline and were followed up almost annually for incident dementia (median follow-up = 4.7 years). Symptom clusters of NPS-as identified from exploratory and confirmatory factor-analyses-were included in the Cox regression to investigate their associations with incident dementia.ResultsThe various NPS showed independent yet differential associations with incident dementia. Although psychotic symptoms were rarely endorsed by the participants, they predicted much higher risk of dementia (HR 3.6, 95% CI 2.0-6.4) than affective symptoms (HR 1.5, 95% CI 1.2-1.8) or agitation symptoms (HR 1.6, 95% CI 1.3-2.1). Psychotic symptoms predicted all dementia subtypes, while affective and agitation symptoms differentially predicted some subtypes. Across dementia subtypes, psychotic symptoms had relatively higher risk estimates than affective or agitation symptoms, with the risk estimates being particularly high in non-Alzheimer's dementia.ConclusionsAmong cognitively normal individuals, the presence of NPS may warrant greater clinical vigilance as precursors to dementia and its subtypes. The findings highlight the need for further research to enrich our understanding on the neurobiological links between various NPS and dementia subtypes. They may also change the clinical approach in managing late-life psychotic symptoms, requiring a greater emphasis on dementia surveillance in the diagnostic criteria of late-life psychotic disorders.

Project description:Background and objectivesIncreased anxious-depressive symptomatology is observed in the preclinical stage of Alzheimer disease (AD), which may accelerate disease progression. We investigated whether β-amyloid, cortical thickness in medial temporal lobe structures, neuroinflammation, and sociodemographic factors were associated with greater anxious-depressive symptoms during the COVID-19 confinement.MethodsThis retrospective observational study included cognitively unimpaired older adults from the Alzheimer's and Families cohort, the majority with a family history of sporadic AD. Participants performed the Hospital Anxiety and Depression Scale (HADS) during the COVID-19 confinement. A subset had available retrospective (on average: 2.4 years before) HADS assessment, amyloid [18F] flutemetamol PET and structural MRI scans, and CSF markers of neuroinflammation (interleukin-6 [IL-6], triggering receptor expressed on myeloid cells 2, and glial fibrillary acidic protein levels). We performed multivariable linear regression models to investigate the associations of prepandemic AD-related biomarkers and sociodemographic factors with HADS scores during the confinement. We further performed an analysis of covariance to adjust by participants' prepandemic anxiety-depression levels. Finally, we explored the role of stress and lifestyle changes (sleep patterns, eating, drinking, smoking habits, and medication use) on the tested associations and performed sex-stratified analyses.ResultsWe included 921 (254 with AD biomarkers) participants. β-amyloid positivity (B = 3.73; 95% CI = 1.1 to 6.36; p = 0.006), caregiving (B = 1.37; 95% CI 0.24-2.5; p = 0.018), sex (women: B = 1.95; 95% CI 1.1-2.79; p < 0.001), younger age (B = -0.12; 95% CI -0.18 to -0.052; p < 0.001), and lower education (B = -0.16; 95% CI -0.28 to -0.042; p = 0.008) were associated with greater anxious-depressive symptoms during the confinement. Considering prepandemic anxiety-depression levels, we further observed an association between lower levels of CSF IL-6 (B = -5.11; 95% CI -10.1 to -0.13; p = 0.044) and greater HADS scores. The results were independent of stress-related variables and lifestyle changes. Stratified analysis revealed that the associations were mainly driven by women.DiscussionOur results link AD-related pathophysiology and neuroinflammation with greater anxious-depressive symptomatology during the COVID-19-related confinement, notably in women. AD pathophysiology may increase neuropsychiatric symptomatology in response to stressors. This association may imply a worse clinical prognosis in people at risk for AD after the pandemic and thus deserves to be considered by clinicians.Trial registration informationClinicalTrials.gov Identifier NCT02485730.

Project description:Cardiovascular disease (CVD) is associated with a higher risk of developing dementia. Studies have found that vascular risk factors are associated with greater amyloid-β (Aβ) and tau burden, which are hallmark neuropathologies of Alzheimer's disease (AD). Evidence for these associations during the preclinical stages of AD, when Aβ and tau pathologies first become detectable, is mixed. Quantifying the effect of vascular risk among cognitively normal individuals can help focus the efforts to develop therapeutic approaches aimed at modifying the course of preclinical AD. Using Bayesian analysis, we examined the relationship of Aβ and tau pathology with concurrent vascular risk among 87 cognitively normal individuals (median age 77, interquartile range 70-83) in the Baltimore Longitudinal Study of Aging. We quantified vascular risk as the probability of developing CVD within 10 years using published equations from the Framingham Heart Study. Aβ and tau pathologies were measured using positron emission tomography. As expected, Aβ positive participants had greater tau in the entorhinal cortex (EC) and inferior temporal gyrus (ITG) (difference in means = 0.09, p < 0.05 for each region), and 10-year CVD risk was positively correlated with white matter lesion burden (r = 0.24, p = 0.03). However, we did not find any associations between CVD risk and Aβ or tau. The data provided over two- and four-fold evidence towards the lack of a correlation between CVD risk and tau in the EC (Bayes factor BF = 2.4) and ITG (BF = 4.0), respectively. We found over three-fold evidence towards the lack of a difference in mean CVD risk by Aβ group (BF = 3.4). These null findings were replicated using a data-driven vascular risk score in the BLSA based on a principal component analysis of eight indicators of vascular health. Our data provide moderate evidence towards the lack of an association between vascular risk and concurrent AD neuropathology among cognitively normal older adults. This finding suggests that vascular risk and AD neuropathology may constitute independent pathways in the development of cognitive impairment and dementia.

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Depressive Symptoms and Biomarkers of Alzheimer's Disease in Cognitively Normal Older Adults.

Publications

Depressive Symptoms and Biomarkers of Alzheimer's Disease in Cognitively Normal Older Adults.

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