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Amyloid-associated depression: a prodromal depression of Alzheimer disease?

ABSTRACT: 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.

SUBMITTER: Sun X

PROVIDER: S-EPMC3042807 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

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Amyloid-associated depression: a prodromal depression of Alzheimer disease?

Sun Xiaoyan X Steffens David C DC Au Rhoda R Folstein Marshal M Summergrad Paul P Yee Jacqueline J Rosenberg Irwin I Mwamburi D Mkaya DM Qiu Wei Qiao WQ

Archives of general psychiatry 20080501 5

<h4>Context</h4>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.<h4>Objective</h4>To characterize plasma Abeta(40):Abeta(42) ratio and cognitive function in elderly individuals with and without depression.<h4>Design</h4>Cross-sectional study.<h4>S ...[more]

PMID: 18458206

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Project description:PurposeTo quantify the effect sizes of regional metabolic and morphometric measures in patients with preclinical and mild Alzheimer disease (AD) to aid in the identification of noninvasive biomarkers for the early detection of AD.Materials and methodsThe study was conducted with institutional review board approval and in compliance with HIPAA regulations. Written informed consent was obtained from each participant or participant's legal guardian. Fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and magnetic resonance (MR) imaging data were analyzed from 80 healthy control (HC) subjects, 68 individuals with AD, and 156 with amnestic mild cognitive impairment (MCI), 69 of whom had single-domain amnestic MCI. Regions of interest (ROIs) were derived after coregistering FDG PET and MR images by using high-throughput, subject-specific procedures. The Cohen d effect sizes were calculated for 42 predefined ROIs across the brain. Statistical comparison of the largest overall effect sizes for MR imaging and PET was performed. Metabolic effect sizes were determined with and without accounting for regional atrophy. Discriminative accuracy of ROIs showing the largest effect sizes were compared by calculating receiver operating characteristic curves.ResultsFor all disease groups, the hippocampus showed the largest morphometric effect size and the entorhinal cortex showed the largest metabolic effect size. In mild AD, the Cohen d effect size for hippocampal volume (1.92) was significantly larger (P < .05) than that for entorhinal metabolism (1.43). Regression of regional atrophy substantially reduced most metabolic effects. For all group comparisons, the areas under the receiver operating characteristic curves were significantly larger for hippocampal volume than for entorhinal metabolism.ConclusionThe current results show no evidence that FDG PET is more sensitive than MR imaging to the degeneration occurring in preclinical and mild AD, suggesting that an MR imaging finding may be a more practical clinical biomarker for early detection of AD.

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Amyloid-associated depression: a prodromal depression of Alzheimer disease?

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Amyloid-associated depression: a prodromal depression of Alzheimer disease?

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