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

Abstract

Context: 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.

Objective: To characterize plasma Abeta(40):Abeta(42) ratio and cognitive function in elderly individuals with and without depression.

Design: Cross-sectional study.

Setting: Homecare agencies.

Participants: 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.

Main outcome measures: Cognitive domains of memory, language, executive, and visuospatial functions according to levels of plasma Abeta(40) and Abeta(42) peptides.

Results: 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.

Conclusion: Amyloid-associated depression may define a subtype of depression representing a prodromal manifestation of Alzheimer disease.

Figure

Quartiles (Q1–Q4) of the ratio of plasma amyloid-β peptide 40 to amyloid-β peptide 42 (Aβ₄₀:Aβ₄₂) and cognitive function among those with and without depression. Different cognitive domains are shown in each Aβ₄₀:Aβ₄₂ quartile among those with and without depression. Values are shown as mean[SE]. P values are for comparisons among the 4 quartiles in those with and without depression.