A high ratio of plasma amyloid-β peptide 40 (Aβ40) to Aβ42, determined by both high Aβ40 and low Aβ42 levels, increases the risk of Alzheimer disease. In a previous study, we reported that depression is also associated with low plasma Aβ42 levels in the elderly population.
To characterize plasma Aβ40:Aβ42 ratio and cognitive function in elderly individuals with and without depression.
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 Aβ40 and Aβ42 peptides.
Subjects with depression had lower plasma Aβ42 levels (median, 14.1 vs 19.2 pg/mL; P = .006) and a higher plasma Aβ40:Aβ42 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 Aβ40:Aβ42 ratio was associated with lower memory score (β = −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 Aβ40:Aβ42 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.