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

Xiaoyan Sun, David C. Steffens, Rhoda Au, Marshal Folstein, Paul Summergrad, Jacqueline Yee, Irwin Rosenberg, D. Mkaya Mwamburi, Qiao Qiu Wei

Research output: Contribution to journalArticlepeer-review


Context: A high ratio of plasma amyloid-β peptide 40 (Aβ40) to Aβ42, determined by both hig hAβ40 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. Objective: To characterize plasma Aβ40: Aβ42 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 Aβ40 and Aβ42 peptides. Results: 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. Conclusion: Amyloid-associated depression may define a subtype of depression representing a prodromal manifestation of Alzheimer disease.

Original languageEnglish (US)
Pages (from-to)542-550
Number of pages9
JournalArchives of general psychiatry
Issue number5
StatePublished - May 2008
Externally publishedYes

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Psychiatry and Mental health


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