Depression severity and sleep efficiency's associations with amyloid burden are additive but dependent on underlying genetic risk in late life depression

Abstract Introduction Evidence linking late‐life depression (LLD) to amyloid beta (Aβ) burden remains mixed, possibly in part due to limited examinations of the confounding role of comorbid sleep disturbance and the moderating role of the apolipoprotein E ( APOE ) ɛ4 gene. Methods We analyzed 110 older adults (ages 65–88, 66% female) with LLD to jointly model depression severity and sleep disturbance's relationship with Aβ, and to examine the moderating role of APOE ɛ4 genotype. Results Depression severity, sleep efficiency, and sleep duration did not demonstrate a direct relationship with Aβ; however, a significant APOE ɛ4 moderation effect occurred for depression severity and sleep efficiency. In APOE ɛ4 carriers only, higher depression severity and lower sleep efficiency were associated with greater total Aβ burden and indicated greater likelihood of reaching clinical cutoffs for amyloid positivity. The effects of depressive symptoms and sleep efficiency were statistically unique and additive. Exploratory analyses demonstrated APOE ɛ4 also moderated the effect of lifetime duration of untreated depression on increased Aβ. Discussion Depression severity and sleep efficiency's relationship with Aβ may be dependent on the presence of the APOE ɛ4 allele. This, among other individual differences, may partially explain mixed findings examining LLD as a risk factor for Alzheimer's disease. Furthermore, these findings do not suggest that the relationship between depression severity and amyloid is explained by the confounding role of sleep duration or sleep efficiency.