Association Of Midlife Depressive Symptoms With Regional Amyloid-Beta And Tau In The Framingham Heart Study

Background: Depressive symptoms predict increased risk for dementia decades before the emergence of cognitive symptoms. Studies in older adults provide preliminary evidence for an association between depressive symptoms and amyloid-beta (A beta) and tau accumulation. It is unknown if similar alterations are observed in midlife when preventive strategies may be most effective.Objective: The study aim was to evaluate the association between depressive symptoms and cerebral A beta and tau in a predominately middle-aged cohort with examination of the apolipoprotein (APOE) epsilon 4 allele as a moderator.Methods: Participants included 201 adults (mean age 53 +/- 8 years) who underwent C-11-Pittsburgh Compound B amyloid and F-18-Flortaucipir tau positron emission tomography (PET) imaging. Depressive symptoms were evaluated with the Center for Epidemiological Studies Depression Scale (CES-D) at the time of PET imaging, as well as eight years prior. Associations between depressive symptoms at both timepoints, as well as depression (CES-D >= 16), with regional A beta and tau PET retention were evaluated with linear regression adjusting for age and sex. Interactions with the APOE epsilon 4 allele were explored.Results: Depressive symptoms and depression were not associated with PET outcomes in the overall sample. However, among APOE epsilon 4 allele carriers, there was a significant cross-sectional association between depressive symptoms and increased tau PET uptake in the entorhinal cortex (beta = 0.446, SE = 0.155, p = 0.006) and amygdala (beta = 0.350, SE = 0.133, p = 0.012).Conclusion: Although longitudinal studies are necessary, the results suggest that APOE epsilon 4 carriers with depressive symptoms may present with higher susceptibility to early tau accumulation in regions integral to affective regulation and memory consolidation.