Association of Midlife Depressive Symptoms with Regional Amyloid-β 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.

Automated summary

The study found that while depressive symptoms and depression were not associated with PET outcomes in the overall sample, there was a significant cross-sectional association between depressive symptoms and increased tau PET uptake in the entorhinal cortex and amygdala among APOE ε4 allele carriers.