Aging
Subjective cognitive decline reflects brain pathology independent of depressive symptoms Nancy Chen* Nancy Chen Chen Chen Chen Chen Chen Chen University of California, Davis
Subjective cognitive decline (SCD) may reflect neurodegenerative processes but is also closely linked to depressive symptoms, which itself is a risk for dementia. We examined whether depressive symptoms mediate associations between SCD and imaging biomarkers of neurodegeneration, cerebrovascular injury, and amyloid burden.
We analyzed an ethnoracially-diverse sample of adults aged 50-101 from harmonized KHANDLE, LA90, and STAR. SCD was measured using the 12-item Everyday Cognition (ECog) (range:1-4; higher=greater SCD). Hippocampal volume and white matter hyperintensities (WMH) were measured using 3T MRI, normalized to intracranial volume and z-standardized. Amyloid burden was assessed using florbetapir PET among a random subset of KHANDLE and LA90 and quantified using standard uptake value ratios (SUVR). The potential mediator, depressive symptoms, was measured by the NIH PROMIS depression toolbox. All measures were assessed at the same or proximate visit. Mediation analyses estimated total, natural direct, and natural indirect effects, adjusted for sex, race/ethnicity, age at scan, education, and cohort.
Participants’ (N=724) mean±SD age was 81.1±10.7, 58% were women, 52% had less than a college education, and 20% identified as Asian, 33% as Black, 19% as Latino, and 25% as White. Mean ECog was 1.38±0.41 and mean amyloid SUVR was 1.10±0.19. Higher (worse) ECog was associated with higher odds of having depressive symptoms (OR=2.69,95%CI=1.77,4.07), and smaller hippocampal volume (bTotalEffect=-0.26,95%CI=-0.43,-0.10;Table 1) with no evidence of mediation by depressive symptoms. Higher ECog was also modestly associated with greater WMH and higher amyloid-SUVR, and neither association showed evidence of mediation.
Greater SCD was associated with neurodegeneration and, to a lesser extent, cerebrovascular injury and amyloid burden. Depressive symptoms did not mediate these associations, suggesting that SCD may reflect underlying brain pathology independent of depression.
