Longitudinal increase in depressive symptoms in relation to neurodegeneration in clinically normal older adults: Findings from the Harvard Aging Brain Study

Abstract

AbstractBackgroundEvidence suggests that depressive symptoms may be early behavioral changes preceding the development of Alzheimer’s Disease (AD). However, the neurobiological trajectory of depressive symptoms in reference to neurodegeneration of the hippocampus—a structure implicated in both mood and memory regulation—remains poorly understood in preclinical AD. In the current study, we examined the impact of baseline hippocampal volume (HV) both independently, and interactively with amyloid‐ß, on longitudinal change in depressive symptoms in clinically normal (CN) older adults.Method270 Harvard Aging Brain Study participants (age:73.5 ±6.1; 58% females) completed annual assessment with the 30‐item Geriatric Depression Scale (GDS) (average follow‐up=4.28 annual visits). All participants were cognitively unimpaired without clinically significant depression at study entry (mean GDS=3.09±2.86; range: (0‐12)). All underwent structural MRI scans and amyloid‐ß (11C‐Pittsburgh Compound B) PET at study year 1. In the primary linear mixed model, the association between dependent variable GDS (for each annual study visit) and HV was examined, with a random intercept and slope for each participant, covariates: age, sex, and education; and the interaction of predictors with time. In a secondary model, HV X cortical amyloid, X time was additionally included as a predictor.ResultIn the primary model, lower baseline HV (ß=‐0.0006; t=‐1.909; 95 % CI (‐1.2 x 10‐3, 1.7 x10‐5); p=0.057), but not its interaction with time (HV X time:(ß =‐0.000; t=‐1.12; 95% CI (‐7x10‐5, 6x10‐5); p=0.903) was marginally associated with higher GDS. In the secondary model, baseline HV and cortical amyloid were not interactive predictors of longitudinal GDS (HV X cortical amyloid X time: (ß =‐0.0001; t=‐0.90; 95% CI (‐4x10‐4, 0.0002); p=0.364).ConclusionLower baseline hippocampal volume is marginally associated with greater depressive symptoms; however, it did not independently, or in synergy with cortical amyloid, predict worsening depressive symptoms over time. These preliminary findings suggest that hippocampal atrophy may not be a predominant indicator of accelerating depression in CN older adults. Of note, our sample was non‐depressed at baseline. Future work in samples with non‐restricted behavioral symptoms and incorporating longitudinal AD biomarkers is needed to better understand neurobiological trajectory and identify targets for treatment at the earliest stages of AD.