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Longitudinal increase in depressive symptoms in relation to neurodegeneration in clinically normal older adults: Findings from the Harvard Aging Brain Study
Author(s) -
Premnath Pranitha,
Marshall Gad A.,
Buckley Rachel F.,
Donovan Nancy,
Jacobs Heidi I.L.,
Amariglio Rebecca,
Vannini Patrizia,
Chou HsiangChin Lori,
Properzi Michael J.,
Quiroz Yakeel T.,
Rentz Dorene M.,
Johnson Keith A.,
Sperling Reisa A.,
Hanseeuw Bernard,
Gatchel Jennifer R.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.047321
Subject(s) - geriatric depression scale , depression (economics) , medicine , longitudinal study , neurodegeneration , mood , pittsburgh compound b , alzheimer's disease , psychology , depressive symptoms , disease , psychiatry , cognition , pathology , economics , macroeconomics
Background Evidence 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. Method 270 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 ( 11 C‐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. Result In 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). Conclusion Lower 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.