Depression modifies age-associated [11C]PiB-PET amyloid burden in a cohort enriched with risk for Alzheimer's disease

Background Depression-especially late-life onset-is associated with age-related cognitive decline and may be a key risk factor for amyloid-beta (A beta) deposition in preclinical Alzheimer's disease (AD). Objective This study assesses whether depressive symptoms modify the relationship between age and A beta burden in a cohort at-risk for AD. Methods N = 238 cognitively unimpaired participants from the Wisconsin Alzheimer's Disease Research Center participated in Pittsburgh Compound-B positron emission tomography (C-11-PiB-PET), where distribution volume ratio scores were used to quantify A beta burden in nine regions of interest (ROIs) susceptible to early A beta burden. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS). Cross-sectional linear regression models examined interactions between age and GDS scores, adjusting for sex, apolipoprotein epsilon 4 (APOE epsilon 4) carriage, and age difference between PET imaging and GDS assessment. GDS-stratified analyses were performed to test within-group associations between age and C-11-PiB-PET A beta aggregation in each ROI, and item-level analyses identified specific depressive symptoms that modified these relationships.ResultsParticipants had a mean age of 68.0 years (SD +/- 8.4), 39.7% were APOE epsilon 4 carriers, 64% were female, and 85.3% were White. GDS scores were largely normal (M = 1.29, SD = 1.61). Age x GDS interactions were significant across all ROIs, and stratified models revealed progressively stronger associations as GDS scores increased. Finally, item-level analyses identified the second and tenth GDS items as significant modifiers across six ROIs and the global composite. Conclusions In a cohort enriched with risk for AD, emerging depressive symptoms amplified the association between age and A beta burden.