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

BackgroundDepression-especially late-life onset-is associated with age-related cognitive decline and may be a key risk factor for amyloid-β (Aβ) deposition in preclinical Alzheimer's disease (AD).ObjectiveThis study assesses whether depressive symptoms modify the relationship between age and Aβ burden in a cohort at-risk for AD.MethodsN = 238 cognitively unimpaired participants from the Wisconsin Alzheimer's Disease Research Center participated in Pittsburgh Compound-B positron emission tomography (¹¹C-PiB-PET), where distribution volume ratio scores were used to quantify Aβ burden in nine regions of interest (ROIs) susceptible to early Aβ 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 ε4 (APOE ε4) carriage, and age difference between PET imaging and GDS assessment. GDS-stratified analyses were performed to test within-group associations between age and ¹¹C-PiB-PET Aβ 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 ε4 carriers, 64% were female, and 85.3% were White. GDS scores were largely normal (M = 1.29, SD = 1.61). Age × 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.ConclusionsIn a cohort enriched with risk for AD, emerging depressive symptoms amplified the association between age and Aβ burden.