Multimodal neuroimaging biomarkers of Alzheimer’s disease in older adults with depression: Preliminary findings from a pilot cohort

Background Subclinical depressive symptoms in older adults have been linked to AD pathology and cognitive decline. However, it’s unclear how these findings translate to the spectrum of clinically significant late life depressive symptoms. To explore this, we examined cross‐sectional associations between depressive symptoms and neuroimaging biomarkers of AD (ATN) in a pilot cohort of older adults with moderate‐to‐severe depressive symptoms and compared these participants to non‐depressed older adults. Method Seventeen community‐dwelling clinically‐normal (CN) older adults meeting DSM5 criteria for major depression (73.4±4.7 y.o., 58.8% female) underwent MRI, amyloid‐(C11‐PiB)‐PET, and tau‐(F18‐FTP)‐PET and completed a clinical battery including the 30‐item Geriatric Depression Scale (GDS) and Preclinical Alzheimer’s Cognitive Composite (PACC). A comparison group of non‐depressed older adults (no history of depression, GDS≤5; 73.0±5.5 y.o., 63.2% female) derived from existing observational studies at our site with similar clinical‐neuroimaging batteries were matched using nearest neighbor propensity score to depressed participants by age, sex, and APOE‐ε4 carrier status in a 4:1 ratio (Table 1). We examined cortical amyloid and regional tau and atrophy in a priori regions of interest (ROI) previously implicated in AD and mood (medial temporal lobe, amygdala, frontal cortex). We utilized t‐tests to explore group differences and linear regressions adjusted for age to investigate associations between depressive symptoms and ATN biomarkers. Result In the depressed group, depressive symptoms were significantly associated with elevated FTP in all ROI and with lower hippocampal volume, but not with cortical PiB (Table 2, Fig. 1). There were no significant group differences compared to non‐depressed controls in cortical PiB, regional FTP, or volume measures; however, participants with depression had worse cognitive performance on the PACC than non‐depressed participants (t=‐2.04, p=0.050). Conclusion Preliminary findings in this pilot sample suggest that moderate‐to‐severe depressive symptoms in older adults may be more closely associated cross‐sectionally with tau and hippocampal volume than cortical amyloid. Future work in a larger depressed cohort and with longitudinal follow‐up is needed to characterize risk in older adults with depression and consider opportunities for AD prevention.