Associations of the Rate of Change in Geriatric Depression Scale with Amyloid and Cerebral Glucose Metabolism in Cognitively Normal Older Adults: A Longitudinal Study

Background: Depression is considered a psychological risk factor for Alzheimer's disease (AD). We sought to examine the differential associations of depression severity with cognitive decline, clinical progression to mild cognitive impairment (MCI) or AD, and neuroimaging markers of AD in cognitively normal older adults. Methods: A total of 522 cognitively normal (CN) participants who underwent assessments for depression (longitudinal geriatric depression scale [GDS] ) and cognitive assessments were included from the Alzheimer Disease Neuroimaging Initiative (ADNI) cohort. The cross-sectional and longitudinal associations of the rate of change in GDS with amyloid-beta (A beta)-positron emission tomography (PET), tau-PET, and F-18-fluorodeoxyglucose (FDG)-PET were explored. Kaplan-Meier survival curves of clinical progression and A beta accumulation were plotted based on mean annual changes in GDS. Mediation analyses were utilized to explore the mediation effects of AD markers. Results: Higher rate of increase in GDS was associated with faster cognitive decline and higher risk of progression to MCI or AD. Moreover, the rate of change in GDS was significantly associated with A beta accumulation and cerebral glucose metabolism. The influences of the rate of change in GDS on cognition and clinical progression were partially mediated by A beta accumulation and cerebral glucose metabolism. Limitations: GDS is a self-reported questionnaire and not the same as a clinical diagnosis of depression. Conclusions: The cognitive and clinical consequences of changes in depressive symptoms partly stem from A beta accumulation and cerebral glucose metabolism, which increases our understanding of how depressive symptoms may increase vulnerability to dementia.