A-4 Amyloid Status Modifies the Association between Subjective Cognitive Decline and Brain MRI Metrics

Abstract

Abstract Objective Subjective cognitive decline (SCD), a potential precursor to Alzheimer’s disease (ad), has been associated with increased neurodegeneration and cerebrovascular disease longitudinally. However, the impact of amyloid status, an early pathological marker of Alzheimer’s disease (ad) on these longitudinal associations is less clear. Here, we related baseline SCD to longitudinal biomarkers of brain health in the context of amyloid status. Method Participants included 139 non-demented older adults (72 ± 7 years) from the Vanderbilt Memory & Aging Project who completed a SCD questionnaire and fasting lumbar-puncture to quantify amyloid status (defined using published cutoffs of amyloid-beta42 levels) at baseline. 3 T brain-MRI to measure gray and white matter hyperintensity (WMH) volumes was collected at baseline, 18-months, 3-years, and 5-years. Linear mixed effects models assessed if baseline SCD X amyloid status was associated with longitudinal total and lobar grey and white matter volumes, covarying for baseline age, sex, race/ethnicity, education, diagnosis, mood, and apolipoprotein-Ee4 status. Models were also stratified by baseline amyloid status. Results Baseline SCD score and amyloid status interacted with total gray (p = 0.02) and WMH volume (p < 0.05). In stratified models, higher total SCD predicted increased inferior lateral ventricular volume (p < 0.001) among amyloid positive individuals. Conversely, in amyloid negative, greater baseline SCD was associated with increased WMH volumes globally (p = 0.03) and in the frontal and parietal lobes (p-values <0.035). Conclusion In the presence of amyloid, the presence of SCD is predictive of neurodegeneration in ad-specific regions. Conversely, SCD without amyloidosis may reflect a cerebrovascular disease, indicated by WMHs. Results highlight how amyloid status may help delineate etiologies of SCD.