A-93: Predictive Value of Plasma ADRD Biomarkers in Cognitive Responsiveness to Lifestyle Modification Intervention in Older Adults With Remitted Late-life Depression

Abstract

Objective: Late-life depression (LLD) increases dementia risk, emphasizing the potential and importance of lifestyle interventions to support cognition. However, no biomarker-based models currently exist to predict their effectiveness. We examined whether plasma Alzheimer’s disease and related dementia (ADRD) biomarkers in older adults with remitted LLD predict cognitive response to a six-month lifestyle intervention, consisting of aerobic exercise or holistic wellness activities. Method/Data Selection: 35 sedentary older adults (mean age=67.7, SD=5.5 years; 71% female; 51% with Mild Cognitive Impairment) with remitted LLD participated in a lifestyle intervention study to optimize cognitive aging. Cognition was assessed using the Neuropsychological Assessment Battery (NAB) and the NIH Toolbox Cognition Battery. ADRD biomarkers were quantified using NULISAseq CNS 120 Panel. Amyloid- and tau-related biomarkers (AB42/40, BD-MAPT, BD-ptau181, BD-ptau-217, BD-ptau-231) were used to predict change in cognitive performance over three- and six-months. Linear regression models adjusted for age, sex, and education were used to assess associations with change in NIH toolbox scores, and Spearman correlations were used to assess associations with change in NAB scores (T-scores). Results/Data Synthesis: Greater baseline BD-MAPT was associated with worse executive function over 3- and 6-months (NIH Toolbox EF Composite: 3-month: β=-0.66, p=0.003; 6-month: β=-0.54, p=0.03). Greater baseline AB42/40 was associated with less decline in executive function over 3-months (β = 0.52, p=0.02). No other biomarkers investigated at baseline predicted cognitive change over the 6-month intervention. Conclusions: In older adults with remitted LLD, many of whom also have MCI, plasma ADRD biomarker profiles may be important to consider when evaluating cognitive responsiveness to lifestyle interventions.