A-8 Sex Modifies the Association between CSF Neurogranin and Cognitive Decline in Older Adults

Abstract

Objective Neurogranin is a postsynaptic protein associated with declining memory and executive functioning in Alzheimer’s disease (ad). While previous research suggests neurogranin concentrations in ad are higher in women, it is unclear whether sex differences exist in earlier disease stages or predict different cognitive outcomes. This study investigates cerebrospinal fluid (CSF) neurogranin in relation to longitudinal cognitive decline in older adults ranging from normal cognition to mild cognitive impairment, assessing for interactions by sex. Method Vanderbilt Memory & Aging Project participants completed baseline fasting lumbar puncture (n = 155, 73 ± 8 years) for neurogranin quantification and serial neuropsychological assessments at 18-month intervals. Linear mixed effect regression adjusting for age, sex (for main effect models), race/ethnicity, education, cognitive diagnosis, depressed mood, and APOE-ε4 carrier status. Results CSF neurogranin predicted worse cognitive decline across multiple domains (p-values <0.05). Sex interactions existed for Boston Naming Test (β = −0.007, p = 0.001), WAIS-IV Coding (β = −0.01, p = 0.02), Hooper Visual Orientation Test (β = −0.005, p = 0.02), and Category (animals) Fluency (β = −0.005, p = 0.048) wherein CSF neurogranin predicted worse decline among women (p-values≤0.03) but not men (p-values≥0.36). Conclusion Results suggest that among nondemented older adults, CSF neurogranin predicts worse longitudinal cognitive decline in women but not in men. Further research is needed to elucidate underlying mechanisms that may account for these differences, such as possible sex hormone factors. These findings highlight the importance of pursuing individualized prevention and treatment approaches to combat accelerated cognitive aging that take into account the possibility of multiple, divergent disease pathways preceding ad and dementia among various demographic groups.