Abstract P504: Prospective Associations of Midlife C3, C4 and Their Changes Since Midlife With Future Cognitive Performance: The Study of Women’s Health Across the Nation HDL Ancillary Study

Abstract

Objective: Almost two-thirds of Americans over 65 with Alzheimer’s disease (AD) are women. The menopause transition is characterized by a systemic inflammatory state which increases atherosclerosis risk predisposing to dementia. Complement system was inappropriately activated in the brain of AD patients, which may contribute to local inflammation correlated with cognitive dysfunction. Complement factor 3 (C3) and 4 (C4) are the most clinically used complement components. Increased serum C3 and the presence of C4 null genes producing less C4 are risk factors of cardiovascular disease (CVD), indicating the necessity of analyzing the ratio of C3 and C4. Since serum C3 and C4 markedly increase over the menopause transition, we aimed to assess the associations of midlife C3, C4, and C3/C4 ratio and their changes since midlife with future cognitive function in women. Design: Repeated measures of serum C3, C4, and measures of working memory (digit span backward test), processing speed (symbol digit modality test), episodic memory immediate and delayed recall (East Boston memory test) were evaluated among midlife women traversing menopause. Mixed effect models were applied to assess the associations. Results: We included 305 women (706 observations) with mean age of 51 (SD=3) and 72% of them being pre- or perimenopausal at baseline. C3 and C4 were measured a median of 1.07 (Q1: 0.94, Q3: 1.81) years before cognitive performance assessment. In final models, higher C4 measured at midlife (baseline) was associated with better future episodic memory levels, and higher midlife C3/C4 ratio was associated with worse future episodic memory ( Table ). Changes in the complement factors were not associated with cognitive measures. Conclusion: Among women, higher midlife C4 and lower midlife C3/C4 ratio, but not changes in C4 or C3/C4 ratio since midlife, were associated with better future episodic memory levels. Midlife complement protein levels could be early markers of cognitive impairment known to be linked with CVD.