Inflammatory and Immune Biomarkers over Midlife and Future Cognition in Women: the SWAN HDL Ancillary Study

OBJECTIVE:Limited research has assessed prospective associations of systemic inflammatory (GlycA) and immune (complement factor 3 [C3] and 4 [C4]) biomarkers with future cognition in midlife women, who potentially experience worsening inflammation around the menopause transition. We aim to assess the associations of midlife serum GlycA, C3, and C4 with future cognitive performance in women. METHODS:Serum GlycA, C3, and C4 were repeatedly measured over 6.1 ± 3.9 years in 503 midlife women (1,234 observations) from the Study of Women's Health Across the Nation high-density lipoprotein ancillary study. Longitudinal measures of working memory, processing speed, and episodic memory, immediate and delayed recall, were administered 1.46 ± 0.95 years later. We applied joint models to examine the associations of baseline biomarkers and their changes since baseline with subsequent cognition. RESULTS:Higher levels of serum GlycA and complement factor 4 at baseline (50.17 ± 2.65 y) were significantly associated with worse working memory and better immediate recall, respectively, over the next decade. Higher baseline complement factor 4 and increases in C3 and C4 since baseline tended to associate with better future immediate and/or delayed recall. CONCLUSIONS:Higher baseline GlycA, rather than its changes since baseline, was associated with lower future working memory, whereas higher baseline complement factor 4 and increases in C3 and C4 since baseline appeared cognitively protective. Targeting inflammation amelioration and immunity improvement over the menopause transition may provide an open avenue to preserve future cognitive health.