Identifying Novel Cardiovascular Biomarkers for Cognitive Performance Across the Menopause TransitionQi, Meiyuzhen (2024) Identifying Novel Cardiovascular Biomarkers for Cognitive Performance Across the Menopause Transition. Doctoral Dissertation, University of Pittsburgh. (Unpublished)
AbstractBackground: Women are disproportionally affected by Alzheimer’s disease (AD). The menopause transition may be a stage with increased AD susceptibility, due to its association with accelerated cardiovascular risks, the most common modifiable risk factors of AD. While traditional cardiovascular risk factors have been associated with processing speed and working memory, we aimed to identify novel cardiovascular biomarkers with potential to link to episodic memory loss, the initial and predominant symptom of AD. Objectives: To assess the associations of cardiovascular fat [epicardial (EAT), paracardial (PAT), and thoracic perivascular adipose tissue (PVAT)] volume and radiodensity (paper 1), serum high-density lipoprotein (HDL) metrics (paper 2), and immune/inflammatory biomarkers [serum complement factor 3 (C3) and 4 (C4) and Glycoprotein acetylation (GlycA)] (paper 3) at and/or over midlife with future cognitive performance. Methods: Participants from the Study of Women’s Health Across the Nation (SWAN) cardiovascular fat ancillary study (paper 1, n=531, age: 50.9±2.9 years) with cognitive performance assessed repeatedly after the cardiovascular fat scan (the baseline) over 13.4 years of median follow up and HDL ancillary study (paper 2 and 3, n=503, age: 50.2±2.7 years) with repeated measurements of HDL and immune/inflammatory biomarkers assessed 1.5±1 years before subsequent cognitive measures over 7.7±4.1 years of follow up. We applied mixed models with multiple imputation (paper 1) and joint models (paper 2 and 3). Results: Greater volume and radiodensity of thoracic PVAT, but not of EAT and PAT, at midlife were associated with higher future delayed recall and lower future working memory and delayed recall levels over time, respectively. Greater increases in HDL phospholipid, apolipoprotein A-1, medium HDL particles, and total HDL particles and less increase in HDL size over midlife, instead of their levels at midlife, were associated with higher subsequent immediate and/or delayed recall. Higher serum C4 and lower C3/C4 ratio and GlycA at midlife, instead of their changes over midlife, were associated with higher subsequent immediate recall and/or working memory. Conclusions: Novel cardiovascular biomarkers distinctively associated with future episodic memory immediate and delayed recall in midlife women implicated their special relationship with AD and potential application in AD prevention and treatment at younger age. Share
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