Riya Manchanda1, Xinrui Shi2, Adlin Pinheiro3, Serkalem Demissie3, Hugo Javier Aparicio4, Vasileios-Arsenios Lioutas5, Oluchi Ekenze6, Alexa Beiser6, Charles DeCarli7, Sudha Seshadri8, Qiong Yang3, Shariq Mohammed2, Jose Romero6
1Boston University Chobanian & Avedisian School of Medicine, 2Boston University School of Medicine, 3Boston University School of Public Health, 4Boston University, 5Beth Israel Deaconess Medical Center, Department of Neurology, 6Boston University School of Medicine - Boston Medical Center, 7University of California at Davis, 8Glenn Biggs Institute for Alzheimer'S and Neurodegenerative Diseases
Objective:
Analyze the relationship between lifetime lipid patterns and dementia among healthy, community-dwelling individuals and examine differences by sex and APOE4 status.
Background:
Dyslipidemia—characterized by abnormal levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), and triglycerides (TRIG)—is known to contribute to cardiovascular disease, and could play a role in neurological outcomes, though research remains inconsistent. Prior studies have relied on short-term lipid measurements when long-term trends may better elucidate cumulative metabolic exposure and its relationship to dementia risk. Also, examining stratified differences by sex and APOE4 carrier status could help identify population-specific patterns.
Design/Methods:
Functional principal component analysis (FPCA) was applied to model trajectories of the four lipid measures before age 60, followed by k-means clustering based on major FPCA scores. In stratified analyses, clusters were derived separately within each stratum. Associations were examined using Cox proportional hazards models, adjusting for age and cohort.
Results:
Among 15,623 participants (47% male; mean baseline age 62 years; 1680 dementia cases), two distinct trajectory clusters were identified for HDL (n=2992), LDL (n=2945), TC (n=6688), and TRIG (n=2998). The lower-risk trajectory served as the reference group. Although higher-risk trajectories showed increased risk of dementia for all lipids, only TC demonstrated a significant correlation. In sex-stratified analyses (mean baseline age: 62.4 for men; 62.5 for women; mean follow-up: 4322 and 4848 days), no significant associations were observed; however, higher TRIG levels were associated with numerically lower dementia risk in men but higher risk in women. This opposing pattern continued when stratified by APOE4 allele. Notably, in women without APOE4, HDL (HR: 1.87, 95%CI: 1.05–3.34) and TRIG (HR: 1.82, 95%CI: 1.05–3.18) were associated with elevated dementia risk.
Conclusions:
Lifetime lipid trajectories may influence dementia risk, with variation by sex and APOE4 status. These findings highlight the importance of considering long-term lipid dynamics and population differences for dementia prevention.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.