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Abstract Details

Lifetime Lipid Trajectories and Dementia in the Framingham Heart Study
Cerebrovascular Disease and Interventional Neurology
S25 - Emerging Stroke Therapies and Risk Stratification (1:48 PM-2:00 PM)
005
Analyze the relationship between lifetime lipid patterns and dementia among healthy, community-dwelling individuals and examine differences by sex and APOE4 status.
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.
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.

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.

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.
Authors/Disclosures
Riya Manchanda
PRESENTER
Miss Manchanda has nothing to disclose.
Ziyan Shi, MD, PhD Dr. Shi has nothing to disclose.
Adlin Pinheiro, MA Ms. Pinheiro has nothing to disclose.
Serkalem Demissie, PhD Prof. Demissie has nothing to disclose.
Hugo Javier Aparicio, MD, MPH (Boston University) Dr. Aparicio has received research support from 好色先生. Dr. Aparicio has received research support from Alzheimer's Association. Dr. Aparicio has received research support from National Institutes of Health. Dr. Aparicio has received personal compensation in the range of $10,000-$49,999 for serving as a expert panelist for the Memory & Healthy Aging Program with Cedars-Sinai.
Vasileios-Arsenios Lioutas, MD (Beth Israel Deaconess Medical Center, Department of Neurology) Dr. Lioutas has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Qmetis. Dr. Lioutas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mindray. The institution of Dr. Lioutas has received research support from NIH. The institution of Dr. Lioutas has received research support from Alzheimer's Association.
Oluchi S. Ekenze Ms. Ekenze has nothing to disclose.
Alexa Beiser Alexa Beiser has nothing to disclose.
Charles S. DeCarli, MD, FAAN (UC Davis Health - Dept of NeurologyAlzheimer's Disease Research Center) Dr. DeCarli has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novo Nordisk. The institution of Dr. DeCarli has received research support from NIH.
Sudha Seshadri, MD, FAAN (Glenn Biggs Institute for Alzheimer'S and Neurodegenerative Diseases) Dr. Seshadri has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Seshadri has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. The institution of Dr. Seshadri has received research support from NIH. The institution of Dr. Seshadri has received research support from Alzheimer Association.
Qiong Yang Qiong Yang has nothing to disclose.
Shariq Mohammed, PhD The institution of Dr. Mohammed has received research support from NIH, Sharecare.
Jose R. Romero, MD (Boston University School of Medicine - Boston Medical Center) The institution of Dr. Romero has received research support from NIH/NIA.