Associations of dietary cholesterol and fat, blood lipids, and risk for dementia in older women vary by APOE genotype

Abstract

Introduction: Whether apolipoprotein E's (APOE's) involvement in lipid metabolism contributes to Alzheimer's disease (AD) risk remains unknown.

Methods: Incident probable dementia and cognitive impairment (probable dementia+mild cognitive impairment) were analyzed in relation to baseline serum lipids (total, low-density lipoprotein [LDL], high-density lipoprotein [HDL], non-HDL cholesterol, total-to-HDL, LDL-to-HDL, remnant cholesterol, and triglycerides) using Mendelian randomization in 5358 postmenopausal women from the Women's Health Initiative Memory Study. We also examined associations of baseline dietary cholesterol and fat with lipids based on APOE status.

Results: After an average of 11.13 years, less favorable lipid levels related to greater dementia and cognitive impairment risk. Dementia (odds ratio [OR] = 3.13; 95% confidence interval [CI]: 2.31 to 4.24) and cognitive impairment (OR = 2.38; 95% CI: 1.85 to 3.06) risk were greatest in relation to higher remnant cholesterol levels. Greater cholesterol consumption related to poorer lipids in APOE4+ compared to APOE3 carriers.

Discussion: APOE4+ carriers consuming more cholesterol had less favorable lipids, which were associated with greater dementia and cognitive impairment risk.

Highlights: Less favorable serum lipids were associated with higher dementia incidence. Mendelian randomization findings suggest causality between lipids and dementia. Lipid levels in older women may be clinical indicators of dementia risk. APOE4 carriers had poorest lipid profiles in relation to cholesterol consumption. APOE risk for dementia may be modifiable through lipid management.

Keywords: Alzheimer's disease; Mendelian randomization; apolipoprotein E; cholesterol; dementia; diet; mild cognitive impairment; women's health initiative memory study.

Figure 1.. APOE Significantly Modifies the Relationships Between Diet and Lipids.

Greater consumption of dietary cholesterol was associated with greater higher LDL, non-HDL, LDL-to-HDL, and total-to-HDL cholesterol levels in APOE4+ compared to APOE3 carriers. Greater consumption of monounsaturated fat and trans fat were associated with higher and lower HDL cholesterol levels, respectively, in APOE2+ compared to APOE3 carriers. SI conversion factor: To convert cholesterol levels to mmol/L, multiply values by 0.0259. To convert triglyceride levels to mmol/L, multiply values by 0.0113. Abbreviations: HDL = high-density lipoprotein; LDL = low-density lipoprotein.