Ira Driscoll

INTRODUCTION Apolipoprotein E4 ( APOE 4) carriers’ tendency toward hypercholesterolemia may contribute to Alzheimer's disease (AD) risk through oxysterols, which traverse the blood‐brain barrier. METHODS Relationships between baseline plasma oxysterols, APOE status, serum lipids, and cognitive impairment risk were examined in 328 postmenopausal women from the Women's Health Initiative Memory Study. Women were followed for 25 years or until incident dementia or cognitive impairment. RESULTS Levels of 24(S)‐hydroxycholesterol (24‐OHC), 27‐hydroxycholesterol (27‐OHC), and 24‐OHC/27‐OHC ratio did not differ by APOE status ( p ’s > 0.05). Higher 24‐OHC and 27‐OHC were associated with higher total, low density lipoprotein (LDL), non‐high density lipoprotein (HDL), remnant, LDL/HDL, and total/HDL cholesterol and triglycerides ( p ’s < 0.05). Higher 24‐OHC/27‐OHC was associated with greater dementia risk (hazard ratio = 1.51, 95% confidence interval:1.02‐2.22), which interaction analyses revealed as significant for APOE 3 and APOE 4+, but not APOE 2+ carriers. DISCUSSION Less favorable lipid profiles were associated with higher oxysterol levels. A higher ratio of 24‐OHC/27‐OHC may contribute to dementia risk in APOE 3 and APOE 4+ carriers.