Cardiovascular risk factors have been increasingly recognized as targets for reducing dementia in late-life, especially late-onset Alzheimer’s disease (AD).
One common modifiable cardiovascular risk factor is dyslipidemia, which affects more than half of US adults.
Some epidemiological studies have reported that midlife high total serum cholesterol (TC) is associated with greater risk of late-onset AD, but the evidence is mixed. A 2017 meta-analysis using data from cohort studies on the association between serum cholesterol and risk of late-life cognitive decline detected significant gaps in the literature, including insufficient data to examine cholesterol subfractions (e.g., high-density lipoprotein cholesterol (HDL-C), non-HDL-C), sex differences, and apolipoprotein E (APOE) interactions. Moreover, studies evaluating midlife cholesterol lacked clear information on age of cholesterol exposure. To address some of these gaps, we evaluated extensive longitudinal clinical data from a prospective cohort with research-quality case ascertainment to determine associations between cholesterol levels at specific ages and subsequent AD risk. We hypothesized that serum cholesterol levels (HDL-C, non-HDL-C) would be associated with subsequent AD risk. Specifically, we hypothesized that higher non-HDL-C levels in individuals in the 50s to 70s would be associated with higher AD risk and that higher HDL-C levels would be associated with lower AD risk.
Conclusion: People with low (120 mg/dL) and high (210 mg/dL) non-HDL-C levels during their 60s and 70s had modestly higher risk of AD than those with intermediate (160 mg/dL) levels. The extreme age bands (50s and 80s) had small sample sizes.