Higher HDL-C Improves Midlife and Future Cognition in Women

Improved serum high-density lipoprotein (HDL) metrics during midlife are associated with enhanced memory and cognitive functions among women, according to study findings published in The Journal of Clinical Endocrinology & Metabolism.

After middle age, women experience faster cognitive decline than men, possibly due to high levels of HDL cholesterol. However, evidence on the association between cognitive performance and HDL among women is limited.

In this prospective cohort study, researchers evaluated the associations between serum HDL metrics, including lipid content and cholesterol efflux capacity (HDL-CEC), and cognitive performance among middle-aged women.

The study enrolled 503 middle-aged women, who had at least 2 pairs of a previous HDL diagnosis and a subsequent cognitive measure from the Study of Women’s Health Across the Nation (SWAN) HDL ancillary study. SWAN is an ongoing, multiracial, longitudinal study examining the physical, biological, and psychological changes that occur during the menopausal transition and how they affect health.

The researchers measured serum HDL metrics, including:

• HDL lipid contents such as HDL-C, HDL phospholipids (HDL-PL), and HDL-triglycerides;
• Protein and subclasses such as apolipoprotein A-1 (apoA-1);
• Small, medium, and large HDL particles (HDL-P); and,
• HDL-CEC.

The researchers conducted the first cognitive test after the initial HDL measurement. They also evaluated working memory and delayed recall using the East Boston Memory Test, the Digit Span Backward Test, and the Symbol Digit Modalities Test. For the current analysis, baseline was defined as the time of the first HDL measurement at middle age. The mean (SD) time difference between pairs of HDL diagnosis and subsequent cognitive measure was 1.46 (0.95) years.

The participants, of whom a majority (76.14%) were in pre- or early perimenopause, had a mean (SD) age of 50.17 years, BMI of 27.98 (6.43) kg/m², and baseline HDL-C of 59.65 (14.37) mg/dL.

Each increase in HDL-PL and apoA-1 over middle age was associated with a 0.08-unit improvement in subsequent immediate recall. Increases in medium HDL and total HDL per SD were associated with higher immediate recall scores by 0.09 and 0.11 units, respectively, and higher delayed recall scores by 0.07 and 0.08 units, respectively. On the other hand, a minor increase in HDL-CEC was associated with greater gains in both immediate (0.11 units) and delayed (0.13 units) recall.

Higher total HDL-P concentration and smaller HDL-P size at midlife were associated with better subsequent performance in immediate recall, delayed recall, and processing speed.

Additionally, greater increases in HDL-PL, apoA-1, medium HDL particles, and total HDL particles, along with smaller increases in HDL size, were associated with improved immediate and delayed recall over time.

Study limitations include the absence of APOE genotype data, unmeasured confounders such as parity and pregnancy history, and lack of adjustment for multiple comparisons.

The study authors concluded, ” Enhancing specific serum HDL metrics during midlife could be promising in cognitive restoration, particularly memory, the initial and predominant symptom of Alzheimer’s disease.”

This article originally appeared on Endocrinology Advisor