Sex-specific associations between serum lipid levels and cognitive performance in older adults: results from a cross-sectional real-world study

Aim: Dyslipidemia and cognitive decline are prevalent in older adults, with their incidence increasing with age. However, the relationship between serum lipid levels and cognitive dysfunction in geriatrics remains unclear, potentially influenced by sex differences. Methods: This study evaluated serum lipid levels and cognitive functions in older adults using a large battery of neuropsychological tests. Dementia was staged with the Clinical Dementia Rating (CDR), classifying participants as cognitively healthy (CDR 0), mildly impaired (CDR 0.5), or with dementia (CDR ≥ 1). Results: The study involved 1283 participants aged over 65 (466 men, 817 women; mean age 79.79 ± 5.93 years). Women had lower education levels, reduced autonomy in activities of daily living (ADL), but greater independence in instrumental ADL. Additionally, women exhibited lower glucose but higher levels of total cholesterol (TC), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) compared to men. Subjects with CDR ≥ 1 had significantly poorer cognitive scores than those with CDR 0 or 0.5. No associations were found between lipid levels and cognition in the CDR 0 group. In men with CDR 0, HDL-C positively correlated with ACE-R Fluency. In the CDR 0.5 group, TC and HDL-C were linked to better cognitive performance. For CDR ≥ 1, TC and HDL-C were associated with improved cognition in women but linked to cognitive decline in men. Conclusion: Elevated late-life cholesterol may protect cognitive function in healthy individuals and those with mild impairment, with a sex-specific impact in dementia, beneficial for women but detrimental for men.