Cholesterol Levels, Hormone Replacement Therapy, and Incident Dementia among Older Adult Women

Previous studies revealed that hormone replacement therapy (HRT) probably has a protective effect for preventing dementia in post-menopausal women. However, the results were still controversial. The association between cholesterol levels and incident dementia in older women is not fully understood either. We conducted a retrospective analysis on a cohort of non-demented women aged older than 50 years, which was registered in the History-based Artificial Intelligence Clinical Dementia Diagnostic System database from September 2015 to August 2021. We followed this cohort longitudinally to examine the rates of conversion to dementia. Using a Cox regression model, we investigated the impact of the quartile of total cholesterol (TC) levels on incident dementia, adjusting for age, sex, education, neuropsychiatric symptoms, neuropsychological assessments, HRT, as well as various vascular risk factors and medications. We examined a cohort of 787 participants, comprising 539 (68.5%) individuals who did not develop dementia (non-converters). Among these non-converters, 68 individuals (12.6%) were treated with HRT. By contrast, there were 248 (31.5%) who did develop dementia (converters). Among the converters, 28 individuals (11.3%) were treated with HRT. The average follow-up durations were 2.9 ± 1.5 and 3.3 ± 1.6 years for non-converters and converters, respectively. Compared to the lowest quartile of TC levels (<153), the hazard ratios (HR) for converting to dementia were 0.61, 0.58, and 0.58 for the second (153-176), third (177-201), and highest (>201) quartiles, respectively (all p < 0.05). However, the low-density lipoprotein cholesterol (LDL-C) level and HRT did not alter the rate of conversion to dementia. In conclusion, the lowest quartile of TC increased incident dementia in post-menopausal women without dementia; however, HRT did not contribute to conversion to dementia. Some studies suggest that post-menopausal women who have reduced estrogen levels might have an increased risk of Alzheimer's disease if they also have high cholesterol. Nonetheless, the evidence is inconclusive, as not all studies support this finding. The "Lower LDL-C is better" strategy for preventing cardiac vascular disease should be re-examined for the possible serial adverse effects of new onset dementia due to very low cholesterol levels.