Variability in Total Cholesterol Concentration Is Associated With the Risk of Dementia: A Nationwide Population-Based Cohort Study

Introduction: Although total cholesterol (TC) variability is suggested as a risk factor for cardiovascular and cerebrovascular disease, there is no previous study to evaluate the association between TC variability and the development of dementia. Methods: Using the Korean National Health Insurance Service-Health Screening Cohort (NHIS-HEALS), the main outcomes were newly diagnosed all-cause dementia, Alzheimer's disease (AD), or vascular dementia (VaD) between January 1, 2008, and December 31, 2015. Visit-to-visit TC variability was measured as variability independent of the mean (TC-VIM), coefficient variance (TC-CV), and standard deviation (TC-SD). Results: In a total of 131,965 Koreans, there were 3,722 all-cause dementia (2.82%), 2,776 AD (2.10%), and 488 VaD (0.37%) during the median follow-up of 8.4 years. Kaplan-Meier curves showed increased cumulative incidences for all in the group of the highest quartiles of TC variability compared to the others. Regression using the Fine and Gray hazards model showed a steadily increasing risk of all-cause dementia with higher quartiles of TC variability. After adjusting for confounders including mean TC level and comparing the highest and lowest TC-VIM quartiles, the hazard ratios (HRs) for all-cause dementia and AD were 1.15 [95% confidence interval (CI) = 1.05-1.27; P = 0.003] and 1.12 (95% CI = 1.00-1.25; P = 0.040), respectively. The incidence of VaD was not significantly higher in the higher-quartile groups compared to that in the lowest-quartile group in TC-VIM variability (HR 1.22; 95% CI = 0.95-1.59; P = 0.122). These associations were consistent with TC variability defined by TC-CV or TC-SD. Conclusions: For the first time, we have demonstrated that a higher visit-to-visit variability in TC independent of mean TC is associated with an increased risk of all-cause dementia and AD in the general population.