Association of long-term exposure to lower low-density lipoprotein cholesterol with neuroimaging metrics: A population-based cohort study

BACKGROUND: Limited evidence exists regarding the relationship between long-term exposure to low concentrations of low-density lipoprotein cholesterol (LDL-C) and brain structural integrity. This study aimed to examine the associations of cumulative low LDL-C exposure with a series of neuroimaging metrics. METHODS: This study included 987 participants (median age 55 years) from a population-based cohort study in China. Serum circulatory LDL-C concentrations were assessed biennially from 2006 to 2018. Prolonged LDL-C exposure was calculated using a time-weighted average (TWA) approach during that period. Brain MRI examinations were performed during 2020-2022. We used generalized linear model to investigate the multivariate-adjusted associations of TWA LDL-C levels with MRI markers of brain tissue volume, white matter microstructural integrity, and white matter hyperintensity (WMH). RESULTS: After full adjustments, TWA LDL-C concentrations of 70-100 mg/dL and less than 70 mg/dL were associated with lower fractional anisotropy value and higher mean diffusivity, axial diffusivity, and radial diffusivity value compared to LDL-C concentrations of 100-130 mg/dL. These associations were particularly prominent in male participants and older participants who were over 50 years. No association was found between relatively lower LDL-C levels and brain tissue volumes or WMH. CONCLUSION: LDL-C concentrations of 70-100 mg/dL and <70 mg/dL are associated with impaired microstructural integrity of brain white matter. TRIAL REGISTRATION: https://clinicaltrials.gov/, NCT05453877.