Inverse Relationship between Apolipoprotein A-I and Cerebral White Matter Lesions: A Cross-Sectional Study in Middle-Aged and Elderly Subjects

BACKGROUND: Apolipoprotein A-I (apoA-I), the major protein for high density lipoprotein, is essential for reverse cholesterol transport. Decreased serum levels of apoA-I have been reported to correlate with subcortical infarction and dementia, both of which are highly related to white matter lesions (WMLs). However, the association between apoA-I and WMLs has never been investigated. In this study, we sought to investigate the association between apoA-I and the presence of WMLs in middle-aged and elderly subjects. METHODS: Consecutive patients aged 50 years and older of our department were prospectively enrolled in this study (n = 1282, 606 men and 676 women, 65.9±9.4 years). All participants underwent MRI scans to assess the presence and severity of WMLs. Multivariate logistic regression analyses were performed to examine the association of apoA-I with WMLs. RESULTS: Patients with WMLs were older and showed significantly higher proportion of male sex, hypertension, diabetes mellitus, previous stroke, and coronary heart disease whereas levels of total cholesterol, high density lipoprotein cholesterol, and apoA-I were lower. After adjustment for potential confounders, the lowest apoA-I quartile was independently associated with an increased risk of WMLs (odds ratio: 1.87, 95% confidence interval: 1.29–2.72). In sex-specific analyses, this relationship was observed only in women. CONCLUSIONS: Our findings demonstrated that apoA-I was inversely associated with the presence of WMLs in middle-aged and elderly subjects. This results suggest that therapies which increase apoA-I concentration may be beneficial to reduce the risk of WMLs, dementia and stroke.