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Background/Aims: This study investigated the relation of midlife blood pressure, total cholesterol, body mass index (BMI), their changes over time, apolipoprotein E, and white matter lesions (WML). Methods: Participants of the Cardiovascular Risk Factors, Aging and Incidence of Dementia study were derived from random, population-based samples previously surveyed in 1972, 1977, 1982 or 1987. In 1998, 1,449 (73%) individuals aged 65–79 years were re-examined (average follow-up 21 years). A subpopulation (n = 112) was scanned with a 1.5-tesla MRI scanner in 1998, and WML were assessed from fluid-attenuated inversion recovery images using a semi-quantitative visual rating scale. Results: Risk of late-life WML was related to midlife overweight (relative risk = 2.53; 95% CI = 1.70–2.89), obesity (2.94; 2.44–3.03), and hypertension (2.73; 1.81–3.08), even after adjustments for several confounding factors. Elevated BMI (>25) (2.26; 1.42–2.62) and hypertension (3.14; 1.83–3.40) from midlife to late life also increased the risk of WML. In addition, an association with WML was seen for decreasing blood pressure (hypertension at midlife but not at late life) (3.25; 2.46–3.41), even after controlling for antihypertensive treatment. Lipid-lowering drugs had a protective effect against WML (0.13; 0.02–0.59). Conclusions: These results indicate that early and sustained vascular risk factor control is associated with a lower likelihood of having more severe WML in late life.

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