Cardiovascular risk factors and small vessel disease of the brain: Blood pressure, white matter lesions, and functional decline in older persons

Several potential vascular risk factors exist for the development and accumulation of subcortical white matter disease in older people. We have reported that in older people followed for up to 4 years white matter hyperintensity (WMH) lesions on magnetic resonance imaging nearly doubled in volume and were associated with alterations in mobility and cognitive function. Herein we review the genetic, metabolic, and vascular risk factors that have been evaluated in association with the development and pathogenesis of WMH in older persons. Our research efforts have focused on systemic hypertension, particularly in the out-of-office setting as 24-hour ambulatory blood pressure (BP) has proven to be a stronger indicator of the progression of WMH in older people and the associated functional decline than doctor's office BP. Based on relations between 24-hour systolic BP levels, the accrual of WMH, and functional decline, we have designed the INFINITY trial, the first interventional study to use ambulatory BP to guide antihypertensive therapy to address this problem in the geriatric population.