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

Abstract

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.

White Matter Hyperintensity Associations with Cerebral Blood Flow in Elderly Subjects Stratified by Cerebrovascular Risk

“…The strongest and most consistent associations with WMH are age and certain cerebrovascular risk factors including diabetes, hypertension, hypercholesterolemia, and cigarette smoking[8, 9, 19–26]. These factors are included in vascular risk measures such as the Framingham score used in this study.…”

Cumulative systolic blood pressure exposure in relation to cognitive function in middle-aged and elderly adults

“…[23,24] Studies have found that systemic hypertension related to accrual of white matter hyperintensity and functional decline. [25,26] …”

Is biological aging accelerated in drug addiction?

“…Brain volume loss encompasses the loss of neurons, synapses, neurotransmitters and receptors, especially in the neocortex, basal forebrain nuclei and brainstem monoaminergic systems. Both brain small vessels [48] and carotid arteries [49] show decrease in lumen diameter with age. Other microscopic changes with senescence include the accumulation of lipofuscin (a pigmented lipid composed of lysosomal digestion), and the proteins hyperphosphorilated tau and beta-amyloid in the form of neurofibrillary tangles and senile plaques [50].…”