This study explored the efficacy of aerobic training (AT) in mitigating white matter hyperintensity (WMH) progression and whether these changes are sex dependent. This was an exploratory analysis of a randomized controlled trial assessing the effect of AT on cognition in people with vascular cognitive impairment. Participants were randomized to a 6 month AT or usual care (control [CON]) group. A subset completed magnetic resonance imaging to quantify WMH volume. Using an analysis of covariance model, we found a significant sex × group interaction (p = .03). Over the 6 month study, AT females demonstrated greater WMH progression than CON females (p = .05). Among males, there was no significant between-group difference (p = .31). Within the AT group, males demonstrated significantly less WMH progression than females (p = .01) at 6 months. Therefore, the effects of AT on WMH progression may vary by sex; that is, AT may curtail WMH progression in males but not females.

Vascular involvement in Alzheimer disease (AD) is not necessarily coincident. Current evidence suggests the neuropathology of Alzheimer type of dementia comprises more than amyloid plaques and neurofibrillary tangles. At least a third of recognized AD cases may exhibit cerebrovascular pathology, which also constitutes distinct small vessel disease. Cerebral amyloid angiopathy, microvascular degeneration affecting the cerebral endothelium and smooth muscle cells, basal lamina alterations, hyalinosis, and fibrosis are frequently evident in AD. These changes may be accompanied by perivascular denervation that is causal in the cognitive decline of AD. In addition, amyloid β protein appears directly involved in the degeneration of both the larger perforating arterial vessels as well as cerebral capillaries, which represent the blood-brain barrier. The cerebrovascular pathology in AD also encompasses macro- and micro-infarctions, hemorrhages, lacunas, and ischemic white-matter changes. An interaction of both perivascular mediators and derived factors would perturb the brain vasculature. Peripheral vascular factors such as long-standing hypertension, atrial fibrillation, coronary or carotid artery disease, and diabetes mellitus are also apparent in AD. These factors would modify the cerebral circulation such that a sustained hypoperfusion or oligemia is impacted upon the aging processes to induce the characteristic pathology.

Understanding of vascular substrates of cognitive decline in the elderly is evoloving to include a major emphasis on the impact of small vessel disease (SVD). While existing concepts of multi-infarct dementia and strategic infarct dementia remain valid, they present difficulty in generalizing clinicopathological correlations from patient to patient. The range and significance of lesions that should be included as manifestations of SVD are unresolved, as is their impact on, and association with, neurodegenerative changes. This mini-review summarizes the authors' views on SVD substrates leading to cognitive decline and proposes priorities for pathological investigations of human cerebrovascular mechanisms leading to cognitive decline.