Cerebral autoregulation, beta amyloid, and white matter hyperintensities are interrelated

Abstract

Emerging studies link vascular risk factors and cerebrovascular health to the prevalence and rates of progression in Alzheimer’s disease (AD). The brain’s ability to maintain constant blood flow across a range of cerebral perfusion pressures, or autoregulation, may both promote and result from small vessel cerebrovascular disease and AD-related amyloid pathology. Here, we examined the relationship among cerebral autoregulation, small vessel cerebrovascular disease, and amyloid deposition in 14 non-demented older adults. Reduced cerebral autoregulation, was associated with increased amyloid deposition and increased white matter hyperintensity volume, which, in turn were positively associated with each other. For the first time in humans, we demonstrate an interrelationship among AD pathology, small vessel cerebrovascular disease, and cerebral autoregulation. Vascular factors and AD pathology are not independent but rather appear to interact.

Clinically silent Alzheimer's and vascular pathologies influence brain networks supporting executive function in healthy older adults

“…Increasing evidence suggests that amyloid accrual and WMHs become linked over time and exacerbate each other (Brickman et al, 2015; Scott et al, 2016). For example, amyloid accrual within blood vessels (i.e.…”

White Matter Hyperintensity Volume and Cerebral Perfusion in Older Individuals with Hypertension Using Arterial Spin-Labeling

“…9,13,14 Finally, as a more general limitation, WMH volume may be linked to impaired autoregulation. 47,48 Because in MR imaging, CBF is measured with the patient in the supine position, in patients with impaired cerebral autoregulation, regional CBF differences that occur while the patient is upright may be obscured. Future studies using arterial spin-labeling to compare WMHs, NAWM, and GM CBF may benefit from new developments that increase signal-to-noise ratios and spatial resolution.…”

A Clinicopathological Investigation of White Matter Hyperintensities and Alzheimer’s Disease Neuropathology

“…WMH refer to regions in the white matter that appear hyperintense on T2 fluid attenuated inversion recovery (FLAIR) sequences. The etiologies of WMH are multifaceted (e.g., gliosis, axonal loss) [9–15], but WMH accompany aging and cardiovascular disease and are often presumed to be of vascular origin and reflect small vessel cerebrovascular disease (CBVD) [9,16–21]. International consensus-based guidelines emphasize the pathologies underlying WMH (along with cerebral amyloid angiopathy [CAA], microbleeds, microinfarcts, among others) as mechanisms of vascular cognitive impairment (VCI) [22].…”

“…A recent study proposed that the underlying pathologies of WMH are a core feature of AD, based on findings that participants with autosomal-dominant AD had increased burden of WMH long before clinical symptom onset and WMH predicted CSF beta-amyloid levels in mutation carriers only [30]. WMH have been shown to predict increased CSF total tau and progressive medial temporal lobe atrophy in AD [31,32], as well as PET cortical amyloid uptake in older adults [16,33] and individuals with AD dementia [34], even more so than traditional AD neuroimaging and cognitive biomarkers [33]. The spatial distribution of WMH in AD has also been shown to be distinct from that found in “normal aging” [35–39], suggesting that WMH may have some degree of specificity to AD.…”