Brain arteriolosclerosis (B-ASC), characterized by pathologic arteriolar wall thickening, is a common finding at autopsy in aged persons and is associated with cognitive impairment. Hypertension and diabetes are widely recognized as risk factors for B-ASC. Recent research indicates other and more complex risk factors and pathogenetic mechanisms. Here, we describe aspects of the unique architecture of brain arterioles, histomorphologic features of B-ASC, relevant neuroimaging findings, epidemiology and association with aging, established genetic risk factors, and the co-occurrence of B-ASC with other neuropathologic conditions such as Alzheimer's disease and limbic-predominant age-related TDP-43 encephalopathy (LATE). There may also be complex physiologic interactions between metabolic syndrome (e.g., hypertension and inflammation) and brain arteriolar pathology. Although there is no universally applied diagnostic methodology, several classification schemes and neuroimaging techniques are used to diagnose and categorize cerebral small vessel disease pathologies that include B-ASC, microinfarcts, microbleeds, lacunar infarcts, and cerebral amyloid angiopathy (CAA). In clinical-pathologic studies that factored in comorbid diseases, B-ASC was independently associated with impairments of global cognition, episodic memory, working memory, and perceptual speed, and has been linked to autonomic dysfunction and motor symptoms including parkinsonism. We conclude by discussing critical knowledge gaps related to B-ASC and suggest that there are probably subcategories of B-ASC that differ in pathogenesis. Observed in over 80% of autopsied individuals beyond 80 years of age, B-ASC is a complex and under-studied contributor to neurologic disability.
Bibliographical noteFunding Information:
We are very grateful to the research volunteers, their families, and clinicians, as well as the other researchers who made this work possible. This study was also supported by California Dept of Public Health Grant A20-2947-5001 and NIH Grants P30 AG028383, R01 AG057187, R01 AG039621, R01 AG055449, K24 AG053435, R56 AG057191, R01 HD064993, U54 NS100717, U01 AG016976, RF1 NS118584, and S10 OD023573. Additional support came from Medical Research Council (MRC, G0500247) and previous Newcastle Centre for Brain Ageing and Vitality (BBSRC, EPSRC, ESRC and MRC, LLHW), and Alzheimer’s Research (ARUK). The Newcastle Brain Tissue Resource is funded in part by a grant from the UK MRC (G0400074), by the Newcastle NIHR Biomedical Research Centre in Ageing and Age Related Diseases award to the Newcastle upon Tyne Hospitals NHS Foundation Trust, and by a grant from the Alzheimer’s Society and ARUK as part of the Brains for Dementia Research Project. See Supplemental Acknowledgement for additional acknowledgments.
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