Contemplating Alzheimer’s Disease and the Contribution of White Matter Hyperintensities
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As the older adult segment of the population increases, Alzheimer’s disease (AD) has emerged as a significant public health epidemic. Over the past 3 decades, advances in the understanding of the biology of AD have led to a somewhat unified hypothesis of disease pathogenesis that emphasizes the precipitating role of beta amyloid protein. However, several lines of evidence suggest that multiple pathologies are necessary for clinical manifestation of the disease. Our focus over the past several years has been on the contribution of small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMH) on magnetic resonance imaging, to AD. White matter hyperintensity volume, particularly in parietal regions, is elevated among individuals with and at risk for AD, predicts future diagnosis of AD, predicts the rate of progression of cognitive symptoms among individuals with AD, and increases over time among individuals destined to develop AD. White matter hyperintensities may represent an independent source of impairment and/or may interact more fundamentally with “primary” AD pathology. Future work should focus on more inclusive models of that better define “normal” vs “pathological” aging.
KeywordsAlzheimer’s disease White matter hyperintensities Cerebrovascular disease
Work presented here was supported in part by grants from the National Institutes of Health (AG034189, AG037212, AG028786, AG029949, AG024708), Alzheimer’s Association, Mary E. Groff Surgical Medical Research and Education Charitable Trust, and Columbia University.
Compliance with Ethics Guidelines
Conflict of Interest
Adam M. Brickman has received travel/accommodations expenses covered or reimbursed from the International Neuropsychological Society (as a board member) and the Alzheimer's Association.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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