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Issue title: Physiopathology of Vascular Risk Factors in Alzheimer's Disease
Guest editors: Jack de la Torre
Article type: Review Article
Authors: Kennelly, Seana; * | Collins, Orlab
Affiliations: [a] Tallaght Hospital, Department of Medical Gerontology, Trinity College Dublin, Dublin, Ireland | [b] Geriatric Medicine, St. Vincent's University Hospital, Dublin, Ireland
Correspondence: [*] Correspondence to: Sean Kennelly, MB, BCh, PhD, MRCPI, Consultant Physician in Geriatric Medicine, Tallaght Hospital, Department of Medical Gerontology, Trinity College Dublin, Dublin, Ireland. Tel.: +353 877997278; Fax: +353 14143244; E-mail: skennelly1976@hotmail.com.
Abstract: Vascular risk factors are implicated in the pathogenesis of Alzheimer's disease (AD). There is an age-dependent relationship between blood pressure and the risk of AD. Given the potential temporal lag that can exist between the two conditions, longitudinal population studies offer the best opportunity to identify a causal relationship. Midlife hypertension increases the risk for AD, yet later-life hypertension does not appear to confer the same risk and may in fact be protective. Low diastolic blood pressure, especially in later-life, is associated with an increased risk of AD. Orthostatic hypotension and other neurocardiovascular syndromes may increase the risk for cognitive impairment and AD. Several physiopathological mechanisms may contribute to this increased risk. Dynamic blood pressure changes and impaired cerebrovascular autoregulation may result in cerebral hypoperfusion. Hypertensive patients also develop cerebral infarcts, resulting in diminished perfusion. Subsequent hypoxia driven pathways result in increased cerebral amyloid-β and phosphorylated tau protein accumulation. Treatment of elevated blood pressure with antihypertensive medications attenuates the risk of AD attributable to elevated midlife hypertension. Certain antihypertensive compounds have neuroprotective properties that may reduce the risk of AD, independent of their effects on blood pressure.
Keywords: Alzheimer's disease, amyloid, antihypertensive, dementia, hypertension, hypotension, orthostatic hypotension
DOI: 10.3233/JAD-2012-120748
Journal: Journal of Alzheimer's Disease, vol. 32, no. 3, pp. 609-621, 2012
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