Hypertension & dementia: pathophysiology & potential utility of antihypertensives in reducing disease burden

Lyon, M., Fullerton, J. L. , Kennedy, S. and Work, L. M. (2023) Hypertension & dementia: pathophysiology & potential utility of antihypertensives in reducing disease burden. Pharmacology and Therapeutics, (doi: 10.1016/j.pharmthera.2023.108575) (PMID:38052309) (In Press)

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Dementia is a common cause of disability and dependency among the elderly due to its progressive neurodegenerative nature. As there is currently no curative therapy, it is of major importance to identify new ways to reduce its prevalence. Hypertension is recognised as a modifiable risk factor for dementia, particularly for the two most common subtypes; vascular dementia (VaD) and Alzheimer's disease (AD). From the current literature, identified through a comprehensive literature search of PubMed and Cochrane Library, this review aims to establish the stage in adulthood when hypertension becomes a risk for cognitive decline and dementia, and whether antihypertensive treatment is effective as a preventative therapy. Observational studies generally found hypertension in mid-life (age 45-64) to be correlated with an increased risk of cognitive decline and dementia incidence, including both VaD and AD. Hypertension manifesting in late life (age ≥ 65) was demonstrated to be less of a risk, to the extent that incidences of high blood pressure (BP) in the very elderly (age ≥ 75) may even be related to reduced incidence of dementias. Despite the evidence linking hypertension to dementia, there were conflicting findings as to whether the use of antihypertensives was beneficial for its prevention and this conflicting evidence and inconsistent results could be due to the methodological differences between the reviewed observational and randomised controlled trials. Furthermore, dihydropyridine calcium channel blockers and potassium-sparing diuretics were proposed to have neuroprotective properties in addition to BP lowering. Overall, if antihypertensives are confirmed to be beneficial by larger-scale homogenous trials with longer follow-up durations, treatment of hypertension, particularly in mid-life, could be an effective strategy to considerably lower the prevalence of dementia. Furthermore, greater clarification of the neuroprotective properties that some antihypertensives possess will allow for better clinical practice guidance on the choice of antihypertensive class for both BP lowering and dementia prevention.

Item Type:Articles
Additional Information:This work was supported by the Chief Scientific Office [Project grant TCS/18/13] (LMW). JLF is currently supported by the British Heart Foundation [Project grant PG/21/10559].
Keywords:Alzheimer’s disease, anti-hypertensives, dementia, hypertension, stroke, vascular dementia.
Status:In Press
Glasgow Author(s) Enlighten ID:Work, Dr Lorraine and Fullerton, Dr Josie and Kennedy, Professor Simon
Authors: Lyon, M., Fullerton, J. L., Kennedy, S., and Work, L. M.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Pharmacology and Therapeutics
ISSN (Online):1879-016X
Published Online:03 December 2023
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in Pharmacology and Therapeutics 2023
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303006Extracellular vesicle mediated microRNA delivery as a therapeutic for ischaemic strokeLorraine WorkOffice of the Chief Scientific Adviser (CSO)TCS/18/13SCMH - Cardiovascular & Metabolic Health
308034Cardiac-targeted exosome-mediated delivery of angiotensin-(1-7) to treat cardiac diseaseStuart NicklinBritish Heart Foundation (BHF)PG/21/10559SCMH - Cardiovascular & Metabolic Health