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Antihypertensive medications ameliorate Alzheimer's disease pathology by slowing its propagation.

ABSTRACT: Introduction:Mounting evidence supports an association between antihypertensive medication use and reduced risk of Alzheimer's disease (AD). Consensus on possible pathological mechanisms remains elusive. Methods:Human brain tissue from a cohort followed to autopsy that included 96 cases of AD (46 medicated for hypertension) and 53 pathological controls (33 also medicated) matched for cerebrovascular disease was available from the New South Wales Brain Banks. Quantified frontal cortex amyloid beta (A?) and tau proteins plus Alzheimer's neuropathologic change scores were analyzed. Results:Univariate analyses found no difference in amounts of AD proteins in the frontal cortex between medication users, but multivariate analyses showed that antihypertensive medication use was associated with a less extensive spread of AD proteins throughout the brain. Discussion:The heterogeneous nature of the antihypertensive medications is consistent with downstream beneficial effects of blood pressure lowering and/or management being associated with the reduced spreading of AD pathology observed.

SUBMITTER: Affleck AJ

PROVIDER: S-EPMC7424255 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Antihypertensive medications ameliorate Alzheimer's disease pathology by slowing its propagation.

Affleck Andrew J AJ Sachdev Perminder S PS Stevens Julia J Halliday Glenda M GM

Alzheimer's & dementia (New York, N. Y.) 20200813 1

<h4>Introduction</h4>Mounting evidence supports an association between antihypertensive medication use and reduced risk of Alzheimer's disease (AD). Consensus on possible pathological mechanisms remains elusive.<h4>Methods</h4>Human brain tissue from a cohort followed to autopsy that included 96 cases of AD (46 medicated for hypertension) and 53 pathological controls (33 also medicated) matched for cerebrovascular disease was available from the New South Wales Brain Banks. Quantified frontal cor ...[more]

PMID: 32802934

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Project description:BackgroundDementia is a major health concern for which prevention and treatment strategies remain elusive. Lowering high blood pressure with specific antihypertensive medications (AHMs) could reduce the burden of disease. We investigated whether specific AHM classes reduced the risk for dementia.MethodsWe did a meta-analysis of individual participant data from eligible observational studies published between Jan 1, 1980, and Jan 1, 2019. Cohorts were eligible for inclusion if they prospectively recruited community-dwelling adults; included more than 2000 participants; collected data for dementia events over at least 5 years; had measured blood pressure and verified use of AHMs; included in-person exams, supplemented with additional data, to capture dementia events; and had followed up cases for mortality. We assessed the association of incident dementia and clinical Alzheimer's disease with use of five AHM classes, within strata of baseline high (systolic blood pressure [SBP] ≥140 mm Hg or diastolic blood pressure [DBP] ≥90 mm Hg) and normal (SBP <140 mm Hg and DBP <90 mm Hg) blood pressure. We used a propensity score to control for confounding factors related to the probability of receiving AHM. Study-specific effect estimates were pooled using random-effects meta-analyses.ResultsSix prospective community-based studies (n=31 090 well phenotyped dementia-free adults older than 55 years) with median follow-ups across cohorts of 7-22 years were eligible for analysis. There were 3728 incident cases of dementia and 1741 incident Alzheimer's disease diagnoses. In the high blood pressure stratum (n=15 537), those using any AHM had a reduced risk for developing dementia (hazard ratio [HR] 0·88, 95% CI 0·79-0·98; p=0·019) and Alzheimer's disease (HR 0·84, 0·73-0·97; p=0·021) compared with those not using AHM. We did not find any significant differences between one drug class versus all others on risk of dementia. In the normal blood pressure stratum (n=15 553), there was no association between AHM use and incident dementia or Alzheimer's disease.InterpretationOver a long period of observation, no evidence was found that a specific AHM drug class was more effective than others in lowering risk of dementia. Among people with hypertensive levels of blood pressure, use of any AHM with efficacy to lower blood pressure might reduce the risk for dementia. These findings suggest future clinical guidelines for hypertension management should also consider the beneficial effect of AHM on the risk for dementia.FundingThe Alzheimer's Drug Discovery Foundation and the National Institute on Aging Intramural Research Program.

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Antihypertensive medications ameliorate Alzheimer's disease pathology by slowing its propagation.

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Antihypertensive medications ameliorate Alzheimer's disease pathology by slowing its propagation.

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