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. 2022 Nov;18(11):2308-2326.
doi: 10.1002/alz.12707. Epub 2022 Jun 27.

Hypertension and Alzheimer's disease pathology at autopsy: A systematic review

Herrer Abdulrahman  1   2 , Jan Willem van Dalen  1   2 , Melina den Brok  1   2 , Caitlin S Latimer  3 , Eric B Larson  4 , Edo Richard  2   5
Affiliations

Hypertension and Alzheimer's disease pathology at autopsy: A systematic review

Herrer Abdulrahman et al. Alzheimers Dement. 2022 Nov.

Abstract

Hypertension is an important risk factor for Alzheimer's disease (AD) and all-cause dementia. The mechanisms underlying this association are unclear. Hypertension may be associated with AD neuropathological changes (ADNC), but reports are sparse and inconsistent. This systematic review included 15 autopsy studies (n = 5879) from observational cohorts. Studies were highly heterogeneous regarding populations, follow-up duration, hypertension operationalization, neuropathological methods, and statistical analyses. Hypertension seems associated with higher plaque and tangle burden, but results are inconsistent. Four studies (n = 3993/5879; 68%), reported clear associations between hypertension and ADNC. Another four suggested that antihypertensive medication may protect against ADNC. Larger studies with longer follow-up reported the strongest relationships. Our findings suggest a positive association between hypertension and ADNC, but effects may be modest, and possibly attenuate with higher hypertension age and antihypertensive medication use. Investigating interactions among plaques, tangles, cerebrovascular pathology, and dementia may be key in better understanding hypertension's role in dementia development.

Keywords: Alzheimer's disease; blood pressure; hypertension; neuritic plaques; neurofibrillary tangles; neuropathology; systematic review.

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Conflict of interest statement

The authors have no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Preferred Reporting Items for Systematic Reviews and Meta‐Analyses flow diagram of selected studies for inclusion
FIGURE 2
FIGURE 2
Associations for the estimated risk of NP and NFT. Studies were grouped based on the statistical methods used. Point estimates for Eglit et al. represent the direct associations for hypertension in a mediation analysis wherein there also was a significant positive relation between hypertension and NP/NFT trough circle of Willis atherosclerosis. BP, blood pressure; CERAD, Consortium to Establish a Registry for Alzheimer's Disease; CI, confidence interval; DBP, diastolic blood pressure; ES, effect size; HTN, hypertension; HTN MED, medicated hypertension; NFT, neurofibrillary tangles; NP, neuritic plaques; SD, standard deviation; SMD, standardized mean difference; SBP, systolic blood pressure
FIGURE 3
FIGURE 3
Potential U‐shaped relation for systolic blood pressure and hippocampal neuropathology. Data from Petrovich et al. Count ratios per categories based on midlife systolic blood pressure. NFT, neurofibrillary tangles; NP, neuritic plaques
See this image and copyright information in PMC

References

    1. Fratiglioni L, De Ronchi D, Agüero‐Torres H. Worldwide prevalence and incidence of dementia. Drugs Aging. 1999;15:365‐375. 10.2165/00002512-199915050-00004 - DOI - PubMed
    1. Kumar A, Singh A, Ekavali. A review on Alzheimer's disease pathophysiology and its management: an update. Pharmacol Rep. 2015;67(2):195‐203. 10.1016/j.pharep.2014.09.004 - DOI - PubMed
    1. James BD, Wilson RS, Boyle PA, Trojanowski JQ, Bennett DA, Schneider JA. TDP‐43 stage, mixed pathologies, and clinical Alzheimer's‐type dementia. Brain. 2016;139(11):2983‐2993. 10.1093/brain/aww224 - DOI - PMC - PubMed
    1. Kawas CH, Kim RC, Sonnen JA, Bullain SS, Trieu T, Corrada MM. Multiple pathologies are common and related to dementia in the oldest‐old: the 90+ Study. Neurology. 2015;85(6):535‐542. 10.1212/WNL.0000000000001831 - DOI - PMC - PubMed
    1. Sonnen JA, Larson EB, Crane PK, et al. Pathological correlates of dementia in a longitudinal, population‐based sample of aging. Ann Neurol. 2007;62(4):406‐413. 10.1002/ana.21208 - DOI - PubMed

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