Evidence map›Paper›PMID 41806233›Full record

ArticleMolecular neurobiology2026

Class-Specific Antihypertensives and Alzheimer's Disease: Genotype- and Hypertension-Stratified Analysis.

Dehao Yang, Ruting Wei, Jinrong Zhu, Jiaxuan Chen, Shiyue Wang, Hejia Cai, Bo Zhang, Bingxin Teng, Bohao Li, Xiaoya Xie and 3 more

Abstract read
PubMed Publisher
In one paragraph

Article in Molecular neurobiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Dehao YangDepartment of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China.
Ruting WeiThe Second School of Medicine, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
Jinrong ZhuThe Second School of Medicine, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
Jiaxuan ChenThe First School of Medicine, School of Information and Engineering, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
Shiyue WangThe First School of Medicine, School of Information and Engineering, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
Hejia CaiThe Second School of Medicine, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
Bo ZhangThe School of Mental Health, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
Bingxin TengThe Second School of Medicine, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
Bohao LiThe First School of Medicine, School of Information and Engineering, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
Xiaoya XieThe School of Mental Health, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
Suwen HuangDepartment of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Shangcai Village, Baixiang Street, Wenzhou, 325035, Zhejiang, China.
Yiyun WengDepartment of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Shangcai Village, Baixiang Street, Wenzhou, 325035, Zhejiang, China. wengyiyun2012@126.com.
Guangyong ChenDepartment of Neurology, The Third Affiliated Hospital of Wenzhou Medical University, No. 108 Wansong Road, Wenzhou, 325035, Zhejiang, China. gychen@wmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antihypertensive medications (AHMs) may modulate Alzheimer's disease (AD) pathogenesis via cerebrovascular or neuroinflammatory pathways, yet evidence remains conflicting. This study investigated causal associations between AHM use and AD risk, focusing on drug classes, blood pressure status, and apolipoprotein E epsilon 4 (APOE ε4) effects. We integrated genetic causal inference with longitudinal survival analyses in a dual-evidence framework. Mendelian randomization (MR) was used to estimate class-specific causal effects at the population level. To examine effect modification by genetic and clinical factors, we analyzed 532 cognitively normal or mildly impaired older adults in ADNI with baseline assessments, with time-to-AD conversion modeled using Cox regression stratified by hypertension history and APOE ε4 status. Overall antihypertensive use showed no significant association with AD risk in hypertensive individuals (HR = 0.71) or APOE ε4 carriers (HR = 0.72). However, ARBs demonstrated protective associations in APOE ε4 carriers (HR = 0.32, 95% CI: 0.12-0.86). MR analysis supported causal protective effects for angiotensin II receptor blockers (ARBs, OR = 0.94, 95% CI: 0.89-0.98), calcium channel blockers (CCBs, OR = 0.93, 95% CI: 0.90-0.97), and beta-blockers (BBs, OR = 0.92, 95% CI: 0.86-0.98), whereas ACEIs lacked MR support and thiazide diuretics showed no benefit. Our findings reveal class-specific antihypertensive effects on AD risk. ARBs demonstrated the strongest protection, particularly in APOE ε4 carriers, while BBs and CCBs showed neuroprotective benefits. Results suggest AD prevention involves mechanisms beyond blood pressure reduction alone, supporting precision medicine with genotype-guided antihypertensive selection for genetically vulnerable individuals.

Indexed as

Alzheimer DiseaseAntihypertensive AgentsHypertensionAgedApolipoprotein E4FemaleGenotypeHumansMaleMendelian Randomization AnalysisAntihypertensive AgentsApolipoprotein E4Alzheimer’s diseaseAPOE ε4 carrierHypertensive patientsLongitudinal clinical cohort analysisTwo-sample Mendelian randomization

Identifiers

PMID41806233

What Socratic holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.