The Use of Antihypertensive Medication and In Vivo Alzheimer's Disease Pathology

IF 7.7 1区医学 Q1 CLINICAL NEUROLOGY Annals of Neurology Pub Date : 2025-02-17 DOI:10.1002/ana.27204

Musung Keum MD, PhD, Min Soo Byun MD, PhD, Dahyun Yi PhD, Hyejin Ahn MA, Gijung Jung RN, PhD, Joon Hyung Jung MD, Nayeong Kong MD, PhD, Jun-Young Lee MD, PhD, Yu Kyeong Kim MD, PhD, Yun-Sang Lee PhD, Koung Mi Kang MD, PhD, Chul-Ho Sohn MD, PhD, Dong Young Lee MD, PhD, for the KBASE Research Group

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Abstract

Objective

We investigated whether the use of antihypertensive medication (AHM) is associated with in vivo Alzheimer's Disease (AD) pathologies in older adults with hypertension and examined if the effect differs by drug-class and blood–brain barrier (BBB) permeability of the drug.

Methods

This cross-sectional study recruited participants from the Korean Brain Aging Study for the Early Diagnosis and Prevention of Alzheimer's Disease. Participants comprised both cognitively normal and impaired older adults diagnosed with hypertension (n = 408). All participants underwent comprehensive clinical assessment and [¹¹C] Pittsburgh Compound B positron emission tomography (PET) for measurement of cerebral β-amyloid (Aβ) deposition. Additionally, a subset of participants (n = 120) was subjected to [¹⁸F] AV-1451 PET to assess tau deposition.

Results

The AHM group (n = 227) exhibited significantly lower Aβ deposition (B [SE] = −0.104 [0.037], p = 0.006) compared to the non-AHM group (n = 181), even after controlling for age, sex, apolipoprotein E ε4-positivity, vascular risk factors, and mean arterial blood pressure. Further analysis by AHM class showed an association between the use of renin-angiotensin system inhibitors (RASi) and less Aβ deposition (B [SE] = −0.143[0.049], p = 0.004). No significant relationships were observed between the use of BBB-permeable AHM and Aβ deposition. Additionally, associations between AHM use and tau deposition did not reach statistical significance.

Interpretation

Our findings suggest that AHM use may be associated with lower Aβ burden in older adults with hypertension. Further studies exploring the underlying mechanism, particularly related to RASi, may provide insights into new therapeutic targets for AD. ANN NEUROL 2025;97:1051–1061

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抗高血压药物的使用与阿尔茨海默病的体内病理。

目的：研究降压药物（AHM）的使用是否与老年高血压患者体内阿尔茨海默病（AD）病理相关，并检查其作用是否因药物类别和药物血脑屏障（BBB）通透性而不同。方法：这项横断面研究从韩国脑老化研究中招募了阿尔茨海默病的早期诊断和预防的参与者。参与者包括认知正常和被诊断为高血压的老年人（n = 408）。所有参与者都进行了全面的临床评估和[11C]匹兹堡化合物B正电子发射断层扫描（PET）来测量大脑β-淀粉样蛋白（Aβ）沉积。此外，一部分参与者（n = 120）接受了[18F] AV-1451 PET来评估tau沉积。结果：AHM组（n = 227）的Aβ沉积（B [SE] = -0.104 [0.037], p = 0.006）明显低于非AHM组（n = 181），即使在控制年龄、性别、载脂蛋白E ε4阳性、血管危险因素和平均动脉血压后也是如此。AHM类的进一步分析显示，肾素-血管紧张素系统抑制剂（RASi）的使用与Aβ沉积减少之间存在关联（B [SE] = -0.143[0.049], p = 0.004）。可渗透血脑屏障的AHM的使用与Aβ沉积之间没有明显的关系。此外，AHM使用与tau沉积之间的关联没有达到统计学意义。解释：我们的研究结果表明，AHM的使用可能与老年高血压患者较低的Aβ负担有关。进一步研究潜在的机制，特别是与RASi相关的机制，可能会为阿尔茨海默病的新治疗靶点提供见解。Ann neurol 2025。

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来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.