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Anti-Hypertensive Drugs Moderate the Relationship of Blood Pressure with Alzheimer’s Pathologies and Neurodegenerative Markers in Non-Demented Hypertensive Older Adults

  • Original Research
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The Journal of Prevention of Alzheimer's Disease Aims and scope Submit manuscript

Abstract

Background

We aimed to explore whether the relationships of blood pressures (BPs) with Alzheimer’s disease (AD) endophenotypes varied by usage of antihypertensive drugs (AHDs).

Methods

A total of 765 non-demented older adults (mean age: 74.4 years; female: 43.1%) with a self-reported history of hypertension were followed for 6 years. Multiple linear regression and linear-mixed effect models were used to investigate the interaction effects of five categories of AHDs (angiotensin-converting enzyme inhibitors [ACEI], angiotensin II receptor blockers [ARBs], β-blocker, calcium channel blockers [CCB], diuretic) with BPs (systolic blood pressure [SBP], diastolic blood pressure [DBP], and pulse pressure [PP]) on AD core pathology and neurodegenerative markers.

Results

After Bonferroni correction, significant interaction effects of BPs with AHDs were observed. Elevated SBP or PP in late-life was associated with higher levels of cerebral Aβ burden (diuretic alone/β-blocker × SBP), higher levels of CSF tau proteins (diuretic × SBP/PR ARBs/CCB × SBP), and lower volume of entorhinal region (β-blocker × SBP, diuretic × PP) only among hypertensive patients who received no antihypertensive treatments, while these associations became compromised or null for users of specific AHDs except for ACEI. Compared to taking other classes of AHDs, elevated SBP in late-life was associated with lower cerebral Aβ burden in diuretic users (padjusted = 0.08) and was associated with higher CSF tau proteins in ACEI alone users (padjusted = 0.03). Longitudinal data validated the above-mentioned interaction effects on changes of cerebral Aβ burden (padjusted < 0.05), CSF tau proteins (padjusted < 0.10), and brain atrophy (padjusted < 0.05).

Conclusions

The relationships of late-life BP with AD pathology and neurodegeneration could be modified by antihypertensive treatments and varied by AHD classification. These findings provide preliminary evidence for tailored BP management strategy for preventing AD among late-life hypertensive adults.

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Availability of data and materials: All data are available upon reasonable request or can be obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu).

Abbreviations

AD:

Alzheimer’s disease

AHDs:

Antihypertensive drugs

ACEI:

Angiotensin-converting enzyme inhibitors

ARBs:

Angiotensin II receptor blockers

CCB:

Calcium channel blockers

BP:

Blood pressure

SBP:

Systolic blood pressure

DBP:

Diastolic blood pressure

PP:

Pulse pressure

Aβ:

β-Amyloid

T-tau:

Total tau

P-tau:

Phosphorylated tau

CSF:

Cerebrospinal fluid

ADNI:

Alzheimer’s Disease Neuroimaging Initiative

AV45-PET:

18F-florbetapir-positron emission tomography

MRI:

Magnetic resonance imaging

EC:

Entorhinal cortex

APOE ε4:

Apolipoprotein E4

SD:

Standard deviation

MLR:

Multiple linear regression

LME:

Linear mixed-effects

MR:

Magnetic resonance.

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Acknowledgements

The authors thank contributors, including the staff at Alzheimer’s Disease Centers who collected samples used in this study, patients, and their families whose help and participation made this work possible. Data collection and sharing for this project were funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abb Vie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; Euroimmun; E Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.

Funding

Funding: This study was supported by grants from the National Natural Science Foundation of China (82001136) and Tai-Shan Scholar Project.

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Authors and Affiliations

  1. Department of Neurology, Qingdao Municipal Hospital, Weifang Medical University, Qingdao, China

    Y. Guo, C.-C. Tan, M. S. Tan, L. Tan & W. Xu

  2. School of Clinical Medicine, Weifang Medical University, Weifang, China

    Y. Guo

  3. Department of Neurology, Qingdao Municipal Hospital, Qingdao, China, Donghai Middle Road, No. 5, Qingdao, China

    W. Xu

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  1. Y. Guo
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Alzheimer’s Disease Neuroimaging Initiative

Contributions

Authors’ contributions: Dr. W X: conceptualization and design of the study, revision of the manuscript. Y G: analysis of data, drafting and revision of the manuscript, and prepared all the figures. C-C T, M-S T, and L T,: revision of the manuscript.

Corresponding author

Correspondence to W. Xu.

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Ethical Approval: The ADNI was approved by institutional review boards of all participating institutions, and written informed consent was obtained from all participants according to the Declaration of Helsinki.

Competing interests: The authors declare that they have no competing interests.

Additional information

The data used in preparation for this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc. edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and / or provided data but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.lord.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

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Guo, Y., Tan, CC., Tan, M.S. et al. Anti-Hypertensive Drugs Moderate the Relationship of Blood Pressure with Alzheimer’s Pathologies and Neurodegenerative Markers in Non-Demented Hypertensive Older Adults. J Prev Alzheimers Dis 11, 672–683 (2024). https://doi.org/10.14283/jpad.2024.40

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