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Antihypertensive Use and the Risk of Alzheimer’s Disease and Related Dementias among Older Adults in the USA

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Abstract

Background

Epidemiological evidence on different classes of antihypertensives and risks of Alzheimer’s disease and related dementias (ADRD) is inconclusive and limited. This study examined the association between antihypertensive use (including therapy type and antihypertensive class) and ADRD diagnoses among older adults with hypertension.

Methods

A retrospective, cross-sectional study was conducted, involving 539 individuals aged ≥ 65 years who used antihypertensives and had ADRD diagnosis selected from 2013 to 2018 Medical Expenditure Panel Survey (MEPS) data. The predictors were therapy type (monotherapy or polytherapy) and class of antihypertensives defined using Multum Lexicon therapeutic classification (with calcium channel blockers [CCBs] as the reference group). Weighted logistic regression was used to assess the relationships of therapy type and class of antihypertensives use with ADRD diagnosis, adjusting for sociodemographic characteristics and health status.

Results

We found no significant difference between monotherapy and polytherapy on the odds of ADRD diagnosis. As to monotherapy, those who used angiotensin-converting enzyme inhibitors (ACEIs) had significantly lower odds of developing AD compared to those who used CCBs (OR 0.36, 95 % CI 0.13–0.99).

Conclusions

Findings of the study suggest the need for evidence-based drug therapy to manage hypertension in later adulthood and warrant further investigation into the mechanism underlying the protective effect of antihypertensives, particularly ACEIs, against the development of AD among older adults with hypertension.

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References

  1. Scotti L, Bassi L, Soranna D, Verde F, Silani V, Torsello A, et al. Association between renin-angiotensin-aldosterone system inhibitors and risk of dementia: a meta-analysis. Pharmacol Res. 2021;166: 105515. https://doi.org/10.1016/j.phrs.2021.105515.

    Article  CAS  PubMed  Google Scholar 

  2. León-Salas B, Olazarán J, Muñiz R, González-Salvador MT, Martínez-Martín P. Caregivers’ estimation of patients’ quality of life (QoL) in Alzheimer’s disease (AD): an approach using the ADRQL. Arch Gerontol Geriatr. 2011;53(1):13–8. https://doi.org/10.1016/j.archger.2010.05.021.

    Article  PubMed  Google Scholar 

  3. Mougias AA, Politis A, Lyketsos CG, Mavreas VG. Quality of life in dementia patients in Athens, Greece: predictive factors and the role of caregiver-related factors. Int Psychogeriatr. 2011;23(3):395–403. https://doi.org/10.1017/S1041610210001262.

    Article  PubMed  Google Scholar 

  4. Gao X, Wang K, Sun F, et al. Associates of Perceived Quality of Life in Chinese Older Adults Living with Cognitive Impairment [published online ahead of print, 2022 Jul 19]. J Gerontol Soc Work. 2022. https://doi.org/10.1080/01634372.2022.2103865.

  5. The World Health Organization. Dementia, https://www.who.int/news-room/fact-sheets/detail/dementia; 2020. Accessed 18 Apr 2021.

  6. Lebouvier T, Chen Y, Duriez P, Pasquier F, Bordet R. Antihypertensive agents in Alzheimer’s disease: beyond vascular protection. Expert Rev Neurother. 2020;20(2):175–87.

    Article  CAS  PubMed  Google Scholar 

  7. Wanleenuwat P, Iwanowski P, Kozubski W. Alzheimer’s dementia: pathogenesis and impact of cardiovascular risk factors on cognitive decline. Postgrad Med. 2019;131(7):415–22.

    Article  PubMed  Google Scholar 

  8. Alzheimer’s Association. 2021 Alzheimer’s Disease Facts and Figures. Alzheimers Dement. 2021;17(3). https://www.alz.org/media/Documents/alzheimers-facts-and-figures.pdf.

  9. Gouveia F, Camins A, Ettcheto M, et al. Targeting brain Renin-Angiotensin System for the prevention and treatment of Alzheimer’s disease: past, present and future. Age Res Rev. 2022;77: 101612. https://doi.org/10.1016/j.arr.2022.101612.

    Article  CAS  Google Scholar 

  10. Lennon MJ, Makkar SR, Crawford JD, Sachdev PS. Midlife hypertension and Alzheimer’s disease: a systematic review and meta-analysis. J Alzheimers Dis. 2019;71:307–16.

    Article  PubMed  Google Scholar 

  11. Silva MVF, Loures CMG, Alves LCV, de Souza LC, Borges KBG, Carvalho MDG. Alzheimer’s disease: risk factors and potentially protective measures. J Biomed Sci. 2019;26(1):33. https://doi.org/10.1186/s12929-019-0524-y.

    Article  PubMed  PubMed Central  Google Scholar 

  12. McGrath ER, Beiser AS, DeCarli C, et al. Blood pressure from mid- to late life and risk of incident dementia. Neurology. 2017;89(24):2447–54. https://doi.org/10.1212/WNL.0000000000004741.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Hakim AM. Small vessel disease. Front Neurol. 2019;10:1020.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Kim K, Ji E, Choi J, et al. Ten-year trends of hypertension treatment and control rate in Korea. Sci Rep. 2021. https://doi.org/10.1038/s41598-021-86199-x.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Uiterwijk R, Huijts M, Staals J, et al. Endothelial activation is associated with cognitive performance in patients with hypertension. Am J Hypertens. 2016;29(4):464–9. https://doi.org/10.1093/ajh/hpv122.

    Article  CAS  PubMed  Google Scholar 

  16. Lopes RA, Neves KB, Tostes RC, Montezano AC, Touyz RM. Downregulation of nuclear factor erythroid 2-related factor and associated antioxidant genes contributes to redox-sensitive vascular dysfunction in hypertension. Hypertension. 2015;66(6):1240–50. https://doi.org/10.1161/HYPERTENSIONAHA.115.06163.

    Article  CAS  PubMed  Google Scholar 

  17. Toth P, Tucsek Z, Sosnowska D, et al. Age-related autoregulatory dysfunction and cerebromicrovascular injury in mice with angiotensin II-induced hypertension. J Cereb Blood Flow Metab. 2013;33(11):1732–42. https://doi.org/10.1038/jcbfm.2013.143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Carnevale D, Mascio G, D’Andrea I, et al. Hypertension induces brain β-amyloid accumulation, cognitive impairment, and memory deterioration through activation of receptor for advanced glycation end products in brain vasculature. Hypertension. 2012;60(1):188–97. https://doi.org/10.1161/HYPERTENSIONAHA.112.195511.

    Article  CAS  PubMed  Google Scholar 

  19. Xu G, Bai F, Lin X, Wang Q, Wu Q, Sun S, et al. Association between antihypertensive drug use and the incidence of cognitive decline and dementia: a meta-analysis of prospective cohort studies. Biomed Res Int. 2017;2017:4368474. https://doi.org/10.1155/2017/4368474.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lennon MJ, Lam BCP, Crawford J, Brodaty H, Kochan NA, Trollor JN, et al. Does antihypertensive use moderate the effect of blood pressure on cognitive decline in older people? J Gerontol A Biol Sci Med Sci. https://doi.org/10.1093/gerona/glaa232.

  21. Peters R, Yasar S, Anderson CS, Andrews S, Antikainen R, Arima H, et al. Investigation of antihypertensive class, dementia, and cognitive decline: a meta-analysis. Neurology. 2020;94(3):e267–81.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Leong SL, Robertson IH, Lawlor B, Vanneste S. Associations between hypertension, treatment, and cognitive function in the Irish Longitudinal Study on Aging. Clin Med. 2020;9:3735.

    CAS  Google Scholar 

  23. Yasar S, Schuchman M, Peters J, Anstey KJ, Carlson MC, Peters R. Relationship between antihypertensive medications and cognitive impairment: Part I. Review of human studies and clinical trials. Curr Hypertens Rep. 2016;18:67. https://doi.org/10.1007/s11906-016-0674-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Robles NR, Cerezo I, Hernandez-Gallego R. Renin-angiotensin system blocking drugs. J Cardiovasc Pharmacol Ther. 2014;19(1):14–33. https://doi.org/10.1177/1074248413501018.

    Article  CAS  PubMed  Google Scholar 

  25. Novotny M, Klimova B, Valis M. Nitrendipine and dementia: forgotten positive facts?. Front Aging Neurosci. 2018;10:418. Published 2018 Dec 18. https://doi.org/10.3389/fnagi.2018.00418.

  26. Ding J, Davis-Plourde KL, Sedaghat S, Tully PJ, Wang W, Phillips C, Pase MP, Himali JJ, Windham BG, Griswold M, Gottesman R. Antihypertensive medications and risk for incident dementia and Alzheimer’s disease: a meta-analysis of individual participant data from prospective cohort studies. Lancet Neurol. 2020;19(1):61–70.

    Article  CAS  PubMed  Google Scholar 

  27. Medical Expenditure Panel Survey, https://www.meps.ahrq.gov/mepsweb/about_meps/survey_back.jsp. Accessed 22 Apr 2021.

  28. An J, Luong T, Qian L, Wei R, Liu R, Muntner P, Brettler J, Jaffe MG, Moran AE, Reynolds K. Treatment patterns and blood pressure control with initiation of combination versus monotherapy antihypertensive regimens. Hypertension. 2021;77(1):103–13.

    Article  CAS  PubMed  Google Scholar 

  29. Deb A, Sambamoorthi U, Thornton JD, Schreus B, Innes K. Direct medical expenditures associated with Alzheimer’s and related dementias (ADRD) in a nationally representative sample of older adults—an excess cost approach. Aging Ment Health. 2018;22(5):619–24.

    Article  PubMed  Google Scholar 

  30. Alzheimer’s Association, 2019 Alzheimer’s disease facts and figures, Alzheimers Dement. 2019;15(3):321–87. https://www.alz.org/media/Documents/alzheimers-facts-and-figures-2019-r.pdf pdf icon[PDF–1.9MB]external icon.

  31. Dai MH, Zheng H, Zeng LD, Zhang Y. The genes associated with early-onset Alzheimer’s disease. Oncotarget. 2018;9(19):15132.

    Article  PubMed  Google Scholar 

  32. Rabinovici GD. Late-onset Alzheimer disease. Continuum (Minneap Minn). 2019;25(1):14–33. https://doi.org/10.1212/CON.0000000000000700.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Park C, Wang G, Ng BP, Fang J, Durthaler JM, Ayala C. The uses and expenses of antihypertensive medications among hypertensive adults. Res Social Adm Pharm. 2020;16(2):183–9. https://doi.org/10.1016/j.sapharm.2019.05.002.

    Article  PubMed  Google Scholar 

  34. Wilson JR, Lorenz KA. Modeling binary correlated responses using SAS, SPSS, and R, ICSA Book Series in Statistics, vol 9. Springer, Cham; 2015, 81–102. https://doi.org/10.1007/978-3-319-23805-0_5.

  35. Maalouf M, Siddiqi M. Weighted logistic regression for large-scale imbalanced and rare events data. Knowl Based Syst. 2014;59:142–8.

    Article  Google Scholar 

  36. Peters R, Booth A, Peters J. A systematic review of calcium channel blocker use and cognitive decline/dementia in the elderly. J Hypertens. 2014;32(10):1945–58.

    Article  CAS  PubMed  Google Scholar 

  37. Yasar S, Corrada M, Brookmeyer R, Kawas C. Calcium channel blockers and risk of AD: the Baltimore Longitudinal Study of Aging. Neurobiol Aging. 2005;26(2):157–63.

    Article  CAS  PubMed  Google Scholar 

  38. Haller H. Effective management of hypertension with dihydropyridine calcium channel blocker-based combination therapy in patients at high cardiovascular risk. Int J Clin Pract. 2008;62(5):781–90. https://doi.org/10.1111/j.1742-1241.2008.01713.x.

    Article  CAS  PubMed  Google Scholar 

  39. Kalar I, Xu H, Secnik J, et al. Calcium channel blockers, survival and ischaemic stroke in patients with dementia: a Swedish registry study. J Intern Med. 2021;289(4):508–22. https://doi.org/10.1111/joim.13170.

    Article  CAS  PubMed  Google Scholar 

  40. Alzheimer’s Association Calcium Hypothesis Workgroup. Calcium Hypothesis of Alzheimer’s disease and brain aging: a framework for integrating new evidence into a comprehensive theory of pathogenesis. Alzheimers Dement. 2017;13(178–82): e17.

    Google Scholar 

  41. Novak V, Hajjar I. The relationship between blood pressure and cognitive function. Nat Rev Cardiol. 2010;7:686–98.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Johnson ML, Parikh N, Kunik ME, Schulz PE, Patel JG, Chen H, Aparasu RR, Morgan RO. Antihypertensive drug use and the risk of dementia in patients with diabetes mellitus. Alzheimers Dement. 2012;8(5):437–44.

    Article  CAS  PubMed  Google Scholar 

  43. van Middelaar T, van Vught LA, van Charante EPM, Eurelings LS, Ligthart SA, van Dalen JW, van den Born BJH, Richard E, van Gool WA. Lower dementia risk with different classes of antihypertensive medication in older patients. J Hypertens. 2017;35(10):2095–101.

    Article  PubMed  Google Scholar 

  44. Ribeiro VT, de Souza LC, Simões E Silva AC. Renin-angiotensin system and Alzheimer’s disease pathophysiology: from the potential interactions to therapeutic perspectives. Protein Pept Lett. 2020;27(6):484–511.

    Article  CAS  PubMed  Google Scholar 

  45. Zhuang S, Wang HF, Wang X, Li J, Xing CM. The association of renin-angiotensin system blockade use with the risks of cognitive impairment of aging and Alzheimer’s disease: a meta-analysis. J Clin Neurosci. 2016;33:32–8.

    Article  CAS  PubMed  Google Scholar 

  46. Yoon SS, Gu Q, Nwankwo T, Wright JD, Hong Y, Burt V. Trends in blood pressure among adults with hypertension: United States, 2003 to 2012. Hypertension. 2015;65:54–61.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank Nahyo A. Jalajel for comments on previous versions of this manuscript.

Author information

Authors and Affiliations

  1. Department of Sociology, Texas State University, 601 University Drive, San Marcos, Texas, 78666, USA

    Xi Pan

  2. Division of Health Services Research, Department of Foundations of Medicine, New York University Long Island School of Medicine, 101 Mineola Boulevard, Suite 3-047, Mineola, NY, 11501, USA

    Donglan Zhang

  3. Health Outcomes Division, College of Pharmacy, The University of Texas at Austin, College of Pharmacy-Health Outcomes and Pharmacy Practice, 2409 University Avenue, STOP A1930, Austin, TX, 78712-1120, USA

    Ji Haeng Heo & Chanhyun Park

  4. Huazhong University of Science and Technology, Wuhan, China

    Gang Li

  5. Department of Pharmaceutical Sciences, Northeast Ohio Medical University, 4209 St, OH-44, Rootstown, OH, 44272, USA

    Christine M. Dengler-Crish

  6. Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place Box 1077, New York, NY, 10029, USA

    Yan Li

  7. Department of Neurology, Columbia University Irving Medical Center, 710 W 168th St, New York, NY, 10033, USA

    Yian Gu

  8. Department of Clinical and Administrative Pharmacy, College of Pharmacy, University of Georgia, 250 W. Green Street, Athens, GA, 30602, USA

    Henry N. Young & Devin L. Lavender

  9. Department of Public Health Sciences, Clemson University, 507 Edwards Hall, Clemson, SC, 29634, USA

    Lu Shi

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Contributions

XP conducted literature review, led data interpretation, and wrote the manuscript. DZ conceived the study, obtained funding, supervised the analyses, interpreted the findings, and edited the manuscript. JHH conceived the study and conducted data management. CP served as a consultant for data management and analyses. GL performed all statistical analyses and revised the manuscript. CMD-C provided critical revisions to the manuscript for important intellectual content. YL, YG, HNY, DLL, and LS provided revisions to the manuscript.

Corresponding author

Correspondence to Xi Pan.

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Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by the National Institute on Minority Health and Health Disparities (NIMHD) R01MD013886-02S1 (Principal Investigator: Donglan Zhang). The sponsor had no role or involvement other than funding. The opinions, results, and conclusions reported here are those of the authors and are independent from the funding source.

Conflicts of Interest/competing interests

Xi Pan, Donglan Zhang, Ji Haeng Heo, Chanhyun Park, Gang Li, Christine M. Dengler-Crish, Yan Li, Yian Gu, Henry N Young, Devin L. Lavender, and Lu Shi declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethics approval

Exempt. Medical Expenditure Panel Survey (MEPS) data are publicly available to any registered user from the Agency for Healthcare Research and Quality. Collection and production of MEPS data have been reviewed and approved by the Research Triangle Institute (RTI) International Institutional Review Board (IRB), established under a multi-project assurance (Federal Assurance Number 3331) granted by the Office for Protection from Research Risks, (OPRR). The study was conducted in accordance with the Declaration of Helsinki.

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Availability of data and material

Anonymized data will be shared at the reasonable request of any bona fide investigator.

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Pan, X., Zhang, D., Heo, J.H. et al. Antihypertensive Use and the Risk of Alzheimer’s Disease and Related Dementias among Older Adults in the USA. Drugs Aging 39, 875–886 (2022). https://doi.org/10.1007/s40266-022-00981-8

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