Generic placeholder image

Current Reviews in Clinical and Experimental Pharmacology

Editor-in-Chief

ISSN (Print): 2772-4328
ISSN (Online): 2772-4336

Meta-Analysis

Angiotensin-Receptor Blockers and the Risk of Alzheimer´s Disease: A Meta-analysis

Author(s): Teodoro J. Oscanoa*, José Amado, Xavier Vidal and Roman Romero-Ortuno

Volume 16, Issue 1, 2021

Published on: 31 January, 2020

Page: [73 - 78] Pages: 6

DOI: 10.2174/1574884715666200131120224

Price: $65

Abstract

Background: Anti-hypertensive medications may reduce the incidence of cognitive disorders. This may be due to reasons beyond their pure hypotensive effect. This study aimed to systematically review the association between the use of Angiotensin-Receptor Blockers (ARBs) and the incidence of Alzheimer’s disease (AD).

Methods: We systematically searched studies reporting the association between ARB use and the incidence of AD.

Results: Ten studies (1 RCT, 2 case-control and 7 cohort studies) met the inclusion criteria. When all observational studies (9) were analyzed, ARB use was associated with a reduced risk of incident AD (HR 0.72, 95% CI: 0.58-0.88, p<0.001). In the only RCT, decrease in the incidence of AD was also significant (HR= 0.31, 95% CI: 0.14-0.68).

Conclusion: ARB use may reduce the risk of incident AD. This association does not imply causation and further research is required to clarify potential mechanisms.

Keywords: Angiotensin-receptor blockers, alzheimer´s disease, elderly, angiotensin II, meta-analysis, pro-oxidant effects.

Graphical Abstract
[1]
Larsson SC, Markus HS. Does treating vascular risk factors prevent dementia and alzheimer’s disease? A systematic review and meta-analysis. J Alzheimers Dis 2018; 64(2): 657-68.
[http://dx.doi.org/10.3233/JAD-180288] [PMID: 29914039]
[2]
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.
[http://dx.doi.org/10.1016/j.jocn.2016.02.036] [PMID: 27475317]
[3]
Nakagawa T, Hasegawa Y, Uekawa K, et al. Transient mild cerebral ischemia significantly deteriorated cognitive impairment in a mouse model of Alzheimer’s disease via angiotensin AT1 receptor. Am J Hypertens 2017; 30(2): 141-50.
[http://dx.doi.org/10.1093/ajh/hpw099] [PMID: 27572961]
[4]
Gebre AK, Altaye BM, Atey TM, Tuem KB, Berhe DF. Targeting renin-angiotensin system against Alzheimer’s disease. Front Pharmacol 2018; 9: 440.
[http://dx.doi.org/10.3389/fphar.2018.00440] [PMID: 29760662]
[5]
Farag E, Sessler DI, Ebrahim Z, et al. The renin angiotensin system and the brain: New developments. J Clin Neurosci 2017; 46: 1-8.
[http://dx.doi.org/10.1016/j.jocn.2017.08.055] [PMID: 28890045]
[6]
Kim-Mitsuyama S, Yamamoto E, Tanaka T, et al. Critical role of angiotensin II in excess salt-induced brain oxidative stress of stroke-prone spontaneously hypertensive rats. Stroke 2005; 36(5): 1083-8.
[http://dx.doi.org/10.1161/01.STR.0000163084.16505.e3] [PMID: 15817892]
[7]
Inaba S, Iwai M, Furuno M, et al. Continuous activation of renin-angiotensin system impairs cognitive function in renin/angiotensinogen transgenic mice. Hypertension 2009; 53(2): 356-62.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.108.123612] [PMID: 19047580]
[8]
Dai HL, Hu WY, Jiang LH, Li L, Gaung XF, Xiao ZC. p38 MAPK inhibition improves synaptic plasticity and memory in angiotensin II-dependent hypertensive mice. Sci Rep 2016; 6: 27600.
[http://dx.doi.org/10.1038/srep27600] [PMID: 27283322]
[9]
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med 2009; 6(7)e1000097
[http://dx.doi.org/10.1371/journal.pmed.1000097] [PMID: 19621072]
[10]
Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010; 25(9): 603-5.
[http://dx.doi.org/10.1007/s10654-010-9491-z] [PMID: 20652370]
[11]
Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 510 (updated March 2011) The Cochrane Collaboration 2011.www.cochrane-handbook.org
[12]
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7(3): 177-88.
[http://dx.doi.org/10.1016/0197-2456(86)90046-2] [PMID: 3802833]
[13]
Yasar S, Xia J, Yao W, et al. Antihypertensive drugs decrease risk of Alzheimer disease: Ginkgo evaluation of memory study. Neurology 2013; 81(10): 896-903.
[http://dx.doi.org/10.1212/WNL.0b013e3182a35228] [PMID: 23911756]
[14]
Hsu CY, Huang CC, Chan WL, et al. Angiotensin-receptor blockers and risk of Alzheimer’s disease in hypertension population-A nationwide cohort study. Circ J 2013; 77(2): 405-10.
[http://dx.doi.org/10.1253/circj.CJ-12-0658] [PMID: 23149416]
[15]
Li NC, Lee A, Whitmer RA, et al. Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis. BMJ 2010; 340: b5465.
[http://dx.doi.org/10.1136/bmj.b5465] [PMID: 20068258]
[16]
Davies NM, Kehoe PG, Ben-Shlomo Y, Martin RM. Associations of anti-hypertensive treatments with Alzheimer’s disease, vascular dementia, and other dementias. J Alzheimers Dis 2011; 26(4): 699-708.
[http://dx.doi.org/10.3233/JAD-2011-110347] [PMID: 21709373]
[17]
Kuan YC, Huang KW, Yen DJ, Hu CJ, Lin CL, Kao CH. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers reduced dementia risk in patients with diabetes mellitus and hypertension. Int J Cardiol 2016; 220: 462-6.
[http://dx.doi.org/10.1016/j.ijcard.2016.06.215] [PMID: 27390970]
[18]
Haag MD, Hofman A, Koudstaal PJ, Breteler MM, Stricker BH. Duration of antihypertensive drug use and risk of dementia: A prospective cohort study. Neurology 2009; 72(20): 1727-34.
[http://dx.doi.org/10.1212/01.wnl.0000345062.86148.3f] [PMID: 19228584]
[19]
Chiu WC, Ho WC, Lin MH, et al. Angiotension receptor blockers reduce the risk of dementia. J Hypertens 2014; 32(4): 938-47.
[http://dx.doi.org/10.1097/HJH.0000000000000086] [PMID: 24406780]
[20]
Hajjar I, Catoe H, Sixta S, et al. Cross-sectional and longitudinal association between antihypertensive medications and cognitive impairment in an elderly population. J Gerontol A Biol Sci Med Sci 2005; 60(1): 67-73.
[http://dx.doi.org/10.1093/gerona/60.1.67] [PMID: 15741285]
[21]
Wincewicz D, et al. Preserved cognition and reduced age-related cognitive decline during treatment with angiotensin II receptor blockers: A 20-year follow-up study. Eur Psychiatry 2017; 41: S372.
[http://dx.doi.org/10.1016/j.eurpsy.2017.02.386]
[22]
Barthold D, Joyce G, Wharton W, Kehoe P, Zissimopoulos J. The association of multiple anti-hypertensive medication classes with Alzheimer’s disease incidence across sex, race, and ethnicity. PLoS One 2018; 13(11)e0206705
[http://dx.doi.org/10.1371/journal.pone.0206705] [PMID: 30383807]
[23]
Levi Marpillat N, Macquin-Mavier I, Tropeano AI, Bachoud-Levi AC, Maison P. Antihypertensive classes, cognitive decline and incidence of dementia: A network meta-analysis. J Hypertens 2013; 31(6): 1073-82.
[http://dx.doi.org/10.1097/HJH.0b013e3283603f53] [PMID: 23552124]
[24]
Lehmann DJ, Cortina-Borja M, Warden DR, et al. Large meta-analysis establishes the ACE insertion-deletion polymorphism as a marker of Alzheimer’s disease. Am J Epidemiol 2005; 162(4): 305-17.
[http://dx.doi.org/10.1093/aje/kwi202] [PMID: 16033878]
[25]
Yang L, Zhou HH, Ye YF, Fan XW, Wang YJ, Meng Y. Association of PS1 1/2, ACE I/D, and LRP C/T polymorphisms with Alzheimer’s disease in the Chinese population: A meta-analysis of case-control studies. Genet Mol Res 2015; 14(1): 1017-24.
[http://dx.doi.org/10.4238/2015.February.6.5] [PMID: 25730041]
[26]
Ho JK, Nation DA. Memory is preserved in older adults taking AT1 receptor blockers. Alzheimers Res Ther 2017; 9(1): 33.
[http://dx.doi.org/10.1186/s13195-017-0255-9] [PMID: 28446207]
[27]
Kehoe PG, Miners S, Love S. Angiotensins in Alzheimer’s disease - friend or foe? Trends Neurosci 2009; 32(12): 619-28.
[http://dx.doi.org/10.1016/j.tins.2009.07.006] [PMID: 19796831]
[28]
Iwai M, Liu HW, Chen R, et al. Possible inhibition of focal cerebral ischemia by angiotensin II type 2 receptor stimulation. Circulation 2004; 110(7): 843-8.
[http://dx.doi.org/10.1161/01.CIR.0000138848.58269.80] [PMID: 15289370]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy