{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:03:45Z","timestamp":1777395825984,"version":"3.51.4"},"reference-count":53,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2022,9,13]]},"abstract":"<jats:p>Background: It is unclear whether the main antihypertensive medication classes (diuretics, calcium channel blockers, beta-blockers, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers (ARBs)) are associated with different risks of cognitive decline. Published evidence is conflicting and stems mainly from observational studies. Objective: To investigate the differential effects of antihypertensives on the risks of developing dementia and cognitive decline, with a specific focus on the vascular component of the mechanisms underlying these interactions. Methods: Older adults with a history of hypertension and without dementia were drawn from the population-based HELIAD cohort. Age-, gender-, education-, and antihypertensive medication- (five dichotomous exposures) adjusted Cox proportional-hazards models and generalized estimating equations were performed to appraise the associations of baseline antihypertensive therapy with dementia incidence and cognitive decline (quantified using a comprehensive neuropsychological battery). Analyses were subsequently adjusted for clinical vascular risk (dyslipidemia, diabetes mellitus, smoking, cardiovascular, and cerebrovascular history) and genetic susceptibility to stroke (using polygenic risk scores generated according to the MEGASTROKE consortium GWAS findings). Results: A total of 776 predominantly female participants (73.61\u00b14.94 years) with hypertension and a mean follow-up of 3.02\u00b10.82 years were analyzed. Baseline treatment was not associated with the risk of incident dementia. ARB users experienced a slower yearly global cognitive [2.5% of a SD, 95% CI\u200a=\u200a(0.1, 4.9)] and language [4.4% of a SD, 95% CI\u200a=\u200a(1.4, 7.4)] decline compared to non-users. The fully adjusted model reproduced similar associations for both global cognitive [\u03b2=\u200a0.027, 95% CI\u200a=\u200a (\u20130.003, 0.057)], and language decline [\u03b2=\u200a0.063, 95% CI\u200a=\u200a(0.023, 0.104)]. Conclusion: ARBs may be superior to other antihypertensive agents in the preservation of cognition, an association probably mediated by vascular-independent mechanisms.<\/jats:p>","DOI":"10.3233\/jad-220439","type":"journal-article","created":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T11:24:41Z","timestamp":1659093881000},"page":"709-719","source":"Crossref","is-referenced-by-count":15,"title":["Antihypertensive Medication Class and the Risk of Dementia and Cognitive Decline in Older Adults: A Secondary Analysis of the Prospective HELIAD Cohort"],"prefix":"10.1177","volume":"89","author":[{"given":"Ioannis","family":"Liampas","sequence":"first","affiliation":[{"name":"Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, Larissa, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Hatzimanolis","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Aiginition Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasileios","family":"Siokas","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, Larissa, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary","family":"Yannakoulia","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Dietetics, Harokopio University, Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary H.","family":"Kosmidis","sequence":"additional","affiliation":[{"name":"Lab of Cognitive Neuroscience, School of Psychology, Aristotle University of Thessaloniki, Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paraskevi","family":"Sakka","sequence":"additional","affiliation":[{"name":"Athens Association of Alzheimer\u2019s Disease and Related Disorders, Marousi, Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgios M.","family":"Hadjigeorgiou","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, Larissa, Greece"},{"name":"Department of Neurology, Medical School, University of Cyprus, Nicosia, Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolaos","family":"Scarmeas","sequence":"additional","affiliation":[{"name":"1st Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece"},{"name":"Taub Institute for Research in Alzheimer\u2019s Disease and the Aging Brain, The Gertrude H. Sergievsky Center, Department of Neurology, Columbia University, New York, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Efthimios","family":"Dardiotis","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, Larissa, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-220439_ref1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1161\/HYPERTENSIONAHA.114.03040","article-title":"Hypertension and dementia","volume":"64","author":"Iadecola","year":"2014","journal-title":"Hypertension"},{"key":"10.3233\/JAD-220439_ref2","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1001\/archneur.64.12.1734","article-title":"Hypertension and the risk of mild cognitive impairment","volume":"64","author":"Reitz","year":"2007","journal-title":"Arch Neurol"},{"key":"10.3233\/JAD-220439_ref3","doi-asserted-by":"crossref","first-page":"e038971","DOI":"10.1136\/bmjopen-2020-038971","article-title":"Treatment of hypertension reduces cognitive decline in older adults: A systematic review and meta-analysis","volume":"10","author":"Gupta","year":"2020","journal-title":"BMJ Open"},{"key":"10.3233\/JAD-220439_ref4","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S1474-4422(19)30393-X","article-title":"Antihypertensive medications and risk for incident dementia and Alzheimer\u2019s disease: A meta-analysis of individual participant data from prospective cohort studies","volume":"19","author":"Ding","year":"2020","journal-title":"Lancet Neurol"},{"key":"10.3233\/JAD-220439_ref5","first-page":"CD004034","article-title":"Pharmacological treatment of hypertension in people without prior cerebrovascular disease for the prevention of cognitive impairment and dementia","volume":"5","author":"Cunningham","year":"2021","journal-title":"Cochrane Database Syst Rev"},{"key":"10.3233\/JAD-220439_ref6","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1212\/WNL.0000000000008732","article-title":"Investigation of antihypertensive class, dementia, and cognitive decline: A meta-analysis. e267-e","volume":"94","author":"Peters","year":"2020","journal-title":"Neurology"},{"key":"10.3233\/JAD-220439_ref7","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1016\/j.jamda.2020.12.019","article-title":"Antihypertensive medication classes and the risk of dementia: A systematic review and network meta-analysis","volume":"22","author":"den Brok","year":"2021","journal-title":"J Am Med Direct Assoc"},{"key":"10.3233\/JAD-220439_ref8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.eurpsy.2017.07.015","article-title":"Effects of different antihypertensive medication groups on cognitive function in older patients: A systematic review","volume":"46","author":"Stuhec","year":"2017","journal-title":"Eur Psychiatry"},{"key":"10.3233\/JAD-220439_ref9","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1016\/j.ijsu.2014.07.013","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for reporting observational studies","volume":"12","author":"von Elm","year":"2014","journal-title":"Int J Surg"},{"key":"10.3233\/JAD-220439_ref10","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1159\/000362723","article-title":"The Hellenic Longitudinal Investigation of Aging and Diet (HELIAD): Rationale, study design, and cohort description","volume":"43","author":"Dardiotis","year":"2014","journal-title":"Neuroepidemiology"},{"key":"10.3233\/JAD-220439_ref11","doi-asserted-by":"publisher","DOI":"10.1080\/13854046.2022.2059011"},{"key":"10.3233\/JAD-220439_ref12","doi-asserted-by":"publisher","DOI":"10.1037\/neu0000843"},{"key":"10.3233\/JAD-220439_ref14","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1093\/arclin\/acs099","article-title":"Development of the Greek Verbal Learning Test: Reliability, construct validity, and normative standards","volume":"28","author":"Vlahou","year":"2013","journal-title":"Arch Clin Neuropsychol"},{"key":"10.3233\/JAD-220439_ref15","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1017\/S1355617704102014","article-title":"The verbal fluency task in the Greek population: Normative data, and clustering and switching strategies","volume":"10","author":"Kosmidis","year":"2004","journal-title":"J Int Neuropsychol Soc"},{"key":"10.3233\/JAD-220439_ref16","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1155\/2010\/423841","article-title":"Adaptation and validation of standardized aphasia tests in different languages: Lessons from the Boston Diagnostic Aphasia Examination\u2013Short Form in Greek","volume":"22","author":"Tsapkini","year":"2010","journal-title":"Behav Neurol"},{"key":"10.3233\/JAD-220439_ref18","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1155\/2010\/956709","article-title":"Cultural factors influencing performance on visuoperceptual neuropsychological tasks","volume":"23","author":"Kosmidis","year":"2010","journal-title":"Behav Neurol"},{"key":"10.3233\/JAD-220439_ref19","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1080\/13803390701346113","article-title":"Do age and education contribute to performance on the clock drawing test? Normative data for the Greek population","volume":"30","author":"Bozikas","year":"2008","journal-title":"J Clin Exp Neuropsychol"},{"key":"10.3233\/JAD-220439_ref20","first-page":"336","article-title":"The Greek Trail Making Test: Preliminary normative data for clinical and research use","volume":"9","author":"Vlahou","year":"2002","journal-title":"Psychology"},{"key":"10.3233\/JAD-220439_ref21","doi-asserted-by":"crossref","first-page":"e2261","DOI":"10.1212\/WNL.0000000000007453","article-title":"Higher probability of prodromal Parkinson disease is related to lower cognitive performance","volume":"92","author":"Bougea","year":"2019","journal-title":"Neurology"},{"key":"10.3233\/JAD-220439_ref22","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"Mini-mental state","volume":"12","author":"Folstein","year":"1975","journal-title":"J Psychiatr Res"},{"issue":"Suppl 1","key":"10.3233\/JAD-220439_ref23","first-page":"159","article-title":"Evaluating premorbid level: Preliminary findings regarding the vulnerability of scores on cognitive measures in patients with MS","volume":"165","author":"Giaglis","year":"2010","journal-title":"J Int Neuropsychol Soc"},{"key":"10.3233\/JAD-220439_ref25","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1212\/WNL.34.7.939","article-title":"Clinical diagnosis of Alzheimer\u2019s disease: Report of the NINCDS-ADRDA Work Group* under the auspices of Department of Health and Human Services Task Force on Alzheimer\u2019s Disease","volume":"34","author":"McKhann","year":"1984","journal-title":"Neurology"},{"key":"10.3233\/JAD-220439_ref26","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/j.1365-2796.2004.01388.x","article-title":"Mild cognitive impairment as a diagnostic entity","volume":"256","author":"Petersen","year":"2004","journal-title":"J Intern Med"},{"key":"10.3233\/JAD-220439_ref27","doi-asserted-by":"crossref","first-page":"739571","DOI":"10.3389\/fnmol.2021.739571","article-title":"Association of the polygenic risk score with the probability of prodromal Parkinson\u2019s disease in older adults","volume":"14","author":"Maraki","year":"2021","journal-title":"Front Mol Neurosci"},{"key":"10.3233\/JAD-220439_ref28","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/s41588-018-0058-3","article-title":"Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes","volume":"50","author":"Malik","year":"2018","journal-title":"Nat Genet"},{"key":"10.3233\/JAD-220439_ref29","doi-asserted-by":"crossref","first-page":"giz082","DOI":"10.1093\/gigascience\/giz082","article-title":"PRSice-2: Polygenic Risk Score software for biobank-scale data","volume":"8","author":"Choi","year":"2019","journal-title":"GigaScience"},{"key":"10.3233\/JAD-220439_ref30","doi-asserted-by":"crossref","first-page":"100909","DOI":"10.1016\/j.yfrne.2021.100909","article-title":"Conventional cardiovascular risk factors in transient global amnesia: Systematic review and proposition of a novel hypothesis","volume":"61","author":"Liampas","year":"2021","journal-title":"Front Neuroendocrinol"},{"key":"10.3233\/JAD-220439_ref31","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3892\/ijmm.2021.4928","article-title":"Role of the central renin-angiotensin system in hypertension","volume":"47","author":"Su","year":"2021","journal-title":"Int J Mol Med"},{"key":"10.3233\/JAD-220439_ref32","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1161\/HYPERTENSIONAHA.115.03624","article-title":"Angiotensin-II, the brain, and hypertension: An update","volume":"66","author":"Young","year":"2015","journal-title":"Hypertension"},{"key":"10.3233\/JAD-220439_ref33","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1161\/HYPERTENSIONAHA.109.138586","article-title":"Angiotensin receptor blocker prevented \u03b2-amyloid-induced cognitive impairment associated with recovery of neurovascular coupling","volume":"54","author":"Takeda","year":"2009","journal-title":"Hypertension"},{"key":"10.3233\/JAD-220439_ref34","doi-asserted-by":"crossref","first-page":"2766","DOI":"10.2174\/138161210793176572","article-title":"Neuroinflammation, oxidative stress and the pathogenesis of Alzheimer\u2019s disease","volume":"16","author":"Agostinho","year":"2010","journal-title":"Curr Pharm Des"},{"key":"10.3233\/JAD-220439_ref35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.arr.2019.01.002","article-title":"Neuroinflammation in mild cognitive impairment and Alzheimer\u2019s disease: A meta-analysis","volume":"50","author":"Bradburn","year":"2019","journal-title":"Ageing Res Rev"},{"key":"10.3233\/JAD-220439_ref36","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s12974-018-1059-y","article-title":"Age-related cognitive impairment is associated with long-term neuroinflammation and oxidative stress in a mouse model of episodic systemic inflammation","volume":"15","author":"d\u2019Avila","year":"2018","journal-title":"J Neuroinflammation"},{"key":"10.3233\/JAD-220439_ref37","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1001\/archneur.59.6.972","article-title":"Increase of brain oxidative stress in mild cognitive impairment: A possible predictor of Alzheimer disease","volume":"59","author":"Pratic\u00f2","year":"2002","journal-title":"Arch Neurol"},{"key":"10.3233\/JAD-220439_ref38","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1042\/CS20120078","article-title":"Angiotensin II AT1 receptor blockers as treatments for inflammatory brain disorders","volume":"123","author":"Saavedra","year":"2012","journal-title":"Clin Sci"},{"key":"10.3233\/JAD-220439_ref39","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s10571-015-0327-y","article-title":"Evidence to consider angiotensin II receptor blockers for the treatment of early Alzheimer\u2019s disease","volume":"36","author":"Saavedra","year":"2016","journal-title":"Cell Mol Neurobiol"},{"key":"10.3233\/JAD-220439_ref40","doi-asserted-by":"crossref","first-page":"484","DOI":"10.2174\/0929866527666191230103739","article-title":"Renin-angiotensin system and Alzheimer\u2019s disease pathophysiology: From the potential interactions to therapeutic perspectives","volume":"27","author":"Ribeiro","year":"2020","journal-title":"Protein Peptide Lett"},{"key":"10.3233\/JAD-220439_ref41","doi-asserted-by":"crossref","first-page":"518","DOI":"10.2174\/1389557516666161025094539","article-title":"Angiotensin mediated oxidative stress and neuroprotective potential of antioxidants and AT1 receptor blockers","volume":"17","author":"Prusty","year":"2017","journal-title":"Mini Rev Med Chem"},{"key":"10.3233\/JAD-220439_ref42","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1007\/s10571-006-9009-0","article-title":"Mechanisms of the anti-ischemic effect of angiotensin II AT 1 receptor antagonists in the brain","volume":"26","author":"Saavedra","year":"2006","journal-title":"Cell Mol Neurobiol"},{"key":"10.3233\/JAD-220439_ref43","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/S0021-5198(19)30762-0","article-title":"Role of the angiotensin II type-2 receptor in the mouse central nervous system","volume":"81","author":"Okuyama","year":"1999","journal-title":"Japan J Pharmacol"},{"key":"10.3233\/JAD-220439_ref44","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1001\/jamaneurol.2015.1001","article-title":"Association between angiotensin receptor blockers and longitudinal decline in tau in mild cognitive impairment","volume":"72","author":"Hajjar","year":"2015","journal-title":"JAMA Neurol"},{"key":"10.3233\/JAD-220439_ref45","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.3233\/JAD-180943","article-title":"Observational study of brain atrophy and cognitive decline comparing a sample of community-dwelling people taking angiotensin converting enzyme inhibitors and angiotensin receptor blockers over time","volume":"68","author":"Moran","year":"2019","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220439_ref46","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.neurobiolaging.2020.12.011","article-title":"Associations between brain amyloid accumulation and the use of angiotensin-converting enzyme inhibitors versus angiotensin receptor blockers","volume":"100","author":"Ouk","year":"2021","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-220439_ref47","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s13195-017-0255-9","article-title":"Memory is preserved in older adults taking AT1 receptor blockers","volume":"9","author":"Ho","year":"2017","journal-title":"Alzheimers Res Ther"},{"key":"10.3233\/JAD-220439_ref48","doi-asserted-by":"crossref","first-page":"e002881","DOI":"10.1136\/bmjopen-2013-002881","article-title":"Effects of centrally acting ACE inhibitors on the rate of cognitive decline in dementia","volume":"3","author":"Gao","year":"2013","journal-title":"BMJ Open"},{"key":"10.3233\/JAD-220439_ref49","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s13195-021-00778-8","article-title":"The use of angiotensin-converting enzyme inhibitors vs. angiotensin receptor blockers and cognitive decline in Alzheimer\u2019s disease: The importance of blood-brain barrier penetration and APOE \u025b4 carrier status","volume":"13","author":"Ouk","year":"2021","journal-title":"Alzheimers Res Ther"},{"key":"10.3233\/JAD-220439_ref50","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1161\/HYPERTENSIONAHA.121.17049","article-title":"Blood-brain barrier crossing renin-angiotensin drugs and cognition in the elderly: A meta-analysis","volume":"78","author":"Ho","year":"2021","journal-title":"Hypertension"},{"key":"10.3233\/JAD-220439_ref51","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s00401-010-0718-6","article-title":"The overlap between neurodegenerative and vascular factors in the pathogenesis of dementia","volume":"120","author":"Iadecola","year":"2010","journal-title":"Acta Neuropathol"},{"key":"10.3233\/JAD-220439_ref52","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1136\/jnnp.2008.164483","article-title":"Attention deficits in Alzheimer\u2019s disease and vascular dementia","volume":"81","author":"McGuinness","year":"2010","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"10.3233\/JAD-220439_ref53","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1002\/gps.2375","article-title":"Executive functioning in Alzheimer\u2019s disease and vascular dementia","volume":"25","author":"McGuinness","year":"2010","journal-title":"Int J Geriatr Psychiatry"},{"key":"10.3233\/JAD-220439_ref54","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1093\/brain\/awy150","article-title":"Effects of amyloid pathology and neurodegeneration on cognitive change in cognitively normal adults","volume":"141","author":"Bilgel","year":"2018","journal-title":"Brain"},{"key":"10.3233\/JAD-220439_ref55","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1212\/01.WNL.0000168877.06011.15","article-title":"Subcortical vascular dementia: Integrating neuropsychological and neuroradiologic data","volume":"65","author":"Price","year":"2005","journal-title":"Neurology"},{"key":"10.3233\/JAD-220439_ref56","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1093\/brain\/awl385","article-title":"Profiles of neuropsychological impairment in autopsy-defined Alzheimer\u2019s disease and cerebrovascular disease","volume":"130","author":"Reed","year":"2007","journal-title":"Brain"}],"container-title":["Journal of Alzheimer's Disease"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JAD-220439","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:06:50Z","timestamp":1777370810000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JAD-220439"}},"subtitle":[],"editor":[{"given":"Ronan","family":"O\u2019Caoimh","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,9,13]]},"references-count":53,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.3233\/jad-220439","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,13]]}}}