Antihypertensive Medication Class and the Risk of Dementia and Cognitive Decline in Older Adults: A Secondary Analysis of the Prospective HELIAD Cohort

Article type: Research Article

Authors: Liampas, Ioannis^a | Hatzimanolis, Alex^b | Siokas, Vasileios^a | Yannakoulia, Mary^c | Kosmidis, Mary H.^d | Sakka, Paraskevi^e | Hadjigeorgiou, Georgios M.^{a; f} | Scarmeas, Nikolaos^{g; h} | Dardiotis, Efthimios^{a; *}

Affiliations: [a] Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, Larissa, Greece | [b] Department of Psychiatry, Aiginition Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece | [c] Department of Nutrition and Dietetics, Harokopio University, Athens, Greece | [d] Lab of Cognitive Neuroscience, School of Psychology, Aristotle University of Thessaloniki, Thessaloniki, Greece | [e] Athens Association of Alzheimer’s Disease and Related Disorders, Marousi, Athens, Greece | [f] Department of Neurology, Medical School, University of Cyprus, Nicosia, Cyprus | [g] 1st Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece | [h] Taub Institute for Research in Alzheimer’s Disease and the Aging Brain, The Gertrude H. Sergievsky Center, Department of Neurology, Columbia University, New York, NY, USA

Correspondence: [*] Correspondence to: Efthimios Dardiotis, Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, Mezourlo Hill, 41100, Larissa, Greece. Tel.: +30 6974224279; E-mail: edar@med.uth.gr.

Abstract: 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±4.94 years) with hypertension and a mean follow-up of 3.02±0.82 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 = (0.1, 4.9)] and language [4.4% of a SD, 95% CI = (1.4, 7.4)] decline compared to non-users. The fully adjusted model reproduced similar associations for both global cognitive [β= 0.027, 95% CI =  (–0.003, 0.057)], and language decline [β= 0.063, 95% CI = (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.

Keywords: Angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, diuretics, genetic predisposition to disease, longitudinal

DOI: 10.3233/JAD-220439

Journal: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 709-719, 2022