Investigation of antihypertensive class, dementia, and cognitive decline: A meta-analysis

Ruth Peters¹, Sevil Yasar², Craig S Anderson², Shea Andrews², Riitta Antikainen², Hisatomi Arima², Nigel Beckett², Joanne C Beer², Anne Suzanne Bertens², Andrew Booth², Martin van Boxtel², Carol Brayne², Henry Brodaty², Michelle C Carlson², John Chalmers², Maria Corrada², Steven DeKosky², Carol Derby², Roger A Dixon², Françoise Forette², Mary Ganguli², Willem A van Gool², Antonio Guaita², Ann M Hever², David B Hogan², Carol Jagger², Mindy Katz², Claudia Kawas², Patrick G Kehoe², Sirkka Keinanen-Kiukaanniemi², Rose Ann Kenny², Sebastian Köhler², Setor K Kunutsor², Jari Laukkanen², Colleen Maxwell², G Peggy McFall², Tessa van Middelaar², Eric P Moll van Charante², Tze-Pin Ng², Jean Peters¹, Iris Rawtaer², Edo Richard², Kenneth Rockwood², Lina Rydén², Perminder S Sachdev², Ingmar Skoog², Johan Skoog², Jan A Staessen², Blossom C M Stephan², Sylvain Sebert², Lutgarde Thijs², Stella Trompet², Phillip J Tully², Christophe Tzourio², Roberta Vaccaro², Eeva Vaaramo², Erin Walsh², Jane Warwick², Kaarin J Anstey²

Affiliations

¹ From Neuroscience Research Australia (R.P., K.J.A.); University of New South Wales (R.P., C.A., H.B., J.C., P.S.S., K.J.A.), Sydney, Australia; Johns Hopkins University (S.Y., M.C.C.), Baltimore, MD; The George Institute for Global Health (C.A., J.C.), Sydney, Australia; The George Institute China at Peking University Health Sciences Center (C.A.), Beijing, China; Icahn School of Medicine at Mount Sinai (S.A.), New York, NY; Center for Life Course Health Research/Geriatrics (R.A., S.K.-K., S.S., E.V.), University of Oulu; Medical Research Center Oulu (R.A.), Oulu University Hospital; Oulu City Hospital (R.A.), Finland; Department of Preventive Medicine and Public Health (H.A.), Fukuoka University, Japan; Guys and St Thomas' NHS Foundation Trust (N.B.), London, UK; University of Pittsburgh (J.C.B., M.G.), PA; Leiden University Medical Centre (A.S.B., S.T.), the Netherlands; University of Sheffield (A.B., J.P.), UK; School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology (M.v.B., S.K.), Maastricht University, the Netherlands; University of Cambridge (C.B.), UK; University of California (M.C., C.K.), Irvine; University of Florida (S.D.), Gainesville; Albert Einstein College of Medicine (C.D., M.K.), New York, NY; University of Alberta (R.A.D., G.P.M.), Edmonton, Canada; International Longevity Centre (F.F.), Paris, France; University of Amsterdam (W.A.v.G., E.P.M.v.C.), the Netherlands; Golgi Cenci Foundation (A.G., R.V.), Milan, Italy; Trinity College Dublin (A.H., R.A.K.), Ireland; University of Calgary (D.B.H.), Canada; Newcastle University (C.J., B.C.M.S.), Newcastle upon Tyne; University of Bristol (P.G.K., S.K.K.), UK; University of Eastern Finland (J.L.), Kuopio; Faculty of Sport and Health Sciences, University of Jyväskylä (J.L.), Finland; School of Pharmacy, University of Waterloo (C.M.), Ontario, Canada; Academic Medical Center (T.v.M., E.R.), Amsterdam; Donders Institute for Brain, Cognition and Behaviour (T.v.M., E.R.), Radboud University Medical Center, Nijmegen, the Netherlands; National University of Singapore (T.-P.N.); Sengkang General Hospital (I.R.), Singhealth Duke-NUS Academic Medical Centre, Singapore; Dalhousie University (K.R.), Halifax, Canada; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy (L.R., I.S.), and Department of Psychology (J.S.), Centre for Ageing and Health (AgeCap) at the University of Gothenburg, Sweden; University of Leuven (J.A.S., L.T.), Belgium; Bordeaux Population Health Research Center (P.J.T., C.T.), UMR 1219, CHU Bordeaux, University of Bordeaux, Inserm, France; University of Adelaide (P.J.T.); Australian National University (E.W.), Canberra, Australia; and University of Warwick (J.W.), Coventry, UK. r.peters@imperial.ac.uk.
² From Neuroscience Research Australia (R.P., K.J.A.); University of New South Wales (R.P., C.A., H.B., J.C., P.S.S., K.J.A.), Sydney, Australia; Johns Hopkins University (S.Y., M.C.C.), Baltimore, MD; The George Institute for Global Health (C.A., J.C.), Sydney, Australia; The George Institute China at Peking University Health Sciences Center (C.A.), Beijing, China; Icahn School of Medicine at Mount Sinai (S.A.), New York, NY; Center for Life Course Health Research/Geriatrics (R.A., S.K.-K., S.S., E.V.), University of Oulu; Medical Research Center Oulu (R.A.), Oulu University Hospital; Oulu City Hospital (R.A.), Finland; Department of Preventive Medicine and Public Health (H.A.), Fukuoka University, Japan; Guys and St Thomas' NHS Foundation Trust (N.B.), London, UK; University of Pittsburgh (J.C.B., M.G.), PA; Leiden University Medical Centre (A.S.B., S.T.), the Netherlands; University of Sheffield (A.B., J.P.), UK; School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology (M.v.B., S.K.), Maastricht University, the Netherlands; University of Cambridge (C.B.), UK; University of California (M.C., C.K.), Irvine; University of Florida (S.D.), Gainesville; Albert Einstein College of Medicine (C.D., M.K.), New York, NY; University of Alberta (R.A.D., G.P.M.), Edmonton, Canada; International Longevity Centre (F.F.), Paris, France; University of Amsterdam (W.A.v.G., E.P.M.v.C.), the Netherlands; Golgi Cenci Foundation (A.G., R.V.), Milan, Italy; Trinity College Dublin (A.H., R.A.K.), Ireland; University of Calgary (D.B.H.), Canada; Newcastle University (C.J., B.C.M.S.), Newcastle upon Tyne; University of Bristol (P.G.K., S.K.K.), UK; University of Eastern Finland (J.L.), Kuopio; Faculty of Sport and Health Sciences, University of Jyväskylä (J.L.), Finland; School of Pharmacy, University of Waterloo (C.M.), Ontario, Canada; Academic Medical Center (T.v.M., E.R.), Amsterdam; Donders Institute for Brain, Cognition and Behaviour (T.v.M., E.R.), Radboud University Medical Center, Nijmegen, the Netherlands; National University of Singapore (T.-P.N.); Sengkang General Hospital (I.R.), Singhealth Duke-NUS Academic Medical Centre, Singapore; Dalhousie University (K.R.), Halifax, Canada; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy (L.R., I.S.), and Department of Psychology (J.S.), Centre for Ageing and Health (AgeCap) at the University of Gothenburg, Sweden; University of Leuven (J.A.S., L.T.), Belgium; Bordeaux Population Health Research Center (P.J.T., C.T.), UMR 1219, CHU Bordeaux, University of Bordeaux, Inserm, France; University of Adelaide (P.J.T.); Australian National University (E.W.), Canberra, Australia; and University of Warwick (J.W.), Coventry, UK.

PMID: 31827004
PMCID: PMC7108807
DOI: 10.1212/WNL.0000000000008732

Meta-Analysis

Investigation of antihypertensive class, dementia, and cognitive decline: A meta-analysis

Ruth Peters et al. Neurology. 2020.

. 2020 Jan 21;94(3):e267-e281.

doi: 10.1212/WNL.0000000000008732. Epub 2019 Dec 11.

Authors

Affiliations

¹ From Neuroscience Research Australia (R.P., K.J.A.); University of New South Wales (R.P., C.A., H.B., J.C., P.S.S., K.J.A.), Sydney, Australia; Johns Hopkins University (S.Y., M.C.C.), Baltimore, MD; The George Institute for Global Health (C.A., J.C.), Sydney, Australia; The George Institute China at Peking University Health Sciences Center (C.A.), Beijing, China; Icahn School of Medicine at Mount Sinai (S.A.), New York, NY; Center for Life Course Health Research/Geriatrics (R.A., S.K.-K., S.S., E.V.), University of Oulu; Medical Research Center Oulu (R.A.), Oulu University Hospital; Oulu City Hospital (R.A.), Finland; Department of Preventive Medicine and Public Health (H.A.), Fukuoka University, Japan; Guys and St Thomas' NHS Foundation Trust (N.B.), London, UK; University of Pittsburgh (J.C.B., M.G.), PA; Leiden University Medical Centre (A.S.B., S.T.), the Netherlands; University of Sheffield (A.B., J.P.), UK; School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology (M.v.B., S.K.), Maastricht University, the Netherlands; University of Cambridge (C.B.), UK; University of California (M.C., C.K.), Irvine; University of Florida (S.D.), Gainesville; Albert Einstein College of Medicine (C.D., M.K.), New York, NY; University of Alberta (R.A.D., G.P.M.), Edmonton, Canada; International Longevity Centre (F.F.), Paris, France; University of Amsterdam (W.A.v.G., E.P.M.v.C.), the Netherlands; Golgi Cenci Foundation (A.G., R.V.), Milan, Italy; Trinity College Dublin (A.H., R.A.K.), Ireland; University of Calgary (D.B.H.), Canada; Newcastle University (C.J., B.C.M.S.), Newcastle upon Tyne; University of Bristol (P.G.K., S.K.K.), UK; University of Eastern Finland (J.L.), Kuopio; Faculty of Sport and Health Sciences, University of Jyväskylä (J.L.), Finland; School of Pharmacy, University of Waterloo (C.M.), Ontario, Canada; Academic Medical Center (T.v.M., E.R.), Amsterdam; Donders Institute for Brain, Cognition and Behaviour (T.v.M., E.R.), Radboud University Medical Center, Nijmegen, the Netherlands; National University of Singapore (T.-P.N.); Sengkang General Hospital (I.R.), Singhealth Duke-NUS Academic Medical Centre, Singapore; Dalhousie University (K.R.), Halifax, Canada; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy (L.R., I.S.), and Department of Psychology (J.S.), Centre for Ageing and Health (AgeCap) at the University of Gothenburg, Sweden; University of Leuven (J.A.S., L.T.), Belgium; Bordeaux Population Health Research Center (P.J.T., C.T.), UMR 1219, CHU Bordeaux, University of Bordeaux, Inserm, France; University of Adelaide (P.J.T.); Australian National University (E.W.), Canberra, Australia; and University of Warwick (J.W.), Coventry, UK. r.peters@imperial.ac.uk.
² From Neuroscience Research Australia (R.P., K.J.A.); University of New South Wales (R.P., C.A., H.B., J.C., P.S.S., K.J.A.), Sydney, Australia; Johns Hopkins University (S.Y., M.C.C.), Baltimore, MD; The George Institute for Global Health (C.A., J.C.), Sydney, Australia; The George Institute China at Peking University Health Sciences Center (C.A.), Beijing, China; Icahn School of Medicine at Mount Sinai (S.A.), New York, NY; Center for Life Course Health Research/Geriatrics (R.A., S.K.-K., S.S., E.V.), University of Oulu; Medical Research Center Oulu (R.A.), Oulu University Hospital; Oulu City Hospital (R.A.), Finland; Department of Preventive Medicine and Public Health (H.A.), Fukuoka University, Japan; Guys and St Thomas' NHS Foundation Trust (N.B.), London, UK; University of Pittsburgh (J.C.B., M.G.), PA; Leiden University Medical Centre (A.S.B., S.T.), the Netherlands; University of Sheffield (A.B., J.P.), UK; School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology (M.v.B., S.K.), Maastricht University, the Netherlands; University of Cambridge (C.B.), UK; University of California (M.C., C.K.), Irvine; University of Florida (S.D.), Gainesville; Albert Einstein College of Medicine (C.D., M.K.), New York, NY; University of Alberta (R.A.D., G.P.M.), Edmonton, Canada; International Longevity Centre (F.F.), Paris, France; University of Amsterdam (W.A.v.G., E.P.M.v.C.), the Netherlands; Golgi Cenci Foundation (A.G., R.V.), Milan, Italy; Trinity College Dublin (A.H., R.A.K.), Ireland; University of Calgary (D.B.H.), Canada; Newcastle University (C.J., B.C.M.S.), Newcastle upon Tyne; University of Bristol (P.G.K., S.K.K.), UK; University of Eastern Finland (J.L.), Kuopio; Faculty of Sport and Health Sciences, University of Jyväskylä (J.L.), Finland; School of Pharmacy, University of Waterloo (C.M.), Ontario, Canada; Academic Medical Center (T.v.M., E.R.), Amsterdam; Donders Institute for Brain, Cognition and Behaviour (T.v.M., E.R.), Radboud University Medical Center, Nijmegen, the Netherlands; National University of Singapore (T.-P.N.); Sengkang General Hospital (I.R.), Singhealth Duke-NUS Academic Medical Centre, Singapore; Dalhousie University (K.R.), Halifax, Canada; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy (L.R., I.S.), and Department of Psychology (J.S.), Centre for Ageing and Health (AgeCap) at the University of Gothenburg, Sweden; University of Leuven (J.A.S., L.T.), Belgium; Bordeaux Population Health Research Center (P.J.T., C.T.), UMR 1219, CHU Bordeaux, University of Bordeaux, Inserm, France; University of Adelaide (P.J.T.); Australian National University (E.W.), Canberra, Australia; and University of Warwick (J.W.), Coventry, UK.

PMID: 31827004
PMCID: PMC7108807
DOI: 10.1212/WNL.0000000000008732

Abstract

Objective: High blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our objective was to determine whether any particular antihypertensive class was associated with a reduced risk of cognitive decline or dementia using comprehensive meta-analysis including reanalysis of original participant data.

Methods: To identify suitable studies, MEDLINE, Embase, and PsycINFO and preexisting study consortia were searched from inception to December 2017. Authors of prospective longitudinal human studies or trials of antihypertensives were contacted for data sharing and collaboration. Outcome measures were incident dementia or incident cognitive decline (classified using the reliable change index method). Data were separated into mid and late-life (>65 years) and each antihypertensive class was compared to no treatment and to treatment with other antihypertensives. Meta-analysis was used to synthesize data.

Results: Over 50,000 participants from 27 studies were included. Among those aged >65 years, with the exception of diuretics, we found no relationship by class with incident cognitive decline or dementia. Diuretic use was suggestive of benefit in some analyses but results were not consistent across follow-up time, comparator group, and outcome. Limited data precluded meaningful analyses in those ≤65 years of age.

Conclusion: Our findings, drawn from the current evidence base, support clinical freedom in the selection of antihypertensive regimens to achieve blood pressure goals.

Clinical trials registration: The review was registered with the international prospective register of systematic reviews (PROSPERO), registration number CRD42016045454.

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Figures

Figure 1. Forest plots showing odds ratios for risk of developing dementia by exposure to each antihypertensive class compared to no treatment in participants aged over 65 years with ≥5 years follow-up
^aAdjusted for sex, age, baseline systolic blood pressure, and education. Additional adjustment for ethnic group in the Einstein Aging Study. ACE-I = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; BB = β-blocker; CCB = calcium channel blocker; CSHA = Canadian Study of Health and Ageing; GEM = Ginkgo Evaluation and Memory trial; HYVET = Hypertension in the Very Elderly Trial; MAAS = Maastricht Ageing Study; MYHAT = Monongahela Valley Independent Elders Survey; PreDIVA = Prevention of Dementia by Intensive Vascular Care; Syst-*Eur =* Systolic Hypertension in Europe.

Figure 2. Forest plots showing odds ratios for risk of developing cognitive decline by exposure to each antihypertensive class compared to no treatment in participants aged over 65 years with ≥5 years follow-up
^aAdjusted for sex, age, baseline systolic blood pressure, and education. ^bCognitive decline classified using the reliable change index and a deterioration in the cognitive screening test, the Mini-Mental State Examination. ACE-I = angiotensin-converting enzyme inhibitor; ALSA = Australian Longitudinal Study of Aging; ARB = angiotensin receptor blocker; BB = β-blocker; CCB = calcium channel blocker; CFAS = Cognitive Function and Ageing Studies; CSHA = Canadian Study of Health and Ageing; GEM = Ginkgo Evaluation and Memory trial; HYVET = Hypertension in the Very Elderly Trial; MAAS = Maastricht Ageing Study; MAS = Sydney Memory and Ageing Study; MYHAT = Monongahela Valley Independent Elders Survey; PATH = Personality and Total Health study; PreDIVA = Prevention of Dementia by Intensive Vascular Care; Syst-*Eur =* Systolic Hypertension in Europe; TILDA = Irish Longitudinal Study on Ageing.

See this image and copyright information in PMC

References

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Investigation of antihypertensive class, dementia, and cognitive decline: A meta-analysis

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Investigation of antihypertensive class, dementia, and cognitive decline: A meta-analysis

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