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August 21, 2018; 91 (8) Article

Association of orthostatic hypotension with incident dementia, stroke, and cognitive decline

Andreea M. Rawlings, Stephen P. Juraschek, Gerardo Heiss, Timothy Hughes, Michelle L. Meyer, Elizabeth Selvin, A. Richey Sharrett, B. Gwen Windham, Rebecca F. Gottesman
First published July 25, 2018, DOI: https://doi.org/10.1212/WNL.0000000000006027
Andreea M. Rawlings
From the Department of Epidemiology (A.M.R., S.P.J., E.S., A.R.S., R.F.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; School of Biological and Population Health Sciences (A.M.R.), Oregon State University, Corvallis; Departments of Medicine (S.P.J.) and Neurology (R.F.G.), Johns Hopkins School of Medicine, Baltimore, MD; Harvard Medical School and Beth Israel Deaconess Medical Center (S.P.J.), Boston MA; Department of Epidemiology (G.H., M.L.M.), University of North Carolina at Chapel Hill; Department of Internal Medicine (T.M.H.), Division of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC; and Division of Geriatrics (B.G.W.), Department of Medicine, University of Mississippi Medical Center, Jackson.
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Stephen P. Juraschek
From the Department of Epidemiology (A.M.R., S.P.J., E.S., A.R.S., R.F.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; School of Biological and Population Health Sciences (A.M.R.), Oregon State University, Corvallis; Departments of Medicine (S.P.J.) and Neurology (R.F.G.), Johns Hopkins School of Medicine, Baltimore, MD; Harvard Medical School and Beth Israel Deaconess Medical Center (S.P.J.), Boston MA; Department of Epidemiology (G.H., M.L.M.), University of North Carolina at Chapel Hill; Department of Internal Medicine (T.M.H.), Division of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC; and Division of Geriatrics (B.G.W.), Department of Medicine, University of Mississippi Medical Center, Jackson.
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Gerardo Heiss
From the Department of Epidemiology (A.M.R., S.P.J., E.S., A.R.S., R.F.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; School of Biological and Population Health Sciences (A.M.R.), Oregon State University, Corvallis; Departments of Medicine (S.P.J.) and Neurology (R.F.G.), Johns Hopkins School of Medicine, Baltimore, MD; Harvard Medical School and Beth Israel Deaconess Medical Center (S.P.J.), Boston MA; Department of Epidemiology (G.H., M.L.M.), University of North Carolina at Chapel Hill; Department of Internal Medicine (T.M.H.), Division of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC; and Division of Geriatrics (B.G.W.), Department of Medicine, University of Mississippi Medical Center, Jackson.
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Timothy Hughes
From the Department of Epidemiology (A.M.R., S.P.J., E.S., A.R.S., R.F.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; School of Biological and Population Health Sciences (A.M.R.), Oregon State University, Corvallis; Departments of Medicine (S.P.J.) and Neurology (R.F.G.), Johns Hopkins School of Medicine, Baltimore, MD; Harvard Medical School and Beth Israel Deaconess Medical Center (S.P.J.), Boston MA; Department of Epidemiology (G.H., M.L.M.), University of North Carolina at Chapel Hill; Department of Internal Medicine (T.M.H.), Division of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC; and Division of Geriatrics (B.G.W.), Department of Medicine, University of Mississippi Medical Center, Jackson.
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Michelle L. Meyer
From the Department of Epidemiology (A.M.R., S.P.J., E.S., A.R.S., R.F.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; School of Biological and Population Health Sciences (A.M.R.), Oregon State University, Corvallis; Departments of Medicine (S.P.J.) and Neurology (R.F.G.), Johns Hopkins School of Medicine, Baltimore, MD; Harvard Medical School and Beth Israel Deaconess Medical Center (S.P.J.), Boston MA; Department of Epidemiology (G.H., M.L.M.), University of North Carolina at Chapel Hill; Department of Internal Medicine (T.M.H.), Division of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC; and Division of Geriatrics (B.G.W.), Department of Medicine, University of Mississippi Medical Center, Jackson.
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Elizabeth Selvin
From the Department of Epidemiology (A.M.R., S.P.J., E.S., A.R.S., R.F.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; School of Biological and Population Health Sciences (A.M.R.), Oregon State University, Corvallis; Departments of Medicine (S.P.J.) and Neurology (R.F.G.), Johns Hopkins School of Medicine, Baltimore, MD; Harvard Medical School and Beth Israel Deaconess Medical Center (S.P.J.), Boston MA; Department of Epidemiology (G.H., M.L.M.), University of North Carolina at Chapel Hill; Department of Internal Medicine (T.M.H.), Division of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC; and Division of Geriatrics (B.G.W.), Department of Medicine, University of Mississippi Medical Center, Jackson.
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A. Richey Sharrett
From the Department of Epidemiology (A.M.R., S.P.J., E.S., A.R.S., R.F.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; School of Biological and Population Health Sciences (A.M.R.), Oregon State University, Corvallis; Departments of Medicine (S.P.J.) and Neurology (R.F.G.), Johns Hopkins School of Medicine, Baltimore, MD; Harvard Medical School and Beth Israel Deaconess Medical Center (S.P.J.), Boston MA; Department of Epidemiology (G.H., M.L.M.), University of North Carolina at Chapel Hill; Department of Internal Medicine (T.M.H.), Division of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC; and Division of Geriatrics (B.G.W.), Department of Medicine, University of Mississippi Medical Center, Jackson.
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B. Gwen Windham
From the Department of Epidemiology (A.M.R., S.P.J., E.S., A.R.S., R.F.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; School of Biological and Population Health Sciences (A.M.R.), Oregon State University, Corvallis; Departments of Medicine (S.P.J.) and Neurology (R.F.G.), Johns Hopkins School of Medicine, Baltimore, MD; Harvard Medical School and Beth Israel Deaconess Medical Center (S.P.J.), Boston MA; Department of Epidemiology (G.H., M.L.M.), University of North Carolina at Chapel Hill; Department of Internal Medicine (T.M.H.), Division of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC; and Division of Geriatrics (B.G.W.), Department of Medicine, University of Mississippi Medical Center, Jackson.
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Rebecca F. Gottesman
From the Department of Epidemiology (A.M.R., S.P.J., E.S., A.R.S., R.F.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; School of Biological and Population Health Sciences (A.M.R.), Oregon State University, Corvallis; Departments of Medicine (S.P.J.) and Neurology (R.F.G.), Johns Hopkins School of Medicine, Baltimore, MD; Harvard Medical School and Beth Israel Deaconess Medical Center (S.P.J.), Boston MA; Department of Epidemiology (G.H., M.L.M.), University of North Carolina at Chapel Hill; Department of Internal Medicine (T.M.H.), Division of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC; and Division of Geriatrics (B.G.W.), Department of Medicine, University of Mississippi Medical Center, Jackson.
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Citation
Association of orthostatic hypotension with incident dementia, stroke, and cognitive decline
Andreea M. Rawlings, Stephen P. Juraschek, Gerardo Heiss, Timothy Hughes, Michelle L. Meyer, Elizabeth Selvin, A. Richey Sharrett, B. Gwen Windham, Rebecca F. Gottesman
Neurology Aug 2018, 91 (8) e759-e768; DOI: 10.1212/WNL.0000000000006027

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Abstract

Objective To examine associations of orthostatic hypotension (OH) with dementia and long-term cognitive decline and to update previously published results in the same cohort for stroke with an additional 16 years of follow-up.

Methods We analyzed data from 11,709 participants without a history of coronary heart disease or stroke who attended the baseline examination (1987–1989) of the prospective Atherosclerosis Risk in Communities (ARIC) study. OH was defined as a drop in systolic blood pressure (BP) of at least 20 mm Hg or a drop in diastolic BP of at least 10 mm Hg on standing. Dementia was ascertained via examination, contact with participants or their proxy, or medical record surveillance. Ischemic stroke was ascertained via cohort surveillance of hospitalizations, cohort follow-up, and linkage with registries. Both outcomes were adjudicated. Cognitive function was ascertained via 3 neuropsychological tests administered in 1990 to 1992 and 1996 to 1998 and a full battery of tests in 2011 to 2013. Scores were summarized and reported as SDs. We used adjusted Cox regression and linear mixed models.

Results Over ≈25 years, 1,068 participants developed dementia and 842 had an ischemic stroke. Compared to persons without OH at baseline, those with OH had a higher risk of dementia (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.20–1.97) and ischemic stroke (HR 2.08, 95% CI 1.65–2.62). Persons with OH had greater, although nonsignificant, cognitive decline over 20 years (SD 0.09, 95% CI −0.02 to 0.21).

Conclusions OH assessed in midlife was independently associated with incident dementia and ischemic stroke. Additional studies are needed to elucidate potential mechanisms for these associations and possible applications for prevention.

Glossary

AD=
Alzheimer disease;
ARIC=
Atherosclerosis Risk in Communities;
BP=
blood pressure;
CI=
confidence interval;
DBP=
diastolic blood pressure;
HDL=
high-density lipoprotein;
HR=
hazard ratio;
ICD-9=
International Classification of Diseases, 9th revision;
OH=
orthostatic hypotension;
SBP=
systolic blood pressure

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • CME Course: NPub.org/cmelist

  • Received September 13, 2017.
  • Accepted in final form May 19, 2018.
  • © 2018 American Academy of Neurology
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Disputes & Debates: Rapid online correspondence

  • Reply to Dr. Kawada & Dr. Young
    • Andreea M. Rawlings, Biostatistician, Johns Hopkins University
    • Rebecca F. Gottesman, Neurologist, Professor of Neurology and Epidemiology, Johns Hopkins University
    Submitted December 27, 2018
  • Reader response: Association of orthostatic hypotension with incident dementia, stroke, and cognitive decline
    • Tomoyuki Kawada, Professor, Nippon Medical School
    Submitted September 04, 2018
  • Orthostatic hypotension and dementia: Associated but not guilty
    • Tim M. Young, BSc, MBBS, MRCP, PhD, FHEA, Consultant Neurologist and UCL Course Tutor, Institute of Neurology, University College London (London, England)
    Submitted August 03, 2018
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