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September 10, 2019; 93 (11) Article

Sex-specific relationship of cardiometabolic syndrome with lower cortical thickness

Si Eun Kim, Jin San Lee, Sookyoung Woo, Seonwoo Kim, Hee Jin Kim, Seongbeom Park, Byung In Lee, Jinse Park, Yeshin Kim, Hyemin Jang, Seung Joo Kim, Soo Hyun Cho, Byungju Lee, View ORCID ProfileSamuel N. Lockhart, Duk L. Na, Sang Won Seo
First published August 23, 2019, DOI: https://doi.org/10.1212/WNL.0000000000008084
Si Eun Kim
From the Departments of Neurology (S.E.K., H.J.K., S.P., H.J., S.J.K., S.H.C., D.L.N., S.W.S.), Clinical Research Design and Evaluation (S.W.S.), and Health Sciences and Technology (D.L.N.), SAIHST, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul; Department of Neurology (S.E.K., B.I.L., J.P.), Inje University College of Medicine, Haeundae Paik Hospital, Busan; Department of Neurology (J.S.L.), Kyung Hee University Hospital; Statistics and Data Center (S.W., S.K.), Center for Clinical Epidemiology (S.W.S.), and Samsung Alzheimer Research Center, Neuroscience Center (H.J.K., S.P., H.J., D.L.N., S.W.S.), Samsung Medical Center, Seoul; Department of Neurology (Y.K.), Kangwon National University College of Medicine, Chuncheon-si, Gangwon-do; Department of Neurology (S.J.K.), Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital; Department of Neurology (S.H.C.), Chonnam National University Hospital, Gwangju; Department of Neurology (B.L.), Yuseong Geriatric Rehabilitation Hospital, Pohang, Korea; and Department of Internal Medicine (S.N.L.), Section of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
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Jin San Lee
From the Departments of Neurology (S.E.K., H.J.K., S.P., H.J., S.J.K., S.H.C., D.L.N., S.W.S.), Clinical Research Design and Evaluation (S.W.S.), and Health Sciences and Technology (D.L.N.), SAIHST, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul; Department of Neurology (S.E.K., B.I.L., J.P.), Inje University College of Medicine, Haeundae Paik Hospital, Busan; Department of Neurology (J.S.L.), Kyung Hee University Hospital; Statistics and Data Center (S.W., S.K.), Center for Clinical Epidemiology (S.W.S.), and Samsung Alzheimer Research Center, Neuroscience Center (H.J.K., S.P., H.J., D.L.N., S.W.S.), Samsung Medical Center, Seoul; Department of Neurology (Y.K.), Kangwon National University College of Medicine, Chuncheon-si, Gangwon-do; Department of Neurology (S.J.K.), Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital; Department of Neurology (S.H.C.), Chonnam National University Hospital, Gwangju; Department of Neurology (B.L.), Yuseong Geriatric Rehabilitation Hospital, Pohang, Korea; and Department of Internal Medicine (S.N.L.), Section of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
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Sookyoung Woo
From the Departments of Neurology (S.E.K., H.J.K., S.P., H.J., S.J.K., S.H.C., D.L.N., S.W.S.), Clinical Research Design and Evaluation (S.W.S.), and Health Sciences and Technology (D.L.N.), SAIHST, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul; Department of Neurology (S.E.K., B.I.L., J.P.), Inje University College of Medicine, Haeundae Paik Hospital, Busan; Department of Neurology (J.S.L.), Kyung Hee University Hospital; Statistics and Data Center (S.W., S.K.), Center for Clinical Epidemiology (S.W.S.), and Samsung Alzheimer Research Center, Neuroscience Center (H.J.K., S.P., H.J., D.L.N., S.W.S.), Samsung Medical Center, Seoul; Department of Neurology (Y.K.), Kangwon National University College of Medicine, Chuncheon-si, Gangwon-do; Department of Neurology (S.J.K.), Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital; Department of Neurology (S.H.C.), Chonnam National University Hospital, Gwangju; Department of Neurology (B.L.), Yuseong Geriatric Rehabilitation Hospital, Pohang, Korea; and Department of Internal Medicine (S.N.L.), Section of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
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Seonwoo Kim
From the Departments of Neurology (S.E.K., H.J.K., S.P., H.J., S.J.K., S.H.C., D.L.N., S.W.S.), Clinical Research Design and Evaluation (S.W.S.), and Health Sciences and Technology (D.L.N.), SAIHST, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul; Department of Neurology (S.E.K., B.I.L., J.P.), Inje University College of Medicine, Haeundae Paik Hospital, Busan; Department of Neurology (J.S.L.), Kyung Hee University Hospital; Statistics and Data Center (S.W., S.K.), Center for Clinical Epidemiology (S.W.S.), and Samsung Alzheimer Research Center, Neuroscience Center (H.J.K., S.P., H.J., D.L.N., S.W.S.), Samsung Medical Center, Seoul; Department of Neurology (Y.K.), Kangwon National University College of Medicine, Chuncheon-si, Gangwon-do; Department of Neurology (S.J.K.), Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital; Department of Neurology (S.H.C.), Chonnam National University Hospital, Gwangju; Department of Neurology (B.L.), Yuseong Geriatric Rehabilitation Hospital, Pohang, Korea; and Department of Internal Medicine (S.N.L.), Section of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
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Hee Jin Kim
From the Departments of Neurology (S.E.K., H.J.K., S.P., H.J., S.J.K., S.H.C., D.L.N., S.W.S.), Clinical Research Design and Evaluation (S.W.S.), and Health Sciences and Technology (D.L.N.), SAIHST, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul; Department of Neurology (S.E.K., B.I.L., J.P.), Inje University College of Medicine, Haeundae Paik Hospital, Busan; Department of Neurology (J.S.L.), Kyung Hee University Hospital; Statistics and Data Center (S.W., S.K.), Center for Clinical Epidemiology (S.W.S.), and Samsung Alzheimer Research Center, Neuroscience Center (H.J.K., S.P., H.J., D.L.N., S.W.S.), Samsung Medical Center, Seoul; Department of Neurology (Y.K.), Kangwon National University College of Medicine, Chuncheon-si, Gangwon-do; Department of Neurology (S.J.K.), Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital; Department of Neurology (S.H.C.), Chonnam National University Hospital, Gwangju; Department of Neurology (B.L.), Yuseong Geriatric Rehabilitation Hospital, Pohang, Korea; and Department of Internal Medicine (S.N.L.), Section of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
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Seongbeom Park
From the Departments of Neurology (S.E.K., H.J.K., S.P., H.J., S.J.K., S.H.C., D.L.N., S.W.S.), Clinical Research Design and Evaluation (S.W.S.), and Health Sciences and Technology (D.L.N.), SAIHST, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul; Department of Neurology (S.E.K., B.I.L., J.P.), Inje University College of Medicine, Haeundae Paik Hospital, Busan; Department of Neurology (J.S.L.), Kyung Hee University Hospital; Statistics and Data Center (S.W., S.K.), Center for Clinical Epidemiology (S.W.S.), and Samsung Alzheimer Research Center, Neuroscience Center (H.J.K., S.P., H.J., D.L.N., S.W.S.), Samsung Medical Center, Seoul; Department of Neurology (Y.K.), Kangwon National University College of Medicine, Chuncheon-si, Gangwon-do; Department of Neurology (S.J.K.), Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital; Department of Neurology (S.H.C.), Chonnam National University Hospital, Gwangju; Department of Neurology (B.L.), Yuseong Geriatric Rehabilitation Hospital, Pohang, Korea; and Department of Internal Medicine (S.N.L.), Section of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
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Byung In Lee
From the Departments of Neurology (S.E.K., H.J.K., S.P., H.J., S.J.K., S.H.C., D.L.N., S.W.S.), Clinical Research Design and Evaluation (S.W.S.), and Health Sciences and Technology (D.L.N.), SAIHST, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul; Department of Neurology (S.E.K., B.I.L., J.P.), Inje University College of Medicine, Haeundae Paik Hospital, Busan; Department of Neurology (J.S.L.), Kyung Hee University Hospital; Statistics and Data Center (S.W., S.K.), Center for Clinical Epidemiology (S.W.S.), and Samsung Alzheimer Research Center, Neuroscience Center (H.J.K., S.P., H.J., D.L.N., S.W.S.), Samsung Medical Center, Seoul; Department of Neurology (Y.K.), Kangwon National University College of Medicine, Chuncheon-si, Gangwon-do; Department of Neurology (S.J.K.), Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital; Department of Neurology (S.H.C.), Chonnam National University Hospital, Gwangju; Department of Neurology (B.L.), Yuseong Geriatric Rehabilitation Hospital, Pohang, Korea; and Department of Internal Medicine (S.N.L.), Section of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
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Jinse Park
From the Departments of Neurology (S.E.K., H.J.K., S.P., H.J., S.J.K., S.H.C., D.L.N., S.W.S.), Clinical Research Design and Evaluation (S.W.S.), and Health Sciences and Technology (D.L.N.), SAIHST, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul; Department of Neurology (S.E.K., B.I.L., J.P.), Inje University College of Medicine, Haeundae Paik Hospital, Busan; Department of Neurology (J.S.L.), Kyung Hee University Hospital; Statistics and Data Center (S.W., S.K.), Center for Clinical Epidemiology (S.W.S.), and Samsung Alzheimer Research Center, Neuroscience Center (H.J.K., S.P., H.J., D.L.N., S.W.S.), Samsung Medical Center, Seoul; Department of Neurology (Y.K.), Kangwon National University College of Medicine, Chuncheon-si, Gangwon-do; Department of Neurology (S.J.K.), Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital; Department of Neurology (S.H.C.), Chonnam National University Hospital, Gwangju; Department of Neurology (B.L.), Yuseong Geriatric Rehabilitation Hospital, Pohang, Korea; and Department of Internal Medicine (S.N.L.), Section of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
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Yeshin Kim
From the Departments of Neurology (S.E.K., H.J.K., S.P., H.J., S.J.K., S.H.C., D.L.N., S.W.S.), Clinical Research Design and Evaluation (S.W.S.), and Health Sciences and Technology (D.L.N.), SAIHST, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul; Department of Neurology (S.E.K., B.I.L., J.P.), Inje University College of Medicine, Haeundae Paik Hospital, Busan; Department of Neurology (J.S.L.), Kyung Hee University Hospital; Statistics and Data Center (S.W., S.K.), Center for Clinical Epidemiology (S.W.S.), and Samsung Alzheimer Research Center, Neuroscience Center (H.J.K., S.P., H.J., D.L.N., S.W.S.), Samsung Medical Center, Seoul; Department of Neurology (Y.K.), Kangwon National University College of Medicine, Chuncheon-si, Gangwon-do; Department of Neurology (S.J.K.), Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital; Department of Neurology (S.H.C.), Chonnam National University Hospital, Gwangju; Department of Neurology (B.L.), Yuseong Geriatric Rehabilitation Hospital, Pohang, Korea; and Department of Internal Medicine (S.N.L.), Section of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
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Hyemin Jang
From the Departments of Neurology (S.E.K., H.J.K., S.P., H.J., S.J.K., S.H.C., D.L.N., S.W.S.), Clinical Research Design and Evaluation (S.W.S.), and Health Sciences and Technology (D.L.N.), SAIHST, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul; Department of Neurology (S.E.K., B.I.L., J.P.), Inje University College of Medicine, Haeundae Paik Hospital, Busan; Department of Neurology (J.S.L.), Kyung Hee University Hospital; Statistics and Data Center (S.W., S.K.), Center for Clinical Epidemiology (S.W.S.), and Samsung Alzheimer Research Center, Neuroscience Center (H.J.K., S.P., H.J., D.L.N., S.W.S.), Samsung Medical Center, Seoul; Department of Neurology (Y.K.), Kangwon National University College of Medicine, Chuncheon-si, Gangwon-do; Department of Neurology (S.J.K.), Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital; Department of Neurology (S.H.C.), Chonnam National University Hospital, Gwangju; Department of Neurology (B.L.), Yuseong Geriatric Rehabilitation Hospital, Pohang, Korea; and Department of Internal Medicine (S.N.L.), Section of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
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Seung Joo Kim
From the Departments of Neurology (S.E.K., H.J.K., S.P., H.J., S.J.K., S.H.C., D.L.N., S.W.S.), Clinical Research Design and Evaluation (S.W.S.), and Health Sciences and Technology (D.L.N.), SAIHST, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul; Department of Neurology (S.E.K., B.I.L., J.P.), Inje University College of Medicine, Haeundae Paik Hospital, Busan; Department of Neurology (J.S.L.), Kyung Hee University Hospital; Statistics and Data Center (S.W., S.K.), Center for Clinical Epidemiology (S.W.S.), and Samsung Alzheimer Research Center, Neuroscience Center (H.J.K., S.P., H.J., D.L.N., S.W.S.), Samsung Medical Center, Seoul; Department of Neurology (Y.K.), Kangwon National University College of Medicine, Chuncheon-si, Gangwon-do; Department of Neurology (S.J.K.), Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital; Department of Neurology (S.H.C.), Chonnam National University Hospital, Gwangju; Department of Neurology (B.L.), Yuseong Geriatric Rehabilitation Hospital, Pohang, Korea; and Department of Internal Medicine (S.N.L.), Section of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
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Soo Hyun Cho
From the Departments of Neurology (S.E.K., H.J.K., S.P., H.J., S.J.K., S.H.C., D.L.N., S.W.S.), Clinical Research Design and Evaluation (S.W.S.), and Health Sciences and Technology (D.L.N.), SAIHST, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul; Department of Neurology (S.E.K., B.I.L., J.P.), Inje University College of Medicine, Haeundae Paik Hospital, Busan; Department of Neurology (J.S.L.), Kyung Hee University Hospital; Statistics and Data Center (S.W., S.K.), Center for Clinical Epidemiology (S.W.S.), and Samsung Alzheimer Research Center, Neuroscience Center (H.J.K., S.P., H.J., D.L.N., S.W.S.), Samsung Medical Center, Seoul; Department of Neurology (Y.K.), Kangwon National University College of Medicine, Chuncheon-si, Gangwon-do; Department of Neurology (S.J.K.), Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital; Department of Neurology (S.H.C.), Chonnam National University Hospital, Gwangju; Department of Neurology (B.L.), Yuseong Geriatric Rehabilitation Hospital, Pohang, Korea; and Department of Internal Medicine (S.N.L.), Section of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
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Byungju Lee
From the Departments of Neurology (S.E.K., H.J.K., S.P., H.J., S.J.K., S.H.C., D.L.N., S.W.S.), Clinical Research Design and Evaluation (S.W.S.), and Health Sciences and Technology (D.L.N.), SAIHST, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul; Department of Neurology (S.E.K., B.I.L., J.P.), Inje University College of Medicine, Haeundae Paik Hospital, Busan; Department of Neurology (J.S.L.), Kyung Hee University Hospital; Statistics and Data Center (S.W., S.K.), Center for Clinical Epidemiology (S.W.S.), and Samsung Alzheimer Research Center, Neuroscience Center (H.J.K., S.P., H.J., D.L.N., S.W.S.), Samsung Medical Center, Seoul; Department of Neurology (Y.K.), Kangwon National University College of Medicine, Chuncheon-si, Gangwon-do; Department of Neurology (S.J.K.), Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital; Department of Neurology (S.H.C.), Chonnam National University Hospital, Gwangju; Department of Neurology (B.L.), Yuseong Geriatric Rehabilitation Hospital, Pohang, Korea; and Department of Internal Medicine (S.N.L.), Section of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
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Samuel N. Lockhart
From the Departments of Neurology (S.E.K., H.J.K., S.P., H.J., S.J.K., S.H.C., D.L.N., S.W.S.), Clinical Research Design and Evaluation (S.W.S.), and Health Sciences and Technology (D.L.N.), SAIHST, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul; Department of Neurology (S.E.K., B.I.L., J.P.), Inje University College of Medicine, Haeundae Paik Hospital, Busan; Department of Neurology (J.S.L.), Kyung Hee University Hospital; Statistics and Data Center (S.W., S.K.), Center for Clinical Epidemiology (S.W.S.), and Samsung Alzheimer Research Center, Neuroscience Center (H.J.K., S.P., H.J., D.L.N., S.W.S.), Samsung Medical Center, Seoul; Department of Neurology (Y.K.), Kangwon National University College of Medicine, Chuncheon-si, Gangwon-do; Department of Neurology (S.J.K.), Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital; Department of Neurology (S.H.C.), Chonnam National University Hospital, Gwangju; Department of Neurology (B.L.), Yuseong Geriatric Rehabilitation Hospital, Pohang, Korea; and Department of Internal Medicine (S.N.L.), Section of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
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  • ORCID record for Samuel N. Lockhart
Duk L. Na
From the Departments of Neurology (S.E.K., H.J.K., S.P., H.J., S.J.K., S.H.C., D.L.N., S.W.S.), Clinical Research Design and Evaluation (S.W.S.), and Health Sciences and Technology (D.L.N.), SAIHST, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul; Department of Neurology (S.E.K., B.I.L., J.P.), Inje University College of Medicine, Haeundae Paik Hospital, Busan; Department of Neurology (J.S.L.), Kyung Hee University Hospital; Statistics and Data Center (S.W., S.K.), Center for Clinical Epidemiology (S.W.S.), and Samsung Alzheimer Research Center, Neuroscience Center (H.J.K., S.P., H.J., D.L.N., S.W.S.), Samsung Medical Center, Seoul; Department of Neurology (Y.K.), Kangwon National University College of Medicine, Chuncheon-si, Gangwon-do; Department of Neurology (S.J.K.), Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital; Department of Neurology (S.H.C.), Chonnam National University Hospital, Gwangju; Department of Neurology (B.L.), Yuseong Geriatric Rehabilitation Hospital, Pohang, Korea; and Department of Internal Medicine (S.N.L.), Section of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
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Sang Won Seo
From the Departments of Neurology (S.E.K., H.J.K., S.P., H.J., S.J.K., S.H.C., D.L.N., S.W.S.), Clinical Research Design and Evaluation (S.W.S.), and Health Sciences and Technology (D.L.N.), SAIHST, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul; Department of Neurology (S.E.K., B.I.L., J.P.), Inje University College of Medicine, Haeundae Paik Hospital, Busan; Department of Neurology (J.S.L.), Kyung Hee University Hospital; Statistics and Data Center (S.W., S.K.), Center for Clinical Epidemiology (S.W.S.), and Samsung Alzheimer Research Center, Neuroscience Center (H.J.K., S.P., H.J., D.L.N., S.W.S.), Samsung Medical Center, Seoul; Department of Neurology (Y.K.), Kangwon National University College of Medicine, Chuncheon-si, Gangwon-do; Department of Neurology (S.J.K.), Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital; Department of Neurology (S.H.C.), Chonnam National University Hospital, Gwangju; Department of Neurology (B.L.), Yuseong Geriatric Rehabilitation Hospital, Pohang, Korea; and Department of Internal Medicine (S.N.L.), Section of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
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Citation
Sex-specific relationship of cardiometabolic syndrome with lower cortical thickness
Si Eun Kim, Jin San Lee, Sookyoung Woo, Seonwoo Kim, Hee Jin Kim, Seongbeom Park, Byung In Lee, Jinse Park, Yeshin Kim, Hyemin Jang, Seung Joo Kim, Soo Hyun Cho, Byungju Lee, Samuel N. Lockhart, Duk L. Na, Sang Won Seo
Neurology Sep 2019, 93 (11) e1045-e1057; DOI: 10.1212/WNL.0000000000008084

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Abstract

Objective To investigate whether cardiometabolic factors were associated with age-related differences in cortical thickness in relation to sex.

Methods In this cross-sectional study, we enrolled 1,322 cognitively normal elderly (≥65 years old) individuals (774 [58.5%] men, 548 [41.5%] women). We measured cortical thickness using a surface-based analysis. We analyzed the associations of cardiometabolic risk factors with cortical thickness using multivariate linear regression models after adjusting for possible confounders and interactions with age.

Result Among women, hypertension (β = −1.119 to −0.024, p < 0.05) and diabetes mellitus (β = −0.920, p = 0.03) were independently associated with lower mean cortical thickness. In addition, there was an interaction effect between obesity (body mass index [BMI] ≥27.5 kg/m2) and age on cortical thickness in women (β = −0.324 to −0.010, p < 0.05), suggesting that age-related differences in cortical thickness were more prominent in obese women compared to women with normal weight. Moreover, low education level (<6 years) was correlated with lower mean cortical thickness (β = −0.053 to −0.046, p < 0.05). Conversely, among men, only being underweight (BMI ≤18.5 kg/m2, β = −2.656 to −0.073, p < 0.05) was associated with lower cortical thickness.

Conclusions Our findings suggest that cortical thickness is more vulnerable to cardiometabolic risk factors in women than in men. Therefore, sex-specific prevention strategies may be needed to protect against accelerated brain aging.

Glossary

BMI=
body mass index;
DM=
diabetes mellitus;
HTN=
hypertension;
IHD=
ischemic heart disease

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.

  • Received August 6, 2018.
  • Accepted in final form April 10, 2019.
  • © 2019 American Academy of Neurology
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