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July 12, 2022; 99 (2) Research Article

Determining Vascular Risk Factors for Dementia and Dementia Risk Prediction Across Mid- to Later Life

The Framingham Heart Study

View ORCID ProfileEmer R. McGrath, View ORCID ProfileAlexa S. Beiser, View ORCID ProfileAdrienne O'Donnell, Jayandra J. Himali, Matthew P. Pase, View ORCID ProfileClaudia L. Satizabal, Sudha Seshadri
First published May 18, 2022, DOI: https://doi.org/10.1212/WNL.0000000000200521
Emer R. McGrath
From the HRB Clinical Research Facility (E.R.M.) and School of Medicine, National University of Ireland Galway; The Framingham Heart Study (E.R.M., A.S.B., A.O., J.J.H., M.P.P., C.L.S., S.S.); Boston University School of Public Health (A.S.B., A.O., J.J.H.); Boston University School of Medicine (A.S.B., J.J.H., S.S.), MA; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases (J.J.H., C.L.S., S.S.), University of Texas Health Sciences Center, San Antonio; The Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Victoria, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
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Alexa S. Beiser
From the HRB Clinical Research Facility (E.R.M.) and School of Medicine, National University of Ireland Galway; The Framingham Heart Study (E.R.M., A.S.B., A.O., J.J.H., M.P.P., C.L.S., S.S.); Boston University School of Public Health (A.S.B., A.O., J.J.H.); Boston University School of Medicine (A.S.B., J.J.H., S.S.), MA; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases (J.J.H., C.L.S., S.S.), University of Texas Health Sciences Center, San Antonio; The Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Victoria, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
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Adrienne O'Donnell
From the HRB Clinical Research Facility (E.R.M.) and School of Medicine, National University of Ireland Galway; The Framingham Heart Study (E.R.M., A.S.B., A.O., J.J.H., M.P.P., C.L.S., S.S.); Boston University School of Public Health (A.S.B., A.O., J.J.H.); Boston University School of Medicine (A.S.B., J.J.H., S.S.), MA; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases (J.J.H., C.L.S., S.S.), University of Texas Health Sciences Center, San Antonio; The Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Victoria, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
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Jayandra J. Himali
From the HRB Clinical Research Facility (E.R.M.) and School of Medicine, National University of Ireland Galway; The Framingham Heart Study (E.R.M., A.S.B., A.O., J.J.H., M.P.P., C.L.S., S.S.); Boston University School of Public Health (A.S.B., A.O., J.J.H.); Boston University School of Medicine (A.S.B., J.J.H., S.S.), MA; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases (J.J.H., C.L.S., S.S.), University of Texas Health Sciences Center, San Antonio; The Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Victoria, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
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Matthew P. Pase
From the HRB Clinical Research Facility (E.R.M.) and School of Medicine, National University of Ireland Galway; The Framingham Heart Study (E.R.M., A.S.B., A.O., J.J.H., M.P.P., C.L.S., S.S.); Boston University School of Public Health (A.S.B., A.O., J.J.H.); Boston University School of Medicine (A.S.B., J.J.H., S.S.), MA; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases (J.J.H., C.L.S., S.S.), University of Texas Health Sciences Center, San Antonio; The Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Victoria, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
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Claudia L. Satizabal
From the HRB Clinical Research Facility (E.R.M.) and School of Medicine, National University of Ireland Galway; The Framingham Heart Study (E.R.M., A.S.B., A.O., J.J.H., M.P.P., C.L.S., S.S.); Boston University School of Public Health (A.S.B., A.O., J.J.H.); Boston University School of Medicine (A.S.B., J.J.H., S.S.), MA; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases (J.J.H., C.L.S., S.S.), University of Texas Health Sciences Center, San Antonio; The Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Victoria, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
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Sudha Seshadri
From the HRB Clinical Research Facility (E.R.M.) and School of Medicine, National University of Ireland Galway; The Framingham Heart Study (E.R.M., A.S.B., A.O., J.J.H., M.P.P., C.L.S., S.S.); Boston University School of Public Health (A.S.B., A.O., J.J.H.); Boston University School of Medicine (A.S.B., J.J.H., S.S.), MA; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases (J.J.H., C.L.S., S.S.), University of Texas Health Sciences Center, San Antonio; The Turner Institute for Brain and Mental Health (M.P.P.), Monash University, Victoria, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
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Citation
Determining Vascular Risk Factors for Dementia and Dementia Risk Prediction Across Mid- to Later Life
The Framingham Heart Study
Emer R. McGrath, Alexa S. Beiser, Adrienne O'Donnell, Jayandra J. Himali, Matthew P. Pase, Claudia L. Satizabal, Sudha Seshadri
Neurology Jul 2022, 99 (2) e142-e153; DOI: 10.1212/WNL.0000000000200521

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Abstract

Background and Objectives The association between vascular risk factors and dementia varies with age, making generalizability of dementia risk prediction rules to individuals of different ages challenging. We determined the most important vascular risk factors for inclusion in age-specific dementia risk scores.

Methods Framingham Heart Study Original and Offspring cohort participants with available data on the Framingham Stroke Risk Profile (FSRP) at midlife (age 55; n = 4,899, 57% women), late life (ages 65 or 70), or later life (ages 75 or 80 [n = 2,386, 62% women]) were followed for 10-year incident dementia risk from ages 65, 70, 75, and 80.

Results Age- and sex-adjusted midlife risk factors associated with 10-year risk of dementia from age 65 included FSRP (hazard ratio [HR] 1.16, 95% CI 1.06–1.26, per 1 SD increment in log-transformed score), diabetes mellitus (DM; HR 4.31, 95% CI 1.97–9.43), and systolic blood pressure (SBP; HR 1.12, 95% CI 1.02–1.24, per 10 mm Hg increment). Late-life risk factors associated with 10-year incident dementia from ages 65 or 70 included FSRP (age 65 only: HR 1.06, 95% CI 1.02–1.10), antihypertensive use (age 65 reported: HR 1.66, 95% CI 1.12–2.46), DM (age 65 reported: HR 1.96, 95% CI 1.09–3.52), atrial fibrillation (age 65 reported: HR 2.30, 95% CI 1.00–5.27), nonstroke cardiovascular disease (nsCVD; age 65 reported: HR 1.95, 95% CI 1.24–3.07), and stroke (age 70 only: HR 3.61, 95% CI 2.21–5.92). Later-life risk factors associated with 10-year incident dementia from ages 75 or 80 included antihypertensive use (age 80 only: HR 0.74, 95% CI 0.62–0.89), DM (age 80 reported: HR 1.40, 95% CI 1.04–1.89), atrial fibrillation (age 80 reported: HR 1.43, 95% CI 1.07–1.92), and stroke (age 80 reported: HR 1.63, 95% CI 1.13–2.35). In stepwise models, SBP and DM at age 55, nsCVD at age 65, DM and stroke at ages 70 and 75, and DM, stroke, and use of antihypertensives (protective) at age 80 were the most important vascular risk factors for dementia.

Discussion Our findings support the use of age-specific dementia risk scores, which should prioritize including, at age 55, SBP and DM; at age 65, nsCVD; at ages 70 and 75, DM and stroke; and at age 80, DM, stroke, and antihypertensive use.

Glossary

AF=
atrial fibrillation;
AUC=
area under the curve;
CVD=
cardiovascular disease;
DM=
diabetes mellitus;
DSM-IV=
Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
FDR=
false discovery rate;
FHS=
Framingham Heart Study;
FSRP=
Framingham Stroke Risk Profile;
HR=
hazard ratio;
MMSE=
Mini-Mental State Examination;
nsCVD=
nonstroke cardiovascular disease;
PGRS=
polygenic risk score;
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.

  • Submitted and externally peer reviewed. The handling editors were Rawan Tarawneh, MD, and José Merino, MD, MPhil.

  • CME Course: NPub.org/cmelist

  • Received September 10, 2021.
  • Accepted in final form February 28, 2022.
  • © 2022 American Academy of Neurology
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