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Abstract

Objective

To determine the joint role of ideal cardiovascular health (CVH) and genetic risk on risk of dementia.

Methods

We categorized CVH on the basis of the American Heart Association Ideal CVH Index and genetic risk through a genetic risk score (GRS) of common genetic variants and the APOE ε4 genotype in 1,211 Framingham Heart Study (FHS) offspring cohort participants. We used multivariable Cox proportional hazards regression models to examine the association between CVH, genetic risk, and incident all-cause dementia with up to 10 years of follow-up (mean 8.4 years, 96 incident dementia cases), adjusting for age, sex, and education.

Results

We observed that a high GRS (>80th percentile) was associated with a 2.6-fold risk of dementia (95% confidence interval [CI] of hazard ratio [HR] 1.23–5.29; p = 0.012) compared with having a low GRS (<20th percentile); carrying at least 1 APOE ε4 allele was associated with a 2.3-fold risk of dementia compared with not carrying an APOE ε4 allele (95% CI of HR 1.49–3.53; p = 0.0002), and having a favorable CVH showed a 0.45-fold lower risk of dementia (95% CI of HR 0.20–1.01; p = 0.0527) compared to having an unfavorable CVH when all 3 components were included in the model. We did not observe an interaction between CVH and GRS (p = 0.99) or APOE ε4 (p = 0.16).

Conclusions

We observed that both genetic risk and CVH contribute additively to dementia risk.

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Link Between Genetic Risk Factors and Cardiovascular Health on Dementia

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Letters to the Editor

Information & Authors

Information

Published In

Neurology®
Volume 95Number 10September 8, 2020
Pages: e1341-e1350
PubMed: 32690788

Publication History

Received: July 29, 2019
Accepted: April 6, 2020
Published online: July 20, 2020
Published in print: September 8, 2020

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Disclosure

The authors report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.

Study Funding

The FHS is supported by the National Heart, Lung, and Blood Institute (contract 75N92019D00031, N01-HC-25195, HHSN268201500001) and by grants from the National Institute on Aging (R01 AG054076, R01 AG049607, R01 AG033193, U01 AG049505, U01 AG052409, RF1 AG059421) and the National Institute of Neurologic Disorders and Stroke (NS0 17950 and UH2 NS100605). Funding for SNP-Health Association Resource Affymetrix genotyping was provided by National Heart, Lung, and Blood Institute contract N02-HL-64278. M.P. Pase is funded by a National Heart Foundation of Australia Future Leader Fellowship (102052).

Authors

Affiliations & Disclosures

Gina M. Peloso, PhD
From the Departments of Biostatistics (G.M.P., A.S.B., V.X., A.L.D.) and Epidemiology (R.S.V.), Boston University School of Public Health; Boston University and NHLBI's Framingham Heart Study (A.S.B., C.L.S., V.X., R.S.V., A.L.D., S.S.), Framingham; Department of Neurology (A.S.B., C.L.S., A.L.D., S.S.), Boston University School of Medicine, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), University of Texas Health Sciences Center, San Antonio; Sections of Preventive Medicine & Epidemiology and Cardiology (V.X., R.S.V.), Department of Medicine, Boston University, MA; Melbourne Dementia Research Centre (M.P.P.), The Florey Institute for Neuroscience and Mental Health; Faculty of Medicine, Dentistry, and Health Sciences (M.P.P.), University of Melbourne, Parkville; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Hawthorn, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
(1) Circulation: Genomic and Precision Medicine, editorial board, 2018 – present (2) Journal of Alzheimer’s Disease, Associate Editor, 2019
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
(1) NIH/NHLBI, R03HL141439, PI, 04/15/18-02/29/20 (2) NIH/NIA, U01AG058589, co-I, 09/30/18-08/31/23 (3) NIH/NHLBI, R25HL147221, co-I, 03/15/19-02/28/22 (4) NIH/HNLBI, R01HL142711-01A1, MPI,07/01/19–06/30/24 (5) VA, VA241-16-D-0012, biostatistician, 03/25/19-03/26/20 (6) NIH/NHLBI, K01HL125751, PI, 12/01/14-11/20/2019
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
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1.
NONE
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Alexa S. Beiser, PhD
From the Departments of Biostatistics (G.M.P., A.S.B., V.X., A.L.D.) and Epidemiology (R.S.V.), Boston University School of Public Health; Boston University and NHLBI's Framingham Heart Study (A.S.B., C.L.S., V.X., R.S.V., A.L.D., S.S.), Framingham; Department of Neurology (A.S.B., C.L.S., A.L.D., S.S.), Boston University School of Medicine, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), University of Texas Health Sciences Center, San Antonio; Sections of Preventive Medicine & Epidemiology and Cardiology (V.X., R.S.V.), Department of Medicine, Boston University, MA; Melbourne Dementia Research Centre (M.P.P.), The Florey Institute for Neuroscience and Mental Health; Faculty of Medicine, Dentistry, and Health Sciences (M.P.P.), University of Melbourne, Parkville; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Hawthorn, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
Brooks Cole, Introductory Applied Statistics, 2005
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NIH/NINDS, biostatistician, 2 R01 NS017950-28, 2009-2014 NIH/NIA, biostatistician, 5 R01 AG08122, 2005-2010 NIH/NIA, biostatistician, 2 R01 AG16495, 2005-2010 NIA/NINDS, biostatistician, 1 R01 AG033040-01, 2009-2013 NIH/NHLBI, biostatistician, R01 HL093029-01A1, 2009-2011
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
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1.
NONE
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NONE
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Claudia L. Satizabal, PhD https://orcid.org/0000-0002-1115-4430
From the Departments of Biostatistics (G.M.P., A.S.B., V.X., A.L.D.) and Epidemiology (R.S.V.), Boston University School of Public Health; Boston University and NHLBI's Framingham Heart Study (A.S.B., C.L.S., V.X., R.S.V., A.L.D., S.S.), Framingham; Department of Neurology (A.S.B., C.L.S., A.L.D., S.S.), Boston University School of Medicine, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), University of Texas Health Sciences Center, San Antonio; Sections of Preventive Medicine & Epidemiology and Cardiology (V.X., R.S.V.), Department of Medicine, Boston University, MA; Melbourne Dementia Research Centre (M.P.P.), The Florey Institute for Neuroscience and Mental Health; Faculty of Medicine, Dentistry, and Health Sciences (M.P.P.), University of Melbourne, Parkville; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Hawthorn, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NIA R01 AG059727, co-PI, 2018-2022
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Alzheimer's Association, AARGD-16-443384
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Vanessa Xanthakis, PhD
From the Departments of Biostatistics (G.M.P., A.S.B., V.X., A.L.D.) and Epidemiology (R.S.V.), Boston University School of Public Health; Boston University and NHLBI's Framingham Heart Study (A.S.B., C.L.S., V.X., R.S.V., A.L.D., S.S.), Framingham; Department of Neurology (A.S.B., C.L.S., A.L.D., S.S.), Boston University School of Medicine, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), University of Texas Health Sciences Center, San Antonio; Sections of Preventive Medicine & Epidemiology and Cardiology (V.X., R.S.V.), Department of Medicine, Boston University, MA; Melbourne Dementia Research Centre (M.P.P.), The Florey Institute for Neuroscience and Mental Health; Faculty of Medicine, Dentistry, and Health Sciences (M.P.P.), University of Melbourne, Parkville; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Hawthorn, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Ramachandran S. Vasan, MD
From the Departments of Biostatistics (G.M.P., A.S.B., V.X., A.L.D.) and Epidemiology (R.S.V.), Boston University School of Public Health; Boston University and NHLBI's Framingham Heart Study (A.S.B., C.L.S., V.X., R.S.V., A.L.D., S.S.), Framingham; Department of Neurology (A.S.B., C.L.S., A.L.D., S.S.), Boston University School of Medicine, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), University of Texas Health Sciences Center, San Antonio; Sections of Preventive Medicine & Epidemiology and Cardiology (V.X., R.S.V.), Department of Medicine, Boston University, MA; Melbourne Dementia Research Centre (M.P.P.), The Florey Institute for Neuroscience and Mental Health; Faculty of Medicine, Dentistry, and Health Sciences (M.P.P.), University of Melbourne, Parkville; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Hawthorn, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NHLBI N0125195, PI, 2010 to date. and HHSN268201500001I, PI to date
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Matthew P. Pase, PhD
From the Departments of Biostatistics (G.M.P., A.S.B., V.X., A.L.D.) and Epidemiology (R.S.V.), Boston University School of Public Health; Boston University and NHLBI's Framingham Heart Study (A.S.B., C.L.S., V.X., R.S.V., A.L.D., S.S.), Framingham; Department of Neurology (A.S.B., C.L.S., A.L.D., S.S.), Boston University School of Medicine, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), University of Texas Health Sciences Center, San Antonio; Sections of Preventive Medicine & Epidemiology and Cardiology (V.X., R.S.V.), Department of Medicine, Boston University, MA; Melbourne Dementia Research Centre (M.P.P.), The Florey Institute for Neuroscience and Mental Health; Faculty of Medicine, Dentistry, and Health Sciences (M.P.P.), University of Melbourne, Parkville; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Hawthorn, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
Journal of Alzheimer's Disease
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
(1) Australian National Health and Medical Research Council (NHMRC) Early Career Fellowship. APP1089698. PI. 2015-2018, (2) Australian National Health and Medical Research Council (NHMRC) Project Grant. APP1158384. PI. 2019-23, (3) Australian National Health and Medical Research Council (NHMRC). Boosting Dementia Research Grant. APP1171816. PI. 2019-24 2023.
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
(1) National Heart Foundation of Australia, (2) Alzheimer's Association, (3) National Stroke Foundation
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Anita L. Destefano, PhD
From the Departments of Biostatistics (G.M.P., A.S.B., V.X., A.L.D.) and Epidemiology (R.S.V.), Boston University School of Public Health; Boston University and NHLBI's Framingham Heart Study (A.S.B., C.L.S., V.X., R.S.V., A.L.D., S.S.), Framingham; Department of Neurology (A.S.B., C.L.S., A.L.D., S.S.), Boston University School of Medicine, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), University of Texas Health Sciences Center, San Antonio; Sections of Preventive Medicine & Epidemiology and Cardiology (V.X., R.S.V.), Department of Medicine, Boston University, MA; Melbourne Dementia Research Centre (M.P.P.), The Florey Institute for Neuroscience and Mental Health; Faculty of Medicine, Dentistry, and Health Sciences (M.P.P.), University of Melbourne, Parkville; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Hawthorn, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
1. NIH/NIDDK R01 DK099269, PI, 07/01/14-05/31/192. NIH/NHLBI HHSN268201500001, Statistical Geneticist02/01/02-03/31/20 3. NIH/NIA R01 AG054076-01 Statistical Geneticist09/01/16- 05/31/216. NIH/NIA U01 AG058589, PI, 09/30/18-08/31/23
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Sudha Seshadri, MD
From the Departments of Biostatistics (G.M.P., A.S.B., V.X., A.L.D.) and Epidemiology (R.S.V.), Boston University School of Public Health; Boston University and NHLBI's Framingham Heart Study (A.S.B., C.L.S., V.X., R.S.V., A.L.D., S.S.), Framingham; Department of Neurology (A.S.B., C.L.S., A.L.D., S.S.), Boston University School of Medicine, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), University of Texas Health Sciences Center, San Antonio; Sections of Preventive Medicine & Epidemiology and Cardiology (V.X., R.S.V.), Department of Medicine, Boston University, MA; Melbourne Dementia Research Centre (M.P.P.), The Florey Institute for Neuroscience and Mental Health; Faculty of Medicine, Dentistry, and Health Sciences (M.P.P.), University of Melbourne, Parkville; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Hawthorn, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NIA AG033040, AG049505, AG049607, AG054076, AG052409, AG058589 NINDS NS017950, NS100605
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
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NONE
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Notes

Correspondence Dr. Peloso [email protected] or Dr. Seshadri [email protected]
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.

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