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Abstract

Objective:

To determine the association of parental family history with risk of dementia by age at onset and sex of affected parent in a population-based cohort.

Methods:

From 2000 to 2002, we assessed parental history of dementia in participants without dementia of the Rotterdam Study. We investigated associations of parental history with risk of dementia until 2015, adjusting for demographics, cardiovascular risk factors, and known genetic risk variants. Furthermore, we determined the association between parental history and markers of neurodegeneration and vascular disease on MRI.

Results:

Of 2,087 participants (mean age 64 years, 55% female), 407 (19.6%) reported a history of dementia in either parent (mean age at diagnosis 79 years). During a mean follow-up of 12.2 years, 142 participants developed dementia. Parental history was associated with risk of dementia independently of known genetic risk factors (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.12–2.48), in particular when parents were diagnosed at younger age (<80 years: HR 2.58, 95% CI 1.61–4.15; ≥80 years: HR 1.01, 95% CI 0.58–1.77). Accordingly, age at diagnosis in probands was highly correlated with age at diagnosis in their parents <80 years (r = 0.57, p = 0.001) but not thereafter (r = 0.17, p = 0.55). Among 1,161 participants without dementia with brain MRI, parental history was related to lower cerebral perfusion and higher burden of white matter lesions and microbleeds. Dementia risk and MRI markers were similar for paternal and maternal history.

Conclusions:

Parental history of dementia increases risk of dementia, primarily when age at parental diagnosis is <80 years. Unexplained heredity may be attributed in part to cerebral hypoperfusion and small vessel disease. We found no evidence of preferential maternal compared to paternal transmission.

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Supplementary Material

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Information & Authors

Information

Published In

Neurology®
Volume 88Number 17April 25, 2017
Pages: 1642-1649
PubMed: 28356461

Publication History

Received: September 15, 2016
Accepted: January 31, 2017
Published online: March 29, 2017
Published in print: April 25, 2017

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Disclosure

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

Study Funding

The Rotterdam Study is sponsored by the Erasmus Medical Centre and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; the Netherlands Genomics Initiative; the Ministry of Education, Culture and Science; the Ministry of Health, Welfare and Sports; the European Commission; and the Municipality of Rotterdam. Further support was obtained from the Netherlands Consortium for Healthy Ageing and the Dutch Heart Foundation (2012T008). None of the funding organizations or sponsors were involved in study design; in collection, analysis, and interpretation of data; in writing of the report; or in the decision to submit the article for publication.

Authors

Affiliations & Disclosures

Frank J. Wolters, MD
Departments of Epidemiology (F.J.W., S.J.v.d.L., C.M.v.D., A.H., M.K.I., M.W.V., M.A.I.), Neurology (F.J.W., P.J.K., M.K.I., M.A.I.), and Radiology and Nuclear Medicine (M.W.V., M.A.I.), Erasmus Medical Centre, Rotterdam, the Netherlands; and Department of Epidemiology (F.J.W., A.H.), Harvard T.H. Chan School of Public Health, 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.
Dutch Heart 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
Sven J. van der Lee, MD
Departments of Epidemiology (F.J.W., S.J.v.d.L., C.M.v.D., A.H., M.K.I., M.W.V., M.A.I.), Neurology (F.J.W., P.J.K., M.K.I., M.A.I.), and Radiology and Nuclear Medicine (M.W.V., M.A.I.), Erasmus Medical Centre, Rotterdam, the Netherlands; and Department of Epidemiology (F.J.W., A.H.), Harvard T.H. Chan School of Public Health, 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
Peter J. Koudstaal, MD, PhD
Departments of Epidemiology (F.J.W., S.J.v.d.L., C.M.v.D., A.H., M.K.I., M.W.V., M.A.I.), Neurology (F.J.W., P.J.K., M.K.I., M.A.I.), and Radiology and Nuclear Medicine (M.W.V., M.A.I.), Erasmus Medical Centre, Rotterdam, the Netherlands; and Department of Epidemiology (F.J.W., A.H.), Harvard T.H. Chan School of Public Health, 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.
Neurologie. Bohn Stafleu. 2015
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
Cornelia M. van Duijn, MD, PhD
Departments of Epidemiology (F.J.W., S.J.v.d.L., C.M.v.D., A.H., M.K.I., M.W.V., M.A.I.), Neurology (F.J.W., P.J.K., M.K.I., M.A.I.), and Radiology and Nuclear Medicine (M.W.V., M.A.I.), Erasmus Medical Centre, Rotterdam, the Netherlands; and Department of Epidemiology (F.J.W., A.H.), Harvard T.H. Chan School of Public Health, 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
Albert Hofman, MD, PhD
Departments of Epidemiology (F.J.W., S.J.v.d.L., C.M.v.D., A.H., M.K.I., M.W.V., M.A.I.), Neurology (F.J.W., P.J.K., M.K.I., M.A.I.), and Radiology and Nuclear Medicine (M.W.V., M.A.I.), Erasmus Medical Centre, Rotterdam, the Netherlands; and Department of Epidemiology (F.J.W., A.H.), Harvard T.H. Chan School of Public Health, Boston, MA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
Editor Eur J Epidemiol from 2000 onwards
Patents:
1.
NONE
Publishing Royalties:
1.
Royalties two Dutch books on epidemiology: Grondslagen der Epidemiologie, Elsevier 2008 Klinische Epidemiologie Elsevier 2000 Investigating neurological disease, Cambridge University press 1996
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
M. Kamran Ikram, MD, PhD
Departments of Epidemiology (F.J.W., S.J.v.d.L., C.M.v.D., A.H., M.K.I., M.W.V., M.A.I.), Neurology (F.J.W., P.J.K., M.K.I., M.A.I.), and Radiology and Nuclear Medicine (M.W.V., M.A.I.), Erasmus Medical Centre, Rotterdam, the Netherlands; and Department of Epidemiology (F.J.W., A.H.), Harvard T.H. Chan School of Public Health, 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
Meike W. Vernooij, MD, PhD
Departments of Epidemiology (F.J.W., S.J.v.d.L., C.M.v.D., A.H., M.K.I., M.W.V., M.A.I.), Neurology (F.J.W., P.J.K., M.K.I., M.A.I.), and Radiology and Nuclear Medicine (M.W.V., M.A.I.), Erasmus Medical Centre, Rotterdam, the Netherlands; and Department of Epidemiology (F.J.W., A.H.), Harvard T.H. Chan School of Public Health, 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.
(1) research fellowship from the Erasmus MC University Medical Center, Rotterdam, the Netherlands (2) a Netherlands Organization of Scientific Research (NWO)/ZonMW clinical fellowship (90700435)
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
M. Arfan Ikram, MD, PhD
Departments of Epidemiology (F.J.W., S.J.v.d.L., C.M.v.D., A.H., M.K.I., M.W.V., M.A.I.), Neurology (F.J.W., P.J.K., M.K.I., M.A.I.), and Radiology and Nuclear Medicine (M.W.V., M.A.I.), Erasmus Medical Centre, Rotterdam, the Netherlands; and Department of Epidemiology (F.J.W., A.H.), Harvard T.H. Chan School of Public Health, Boston, MA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
(1) Biogen, speaker honorarium
Editorial Boards:
1.
(1) Neuroepidemiology, Editorial Board Member, 2011-2017, (2) PLoS One, Academic Editor, 2013-2017, (3) Journal of Alzheimer Disease, Academic Editor, 2017, (4) European Journal of Clinical Investigation, 2016-2017
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.
(1) Janssen Prevention Center
Research Support, Government Entities:
1.
(1) Netherlands Organization for Health Research and Development, ZonMW: 916.13.054, PI, 2012-2016, (2) European Research Council, PI, 2016-2020, (3) Joint Programme in Neurodegenerative Diseases, PI, 2014-2017
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
(1) the Netherlands Heart Foundation (2009B102 and 2012T008), (2) Internationaal Parkinson Fonds, (3) Internationale Stichting Alzheimer Onderzoek (#12533), (4) Alzheimer Association, (5) Alzheimer Nederland, (6) Institute for Scientific Information on Coffee
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

Notes

Correspondence to Dr. Ikram: [email protected]
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Author Contributions

All authors have made a substantial intellectual contribution to design of the study (A.H., C.M.v.D., M.W.V., M.A.I.), acquisition of data (P.J.K., F.J.W., S.J.v.d.L., M.K.I.), analysis and interpretation of data (F.J.W., M.A.I., M.W.V.), drafting the manuscript (F.J.W.), or revising it critically for important intellectual content (P.J.K., A.H., M.K.I., M.W.V., S.J.v.d.L., C.M.v.D, M.A.I.). All authors approved the final version of the manuscript for publication. M.A.I. had full access to the data in the study and takes responsibility for data integrity and accuracy of data analysis.

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