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Dementia and Cognitive Impairment

Association Between Age at Diabetes Onset and Subsequent Risk of Dementia

Educational Objective
To understand the association of dementia and type 2 diabetes.

1 Credit CME

JAMA

Published Online: April 27, 2021

Original Investigation

Article Information and Disclosures

Claudio Barbiellini Amidei, MD^1,2;

Aurore Fayosse, MSc¹;

Julien Dumurgier, PhD^1,3;

et al

Marcos D. Machado-Fragua, PhD¹;

Adam G. Tabak, PhD^4,5,6;

Thomas van Sloten, PhD⁷;

Mika Kivimäki, PhD^2,4;

Aline Dugravot, MSc¹;

Séverine Sabia, PhD^1,4;

Archana Singh-Manoux, PhD^1,4

Author Affiliations

¹Epidemiology of Ageing and Neurodegenerative Diseases, Université de Paris, Inserm U1153, Paris, France
²Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padua, Padua, Italy
³Cognitive Neurology Center, Lariboisière – Fernand Widal Hospital, AP-HP, Université de Paris, Paris, France
⁴Department of Epidemiology and Public Health, University College London, United Kingdom
⁵Department of Internal Medicine and Oncology, Semmelweis University Faculty of Medicine, Budapest, Hungary
⁶Department of Public Health, Semmelweis University Faculty of Medicine, Budapest, Hungary
⁷Cardiovascular Research Institute Maastricht (CARIM), Department of Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands

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Original Investigation

Effect of Depression and Diabetes Mellitus on Dementia Risk

Wayne Katon, MD; Henrik Sondergaard Pedersen, MSc; Anette Riisgaard Ribe, MD; Morten Fenger-Grøn, MSc; Dimitry Davydow, MD, MPH; Frans Boch Waldorff, MD, PhD; Mogens Vestergaard, MD, PhD
Original Investigation

Association of Haptoglobin Gene Polymorphism With Cognitive Function and Decline

Michal S. Beeri, PhD; Hung-Mo Lin, PhD; Mary Sano, PhD; Ramit Ravona-Springer, MD; Xiaoyu Liu, MS; Barbara B. Bendlin, PhD; Carey E. Gleason, PhD; Elizabeth Guerrero-Berroa, PhD; Laili Soleimani, MD; Lenore J. Launer, PhD; Scott Ehrenberg; Orit Lache, MSc; Yaakov K. Seligman, BS; Andrew P. Levy, MD, PhD
Original Investigation

Assessment of Advanced Glycation End Products and Receptors and the Risk of Dementia

Jinluan Chen, MSc; Sanne S. Mooldijk, BSc; Silvan Licher, MD, MSc; Komal Waqas, MD; M. Kamran Ikram, MD, PhD; André G. Uitterlinden, PhD; M. Carola Zillikens, MD, PhD; M. Arfan Ikram, MD, PhD
Comment & Response

Age at Diabetes Onset and Subsequent Risk of Dementia—Reply

Claudio Barbiellini Amidei, MD; Aurore Fayosse, MSc; Archana Singh-Manoux, PhD
Comment & Response

Age at Diabetes Onset and Subsequent Risk of Dementia

Rui Gao, MD, PhD; Ruiqun Wang, MD; Chan Chen, MD, PhD

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Key Points

Question What is the association between age at onset of type 2 diabetes and subsequent risk of dementia?

Findings In this prospective cohort study of 10 095 participants, younger age at onset of type 2 diabetes was significantly associated with higher risk for incident dementia; at age 70, the hazard ratio for every 5-year earlier age at type 2 diabetes onset was 1.24.

Meaning Younger age at diabetes onset was associated with higher risk of subsequent dementia.

Abstract

Importance Trends in type 2 diabetes show an increase in prevalence along with younger age of onset. While vascular complications of early-onset type 2 diabetes are known, the associations with dementia remains unclear.

Objective To determine whether younger age at diabetes onset is more strongly associated with incidence of dementia.

Design, Setting, and Participants Population-based study in the UK, the Whitehall II prospective cohort study, established in 1985-1988, with clinical examinations in 1991-1993, 1997-1999, 2002-2004, 2007-2009, 2012-2013, and 2015-2016, and linkage to electronic health records until March 2019. The date of final follow-up was March 31, 2019.

Exposures Type 2 diabetes, defined as a fasting blood glucose level greater than or equal to 126 mg/dL at clinical examination, physician-diagnosed type 2 diabetes, use of diabetes medication, or hospital record of diabetes between 1985 and 2019.

Main Outcomes and Measures Incident dementia ascertained through linkage to electronic health records.

Results Among 10 095 participants (67.3% men; aged 35-55 years in 1985-1988), a total of 1710 cases of diabetes and 639 cases of dementia were recorded over a median follow-up of 31.7 years. Dementia rates per 1000 person-years were 8.9 in participants without diabetes at age 70 years, and rates were 10.0 per 1000 person-years for participants with diabetes onset up to 5 years earlier, 13.0 for 6 to 10 years earlier, and 18.3 for more than 10 years earlier. In multivariable-adjusted analyses, compared with participants without diabetes at age 70, the hazard ratio (HR) of dementia in participants with diabetes onset more than 10 years earlier was 2.12 (95% CI, 1.50-3.00), 1.49 (95% CI, 0.95-2.32) for diabetes onset 6 to 10 years earlier, and 1.11 (95% CI, 0.70-1.76) for diabetes onset 5 years earlier or less; linear trend test (P < .001) indicated a graded association between age at onset of type 2 diabetes and dementia. At age 70, every 5-year younger age at onset of type 2 diabetes was significantly associated with an HR of dementia of 1.24 (95% CI, 1.06-1.46) in analyses adjusted for sociodemographic factors, health behaviors, and health-related measures.

Conclusions and Relevance In this longitudinal cohort study with a median follow-up of 31.7 years, younger age at onset of diabetes was significantly associated with higher risk of subsequent dementia.

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Article Information

Corresponding Author: Archana Singh-Manoux, PhD, EpiAgeing, Université de Paris, Inserm U1153, 10 Avenue de Verdun, 75010 Paris, France (archana.singh-manoux@inserm.fr).

Accepted for Publication: March 2, 2021.

Author Contributions: Ms Fayosse and Dr Singh-Manoux had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Dr Barbiellini Amidei and Ms Fayosse contributed equally to this article.

Concept and design: Barbiellini Amidei, Dugravot, Sabia, Singh-Manoux.

Acquisition, analysis, or interpretation of data: Barbiellini Amidei, Fayosse, Dumurgier, Machado-Fragua, Tabak, van Sloten, Kivimaki, Sabia, Singh-Manoux.

Drafting of the manuscript: Barbiellini Amidei, Singh-Manoux.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Barbiellini Amidei, Fayosse, Dumurgier, Dugravot, Sabia.

Obtained funding: Kivimaki, Singh-Manoux.

Administrative, technical, or material support: Singh-Manoux.

Supervision: Barbiellini Amidei, Fayosse, Singh-Manoux.

Conflict of Interest Disclosures: Dr Tabak reported salary supported by grants from the UK Medical Research Council (MRC) (S011676) and NordForsk (the Nordic Research Programme on Health and Welfare, 75021) during the conduct of the study. Dr van Sloten reported grants from the Netherlands Organization for Scientific Research and the Netherlands Organization for Health Research and Development (VENI research grant 916.19.074) and the Dutch Heart Foundation (2018T025) outside the submitted work. Dr Kivimaki reported grants from the UK MRC (R024227; S011676), the National Institute on Aging (NIA), National Institutes of Health (NIH) (R01AG056477; RF1AG062553), NordForsk (70521), and the Academy of Finland (311492) during the conduct of the study. Dr Sabia reported a grant from the French National Research Agency (ANR-19-CE36-0004-01). Dr Singh-Manoux reported grants from NIH (R01AG056477; RF1AG062553), the UK MRC (R024227; S011676), and the British Heart Foundation (BHF) (RG/16/11/32334) during the conduct of the study. No other disclosures were reported.

Funding/Support: The Whitehall II study is supported by grants from NIA, NIH (R01AG056477; RF1AG062553); UK MRC (R024227; S011676); the BHF (RG/16/11/32334); and the Wellcome Trust (221854/Z/20/Z). Dr Tabak is supported by the UK MRC (S011676) and NordForsk (75021). Dr Kivimaki is supported by NordForsk (70521) and the Academy of Finland (311492). Dr Van Sloten is supported by the Netherlands Organization for Scientific Research (VENI research grant 916.19.074) and the Dutch Heart Foundation (research grant 2018T025).

Role of the Funder/Sponsor: The NIH, MRC, and BHF had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank all of the participating civil service departments and their welfare, personnel, and establishment officers; the British Occupational Health and Safety Agency; the British Council of Civil Service Unions; all participating civil servants in the Whitehall II study; and all members of the Whitehall II study team. The Whitehall II Study team comprises research scientists, statisticians, study coordinators, nurses, data managers, administrative assistants, and data entry staff, who make the study possible.

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Association Between Age at Diabetes Onset and Subsequent Risk of Dementia

Effect of Depression and Diabetes Mellitus on Dementia Risk

Association of Haptoglobin Gene Polymorphism With Cognitive Function and Decline

Assessment of Advanced Glycation End Products and Receptors and the Risk of Dementia

Age at Diabetes Onset and Subsequent Risk of Dementia—Reply

Age at Diabetes Onset and Subsequent Risk of Dementia

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