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Original Investigation
April 27, 2021

Association Between Age at Diabetes Onset and Subsequent Risk of Dementia

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
JAMA. 2021;325(16):1640-1649. doi:10.1001/jama.2021.4001
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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