Younger age at type 2 diabetes onset linked to higher risk of subsequent dementia

Earlier onset of type 2 diabetes was significantly associated with increased risk of dementia in a recent longitudinal study.

Researchers looked at data from the Whitehall II study, an ongoing, population-based, prospective cohort study in the U.K., to assess whether younger age at type 2 diabetes onset was more strongly associated with incidence of dementia. The study was established in 1985 to 1988 to follow 6,895 men and 3,413 women ages 35 to 55 years who were employed in London-based government departments. Participants received follow-up clinical examinations about every four to five years. In addition to data collection within the study, follow-up data were gathered from the electronic medical records of the National Health Service for all but 10 of the participants. Results were published online on April 27 by JAMA.

Among 10,095 participants included in the current analysis, 1,710 cases of diabetes and 639 cases of dementia were recorded over a median follow-up of 31.7 years. Age at diabetes onset ranged from 35 to 75 years. Dementia rates were 8.9 per 1,000 person-years in participants without diabetes at age 70 years, and rates increased to 10.0, 13.0, and 18.3 per 1,000 person-years for participants who developed diabetes in the five years before age 70 years, six to 10 years before, and more than 10 years before, respectively. Diabetes accompanied by stroke was associated with additional increased risk of dementia (hazard ratio [HR], 2.17 [95% CI, 1.05 to 4.48]), and the highest risk of dementia was seen in those with diabetes, stroke, coronary heart disease, and heart failure (HR, 4.99 [95% CI, 2.19 to 11.37]), although these analyses were based on small numbers of patients.

In multivariable-adjusted analyses, compared with participants without diabetes at age 70 years, the HR of dementia was 2.12 (95% CI, 1.50 to 3.00) in participants with diabetes onset more than 10 years earlier, 1.49 (95% CI, 0.95 to 2.32) for diabetes onset six to 10 years earlier, and 1.11 (95% CI, 0.70 to 1.76) for diabetes onset five or fewer years earlier (P<0.001 for trend). At age 70, every five additional years with type 2 diabetes was associated with an HR of dementia of 1.24 (95% CI, 1.06 to 1.46) in analyses adjusted for sociodemographic factors, health behaviors, and health-related measures. In contrast, prediabetes, fasting glucose, and the Finnish Diabetes Risk Score were not significantly associated with dementia risk, irrespective of age at assessment.

Among other limitations, the study authors noted that they were unable to distinguish among dementia subtypes, which precluded estimation of the association between diabetes and Alzheimer's disease and major subtypes of dementia, such as vascular dementia. They added that rates of diabetes and dementia in the study participants were lower than in the general U.K. population.

“Taken together, these findings highlight the importance of age at onset of diabetes and cardiovascular comorbidity in persons with diabetes for risk of dementia,” the authors wrote.