Association Between Age at Diabetes Onset and Subsequent Risk of 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.

Figure.. Association of Finnish Diabetes Risk Score at Ages 55, 60, 65, and 70 Years With Incidence of Dementia

Analyses were adjusted for age, sex, race, education, and birth cohort (5-year groups). The gray shading indicates the 95% CI. All figures were produced using restricted cubic spline (4 knots) and the untransformed Finnish Diabetes Risk Score (FINDRISC; score range, 0-26 [age, 0-4 points; family history of diabetes, 0-5 points; vegetable and fruit intake, 0-2 points; physical activity, 0-2 points; medical treatment of hypertension, 0-2 points; history of high blood glucose, 0-5 points; body mass index, 0-3 points; and waist circumference, 0-4 points]). A rating score between 0 and 14 points indicates a low to moderate risk of diabetes, 15 to 20 points indicates a high risk of diabetes, and greater than 20 points indicates a very high risk of diabetes. The hazard ratio (HR) estimates are for a 5-point higher FINDRISC score (for age 55 y: HR, 1.16 [95% CI, 0.99-1.35]; for age 60 y: HR, 1.08 [95% CI, 0.93-1.25]; for age 65 y: HR, 0.95 [95% CI, 0.82-1.11]; and for age 70 y: HR, 0.96 [95% CI, 0.82-1.14].