Study Finds Age at Diabetes Onset Significantly Associated With Incident Dementia

Investigators sought to determine whether age at onset of diabetes is associated with incident dementia.

Age at onset of diabetes was found to be significantly associated with incident dementia, with younger diabetes onset age associated with increased risk of developing dementia, according to the results of a study published in JAMA.

In order to determine if a younger age at onset of diabetes is associated with dementia incidence, researchers used data from the ongoing Whitehall II prospective cohort study that included evaluations conducted every 4 to 5 years of 10,308 adults employed in London, as well as follow-up information obtained via electronic health records.

The investigators collected information on type 2 diabetes, diabetes risk, and prediabetes. The primary study outcome was incident dementia, determined through linkage to 3 national registries in the United Kingdom.

Between 1985 and 2019, 6.3% of participants were diagnosed with dementia. These individuals were more likely to have chronic conditions throughout the follow-up period and to have a worse cardiovascular risk profile at the age of 60.

During the study period, 16.9% of patients developed diabetes; within this group, 8.9% were subsequently diagnosed with dementia. At 55 years of age, the dementia rate per 1000 person-years was 3.14 in participants without diabetes compared with 5.06 in participants with diabetes (hazard ratio [HR], 2.14; 95% CI, 1.44-3.17). By the age of 70, dementia rates were 8.85 and 13.88 per 1000 person-years in participants with and without diabetes, respectively (HR, 1.58; 95% CI, 1.22-2.03).

As nearly half (48.3%) of the diabetes cases were diagnosed after 70 years of age, all cases were analyzed by treating diabetes as a time-varying measure. Results of these analyses showed a fully adjusted HR for dementia of 1.40 (95% CI, 1.15-1.70), with dementia rates of 1.76 and 6.25 per 1000 person-years in participants without and with diabetes, respectively.

At ages 60, 65, and 70, earlier age at onset of diabetes was more strongly associated with dementia. Results of fully adjusted analyses that compared participants without diabetes at age 65 found that diabetes onset from 0 to 5 years earlier and 6 to 10 years earlier was “significantly associated” with subsequent dementia (HR, 1.53; 95% CI, 1.03-2.29; dementia rate, 8.63/1000 person-years, and HR, 2.03; 95% CI, 1.48-2.79; dementia rate, 10.51/1000 person-years, respectively).

When diabetes diagnosis at age 70 was considered, the dementia HR in participants with diabetes onset more than 10 years earlier was 2.12 (95% CI, 1.50-3.00; dementia rate, 18.30/1000 person years) compared with 1.49 and 1.11 in participants with diabetes onset 6 to 10 and 0 to 5 years earlier, respectively (95% CI, 0.95-2.32, dementia rate, 12.99/1000 person-years and 95% CI, 0.70-1.76; dementia rate, 10.00/1000 person-years, respectively).

By 70 years of age, each 5-years younger age at onset of diabetes was “significantly associated” with a 1.24 HR of dementia in fully adjusted analyses (95% CI, 1.06-1.46).

The investigators found that participants with younger-onset diabetes were also younger at onset of dementia. When diabetes status was examined at 65 years of age, mean age at dementia diagnosis was 77.5±5.3 years in participants without diabetes, 76.7±5.5 years in participants with onset of diabetes between the ages of 61 and 65, and 75.8±5.5 years in participants with onset of diabetes at age 60 or younger.

Results of cardiovascular comorbidity analyses — including coronary heart disease, heart failure, and stroke — in participants with diabetes (n=1710) showed that compared with diabetes alone, diabetes plus stroke is significantly associated with a higher dementia risk (9 cases in 58 people, dementia rate, 24.32/1000 person-years; HR, 2.17; 95% CI, 1.05-4.48). When all 3 cardiovascular comorbidities were present, the HR for dementia was 4.99 (95% CI, 2.19-11.37; 7 dementia cases in 22 people; dementia rate, 77.77/1000 person-years).

Study limitations include an inability to distinguish dementia subtypes, an overall healthier participant population compared with the general population due to the longitudinal nature of the study, incomplete data on glycated hemoglobin, and the use of electronic health record linkage, rather than in-person screening, to determine dementia diagnosis.

“In this longitudinal cohort study…younger age at onset of diabetes was significantly associated with a higher risk of subsequent dementia,” the researchers concluded. “Continuing follow-up in the study will allow further examination of the importance of age at onset of type 2 diabetes for dementia.”


Amidei CB, Fayosse A, Dumurgier J, et al. Association between age at diabetes onset and subsequent risk of dementia. JAMA. 2021;325(16):1640-1649. doi:10.1001/jama.2021.4001