Earlier Age at Type 2 Diabetes Onset May Lead to Higher Dementia Risk

Implementing preventive measures for prediabetes reduces the risk for dementia, according to the findings of a large population-based cohort study published in the journal Diabetologia. 

While there is an established link between type 2 diabetes and dementia risk, the association between prediabetes and dementia risk is unclear. For the study, researchers assessed whether prediabetes interventions can mitigate dementia risk. 

The researchers collected data from the Atherosclerosis Risk in Communities (ARIC) study, which recruited 15,792 patients from 4 US counties: Forsyth County, North Carolina; Jackson, Mississippi; suburbs of Minneapolis, Minnesota; and Washington County, Maryland.

The researchers defined prediabetes as an HbA1c of 39 to 46 mmol/mol (5.7-6.4%). Individuals with an HbA1c of less than 39 mmol/mol (5.7%) were considered the reference population. Incident diabetes was considered a self-reported physician diagnosis of diabetes or filling a diabetes medication. 

Dementia status was determined by cognitive function assessments reviewed by a committee. A definitive dementia diagnosis was made by an expert panel of neuropsychologists and physicians. 

Of the 11,656 study participants without diabetes at baseline, 20% had prediabetes. The average age of participants was 56.8 (standard deviation [SD], 5.7 years) and 55.4% were women. 

Participants with prediabetes (39.5%) were more likely to be Black, compared with those without prediabetes (16.7%). Additionally, individuals with prediabetes were more likely to have an education level lower than high school, compared with those without prediabetes (30.2% vs 17.0%).

A total of 3,143 individuals developed diabetes during a median follow-up period of 15.9 years. Participants with prediabetes (44.6%) were more likely to develop diabetes compared with those without diabetes (22.5%).

There were 2,247 participants who developed dementia during a median follow-up period of 24.7 years. Among patients with prediabetes, the incidence of dementia was higher in those who developed diabetes (23.9%), compared with those without diabetes (20.5%).

After adjusting for patient demographics, the analysis revealed that prediabetes was significantly associated with incident dementia (hazard ratio [HR], 1.19; 95% CI, 1.07-1.31). However, when adjusting for incident diabetes as a time-related variable, the association was no longer statistically significant (HR, 1.09; 95% CI, 0.98-1.21). Similar results were seen in models that adjusted for lifestyle and clinical risk factors before (HR, 1.12; 95% CI, 1.01-1.24) and after (HR 1.05; 95% CI, 0.94-1.16) the incident diabetes adjustment.

Individuals with an earlier age at diabetes onset had a stronger association with dementia risk and analysis was stratified using the following age ranges:

• Diabetes onset before 60 years (HR, 2.92; 95% CI, 2.06-4.14)
• Diabetes onset at 60-69 years (HR, 1.73; 95% CI, 1.47-2.04)
• Diabetes onset at 70-79 years (HR, 1.23; 95% CI, 1.08-1.40)

“Our study suggests that prediabetes is associated with dementia but this association is primarily explained by the development of clinical diabetes,” the researchers concluded.

Study limitations included the lack of repeated measurements for diabetes markers, the inability to differentiate dementia subtypes, and the lack of documentation of prediabetes at baseline.