Impact of modifiable risk factors, including diabetes, and diabetes-related complications, on dementia risk in older U.S. adults: mutually adjusted estimates from a population-based cohort.

AIMS: Diabetes is an established dementia risk factor, but the contribution of diabetes-related complications remains unclear. Using mutually adjusted models based on the Lancet Commission framework for dementia prevention, we assessed 12 of 14 modifiable risk factors and evaluated whether diabetes-related complications independently increased dementia risk.

METHODS

We used data from the All of Us Research Program, including adults aged > 50 years without prior dementia. Incident dementia, risk factors, and diabetes-related complications were defined from electronic health records, surveys, or both. Cox proportional hazards models estimated hazard ratios (HRs). Mutually adjusted risk estimates were used to calculate population attributable fractions (PAFs).

RESULTS

Among 83,370 participants, lower education, smoking, diabetes, obesity, hypertension, traumatic brain injury, depression, and social isolation were associated with dementia risk. Total adjusted PAF was 11.1% led by depression (4.6%), lower education (1.7%), and diabetes (1.6%). Complications associated with dementia included neuropathy (PAF 1.2%), stroke (0.6%), chronic kidney disease (0.2%), peripheral vascular disease (0.2%) and amputation (0.1%). Total adjusted PAF was unchanged by adding diabetes-related complications (10.7%).

CONCLUSIONS

Total adjusted PAF was lower than the Lancet estimate (11.1% vs. 45.2%). Several diabetes-related complications were independently associated with dementia risk, but adding complications did not change the total PAF.