Type I diabetes and incident dementia: a prospective study in the All of Us cohort

Although diabetes mellitus (DM) is a well-established determinant of dementia risk, most studies have evaluated type 2 DM (T2DM) or any DM without considering type 1 DM (T1DM) separately. Questions remain about the influence of T1DM on risk of dementia.

Objective

To evaluate associations of T1DM and T2DM with incident dementia using linked electronic health records (EHRs).

Design, Setting, Participants

This cohort study used data from the All of Us (AoU) cohort, a convenience sample of US adults. Eligible participants were ≥ 50 years, completed baseline surveys, and had EHR information. Enrollment began in 2017, with data available through October 2023, including records prior to enrollment in AoU. Mean follow-up was 2.4 years.

Exposures

We developed and validated an algorithm to distinguish DM type using three reference measures: (1) self-report diabetes type; (2) C-peptide values; and (3) islet-specific autoantibodies (ISAs). Participants were classified as no DM, T1DM, or T2DM based on number of T1DM encounters.

Main Outcomes and Measures

Incident dementia was identified based on ICD-9, ICD-10, and SNOMED codes in participants’ EHRs.

Results

Among 283,965 participants (mean [SD] age 64.62 [8.96] years; 56.7% women); 60.3% identified as Non-Hispanic White; 13.3% as Hispanic/Latino; and 26.4% as Non-Hispanic Other. Optimal DM classification algorithm cutoas varied by reference standard: (1) self-reported diabetes: ≥ 1 T1DM EHR encounter (sensitivity: 0.59; specificity: 0.90); (2) C-peptide: ≥ 3 T1DM EHR encounters (sensitivity: 0.76; specificity: 0.79); and (3) ISAs: ≥ 4 T1DM EHR encounters (sensitivity: 0.48; specificity: 0.74). Using at least one T1DM encounter cutoa, 5,444 participants were classified with T1DM. Compared with those without DM, participants with T1DM had higher incidence of dementia (sociodemographic-adjusted HR = 2.79; 95% CI: 2.26-3.45); those with T2DM also had elevated risk (sociodemographic-adjusted HR = 2.09; 95% CI: 1.88-2.33). Results were similar across gender and race and ethnicity stratified groups.

Conclusion and Relevance

In this cohort, participants with diabetes had a higher dementia risk than did those without DM, with the highest risk among those with T1DM. These findings highlight the need to better understand mechanisms linking T1DM and dementia in aging populations.