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

Importance 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.

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.

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.

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. Competing Interest Statement The authors have declared no competing interest. Funding Statement This study did not receive dedicated funding. However, KDS was supported by NIH/NIA. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Institutional Review Board of Boston University Medical Campus waived ethical approved for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability The data and relevant code used in this study are made available to researchers who have access to the All of Us registered and controlled data tiers via the Research Hub.