Longitudinal associations of depression and diabetes with Alzheimer's disease and related dementias risk among American Indian and Alaska Native peoples

J Gerontol A Biol Sci Med Sci. 2025 Jul 24;80(8):glaf123. doi: 10.1093/gerona/glaf123.

Abstract

Background: Alzheimer's disease and related dementias (ADRD) research worldwide indicate that it is more common in Indigenous than in non-Indigenous populations. We examined the relationship of depression and diabetes, alone and together, with incident ADRD in a large sample of American Indian and Alaska Native (AIAN) peoples.

Methods: We examined a sample of 65,801 AIAN peoples aged ≥ 45 years in fiscal year 2007 who were ADRD-free between FY2007-09. Cox proportional hazard models were employed to estimate associations between ADRD risk and baseline depression and diabetes, adjusting for potential confounding variables.

Results: We found 2.3% received an ADRD diagnosis during FY2010-13. Compared to persons with neither depression nor diabetes, the fully adjusted hazard ratio (HR) for those aged ≥ 45 years with depression and diabetes was 1.82 (95% CI 1.53-2.16) for ADRD and those with depression only had a hazard ratio of 1.70 (95% CI 1.44-2.00). A significant relationship was not found between diabetes only and ADRD risk. Compared with women without depression, the adjusted risk of ADRD was 50% higher (HR = 1.50, 95% CI 1.30-1.73) for women with depression, while 115% higher (HR = 2.15, 95% CI 1.76-2.61) for men with depression.

Conclusions: Depression is associated with a substantially higher risk of ADRD among adult AIAN peoples. This association varies by sex and age, with the strongest association observed among relatively young men. Helpful future efforts include ensuring clinical and behavioral services for AIAN peoples provide regular mental health screening and any needed treatment.

Keywords: cognition; comorbidity; hazard ratios; incidence; mental health.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alaska Natives* / statistics & numerical data
  • Alzheimer Disease* / epidemiology
  • Alzheimer Disease* / ethnology
  • Dementia* / epidemiology
  • Dementia* / ethnology
  • Depression* / complications
  • Depression* / epidemiology
  • Depression* / ethnology
  • Diabetes Mellitus* / epidemiology
  • Diabetes Mellitus* / ethnology
  • Female
  • Humans
  • Incidence
  • Indians, North American* / statistics & numerical data
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Risk Factors
  • United States / epidemiology