Impact of Type 2 Diabetes and Postmenopausal Hormone Therapy on Incidence of Cognitive Impairment in Older Women

Diabetes Care. 2015 Dec;38(12):2316-24. doi: 10.2337/dc15-1385. Epub 2015 Oct 20.

Abstract

Objective: In older women, higher levels of estrogen may exacerbate the increased risk for cognitive impairment conveyed by diabetes. We examined whether the effect of postmenopausal hormone therapy (HT) on cognitive impairment incidence differs depending on type 2 diabetes.

Research design and methods: The Women's Health Initiative (WHI) randomized clinical trials assigned women to HT (0.625 mg/day conjugated equine estrogens with or without [i.e., unopposed] 2.5 mg/day medroxyprogesterone acetate) or matching placebo for an average of 4.7-5.9 years. A total of 7,233 women, aged 65-80 years, were classified according to type 2 diabetes status and followed for probable dementia and cognitive impairment (mild cognitive impairment or dementia).

Results: Through a maximum of 18 years of follow-up, women with diabetes had increased risk of probable dementia (hazard ratio [HR] 1.54 [95% CI 1.16-2.06]) and cognitive impairment (HR 1.83 [1.50-2.23]). The combination of diabetes and random assignment to HT increased their risk of dementia (HR 2.12 [1.47-3.06]) and cognitive impairment (HR 2.20 [1.70-2.87]) compared with women without these conditions, interaction P = 0.09 and P = 0.08. These interactions appeared to be limited to women assigned to unopposed conjugated equine estrogens.

Conclusions: These analyses provide additional support to a prior report that higher levels of estrogen may exacerbate risks that type 2 diabetes poses for cognitive function in older women. The role estrogen plays in suppressing non-glucose-based energy sources in the brain may explain this interaction.

Trial registration: ClinicalTrials.gov NCT00000611.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Brain / drug effects
  • Brain / metabolism
  • Brain / physiopathology
  • Cognition / drug effects*
  • Cognition / physiology
  • Cognition Disorders / chemically induced*
  • Cognition Disorders / physiopathology
  • Dementia / chemically induced*
  • Dementia / physiopathology
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Estrogen Replacement Therapy / adverse effects*
  • Estrogens / blood
  • Estrogens, Conjugated (USP) / adverse effects
  • Female
  • Glucose / metabolism
  • Humans
  • Incidence
  • Medroxyprogesterone Acetate / adverse effects
  • Postmenopause
  • Randomized Controlled Trials as Topic
  • Risk

Substances

  • Estrogens
  • Estrogens, Conjugated (USP)
  • Medroxyprogesterone Acetate
  • Glucose

Associated data

  • ClinicalTrials.gov/NCT00000611