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

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

Author information

1
Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC mespelan@wakehealth.edu.
2
Departments of Pharmacology and Pharmaceutical Sciences, Biomedical Engineering, and Neurology, University of Southern California, Los Angeles, CA.
3
Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
4
Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
5
Departments of Epidemiology and Biostatistics, Psychiatry, and Neurology, University of California, San Francisco, San Francisco, CA.
6
Veterans Affairs Palo Alto Health Care System, Stanford University School of Medicine, Stanford, CA Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA.
7
Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, NC.
8
Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN.
9
Department of Internal Medicine, Ohio State University, Columbus, OH.
10
Laboratory of Behavioral Neuroscience, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD.

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.

PMID:
26486190
PMCID:
PMC4657616
DOI:
10.2337/dc15-1385
[Indexed for MEDLINE]
Free PMC Article

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