Impact of type 2 diabetes and postmenopausal hormone therapy on incidence of cognitive impairment in older women

Mark A. Espeland, Roberta Diaz Brinton, Christina Hugenschmidt, Jo Ann E. Manson, Suzanne Craft, Kristine Yaffe, Julie Weitlauf, Leslie Vaughan, Karen Johnson, Claudia B. Padula, Rebecca D. Jackson, Susan M. Resnick

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 TheWomen's Health Initiative (WHI) randomized clinical trials assignedwomen to HT (0.625 mg/day conjugated equine estrogens with or without [i.e., unopposed] 2.5 mg/daymedroxyprogesterone acetate) or matching placebo for an average of 4.7-5.9 years. A total of 7,233women, 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 maximumof 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 estrogenmay 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.

Original languageEnglish (US)
Pages (from-to)2316-2324
Number of pages9
JournalDiabetes care
Volume38
Issue number12
DOIs
StatePublished - Dec 1 2015

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Type 2 Diabetes Mellitus
Hormones
Dementia
Incidence
Conjugated (USP) Estrogens
Estrogens
Therapeutics
Cognition
Cognitive Dysfunction
Acetates
Randomized Controlled Trials
Placebos
Health
Brain

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

Espeland, M. A., Brinton, R. D., Hugenschmidt, C., Manson, J. A. E., Craft, S., Yaffe, K., ... Resnick, S. M. (2015). Impact of type 2 diabetes and postmenopausal hormone therapy on incidence of cognitive impairment in older women. Diabetes care, 38(12), 2316-2324. https://doi.org/10.2337/dc15-1385

Impact of type 2 diabetes and postmenopausal hormone therapy on incidence of cognitive impairment in older women. / Espeland, Mark A.; Brinton, Roberta Diaz; Hugenschmidt, Christina; Manson, Jo Ann E.; Craft, Suzanne; Yaffe, Kristine; Weitlauf, Julie; Vaughan, Leslie; Johnson, Karen; Padula, Claudia B.; Jackson, Rebecca D.; Resnick, Susan M.

In: Diabetes care, Vol. 38, No. 12, 01.12.2015, p. 2316-2324.

Research output: Contribution to journalArticle

Espeland, MA, Brinton, RD, Hugenschmidt, C, Manson, JAE, Craft, S, Yaffe, K, Weitlauf, J, Vaughan, L, Johnson, K, Padula, CB, Jackson, RD & Resnick, SM 2015, 'Impact of type 2 diabetes and postmenopausal hormone therapy on incidence of cognitive impairment in older women', Diabetes care, vol. 38, no. 12, pp. 2316-2324. https://doi.org/10.2337/dc15-1385
Espeland MA, Brinton RD, Hugenschmidt C, Manson JAE, Craft S, Yaffe K et al. Impact of type 2 diabetes and postmenopausal hormone therapy on incidence of cognitive impairment in older women. Diabetes care. 2015 Dec 1;38(12):2316-2324. https://doi.org/10.2337/dc15-1385
Espeland, Mark A. ; Brinton, Roberta Diaz ; Hugenschmidt, Christina ; Manson, Jo Ann E. ; Craft, Suzanne ; Yaffe, Kristine ; Weitlauf, Julie ; Vaughan, Leslie ; Johnson, Karen ; Padula, Claudia B. ; Jackson, Rebecca D. ; Resnick, Susan M. / Impact of type 2 diabetes and postmenopausal hormone therapy on incidence of cognitive impairment in older women. In: Diabetes care. 2015 ; Vol. 38, No. 12. pp. 2316-2324.
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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 TheWomen's Health Initiative (WHI) randomized clinical trials assignedwomen to HT (0.625 mg/day conjugated equine estrogens with or without [i.e., unopposed] 2.5 mg/daymedroxyprogesterone acetate) or matching placebo for an average of 4.7-5.9 years. A total of 7,233women, 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 maximumof 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 estrogenmay 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.",
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AU - Yaffe, Kristine

AU - Weitlauf, Julie

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N2 - 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 TheWomen's Health Initiative (WHI) randomized clinical trials assignedwomen to HT (0.625 mg/day conjugated equine estrogens with or without [i.e., unopposed] 2.5 mg/daymedroxyprogesterone acetate) or matching placebo for an average of 4.7-5.9 years. A total of 7,233women, 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 maximumof 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 estrogenmay 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.

AB - 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 TheWomen's Health Initiative (WHI) randomized clinical trials assignedwomen to HT (0.625 mg/day conjugated equine estrogens with or without [i.e., unopposed] 2.5 mg/daymedroxyprogesterone acetate) or matching placebo for an average of 4.7-5.9 years. A total of 7,233women, 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 maximumof 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 estrogenmay 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.

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