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, JoAnn E Manson, Suzanne Craft, Kristine Yaffe, Julie Weitlauf, Leslie Vaughan, Karen C Johnson, Claudia B Padula, Rebecca D Jackson, Susan M Resnick, WHIMS Study Group, Sally Shumaker, Mark Espeland, Stephen Rapp, Claudine Legault, Laura Coker, Maggie Dailey, Michelle Naughton, Beverly Snively, Iris Leng, Kaycee Sink, Beverley Jones, Leslie Vaughan, Dan Beavers, Ramon Casanova, Laura D Baker, Suzanne Danhauer, Kathleen Hayden, Bev Levine, Cheryl Summerville, Debbie Pleasants, Sonya Ashburn, Debbie Booth, Brad Caudle, Doris Clark, Heather Dailey, Josh Evans, Ashley Lentz, Gina Miller, Anne Safrit, Patricia Hogan, Sarah Gaussoin, Darrin Harris, Julia Robertson, Debbie Steinberg, Katelyn R Garcia, Debbie Allen, Kelci Lewis, Linda Allred, Candace Goode, Sylvia Wassertheil-Smoller, Aleksandar Rajkovic, JoAnn Manson, Lawrence Phillips, Andrea LaCroix, Richard Katz, Rowan Chlebowski, Frances Lynch, Bette Caan, Jane Morley Kotchen, Barbara Howard, Charles Eaton, Sandra Weintraub, Lynda Powell, Dorothy Lane, Rebecca Jackson, Beth Lewis, Cynthia Thompson, Jean Wactawski-Wende, John Robbins, Allan Hubbell, Lauren Nathan, Margery Gass, Marian Limacher, Kamal Masaki, Jennifer Robinson, Judith Ockene, Norman Lasser, John Kostis, Richard Grimm, Robert Brunner, Carol Murphy, Lewis Kuller, Karen Johnson, Donald Royall, Shirley Beresford, Gloria Sarto, Mara Vitolins, Michael Simon, Garnet Anderson, Ross Prentice, Andrea LaCroix, Charles Kooperberg, JoAnn E Manson, Barbara V Howard, Marcia L Stefanick, Rebecca Jackson, Jean Wactawski-Wende, Marian Limacher, Robert Wallace, Lewis Kuller, Sally Shumaker, Neil Buckholtz, Susan Molchan, Susan Resnick, Jacques Rossouw, Linda Pottern, Mark A Espeland, Roberta Diaz Brinton, Christina Hugenschmidt, JoAnn E Manson, Suzanne Craft, Kristine Yaffe, Julie Weitlauf, Leslie Vaughan, Karen C Johnson, Claudia B Padula, Rebecca D Jackson, Susan M Resnick, WHIMS Study Group, Sally Shumaker, Mark Espeland, Stephen Rapp, Claudine Legault, Laura Coker, Maggie Dailey, Michelle Naughton, Beverly Snively, Iris Leng, Kaycee Sink, Beverley Jones, Leslie Vaughan, Dan Beavers, Ramon Casanova, Laura D Baker, Suzanne Danhauer, Kathleen Hayden, Bev Levine, Cheryl Summerville, Debbie Pleasants, Sonya Ashburn, Debbie Booth, Brad Caudle, Doris Clark, Heather Dailey, Josh Evans, Ashley Lentz, Gina Miller, Anne Safrit, Patricia Hogan, Sarah Gaussoin, Darrin Harris, Julia Robertson, Debbie Steinberg, Katelyn R Garcia, Debbie Allen, Kelci Lewis, Linda Allred, Candace Goode, Sylvia Wassertheil-Smoller, Aleksandar Rajkovic, JoAnn Manson, Lawrence Phillips, Andrea LaCroix, Richard Katz, Rowan Chlebowski, Frances Lynch, Bette Caan, Jane Morley Kotchen, Barbara Howard, Charles Eaton, Sandra Weintraub, Lynda Powell, Dorothy Lane, Rebecca Jackson, Beth Lewis, Cynthia Thompson, Jean Wactawski-Wende, John Robbins, Allan Hubbell, Lauren Nathan, Margery Gass, Marian Limacher, Kamal Masaki, Jennifer Robinson, Judith Ockene, Norman Lasser, John Kostis, Richard Grimm, Robert Brunner, Carol Murphy, Lewis Kuller, Karen Johnson, Donald Royall, Shirley Beresford, Gloria Sarto, Mara Vitolins, Michael Simon, Garnet Anderson, Ross Prentice, Andrea LaCroix, Charles Kooperberg, JoAnn E Manson, Barbara V Howard, Marcia L Stefanick, Rebecca Jackson, Jean Wactawski-Wende, Marian Limacher, Robert Wallace, Lewis Kuller, Sally Shumaker, Neil Buckholtz, Susan Molchan, Susan Resnick, Jacques Rossouw, Linda Pottern

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.

© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Figures

Figure 1
Figure 1
Cumulative hazard of probable dementia (A) and cognitive impairment (B) over 18 years for women grouped by diabetes (DM) and assignment to HT or placebo (PL).

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Source: PubMed

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