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From the Departments of Psychiatry (Dr. Yaffe), Neurology (Dr. Yaffe), Epidemiology (Drs. Yaffe and Kanaya, and T. Blackwell), and Medicine (Dr. Kanaya and N. Davidowitz), University of California, San Francisco; the San Francisco VA Medical Center (Dr. Yaffe); Department of Community and Family Medicine (Dr. Barrett-Connor), University of California San Diego, La Jolla; and Lilly Research Laboratories (Dr. Krueger), Eli Lilly and Company, Indianapolis, IN.
Address correspondence and reprint requests to Dr. Kristine Yaffe, University of California, San Francisco, Box 181 4150 Clement St., San Francisco, CA 94121; e-mail: kyaffe{at}itsa.ucsf.edu
Objective: To investigate the association between diabetes and impaired fasting glucose (IFG) and cognition and risk of developing both dementia and mild cognitive impairment (MCI) in older women.
Methods: The authors analyzed data from a 4-year randomized trial of raloxifene among 7,027 osteoporotic postmenopausal women (mean age, 66.3 years) at 178 sites. Diabetes was defined by history, fasting blood glucose 
7.0 mmol/L (126 mg/dL), or use of hypoglycemic agents; IFG was defined as fasting glucose <7.0 mmol/L but >6.11 mmol/L (110 mg/dL); all others were considered to have normal glucose (NG). The main outcome was baseline and 4-year change on five standardized cognitive tests (z scores with lower scores indicating worse performance) and risk of developing clinically significant impairment (dementia, mild cognitive impairment, or very low cognitive score).
Results: A total of 267 (3.8%) women had diabetes and 297 (4.2%) had IFG. Women with IFG had worse baseline cognitive scores compared to women with NG but better scores than diabetics (age-adjusted composite z score based on five tests: NG 0.40, 95% CI 0.30 to 0.49; IFG 0.14, 95% CI –0.36 to 0.64; diabetics –0.78, 95% CI –1.23 to –0.33; p < 0.001). There was greater 4-year decline among diabetics (age and treatment-adjusted composite z score: NG –0.05, 95% CI –0.16 to 0.05; IFG 0.11, 95% CI –0.53 to 0.75; diabetics –1.00, 95% CI –1.50 to –0.50; p = 0.001). Further adjustment for education, race, and depression led to similar results. Risk of developing cognitive impairment among women with IFG or diabetes was increased by almost twofold (age and treatment-adjusted OR = 1.64; 95% CI 1.03 to 2.61 for IFG; OR = 1.79; 95% CI 1.14 to 2.81 for diabetics).
Conclusions: Diabetic as well as pre-diabetic women have impaired cognitive performance and greater risk of developing cognitive impairment.
Received September 14, 2003. Accepted in final form April 26, 2004.
Dr. Yaffe has received honoraria from Eli Lilly & Co. T. Blackwell has a percentage of her salary paid by Eli Lilly & Co. Dr. Barrett-Connor has received grants and consultant fees from Eli Lilly & Co. Dr. Krueger owns stock in Eli Lilly in excess of $10,000.
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