Glycosylated hemoglobin level and development of mild cognitive impairment or dementia in older women.

Background: Biological mechanisms linking diabetes and cognition continue to grow, yet the association remains controversial in elders. Whether glycosylated hemoglobin (HbA 1C ) level, a marker of glucose control, is predictive of the development of cognitive impairment or dementia is unknown. We determined the association between HbA 1C level and risk of developing cognitive impairment in older women, mostly without diabetes. Methods: We studied 1983 postmenopausal women (mean age, 67.2 years) with osteoporosis who had HbA 1C level measured at baseline. Development of mild cognitive impairment (MCI) or dementia over 4 years was determined as part of a dementia ancillary study. We analyzed risk of MCI or dementia for every 1% of HbA 1C as well as risk associated with HbA 1C ≥ 7%. Results: The mean level of HbA 1C was 5.8% (range 3.0% to 12.1%) and 86 (4.3%) women developed MCI or dementia. For every 1% increase in HbA 1C , women had a greater age-adjusted likelihood of developing MCI (OR= 1.50; 95% CI 1.14-1.97) and of developing MCI or dementia (OR=1.40; 95% CI 1.08 - 1.83). For those with HbA 1C level £ 7% (n=49), the age-adjusted risk for developing MCI was increased nearly 4-fold (OR= 3.70; 95% CI 1.51-9.09) and was increased nearly 3-fold for developing MCI or dementia (OR=2.86; 95% CI 1.17-6.98). When we excluded women with diagnosed diabetes (n=53), the association between HbA IC and MCI lessened somewhat but remained elevated (unadjusted OR=1.59; 95% CI 1.01-2.50; age-adjusted OR=1.42; 95% CI 0.89-2.28). Multivariate analyses adjusted for age, education, race, depression, alcohol use and treatment with raloxifene yielded similar results. Interpretation: We found an association between HbA 1C level and risk of developing MCI or dementia in postmenopausal osteoporotic women primarily without diabetes. Our findings support the hypothesis that glucose dysregulation is a predictor for cognitive impairment.