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Diabetes, Glucose Control, and 9-Year Cognitive Decline Among Older Adults Without Dementia

Kristine Yaffe, MD; Cherie Falvey, MPH; Nathan Hamilton, MA; Ann V. Schwartz, PhD, MPH; Eleanor M. Simonsick, PhD; Suzanne Satterfield, MD, DrPh; Jane A. Cauley, DrPH; Caterina Rosano, MD; Lenore J. Launer, PhD; Elsa S. Strotmeyer, PhD, MPH; Tamara B. Harris, MD
Arch Neurol. 2012;69(9):1170-1175. doi:10.1001/archneurol.2012.1117.
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Objectives  To determine if prevalent and incident diabetes mellitus (DM) increase risk of cognitive decline and if, among elderly adults with DM, poor glucose control is related to worse cognitive performance.

Design  Prospective cohort study.

Setting  Health, Aging, and Body Composition Study at 2 community clinics.

Participants  A total of 3069 elderly adults (mean age, 74.2 years; 42% black; 52% female).

Main Outcome Measures  Participants completed the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and selected intervals over 10 years. Diabetes mellitus status was determined at baseline and during follow-up visits. Glycosylated hemoglobin A1c level was measured at years 1 (baseline), 4, 6, and 10 from fasting whole blood.

Results  At baseline, 717 participants (23.4%) had prevalent DM and 2352 (76.6%) were without DM, 159 of whom developed incident DM during follow-up. Participants with prevalent DM had lower baseline test scores than participants without DM (3MS: 88.8 vs 90.9; DSST: 32.5 vs 36.3, respectively; t = 6.09; P = .001 for both tests). Results from mixed-effects models showed a similar pattern for 9-year decline (3MS: −6.0- vs −4.5-point decline; t = 2.66; P = .008; DSST: −7.9- vs −5.7-point decline; t = 3.69; P = .001, respectively). Participants with incident DM tended to have baseline and 9-year decline scores between the other 2 groups but were not statistically different from the group without DM. Multivariate adjustment for demographics and medical comorbidities produced similar results. Among participants with prevalent DM, glycosylated hemoglobin A1c level was associated with lower average mean cognitive scores (3MS: F = 8.2; P for overall = .003; DSST: F = 3.4; P for overall = .04), even after multivariate adjustment.

Conclusion  Among well-functioning older adults, DM and poor glucose control among those with DM are associated with worse cognitive function and greater decline. This suggests that severity of DM may contribute to accelerated cognitive aging.

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Grahic Jump Location

Figure 1. Baseline and 9-year cognitive decline scores by diabetes mellitus (DM) status, adjusting for age, race, sex, and education. A, Modified Mini-Mental State Examination (3MS) scores. *Baseline 3MS score: prevalent DM vs normal, t = 2.5; P value = .01; incident DM vs normal, t = 1.69; P value = .09. †3MS 9-year decline slope: prevalent DM vs normal, t = 2.37; P value = .02. B, Digit Symbol Substitution Test (DSST) scores. *Baseline DSST score: prevalent DM vs normal, t = 2.24; P value = .03. †DSST 9-year decline slope: prevalent DM vs normal, t = 3.25; P value = .001.

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Grahic Jump Location

Figure 2. Unadjusted Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) scores by glycosylated hemoglobin A1c (HbA1c) level at mean time of follow-up. The error bars indicate standard error.

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