Rosiglitazone and cognitive stability in older individuals with type 2 diabetes and mild cognitive impairment

Abstract

OBJECTIVE- Studies have suggested that insulin resistance plays a role in cognitive impairment in individuals with type 2 diabetes. We aimed to determine whether an improvement in insulin resistance could explain cognitive performance variations over 36 weeks in older individuals with mild cognitive impairment (MCI) and type 2 diabetes. RESEARCH DESIGN AND METHODS- A total of 97 older individuals (mean ± SD age 76±6 years) who had recently (<2 months) started an antidiabetes treatment of metformin (500 mg twice a day) (n = 30) or metformin (500 mg/day)+rosiglitazone (4 mg/day) (n = 32) or diet (n = 35) volunteered. The neuropsychological test battery consisted of the Mini-Mental State Examination (MMSE), Rey Verbal Auditory Learning Test (RAVLT) total recall, and Trail Making Tests (TMT-A and TMT-B) performed at baseline and every 12 weeks for 36 weeks along with clinical testing. RESULTS- At baseline, no significant differences were found between groups in clinical or neuropsychological parameters. Mean±SD values in the entire population were as follows: A1C 7.5±0.5%, fasting plasma glucose (FPG) 8.6±1.3 mmol/l, fasting plasma insulin (FPI) 148± 74 pmol/l, MMSE 24.9±2.4, TMT-A 61.6±42.0, TMT-B 162.8±78.7, the difference between TMT-B and TMT-A [DIFFBA] 101.2 ± 58.1, and RAVLT 24.3 ± 2.1. At follow-up, ANOVA models tested changes in metabolic control parameters (FPI, FPG, and A1C). Such parameters improved in the metformin and metformin/rosiglitazone groups (P trend < 0.05 in both groups). ANCOVA repeated models showed that results for the metformin/rosiglitazone group remained stable for all neuropsychological tests, and results for the diet group remained stable for the MMSE and TMT-A and declined for the TMT-B (P trend = 0.024), executive efficiency (DIFFBA) (P trend = 0.026), and RAVLT memory test (P trend = 0.011). Results for the metformin group remained stable for the MMSE and TMTs but declined for the RAVLT (P trend=0.011). With use of linear mixed-effects models, the interaction term, FPI X time, correlated with cognitive stability on the RAVLT in the metformin/rosiglitazone group (β = -1.899; P = 0.009). CONCLUSIONS- Rosiglitazone may protect against cognitive decline in older individuals with type 2 diabetes and MCI. © 2010 by the American Diabetes Association.