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

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 ( 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 (Ptrend < 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 (Ptrend = 0.024), executive efficiency (DIFFBA) (Ptrend = 0.026), and RAVLT memory test (Ptrend = 0.011). Results for the metformin group remained stable for the MMSE and TMTs but declined for the RAVLT (Ptrend = 0.011). With use of linear mixed-effects models, the interaction term, FPI × 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.