Rosiglitazone and Cognitive Stability in Older Individuals With Type 2 Diabetes and Mild Cognitive Impairment

  1. Giuseppe Paolisso, MD5
  1. 1Italian National Research Center on Aging, Ancona, Italy;
  2. 2Department of General Pathology, Second University of Naples, Naples, Italy;
  3. 3Nuclear Medicine Division, Second University of Naples, Naples, Italy;
  4. 4Department of Geriatric Medicine, “Santa Scolastica” Hospital, Cassino, Italy;
  5. 5Department of Geriatric Medicine and Metabolic Diseases, Second University of Naples, Naples, Italy.
  1. Corresponding author: Giuseppe Paolisso, giuseppe.paolisso{at}


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 (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.


  • The Second University of Naples retained access to all study data, and the sponsor did not participate in the study.

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  1. Diabetes Care vol. 33 no. 8 1706-1711
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