Rosiglitazone and cognitive stability in older individuals 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 (<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 (beta = -1.899; P = 0.009). CONCLUSIONS: Rosiglitazone may protect against cognitive decline in older individuals with type 2 diabetes and MCI.

Arterial stiffness and cognition in elderly persons with impaired glucose tolerance and microalbuminuria.

BACKGROUND: Cognitive decline that occurs frequently in impaired glucose tolerance (IGT) may be largely due to endothelial dysfunction. We assessed: (i) the relationships between impact of urinary albumin excretion rate (UAER), as marker of generalized endothelial dysfunction, and cognition; (ii) if cognitive decline could be explained by arterial stiffening using pulse wave velocity (PWV). METHODS: One hundred forty older patients (age range 70-85 years) with IGT and no dementia were selected. Patients were classified according to 24-hour UAER: normoalbuminuric (NA) (UAER<20 microg/min) or microalbuminuric (MA) (UAER between 20 and 199 microg/min). Cognitive abilities were assessed by the Mini-Mental State Examination (MMSE) and a composite score of executive and attention functioning (CCS) at baseline and after 12 months of follow-up. RESULTS: In MA patients (n=80), increased UAERs correlated with intimal media thickness (IMT) (r=0.268; p=02) and PWV (r=0.310; p=004). In the same group, increased UAERs were correlated with MMSE and CCS even after adjusting for age and mean arterial blood pressure (MABP). After adding PWV, the associations among UAERs, MMSE, and CCS were no longer significant. In MA patients, PWV correlated with IMT, MMSE, and CCS. In NA patients, no significant correlations were found among UAERs, MMSE, and CCS. At follow-up, baseline UAERs predicted an approximately 20% risk of poor cognition (according to MMSE and CCS) after adjusting for confounders. After adding PWV, UAERs no longer predicted cognitive performance. CONCLUSIONS: MA older persons with IGT showed a decline in cognition performance that may be partially explained by arterial stiffness.