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.


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.
Abbatecola
Angela M
AM
Italian National Research Center on Aging, Ancona, Italy.
Lattanzio
Fabrizia
F
Molinari
Anna M
AM
Cioffi
Michele
M
Mansi
Luigi
L
Rambaldi
Pierfrancesco
P
DiCioccio
Luigi
L
Cacciapuoti
Federico
F
Canonico
Raffaele
R
Paolisso
Giuseppe
G
D000368:Aged; D000369:Aged, 80 and over; D003071:Cognition / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone