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• DPP-4i showed beneficial effects on glycaemia and cognitive impairment. • DPP-4i reduce hypoglycemic events and the related damage on cognitive function. • We evaluated the effect of vildagliptin on MMSE in diabetic elderly with MCI. • Our results showed a stable MMSE in patients after treatment with vildagliptin. There is an unclear association between type 2 diabetes and mild cognitive impairment in the elderly. Both diseases are more prevalent in the older adults compared to the younger counterpart. Some anti-diabetic drugs seem to influence positively the evolution of mild cognitive impairment. This retrospective study investigated the effect of vildagliptin, an inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4), on the cognitive functioning of elderly diabetic patients with mild cognitive impairment (MCI) documented at mini mental state examination (MMSE). We included 60 diabetic elderly people which were divided in 2 groups: Group A, 30 patients with HbA 1 c (glycated hemoglobin) ≤7.5% and treated with metformin, and Group B, 30 patients with HbA 1 c >7.5%, and treated with metformin plus vildagliptin. We collected data on MMSE, fasting plasma glucose (FPG) and HbA 1 c at baseline and after 180 ± 10 days from the beginning of treatment. The two groups exhibited significantly different values in FPG (P < 0.05) and HbA 1 c (P < 0.01) at baseline, and in MMSE score (P < 0.001) after treatment. The intragroup comparison showed a significant (P < 0.05) reduction in MMSE score in group A, and in HbA1c (P = 0.01) in group B. Vildagliptin in addition to metformin resulted in the maintenance of MMSE score, showing a protecting role on cognitive functioning compared to the metformin only group. [ABSTRACT FROM AUTHOR]