Dipeptidyl Peptidase-4 Inhibitors Have Protective Effect on Cognitive Impairment in Aged Diabetic Patients With Mild Cognitive Impairment

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Abstract
Older adults with type 2 diabetes have an increased risk for mild and severe cognitive impairment probably as consequence of chronic hyperglycemia or fasting plasma glucose levels. Variability in glucose level and recurrent hypoglycemic episodes are also associated with cognitive impairment. Dipeptidyl peptidase-4 inhibitor (DPP-4I) therapy affects glycemic variability. The purpose of this study was to evaluate the effect of DPP-4I therapy on changes in cognitive function in older patients with type 2 diabetes complicated by mild cognitive impairment. This retrospective longitudinal study used data from a database of 240 older patients with type 2 diabetes, “drug naive,” affected by mild cognitive impairment, subsequently treated for 2 years with antidiabetic drugs (DPP-4I group: DPP-4I + metformin, n = 120; SU group: sulfonylurea + metformin, n = 120) and reassessed in our ambulatory by comprehensive clinical, cognitive, instrumental examinations, and continuous subcutaneous glucose monitoring. At baseline, larger mean amplitude of glycemic excursion values correlated with poorer Mini-Mental State Examination and composite cognitive function scores. We found that higher body mass index, higher 2-hour postprandial glucose, and greater mean amplitude of glycemic excursion values measured at baseline were significant independent predictors of cognitive worsening. In addition, reduction in mean amplitude of glycemic excursions and the use of DPP-4I therapy predicted improvement in cognitive functions. In older patients with type 2 diabetes affected by mild cognitive impairment, DPP-4I administration improves glucose control and protects against worsening in cognitive functioning.

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