Abstract
Objective: Recent studies have suggested that metformin can penetrate the blood–brain barrier, protecting neurons via anti-inflammatory action and improvement of brain energy metabolism. In this study, we aim to investigate the effect of metformin on cognitive function in patients with abnormal glucose metabolism and non-dementia vascular cognitive impairment (NDVCI).Methods: One hundred patients with NDVCI and abnormal glucose metabolism were randomly allocated into two groups: metformin and donepezil (n = 50) or acarbose and donepezil (n = 50). The neuropsychological status, glucose metabolism, and common carotid arteries intima–media thickness (CCA-IMT) before and after a year of treatment, were measured and compared between the groups.Results: Ninety four patients completed all the assessment and follow-up. After a year of treatment, there was a decrease in Alzheimer’s disease Assessment Scale-Cognitive Subscale scores and the duration of the Trail Making Test in the metformin-donepezil group. Furthermore, these patients showed a significant increase in World Health Organization–University of California–Los Angeles Auditory Verbal Learning Test scores after treatment (all P < 0.05). However, there was no obvious improvement in cognitive function in the acarbose-donepezil group. We also observed a significant decrease in the level of fasting insulin and insulin resistance (IR) index in the metformin-donepezil group, with a lower CCA-IMT value than that in the acarbose-donepezil group after a year of treatment (P < 0.05).Conclusion: We conclude that metformin can improve cognitive function in patients with NDVCI and abnormal glucose metabolism, especially in terms of performance function. Improved cognitive function may be related to improvement of IR and the attenuated progression of IMT.Trial Registration: ChiCTR-IPR-17011855.
Highlights
Vascular cognitive impairment (VCI) refers to a syndrome in which there is evidence of clinical stroke or subclinical vascular brain damage, with damage to at least one domain of cognitive function (Gorelick et al, 2011; Platt and Riedel, 2011; Umemura et al, 2011; Sachdev et al, 2014)
We aim to investigate the effect of metformin on cognitive function in patients with abnormal glucose metabolism and non-dementia vascular cognitive impairment (NDVCI)
We observed a significant decrease in the level of fasting insulin and insulin resistance (IR) index in the metformin-donepezil group, with a lower common carotid arteries intima–media thickness (CCA-IMT) value than that in the acarbose-donepezil group after a year of treatment (P < 0.05)
Summary
Vascular cognitive impairment (VCI) refers to a syndrome in which there is evidence of clinical stroke or subclinical vascular brain damage, with damage to at least one domain of cognitive function (Gorelick et al, 2011; Platt and Riedel, 2011; Umemura et al, 2011; Sachdev et al, 2014). Non-dementia vascular cognitive impairment (NDVCI) and vascular dementia (VD) are two stages of VCI that can involve various cognitive domains, especially in NDVCI (Sun et al, 2015). NDVCI is often overlooked by patients and clinicians because the patient’s daily abilities are not affected. About 50% of patients with NDVCI will progress to dementia within 5 years (Sutton et al, 2012). The early diagnosis and intervention of NDVCI is becoming the focus of worldwide stroke research and therapy
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