Long-Term Use of Metformin Is Associated With Reduced Risk of Cognitive Impairment With Alleviation of Cerebral Small Vessel Disease Burden in Patients With Type 2 Diabetes

Zhenjie Teng; Jing Feng; Qianqian Qi; Yanhong Dong; Yining Xiao; Xiaohua Xie; Nan Meng; Huifang Chen; Wenhui Zhang; Peiyuan Lv

doi:10.3389/fnagi.2021.773797

Long-Term Use of Metformin Is Associated With Reduced Risk of Cognitive Impairment With Alleviation of Cerebral Small Vessel Disease Burden in Patients With Type 2 Diabetes

Front Aging Neurosci. 2021 Oct 29:13:773797. doi: 10.3389/fnagi.2021.773797. eCollection 2021.

Authors

Zhenjie Teng^{1

2}, Jing Feng³, Qianqian Qi^{1

2}, Yanhong Dong², Yining Xiao^{1

2}, Xiaohua Xie², Nan Meng², Huifang Chen², Wenhui Zhang⁴, Peiyuan Lv^{1

2}

Affiliations

¹ Department of Neurology, Hebei Medical University, Shijiazhuang, China.
² Department of Neurology, Hebei General Hospital, Shijiazhuang, China.
³ Department of Endocrinology, Hebei General Hospital, Shijiazhuang, China.
⁴ Memory Clinic, Hebei General Hospital, Shijiazhuang, China.

Abstract

Objective: Type 2 diabetes (T2D) is a risk factor for cognitive impairment and cerebral small vessel disease (CSVD). The relation of metformin use and cognitive impairment or CSVD is not clear. The objective of this study was to investigate the cross-sectional effects of long-term use of metformin on total CSVD burden and cognitive function in patients with T2D. Methods: A total of 234 participants with T2D from the memory clinic in Hebei General Hospital were enrolled in this retrospective study. Duration of metformin use and dosage were recorded. Along with cerebral magnetic resonance imaging (MRI) examination, Mini-Mental State Examination (MMSE) was also performed to assess their cognitive status. We determined the validated total CSVD score (ranging from 0-4) by combining four markers of CSVD that were visually rated. We used binary logistic regression analysis, ordinal logistic regression analysis and mediation analysis to assess the relation of long-term use of metformin with CSVD burden and cognitive function. Results: Binary logistic regression analysis showed long-term use of metformin was associated with reducing the risk of cognitive impairment (OR: 0.446; 95% Confidence Interval (CI): 0.249 to 0.800; P = 0.007), after adjustment of potential confounders, such as total CSVD burden score, age, HbA1c, hypertension, history of stroke, homocysteine, body mass index, TG and HDL-C. Ordinal logistic regression analysis suggested that long-term use of metformin was associated with alleviation of total CSVD burden score (OR: 0.583; 95% CI: 0.359 to 0.943; P = 0.027), after adjusting for age, HbA1c, hypertension, history of stroke, homocysteine, body mass index, TG and HDL-C. Mediation analysis showed significant mediation by the presence of severe CSVD burden score for long-term use of metformin in relation to cognitive impairment. Conclusion: Long-term use of metformin was associated with lower rates of cognitive impairment and lower total CSVD burden score in patients with T2D. A proportion of the relation between long-term use of metformin and cognitive impairment may be attributable to alleviation of CSVD burden.

Keywords: cerebral small vessel disease; cognitive impairment; diabetes; metformin; relationship.