|
|
Pharmacy Information 2026
糖尿病用药与老年2型糖尿病患者认知功能的相关性研究
|
Abstract:
目的：探讨老年2型糖尿病患者不同降糖方案与多维度认知功能之间的相关性。方法：基于2011~2014年NHANES数据库，纳入647名60岁及以上的T2DM患者。通过CERAD即时与延迟回忆、动物流畅性及数字符号替代测试评估认知功能。采用t检验比较不同药物组间的认知z分数差异，并利用校正后的Logistic回归模型分析药物与各维度认知障碍的关联。结果：二甲双胍组在综合认知分数上显著优于不服药组(Mean Difference = 0.28, 95% CI: 0.10~0.46, P = 0.002)。在调整了混杂因素后的Logistic回归显示，二甲双胍可显著降低即时回忆障碍(OR = 0.29, 95% CI: 0.13~0.63)及综合认知功能障碍(OR = 0.33, 95% CI: 0.16~0.71)的风险。交互分析均未见统计学意义(Pinteraction > 0.05)。结论：二甲双胍的使用与老年T2DM患者较低的认知障碍风险独立相关，其保护效应具有跨人群的一致性。
Objective: To investigate the correlation between different hypoglycemic regimens and multidimensional cognitive function in elderly patients with Type 2 Diabetes Mellitus (T2DM). Methods: Based on the 2011-2014 National Health and Nutrition Examination Survey (NHANES) database, 647 T2DM patients aged 60 years and older were included. Cognitive function was assessed using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) immediate and delayed recall tests, Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Weighted t-tests were used to compare differences in cognitive z-scores between different medication groups, and adjusted logistic regression models were employed to analyze the association between medications and cognitive impairment in various dimensions. Results: The metformin group showed significantly better overall cognitive scores compared to the no-medication group (Mean Difference = 0.28, 95% CI: 0.10~0.46, P = 0.002). After adjusting for confounding factors, logistic regression indicated that metformin significantly reduced the risk of immediate recall impairment (OR = 0.29, 95% CI: 0.13~0.63) and overall cognitive impairment (OR = 0.33, 95% CI: 0.16~0.71). Interaction analyses showed no statistical significance (Pinteraction > 0.05). Conclusion: The use of metformin is independently associated with a lower risk of cognitive impairment in elderly T2DM patients, with consistent protective effects across populations. This study highlights the potential neuroprotective benefits of metformin beyond glycemic control, providing evidence for clinical decision-making in balancing blood sugar management and cognitive preservation in older adults.
| [1] | Mayeda, E.R., Whitmer, R.A. and Yaffe, K. (2015) Diabetes and Cognition. Clinics in Geriatric Medicine, 31, 101-115. https://doi.org/10.1016/j.cger.2014.08.021 |
| [2] | Dandona, P. (2004) Inflammation: The Link between Insulin Resistance, Obesity and Diabetes. Trends in Immunology, 25, 4-7. https://doi.org/10.1016/j.it.2003.10.013 |
| [3] | Gorelick, P.B., Scuteri, A., Black, S.E., DeCarli, C., Greenberg, S.M., Iadecola, C., et al. (2011) Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals from the American Heart Association/American Stroke Association. Stroke, 42, 2672-2713. https://doi.org/10.1161/str.0b013e3182299496 |
| [4] | American Diabetes Association (2013) Standards of Medical Care in Diabetes—2014. Diabetes Care, 37, S14-S80. https://doi.org/10.2337/dc14-s014 |
| [5] | Craft, S., Cholerton, B. and Baker, L.D. (2012) Insulin and Alzheimer’s Disease: Untangling the Web. Journal of Alzheimer’s Disease, 33, S263-S275. https://doi.org/10.3233/jad-2012-129042 |
| [6] | Munshi, M.N. (2017) Cognitive Dysfunction in Older Adults with Diabetes: What a Clinician Needs to Know. Diabetes Care, 40, 461-467. https://doi.org/10.2337/dc16-1229 |
| [7] | Munshi, M., Grande, L., Hayes, M., Ayres, D., Suhl, E., Capelson, R., et al. (2006) Cognitive Dysfunction Is Associated with Poor Diabetes Control in Older Adults. Diabetes Care, 29, 1794-1799. https://doi.org/10.2337/dc06-0506 |
| [8] | Foretz, M., Guigas, B., Bertrand, L., Pollak, M. and Viollet, B. (2014) Metformin: From Mechanisms of Action to Therapies. Cell Metabolism, 20, 953-966. https://doi.org/10.1016/j.cmet.2014.09.018 |
| [9] | Ou, Z., Kong, X., Sun, X., He, X., Zhang, L., Gong, Z., et al. (2018) Metformin Treatment Prevents Amyloid Plaque Deposition and Memory Impairment in APP/PS1 Mice. Brain, Behavior, and Immunity, 69, 351-363. https://doi.org/10.1016/j.bbi.2017.12.009 |
| [10] | Chiang, M., Cheng, Y., Chen, S., Yen, C. and Huang, R. (2016) Metformin Activation of AMPK-Dependent Pathways Is Neuroprotective in Human Neural Stem Cells against Amyloid-Beta-Induced Mitochondrial Dysfunction. Experimental Cell Research, 347, 322-331. https://doi.org/10.1016/j.yexcr.2016.08.013 |
| [11] | Rena, G., Hardie, D.G. and Pearson, E.R. (2017) The Mechanisms of Action of Metformin. Diabetologia, 60, 1577-1585. https://doi.org/10.1007/s00125-017-4342-z |
| [12] | Campbell, J.M., Stephenson, M.D., de Courten, B., Chapman, I., Bellman, S.M. and Aromataris, E. (2018) Metformin Use Associated with Reduced Risk of Dementia in Patients with Diabetes: A Systematic Review and Meta-Analysis. Journal of Alzheimer’s Disease, 65, 1225-1236. https://doi.org/10.3233/jad-180263 |
| [13] | Khattar, D., Khaliq, F., Vaney, N. and Madhu, S.V. (2016) Is Metformin-Induced Vitamin B12 Deficiency Responsible for Cognitive Decline in Type 2 Diabetes? Indian Journal of Psychological Medicine, 38, 285-290. https://doi.org/10.4103/0253-7176.185952 |
| [14] | NHANES Questionnaires. NHANES Questionnaires, Datasets, and Related Documentation. https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/default.aspx |
| [15] | Barini, E., Antico, O., Zhao, Y., Asta, F., Tucci, V., Catelani, T., et al. (2016) Metformin Promotes Tau Aggregation and Exacerbates Abnormal Behavior in a Mouse Model of Tauopathy. Molecular Neurodegeneration, 11, Article No. 16. https://doi.org/10.1186/s13024-016-0082-7 |
| [16] | Salminen, A., Kaarniranta, K., Haapasalo, A., Soininen, H. and Hiltunen, M. (2011) AMP‐Activated Protein Kinase: A Potential Player in Alzheimer’s Disease. Journal of Neurochemistry, 118, 460-474. https://doi.org/10.1111/j.1471-4159.2011.07331.x |
| [17] | Ning, P., Luo, A., Mu, X., Xu, Y. and Li, T. (2022) Exploring the Dual Character of Metformin in Alzheimer’s Disease. Neuropharmacology, 207, Article ID: 108966. https://doi.org/10.1016/j.neuropharm.2022.108966 |
| [18] | He, Y., Li, Z., Shi, X., Ding, J. and Wang, X. (2023) Metformin Attenuates White Matter Injury and Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion. Journal of Cerebral Blood Flow & Metabolism, 43, 78-94. https://doi.org/10.1177/0271678x231175189 |
| [19] | Liu, Y., Tang, G., Li, Y., Wang, Y., Chen, X., Gu, X., et al. (2014) Metformin Attenuates Blood-Brain Barrier Disruption in Mice Following Middle Cerebral Artery Occlusion. Journal of Neuroinflammation, 11, Article No. 177. https://doi.org/10.1186/s12974-014-0177-4 |
| [20] | Calkin, C., McClelland, C., Cairns, K., Kamintsky, L. and Friedman, A. (2021) Insulin Resistance and Blood-Brain Barrier Dysfunction Underlie Neuroprogression in Bipolar Disorder. Frontiers in Psychiatry, 12, Article ID: 636174. https://doi.org/10.3389/fpsyt.2021.636174 |
| [21] | Whitmer, R.A. (2009) Hypoglycemic Episodes and Risk of Dementia in Older Patients with Type 2 Diabetes Mellitus. JAMA, 301, 1565-1572. https://doi.org/10.1001/jama.2009.460 |
| [22] | Graveling, A.J., Deary, I.J. and Frier, B.M. (2013) Acute Hypoglycemia Impairs Executive Cognitive Function in Adults with and without Type 1 Diabetes. Diabetes Care, 36, 3240-3246. https://doi.org/10.2337/dc13-0194 |
| [23] | MacLeod, K.M., Gold, A.E., Ebmeier, K.P., Hepburn, D.A., Deary, I.J., Goodwin, G.M., et al. (1996) The Effects of Acute Hypoglycemia on Relative Cerebral Blood Flow Distribution in Patients with Type I (Insulin-Dependent) Diabetes and Impaired Hypoglycemia Awareness. Metabolism, 45, 974-980. https://doi.org/10.1016/s0026-0495(96)90266-8 |
