Long-Term Metformin Usage and Cognitive Function among Older Adults with Diabetes

Abstract

Evidence strongly supports the important role of insulin resistance in cognitive decline and dementia and suggests that insulin sensitizers may protect against cognitive decline in diabetic and pre-diabetic individuals. Inconclusive results have been reported in clinical trials of rosiglitazone, an insulin sensitizer that also increases cardiovascular mortality risks. No study has yet reported a protective cognitive effect of metformin, an insulin-sensitizing biguanide widely used in diabetic patients. We studied 365 older persons aged 55 and over in the population-based Singapore Longitudinal Aging Study with diabetes who were followed up over 4 years. The odds ratios (OR) of association of metformin use (n = 204) versus non-use (n = 161) with cognitive impairment (Mini-Mental State Exam ≤ 23), and by duration: up to 6 years (n = 114) and more than 6 years (n = 90) were evaluated in cross-sectional and longitudinal multivariate analyses. Controlling for age, education, diabetes duration, fasting blood glucose, vascular and non-vascular risk factors, metformin use showed a significant inverse association with cognitive impairment in longitudinal analysis (OR = 0.49, 95% CI 0.25-0.95). Metformin use showed significant linear trends of association across duration of use in cross-sectional and longitudinal analyses (p = 0.018 and p = 0.002, respectively), with use for more than 6 years significantly associated with lowest risk of cognitive impairment in both cross-sectional analysis (OR = 0.30, 95% CI 0.11-0.80) and in longitudinal analysis (OR = 0.27, 95% CI 0.12-0.60). No significant interactive effects of metformin use with APOE-ε4, depression, or fasting glucose level were observed. Among individuals with diabetes, long-term treatment with metformin may reduce the risk of cognitive decline. Further studies should establish the role of hyperglycemia and insulin resistance, and the protective role of metformin in the risk of cognitive decline and dementia.

Metformin: A Hopeful Promise in Aging Research

“…Moreover, diabetic and cardiovascular disease patients who are prescribed metformin have increased rates of survival (Scarpello 2003;Yin et al 2013), and it was recently proposed that metformin might promote longevity by preventing frailty in older adults with T2DM (Wang et al 2014). Chronic treatment with metformin among patients with diabetes might reduce the risk of cognitive decline and dementia (Ng et al 2014;Patrone et al 2014) and improve survival in several types of cancer (Greenhill 2015;Ko et al 2015;Lin et al 2015;Rego et al 2015).…”

The neurobiology of the Prader-Willi phenotype of fragile X syndrome

“…Interestingly, pharmacological restoration using metformin, rescued memory deficits in the dfmr1 (54). Metformin is known to decrease body mass index (BMI) and to prevent cognitive deficits in individuals with diabetes (55)(56)(57)(58)(59). Metformin decreases protein synthesis and insulin-signaling via the AMPK/Akt/ mTOR pathway, it also inhibits the lipid and sterol biosynthetic pathways (60)(61)(62)(63) (Figure 3).…”

Síndrome de Vogt-Koyanagi-Harada: presentación de un caso clínico.

“…[5][6][7] Existen cinco criterios clínicos que ayudan a establecer las tres formas clínicas del síndrome VKH y permiten descartar los otros diagnósticos diferenciales, en dependencia de la presencia o ausencia de estos criterios (tabla). Por lo tanto se considera VKH completo cuando los cinco criterios están presentes; VKH incompleto, cuando los criterios del 1 al 3 se encuentran presentes obligatoriamente y del 4 al 5 pueden estar o no presentes; y por último VKH probable cuando se trata de una condición ocular aislada teniendo presentes solo los criterios del 1 al 3.…”