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Metformin intake associates with better cognitive function in patients with Huntington's disease.

ABSTRACT: Huntington's disease (HD) is an inherited, dominant neurodegenerative disorder caused by an abnormal expansion of CAG triplets in the huntingtin gene (htt). Despite extensive efforts to modify the progression of HD thus far only symptomatic treatment is available. Recent work suggests that treating invertebrate and mice HD models with metformin, a well-known AMPK activator which is used worldwide to treat type 2-diabetes, reduces mutant huntingtin from cells and alleviates many of the phenotypes associated to HD. Herein we report statistical analyses of a sample population of participants in the Enroll-HD database, a world-wide observational study on HD, to assess the effect of metformin intake in HD patients respect to cognitive status using linear models. This cross-sectional study shows for the first time that the use of metformin associates with better cognitive function in HD patients.

SUBMITTER: Hervas D

PROVIDER: S-EPMC5478119 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Metformin intake associates with better cognitive function in patients with Huntington's disease.

Hervás David D Fornés-Ferrer Victoria V Gómez-Escribano Ana Pilar AP Sequedo María Dolores MD Peiró Carmen C Millán José María JM Vázquez-Manrique Rafael P RP

PloS one 20170620 6

Huntington's disease (HD) is an inherited, dominant neurodegenerative disorder caused by an abnormal expansion of CAG triplets in the huntingtin gene (htt). Despite extensive efforts to modify the progression of HD thus far only symptomatic treatment is available. Recent work suggests that treating invertebrate and mice HD models with metformin, a well-known AMPK activator which is used worldwide to treat type 2-diabetes, reduces mutant huntingtin from cells and alleviates many of the phenotypes ...[more]

PMID: 28632780

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Project description:BackgroundThe objective of this case-control study was to identify any association of metformin intake with the survival of patients with ovarian cancer.MethodsIn this retrospective case-control study, women with ovarian cancer who received metformin (cases) were compared with women with ovarian cancer who did not receive metformin (controls). A 2-layered analysis was conducted. In preliminary analysis, all cases (the OC cohort) were compared with controls at a 1:2 ratio. Subsequently, in definitive analysis, only patients who had epithelial ovarian cancer (the EOC cohort) were compared with controls at a 1:3 ratio. In the EOC cohort, cases were matched with controls for age (±5 years), International Federation of Gynecology and Obstetrics stage, and residual disease. Prognostic variables and disease specific survival were compared using chi-square tests, the Kaplan-Meier (log-rank) method, and Cox proportional hazards analysis.ResultsIn a preliminary analysis of the OC cohort (72 cases and 143 controls), cases had better survival (5-year disease-specific survival for cases vs controls, 73% vs 44%; P = .0002). In the definitive analysis of the EOC cohort (61 cases and 178 controls), the distribution of age, disease stage, optimal cytoreduction, serous histology, and platinum chemotherapy remained similar between cases and controls (P > .05). Despite these similarities, cases had significantly better survival (5-year disease-specific survival for cases vs controls, 67% vs 47%; P = .007). On multivariate analysis, metformin remained an independent predictor of survival (hazard ratio, 2.2; 95% confidence interval, 1.2-3.8; P = .007) after controlling for disease stage, grade, histology, chemotherapy, body mass index, and surgical cytoreduction.ConclusionsThe results of this study indicated an association of metformin intake with survival in patients with ovarian cancer. The receipt of metformin was associated with better survival, and the authors concluded that metformin is worthy of clinical trials in ovarian cancer.

Project description:Decades of research and experimental studies have investigated Huntington's disease (HD), a rare neurodegenerative disease. Similarly, several studies have investigated whether high/moderate adherence to the Mediterranean Diet and specific macro and micronutrients can decrease cognitive loss and provide a neuroprotective function to neurons. This review systematically identifies and examines studies that have investigated Mediterranean Diet adherence, micro- and macronutrients, supplementation and caloric intake in people with HD, in order to identify if dietary exposures resulted in improvement of disease symptoms, a delay in age of onset or if they contributed to an earlier age of onset in people with HD. A systematic search of PubMed, Directory of open access journal and HubMed was performed independently by two reviewers using specific search terms criteria for studies. The identified abstracts were screened and the studies were included in the review if they satisfied predetermined inclusion criteria. Reference screening of included studies was also performed. A total of 18 studies were included in the review. A few studies found that patients who had high/moderate adherence to Mediterranean Diet showed a slight improvement in their Unified Huntington's Disease Rating Scale and Total Functional Capacity. In addition, people with HD who had high Mediterranean Diet adherence showed an improvement in both cognitive and motor scores and had a better quality of life compared to patients who had low Mediterranean Diet adherence. Furthermore, a few studies showed that supplementation with specific nutrients, such as triheaptanoin, L-acetyl-carnitine and creatine, had no beneficial effect on the patients' Unified Huntington's Disease Rating Scale score. A few studies suggest that the Mediterranean Diet may confer a motor and cognitive benefit to people with HD. Unfortunately, there was little consistency among study findings. It is important for more research to be conducted to have a better understanding of which dietary exposures are beneficial and may result delaying age of onset or disease progression in people with HD.

Dataset Information

Metformin intake associates with better cognitive function in patients with Huntington's disease.

Publications

Metformin intake associates with better cognitive function in patients with Huntington's disease.

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