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

David Hervás, Victoria Fornés-Ferrer, Ana Pilar Gómez-Escribano, María Dolores Sequedo, Carmen Peiró, José María Millán, Rafael P Vázquez-Manrique, David Hervás, Victoria Fornés-Ferrer, Ana Pilar Gómez-Escribano, María Dolores Sequedo, Carmen Peiró, José María Millán, Rafael P Vázquez-Manrique

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Partial dependence plots showing the…
Fig 1. Partial dependence plots showing the interaction between metformin intake and HD status regarding cognitive scores.
(A-F) Result of the analysis of the different cognitive tests. G Graph showing the result of the analysis of all cognitive tests (Cognitive Score). These plots are produced using the estimates from the fitted linear regression models, so cognitive values are adjusted for age, gender, BMI and ISCED. The p-values included are assessing the effect of the interactions, that is, the differential effect of metformin intake in HD-patients compared to controls.
Fig 2. Partial dependence plot showing the…
Fig 2. Partial dependence plot showing the interaction between metformin intake and motor impairment (UHDRS Motorscore).
Result of the analysis of the UHDRS Motorscore. This plot was produced using the estimates from the fitted linear regression models, so the UHDRS Motorscore values are adjusted for age, gender, BMI and ISCED. The p-value is assessing the effect of the interaction, that is, the differential effect of metformin intake in HD-patients compared to controls.

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