ALS phenotype is influenced by age, sex, and genetics. A population-based study

A. Chiò, C. Moglia, A. Canosa, U. Manera, F. D’Ovidio, R. Vasta, M. Grassano, M. Brunetti, M. Barberis, L. Corrado, S. D’Alfonso, B. Iazzolino, L. Peotta, M. F. Sarnelli, V. Solara, J. P. Zucchetti, F. De Marchi, L. Mazzini, G. Mora, and A. Calvo

Neurology 2020;94:e802-e810.

Selezionato dal Lettore: Leonardo Biscetti - Ospedale Santa Maria della Misericordia Perugia

In this  study, authors investigated, in a large sample of patients with amyotrophic lateral sclerosis (ALS), the relationship between clinical phenotype, age, sex and genetic features.  The Authors found that the onset and early progression of motor and cognitive manifestations of ALS is strongly determined by at least 2 demographic factors, age and sex, and, to some extent, also by genetic variations. In particular, the frequency of bulbar phenotype increased with aging, while the frequency of primary upper motoneuron and of classic phenotypes decreased. Male sex was associated with flail arm and respiratory phenotypes, female sex with bulbar phenotype, but only through an interaction with age. C9orf72 expansions was related to a 2-fold increase of bulbar phenotype and SOD1 mutations to a 3.5-fold increased frequency of flail leg phenotype and a 3.5-fold reduced frequency of bulbar phenotype. Finally, authors found a strong interrelation between motor and cognitive phenotypes, with a higher propensity of patients with bulbar phenotype to develop fronto-temporal dementia, and an increased risk of developing cognitive impairment with increasing age.

This study represent a significant contribution in the field of ALS: in fact, it suggests the possibility of re-classifying patients into homogeneous subgroups, opening the road of future, accurate studies about the pathogenesis of the disease. This could be of particular interest especially in the view of desirable, future targeting therapy.