To assess the association, at diagnosis, between amyotrophic lateral sclerosis (ALS) and dementia in a large cohort of well-characterized Italian patients. We investigated the phenotypic profile of 1638 incident patients with definite, probable or laboratory-supported probable ALS, diagnosed from January 2009 to December 2013 in 13 Italian Referral Centers, located in 10 Italian Regions, and classified in two independent subsamples accounting for presence or not of dementia. The collected ALS features, including survival and other follow-up data, were compared between the two subgroups using a one-way analysis of variance and Chi-square test, as appropriate, logistic regression models and Kaplan-Meier survival analysis. Between-subgroup comparisons showed an older age at clinical observation (p = .006), at onset and at diagnosis (p = .002) in demented versus non demented ALS patients. After adjustment for these variables, diagnosis of dementia was significantly associated with higher odds of family history of ALS (p = .001) and frontotemporal dementia (p = .003) and of bulbar onset (p = .004), and lower odds of flail leg phenotype (p = .019) and spinal onset (p = .008). The median survival time was shorter in demented versus non-demented patients, especially in case of classical, bulbar and flail limb phenotypes and both bulbar and spinal onset. Our multicenter study emphasized the importance of an early diagnosis of comorbid dementia in ALS patients, which may have clinical impact and prognostic relevance. Moreover, our results may give further inputs to validation of ALS-specific tools for the screening of cognitive impairment in clinical practice.
Keywords: Amyotrophic lateral sclerosis; Clinical phenotype; Dementia; Survival.