Cognitive deficits in ALS patients with mutations.

Objective: Cognitive decline is common in patients with amyotrophic lateral sclerosis (ALS), especially in carriers of the mutation . However, cognitive impairment is poorly understood in carriers of mutations in other genes causing ALS. We performed a comprehensive neuropsychological testing in patients with mutations in the (m) gene.

Methods: We examined 5 cognitive domains in 48 symptomatic patients with either hereditary or sporadic ALS. These were compared with 37 matched controls.

Results: Carriers of -mutations and sporadic ALS had circumscribed deficits, but in a pattern different from . All groups had deficits in working memory, although mcarriers significantly outperform sporadic ALS and in an attention-driven visuospatial task involving copying a complex figure. Carriers of the D90A- mutation overall performed as well as or better than carriers of other mutations, except complex working memory. Bayesian analyses suggest (with evidence of moderate strength) that tasks involving the language domain did not differ between controls, m and sporadic ALS.

Conclusion: Distinct cognitive impairments are prevalent in different ALS-syndromes and vary in patients with different pathogenic mutations. The type and degree of impairment differed depending on genotype and was significantly least pronounced in patients homozygous for the D90A mutation. The presence of cognitive deficits may influence optimal clinical management and intervention. We propose that cognitive assessment should be included in the routine examination of new patients suspected of ALS. Neuropsychological assessment is an under-recognized outcome parameter in clinical drug trials.