Background: The most frequent form of autosomal dominant hereditary spastic paraparesis is associated with the SPG4 locus, described originally as a pure form of the disease. Mutations of the SPG4 gene have been increasingly associated with reports of cognitive impairment.
Objective: To investigate cognitive function in 10 families with hereditary spastic paraparesis due to mutations in the SPG4 gene, using intrafamilial control subjects.
Patients and methods: Neuropsychological examinations, including the Cambridge Cognitive Evaluation, were conducted in 29 carriers with identified SPG4 mutations and 29 intrafamilial controls.
Results: Carriers were not demented but had a subclinical cognitive impairment primarily affecting executive functions. The dysfunction was more severe in those carriers older than 50 years, but was correlated with the progression of the disease, not with age. Disease progression and cognitive impairment appeared to be more severe in the carriers of missense mutations than in those with truncating mutations.
Conclusion: Asymptomatic cognitive impairment mostly affecting executive functions is present in SPG4 mutation carriers and is more frequent in those with missense mutations.