Subtle cognitive impairment but no dementia in patients with spastin mutations.
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.


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.


CONCLUSIONS
Asymptomatic cognitive impairment mostly affecting executive functions is present in SPG4 mutation carriers and is more frequent in those with missense mutations.
Tallaksen
Chantal M E
CM
Institut National de la Santé et de la Recherche Médicale Unit 289, Fédération de Neurologie, Hôpital de la Salpêtrière, 47 boulevard de l'Hôpital, 75013 Paris, France.
Guichart-Gomez
Elodie
E
Verpillat
Patrice
P
Hahn-Barma
Valerie
V
Ruberg
Merle
M
Fontaine
Bertrand
B
Brice
Alexis
A
Dubois
Bruno
B
Durr
Alexandra
A
D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D003071:Cognition; D004252:DNA Mutational Analysis; D003704:Dementia / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009483:Neuropsychological Tests; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics / Q000503:physiopathology*; D000074181:Spastin
D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human