Title:Cognitive Dysfunction in FMR1 Premutation Carriers
Volume: 9
Issue: 1
Author(s): Andreea Seritan, Jennifer Cogswell and Jim Grigsby
Affiliation:
Keywords:
Cognition, Dementia, Executive function, FMR1 premutation, FXTAS, Memory
Abstract: Premutation carriers of the fragile X mental retardation gene (especially men) older than 50 may develop a
neurodegenerative disease, the fragile X-associated tremor/ataxia syndrome (FXTAS). Carriers may present with varied
cognitive impairments. Attention, working memory, declarative and procedural learning, information processing speed,
and recall are among the cognitive domains affected. Executive dysfunction is a prominent deficit, which has been
demonstrated mostly in men with FXTAS. In more advanced stages of FXTAS, both men and women may develop a
mixed cortical-subcortical dementia, manifested by psychomotor slowing and deficits in attention, retrieval, recall,
visuospatial skills, occasional apraxia, as well as overt personality changes. Studies have shown dementia rates as high as
37-42% in older men with FXTAS, although more research is needed to understand the prevalence and risk factors of
dementia in women with FXTAS. Neuropsychiatric symptoms are common and reflect the dysfunction of underlying
frontal-subcortical neural circuits, along with components of the cerebellar cognitive affective syndrome. These include
labile or depressed mood, anxiety, disinhibition, impulsivity, and (rarely) psychotic symptoms. In this paper we review the
information available to date regarding the prevalence and clinical picture of FXTAS dementia. Differential diagnosis
may be difficult, given overlapping motor and non-motor signs with several other neurodegenerative diseases. Anecdotal
response to cholinesterase inhibitors and memantine has been reported, while symptomatic treatments can address the
neuropsychiatric manifestations of FXTAS dementia.
