Dementia in fragile X‐associated tremor/ataxia syndrome (FXTAS): Comparison with Alzheimer's disease

Abstract

Background-Neurocognitive deficits in fragile X-associated tremor/ataxia syndrome (FXTAS) involve attentional control, working memory, executive functioning, and declarative and procedural learning. To date, no studies comparing FXTAS with other dementias have been done. We characterize the dementia in FXTAS, comparing it with Alzheimer's disease.

Current research, diagnosis, and treatment of fragile X-associated tremor/ataxia syndrome

“…Dementia was found in 21-50% males with FXTAS (32,36). In females with FXTAS, however, dementia is far less common (36,37) and it has been reported in only a few cases (41)(42)(43)(44)(45). Females with FXTAS may also exhibit parkinsonism, although at a lower rate than in males with FXTAS (34).…”

“…After the tremor onset, the median onset of ataxia was 2 years later; onset of falls was 6 years later; dependence on a walking aid was 15 years later; and death was 21 years later (35). The rate of progression of FXTAS varies and life expectancy is between 5 to 25 years after the onset of the symptoms (36).…”

“…The proportion of normal FMR1 alleles on the active X chromosome (activation ratio) is thought to modulate the phenotypic severity in females (38); however, double heterozygous female have been reported and they seem to have a similar clinical presentation to heterozygous females (39,40). Dementia was found in 21-50% males with FXTAS (32,36). In females with FXTAS, however, dementia is far less common (36,37) and it has been reported in only a few cases (41)(42)(43)(44)(45).…”

Neuroimaging - Clinical Applications

“…Cognitive decline in FXTAS usually occurs in men, after a long duration of extrapyramidal disturbances, but it may also occur in women. Typically in men, a clinical picture similar distinct from Alzheimer´s disease (Seritan et al, 2008), and more similar to patients with fronto-temporal lobar degeneration occurs (FTLD) (Burgeois et al, 2009). Although there is little evidence from MRI in these patients, particularly in women (Al Hinti et al, 2007;Karmon et al, 2008), more recently, two cases of mother-to-daughter transmission were reported (Rodriguez-Revenga et al, 2010).…”

Neuroimaging in Fragile X-Associated

“…In males, initially mild cognitive problems can accomplish criteria for dementia after 5 to 10 years of evolution (Grisby et al, 2007). Extension of the neurodegenerative process to prefrontal and temporal structures seems to account for the progression of cognitive defects in FXTAS patients (Seritan et al, 2008). While balance problems and tremor seem to be the consequence of the progressive degeneration of middle cerebellar peduncles and associated cerebellar structures, both cognitive and behavioural problems in FXTAS are associated with diffuse cortical and white-matter subcortical degeneration (Hashimoto et al, 2011).…”