Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disease with motor, psychiatric, and cognitive manifestations that occurs in carriers of the fragile X mental retardation 1 (FMR1) gene premutations. This was a retrospective chart review of 196 individuals (127 men, 69 women) with FXTAS. Forty-six (23%) participants were cognitively impaired, of whom 19 (10%) had dementia. Risk factors for dementia were examined (CGG repeat size; alcohol, benzodiazepine, and opioid use; diabetes; hyperlipidemia; hypertension; hypothyroidism; obesity; sleep apnea; surgeries with general anesthesia; depression; and family history of dementia). Thirteen individuals with FXTAS and dementia were compared with thirteen cognitively intact individuals matched on age, gender, and FXTAS stage. CGG repeat size was significantly higher (mean 98.5, SD = 22.2) in the dementia group, compared to the cognitively intact group (mean = 81.6, SD = 11.5; p=0.0256). These results show that CGG repeat size is a risk factor for FXTAS dementia.
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