Abstract
The FMR1 gene premutation (55-200 CGG repeats) is usually associated with a wide range of symptoms and phenotypes within the Fragile X-tremor/ataxia syndrome (FXTAS), but may also manifest as predominant or isolated cognitive decline. We describe three male patients referred for progressive cognitive impairment and behavioral changes. Standard work-up, including MRI, FDG-PET, CSF biomarkers, and neuropsychological testing, excluded common dementias. Brain MRI imaging revealed callosal and peduncular white matter changes, while 18FDG-PET showed consistent anterior cingulate hypometabolism. Genetic analysis confirmed FMR1 premutation in all cases. Clinicians in memory clinics should consider this diagnosis in cases of unexplained cognitive decline.