Age-related functional brain changes in FMR1 premutation carriers

The FMR1 premutation confers a 40–60% risk for males of developing a neurodegenerative disease called the Fragile X-associated Tremor Ataxia Syndrome (FXTAS). FXTAS is a late-onset disease that primarily involves progressive symptoms of tremor and ataxia, as well as cognitive decline that can develop into dementia in some patients. At present, it is not clear whether changes to brain function are detectable in motor regions prior to the onset of frank symptomatology. The present study therefore aimed to utilize an fMRI motor task for the first time in an asymptomatic premutation population.Premutation carriers without a diagnosis of FXTAS (n=17) and a group of healthy male controls (n=17), with an age range of 24–68years old, were recruited for this cross-sectional study. This study utilized neuroimaging, molecular and clinical measurements, employing an fMRI finger-tapping task with a block design consisting of sequential finger-tapping, random finger-tapping and rest conditions. The imaging analysis contrasted the sequential and random conditions to investigate activation changes in response to a change in task demand. Additionally, measurements were obtained of participant tremor, co-ordination and balance using the CATSYS-2000 system and measures of FMR1 mRNA were quantified from peripheral blood samples using quantitative real-time PCR methodology.Premutation carriers demonstrated significantly less cerebellar activation than controls during sequential versus random finger tapping (FWEcorr<0.001). In addition, there was a significant age by group interaction in the hippocampus, inferior parietal cortex and temporal cortex originating from a more negative relationship between brain activation and age in the carrier group compared to the controls (FWEcorr<0.001).Here, we present for the first time functional imaging-based evidence for early movement-related neurodegeneration in Fragile X premutation carriers. These changes pre-exist the diagnosis of FXTAS and are greatest in older carriers suggesting that they may be indicative of FXTAS vulnerability. Keywords: Fragile X premutation, FXTAS, fMRI, Neuroimaging, Neurodegeneratio

Tremor and hand-arm vibration syndrome (HAVS) in road maintenance workers

OBJECTIVES: The aim of this study was to evaluate postural and rest tremor among workers using vibrating hand tools, taking into account the possible effects of toxicants such as alcohol and tobacco. A further aim was to study workers diagnosed with hand-arm vibration syndrome (HAVS) at the time of examination. METHODS: This study comprises 103 road maintenance workers, 55 exposed to vibrating hand tools (age 41.0 years; range 21–62) and 48 referents (age 38.5 years; range 19–64). They were examined with the CATSYS Tremor Pen(®). Exposure to vibrating tools and serum biomarkers of alcohol and tobacco consumption were measured. RESULTS: Cumulative exposure to vibrating tools was associated with increased postural (p < 0.01) and rest tremor (p < 0.05) and with a higher Center Frequency of postural tremor (p < 0.01) among smokers and users of smokeless tobacco. Rest tremor Center Frequency was higher than postural tremor frequency (p < 0.001). CONCLUSIONS: The main findings indicate an association between cumulative exposure to hand-held vibrating tools, tremor parameters and consumption of tobacco products. The hand position is important when testing for tremor. Rest tremor had a higher Center Frequency. Postural tremor was more strongly associated with exposure than rest tremor. The finding of increased tremor among the HAVS subjects indicated that tremor might be a part of the clinical picture of a HAVS diagnosis. As with all cross-sectional studies, inferences should be made with caution when drawing conclusions about associations between exposure and possible effects. Future research using longitudinal design is required to validate the findings of the present study