Neuropsychological and motor deficits in Parkinson's disease that may contribute to driving impairment were examined in a cohort study comparing patients with Parkinson's disease (PD) to patients with Alzheimer's disease (AD) and to healthy elderly controls.

Previous imaging studies in the Machado-Joseph disease (MJD/SCA3) have mostly concentrated on the cerebellum and brainstem. Our goal was to perform a whole brain longitudinal evaluation. METHODSWe included 45 patients and 51 controls, who underwent two brain magnetic resonance imaging and magnetic resonance spectroscopy (mean interval of 12.5 ± 1.5 months). We used voxel-based morphometry (VBM) and the MarsBar analysis toolbox to extract grey matter density (GMD) values from regions of interest. We used a linear regression model and a general linear model to correlate GMD with clinical markers, and paired t-test for the longitudinal evaluation. RESULTSWe observed decreased GMD (P < .01) at frontal, parietal, temporal and occipital lobes, subcortical grey matter, cerebellum, and brainstem. White matter atrophy was restricted to the cerebellum. Age, CAG, and disease duration predicted GMD in different areas, but age and CAG were the most important predictors. The longitudinal analysis failed to demonstrate changes. Changes in regions other than the cerebellum appeared to contribute significantly to the final International Cooperative Ataxia Rating Scale score. CONCLUSIONWe confirmed cortical involvement in MJD/SCA3. The most important factors in predicting GMD were age and CAG. The lack of progression of atrophy may indicate floor effect and/or short duration of follow-up.

Machado-Joseph disease or spinocerebellar ataxia 3 (MJD/SCA3) is a clinically heterogeneous, neurodegenerative disorder characterized by varying degrees of ataxia, ophthalmoplegia, peripheral neuropathy, pyramidal dysfunction and movement disorder. MJD/SCA3 is caused by a CAG repeat expansion mutation in the protein coding region of the ATXN3 gene located at chromosome 14q32.1. Current hypotheses regarding pathogenesis favor the view that mutated ataxin-3, with its polyglutamine expansion, is prone to adopt an abnormal conformation, engage in altered proteinprotein interactions and aggregate. Expanded CAG repeat length correlates with the range and severity of the clinical manifestations and inversely correlates with age of disease onset. Though MJD/SCA3 is classically described as affecting the cerebellum, brain stem and basal ganglia, recent neuropathology and neuroimaging series demonstrate involvement of other areas such as the thalamus and cerebral cortex. Clinically, much emphasis has been placed in the description and recognition of the non-motor symptoms observed in these patients, such as pain, cramps, fatigue and depression. Currently, no disease modifying treatment exists for MJD/SCA3. Standard of care includes genetic counseling, exercise/physical therapy programs, and speech and swallow evaluation. Symptomatic treatment for clinical findings such as depression, sleep disorders, parkinsonism, dystonia, cramps, and pain is important to improve the quality of life for those with MJD/SCA3.

Previous studies demonstrated cognitive impairments in spinocerebellar ataxia type 3 (SCA3/MJD); however, there is no consensus about the cognitive domains affected and the correlation with structural brain abnormalities. We investigated the neuropsychological profile and 3T-MRI findings, including high-resolution T1-images, diffusion tensor imaging and magnetic resonance spectroscopy of 32 patients with SCA3/MJD and 32 age-, gender- and educational level-matched healthy controls. We reviewed patients' clinical history and CAG repeat length, and performed assessment and rating of ataxia (SARA)-Brazilian version and the neuropsychiatric inventory. Patients presented worse performance in episodic and working memory and Beck inventories (depression and anxiety). SCA3/MJD patients had a reduction of gray matter volume (GM) in the cerebellum, putamen, cingulum, precentral and parietal lobe. A positive correlation was identified between the cognitive findings and GM of temporal, frontal, parietal, culmen and insula. We observed positive correlation between the brainstem's fractional anisotropy and digit span-forward. The following cerebellar metabolite groups (measured relative to creatine) were reduced in patients: N-acetyl-aspartate (NAA), NAA + N-acetyl-aspartate-glutamate and glutamate + glutamine (Glx). We found a positive correlation between Corsi's block-tapping task forward with Glx; semantic verbal fluency with phosphorylcholine and glycerophosphorylcholine; digits span-forward with NAA. The cognitive impairments in SCA3/MJD are associated not only with cerebellar and brainstem abnormalities, but also with neuroimaging evidence of diffuse neuronal and axonal dysfunction, particularly in temporal, frontal, parietal and insular areas.