Abstract
BackgroundCognitive decline is a common non-motor feature characterizing Spinocerebellar Ataxia type 2 (SCA2) during the prodromal stage, nevertheless a reduced number of surrogate biomarkers of these alterations have been described.ObjectiveTo provide insights into cognitive dysfunction in SCA2 patients using P300 event-related potentials (ERP) and to evaluate these measures as biomarkers of the disease.MethodsA cross-sectional study was performed with 30 SCA2 patients, 20 preclinical carriers and 33 healthy controls, who underwent visual, auditory P300 ERPs, and neurological examinations and ataxia scoring.ResultsSCA2 patients showed significant increase in P300 latencies and decrease of P300 amplitudes for visual and auditory stimuli, whereas preclinical carriers exhibit a less severe, but significant prolongation of P300 latencies. Multiple regression analyses disclosed a significant effect of SARA score on visual P300 abnormalities in patients as well as of the time to ataxia onset on visual P300 latencies in preclinical carriers.ConclusionsThis paper demonstrated the role of P300 ERP for the study of attentional, discriminative and working memory abnormalities in SCA2 patients and for the search of surrogate biomarkers from prodromal to the symptomatic stages. Moreover, our findings provide psychophysiological evidences supporting the cerebellar involvement in cognitive processes and allows us to identify promising outcome measures for future trials focusing on cognitive dysfunction.
Highlights
Cognitive decline is a common non-motor feature characterizing Spinocerebellar Ataxia type 2 (SCA2) during the prodromal stage, a reduced number of surrogate biomarkers of these alterations have been described
The disease is caused by the expansion of the Citosine-Adenine-Guanine (CAG)-repeat tract in the coding region of the ATXN2 gene, causing the expression of an abnormally long polyglutamine tract in the ataxin-2 protein which acquires neurotoxic functions resulting in neuronal loss of the cerebellum, brainstem, brain cortex and spinal cord [1, 2]
Clinical findings Aside from the cerebellar syndrome, the most frequent disease features of SCA2 patients were the slowing of saccade eye movements (93.3%) and sensory abnormalities (83.3%)
Summary
Cognitive decline is a common non-motor feature characterizing Spinocerebellar Ataxia type 2 (SCA2) during the prodromal stage, a reduced number of surrogate biomarkers of these alterations have been described. Spinocerebellar Ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disorder. Clinical features of SCA2 comprise a Globally, SCA2 is the second most common autosomal dominant cerebellar ataxia, after SCA3, but is the most prevalent subtype in Mexico, Italy, India and Cuba. No effective neuroprotective treatments are currently available for this disease, symptomatic treatments can improve some motor. The event-related evoked potentials (ERP) have become in useful tools as electroencephalographic (EEG)-based methods for studying the brain’s synaptic function during cognitive processes in these diseases [11,12,13,14,15]. The P300 component of the ERP has been widely applied because it reflects the neurophysiologic substrate of cognitive processes such as attention, discrimination, and working memory [16]
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