Motor and cognitive impairments in spinocerebellar ataxia type 7 and its correlations with cortical volumes

Abstract

Spinocerebellar Ataxia Type 7 (SCA7) is a neurodegenerative disorder caused by cytosine‐adenine‐guanine (CAG) repeat expansion. It is clinically characterized by ataxia and visual loss. To date, little is known about SCA7 cognitive impairments and its relationship with grey matter volume (GMV) changes. The aim of this study was to explore SCA7 patients’ performance in specific components of auditory‐verbal neuropsychological tests and to correlate their scores with genetic mutation, severity of ataxia and GMV. We assessed verbal memory and verbal fluency proficiencies in 31 genetically confirmed SCA7 patients, and compared their results with 32 healthy matched volunteers; we also correlated CAG repeats and severity of motor symptoms with performance in the auditory‐verbal tests. SCA7 patients exhibited deficiencies in several components of these cognitive tasks, which were independent of motor impairments and showed no relation to CAG repeats. Based on Resonance Images performed in 27 patients we found association between ataxia severity and GMV in “sensoriomotor” cerebellum, as well as correlations of impaired verbal memory and semantic fluency scores with GMV in association cortices, including the right parahippocampal gyrus. To our knowledge, this is the first report of deficits in the organization of semantic information and in the evocation of verbal material, as well as greater susceptibility to proactive interference in SCA7 patients. These findings bring novel information about specific cognitive abilities in SCA7 patients, particularly verbal memory and fluency, and their relation with GMV variations in circumscribed brain regions, including association cortices known to have functional relationships with the cerebellum.

Molecular Targets and Therapeutic Strategies in Spinocerebellar Ataxia Type 7

“…The unique pattern of cerebellar damages distinguishes SCA7 from other subtypes of SCA [52]. Structural and functional magnetic resonance imaging and fractional anisotropy further confirmed widespread but regio-specific alterations of diverse extracerebellar grey and white matters [38,51,53,54]. Using a new tractography method, the fixel-based analysis, Adanyeguh et al [55] were able to document longitudinal volumetric changes in the cerebellum and pons as well as in the corpus callosum in SCA7 patients, which might prove useful as disease biomarkers.…”

“…There is a close relationship between cerebellar volume and the motor impairment in people with SCA7 [51]. Lobules IX and X as well as lobules I, II, and VIIIb of cerebellum appear particularly vulnerable [38]. The unique pattern of cerebellar damages distinguishes SCA7 from other subtypes of SCA [52].…”

“…Common symptoms include spastic ataxia gait, dysarthria, dysphagia, slow eye movement, ophthalmoplegia, prominent hyperreflexia with crossed supraclavicular, pectoral and hip adductor reflexes, spasticity of the lower limbs, and pyramidal signs [3,4,[33][34][35]. SCA7 patients with difficulties in attributing emotions and with cognitive impairment affecting verbal memory and fluency were also reported [36][37][38]. It is also proposed that extracerebellar component of SCA7 accounts for sudden changes in laryngeal muscle tone, producing instability in the voice [39].…”

Cognitive Decline and White Matter Integrity Degradation in Myotonic Dystrophy Type I

“…We used a t ‐student or a Mann–Whitney U test, where applicable. We corrected by False Discovery Rate (FDR) for multiple comparisons with q = .05, and we calculated the effect size with a Cohn's d or a statistics r , where applicable 17 …”

“…CANTAB tests with different difficulty levels were analyzed using a mixed Analysis of Variance model for independent variables. The cognitive results of control and patient group were taken as the between subject factor and the levels of each stage were considered as the intrasubject factor 17 …”