Social Cognition in Patients With Cerebellar Neurodegenerative Disorders

ObjectiveCerebellar neurodegenerative disorders (CDs) are a heterogeneous group of disorders. It is known that the cerebellum plays a role not only in motor, but also in cognitive and social cognitive functions. The aim of this study was to investigate social cognition in patients with different CDs.Materials and MethodsSocial cognition was examined in 34 patients, 12 with spinocerebellar ataxia type 1 (SCA1), 6 with spinocerebellar ataxia type 2 (SCA2), and 16 with idiopathic late onset cerebellar ataxia (ILOCA). All patients were clinically evaluated using the Scale for the Rating and Assessment of Ataxia. In addition, 34 age, sex, and education-matched healthy control (HC) subjects were similarly analyzed. Social cognition was studied using two tests: the Faux Pas Recognition Test and the Reading the Mind in the Eyes Test (RMET). An appropriate array of neuropsychological tests was used to assess the global cognitive status as well as the frontal functions and mood.ResultsCD patients achieved significantly worse results on both tests of social cognition compared to the HCs. The SCA1 + 2 group achieved the poorest results on the Faux Pas Recognition Test and exhibited poor performance on all cognitive tests, but was only significantly worse compared to the ILOCA group on the Free and Cued Selective Reminding Test (FCSRT) – recognition. The patients in the SCA1 + 2 and ILOCA groups obtained similar scores on RMET. In the SCA1 + 2 group the findings significantly correlated with clinical parameters of disease severity and duration and executive functions (EFs), and with mood and executive functions in the ILOCA group. In the SCA group EFs appeared as the only significant predictor of RMET achievement. The Boston Naming Test (BTN) was a significant predictor of the CD patients’ achievement on RMET, while the BTN, the Trail Making Test Part A and FCSRT – Delayed free recall predicted their performance on the Faux Pas Recognition Test.ConclusionPatients with CD have social cognitive impairments as demonstrated by the Faux Pas Test and the RMET test results. The SCA1 and 2 patients exhibited a more pronounced impairment compared with the ILOCA patients. The independent cognitive predictors of social cognition impairment were EFs and language.

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Very late-onset sporadic spinocerebellar ataxia type 17

Acta Neurologica Belgica ◽

10.1007/s13760-021-01657-7 ◽

2021 ◽

Author(s):

Ko-Eun Choi ◽

Sang-Won Yoo ◽

Joong-Seok Kim

Keyword(s):

Spinocerebellar Ataxia ◽

Late Onset ◽

Spinocerebellar Ataxia Type ◽

Spinocerebellar Ataxia Type 17

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The neurobiological underpinning of the social cognition impairments in patients with spinocerebellar ataxia type 2

Cortex ◽

10.1016/j.cortex.2020.12.027 ◽

2021 ◽

Author(s):

Silvia Clausi ◽

Giusy Olivito ◽

Libera Siciliano ◽

Michela Lupo ◽

Marco Bozzali ◽

...

Keyword(s):

Social Cognition ◽

Spinocerebellar Ataxia ◽

Spinocerebellar Ataxia Type ◽

Spinocerebellar Ataxia Type 2 ◽

The Social

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Spinocerebellar ataxia type 6 in Brazil

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2008000500015 ◽

2008 ◽

Vol 66 (3b) ◽

pp. 691-694 ◽

Cited By ~ 13

Author(s):

Hélio A.G. Teive ◽

Renato Puppi Munhoz ◽

Salmo Raskin ◽

Lineu César Werneck

Keyword(s):

Cerebellar Ataxia ◽

Spinocerebellar Ataxia ◽

Late Onset ◽

Cag Repeat ◽

Autosomal Dominant Cerebellar Ataxia ◽

Spinocerebellar Ataxia Type ◽

Spinocerebellar Ataxia Type 6 ◽

Voltage Dependent ◽

Pure Cerebellar Ataxia ◽

Japanese Ancestry

Spinocerebellar ataxia type 6 (SCA 6) is an autosomal dominant cerebellar ataxia caused by CAG repeat expansion in the SCA6 gene, a alpha 1A voltage-dependent calcium channel subunit gene on chromosome 19p13. SCA-6 is characterized predominantly by slowly progressive pure cerebellar ataxia with late onset. We report three index patients, with pure, late onset, cerebellar ataxia, belonging to three different Brazilian families, all of them with Japanese ancestry, from Hokkaido island of Japan.

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Action perception recruits the cerebellum and is impaired in patients with spinocerebellar ataxia

Brain ◽

10.1093/brain/awz337 ◽

2019 ◽

Vol 142 (12) ◽

pp. 3791-3805 ◽

Cited By ~ 3

Author(s):

Abdel R Abdelgabar ◽

Judith Suttrup ◽

Robin Broersen ◽

Ritu Bhandari ◽

Samuel Picard ◽

...

Keyword(s):

Social Cognition ◽

Spinocerebellar Ataxia ◽

Spinocerebellar Ataxia Type ◽

Action Perception ◽

Spinocerebellar Ataxia Type 6

Using a combination of neuroimaging and behavioural studies, Abdelgabar et al. show that the cerebellum helps us perceive the actions of others. Disorders such as spinocerebellar ataxia type 6, which disrupt cerebellar functioning, impair our ability to perceive the kinematics of other people’s actions, with potential implications for social cognition.

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Cerebellar developmental deficits underlie neurodegenerative disorder spinocerebellar ataxia type 23

10.21203/rs.3.rs-26966/v1 ◽

2020 ◽

Author(s):

Cleo JLM Smeets ◽

Kai Y Ma ◽

Simon E Fisher ◽

Dineke S Verbeek

Keyword(s):

Spinocerebellar Ataxia ◽

Neurodegenerative Disorder ◽

Late Onset ◽

Protein A ◽

Spinocerebellar Ataxia Type ◽

Gabaergic Interneuron ◽

Altered Expression ◽

Developmental Abnormalities ◽

Limb Ataxia ◽

Gabaergic Synapses

Abstract Background Spinocerebellar ataxia type 23 (SCA23) is a late-onset neurodegenerative disorder characterized by slowly progressive gait and limb ataxia, for which there is no therapy available. It is caused by mutations in PDYN, which encodes the opioid precursor protein prodynorphin (PDYN). PDYN is processed into the opioid peptides α-neoendorphin, and dynorphins (Dyn) A and B; inhibitory neurotransmitters that function in pain signalling, stress-induced responses, and addiction. Mutations causing SCA23 mostly affect Dyn A, leading to loss of secondary structure and increased peptide stability. PDYNR212W mice express human PDYN containing the SCA23 p.R212W mutation. These mice show gait deficits and progressive loss of motor function from 3 months of age. The cerebella of PDYNR212W mice show climbing fibre (CF) deficits from 3 months of age and Purkinje cell (PC) loss from 12 months of age. A mouse model for SCA1 showed similar CF deficits, and a recent study found additional developmental abnormalities, namely hyperproliferation of stem cells leading to increased GABAergic interneuron connectivity and non-cell autonomous disruption of PC function. As SCA23 mice show a similar pathology to SCA1 mice in adulthood, we hypothesized that SCA23 may also follow SCA1 pathology during development. Methods In the present study, we examined the cerebella of PDYNR212W mice during cerebellar development, from 2 to 8 weeks of age, using immunohistochemistry, protein, and RNA analysis. Results We uncovered developmental deficits from 2 weeks of age, namely a reduced number of GABAergic synapses on PC soma in PDYNR212W mice, possibly leading to the observed delay in early phase CF elimination between 2 and 3 weeks of age. Furthermore, CFs did not reach terminal height leaving proximal PC dendrites open to be occupied by parallel fibres (PFs). The observed increase in vGlut1 protein -a marker for PF-PC synapses- indicates that PFs indeed take over CF territory and have increased connectivity with PCs. Additionally, we detected altered expression of several critical Ca2+ channel subunits, potentially contributing to altered Ca2+ transients in PDYNR212W cerebella. Conclusions These findings indicate that developmental abnormalities contribute to the SCA23 pathology and uncover a developmental role for PDYN in the cerebellum.

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Late-onset oro-facial dyskinesia in Spinocerebellar Ataxia type 2: a case report

BMC Neurology ◽

10.1186/s12883-020-01739-8 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Floriana Giardina ◽

Giuseppe Lanza ◽

Francesco Calì ◽

Raffaele Ferri

Keyword(s):

Case Report ◽

Spinocerebellar Ataxia ◽

Late Onset ◽

Spinocerebellar Ataxia Type ◽

Spinocerebellar Ataxia Type 2 ◽

Facial Dyskinesia

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The Contribution of the Cerebellum to Cognition in Spinocerebellar Ataxia Type 6

Behavioural Neurology ◽

10.1155/2010/724861 ◽

2010 ◽

Vol 23 (1-2) ◽

pp. 3-15 ◽

Cited By ~ 22

Author(s):

Freya E. Cooper ◽

Manon Grube ◽

Kelly J. Elsegood ◽

John L. Welch ◽

Thomas P. Kelly ◽

...

Keyword(s):

Executive Function ◽

Spinocerebellar Ataxia ◽

Late Onset ◽

Individual Performance ◽

Intellectual Ability ◽

Spinocerebellar Ataxia Type ◽

Adult Intelligence Scale ◽

Spinocerebellar Ataxia Type 6 ◽

Significant Impairment ◽

Motor Difficulties

This study sought evidence for a specific cerebellar contribution to cognition by characterising the cognitive phenotype of Spinocerebellar Ataxia Type 6 (SCA-6); an autosomal dominant genetic disease which causes a highly specific late-onset cerebellar degeneration. A comprehensive neuropsychological assessment was administered to 27 patients with genetically confirmed SCA-6. General intellectual ability, memory and executive function were examined using internationally standardised tests (Wechsler Adult Intelligence Scale-III, Wechsler Memory Scale-III, Delis and Kaplan Executive Function System, Brixton Spatial Anticipation test). The patient group showed no evidence of intellectual or memory decline. However, tests of executive function involving skills of cognitive flexibility, inhibition of response and verbal reasoning and abstraction demonstrated significant impairment at the group level with large effect sizes. The results demonstrate an executive deficit due to SCA-6 that can be conceptualised as parallel to the motor difficulties suffered by these patients: the data support a role for the cerebellum in the regulation and coordination of cognitive, as well as motor processes that is relevant to individual performance.

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Normal Aging and Executive Functions in “Old-Old” Community Dwellers: Poor Performance Is Not an Inevitable Outcome

International Psychogeriatrics ◽

10.1017/s1041610202008359 ◽

2002 ◽

Vol 14 (2) ◽

pp. 139-159 ◽

Cited By ~ 20

Author(s):

Olivier Piguet ◽

David A. Grayson ◽

G. Anthony Broe ◽

Robyn L. Tate ◽

Hayley P. Bennett ◽

...

Keyword(s):

Executive Functions ◽

Neurodegenerative Disorders ◽

Cognitive Abilities ◽

Poor Performance ◽

Normal Aging ◽

Psychological Variables ◽

Problem Resolution ◽

Age Related ◽

The Impact ◽

Community Dwellers

Background: Studies on normal aging and cognitive functioning commonly describe early and more pronounced age-related changes in executive functions (EFs) compared to other cognitive abilities. Two of the three most common neurodegenerative disorders associated with aging (vascular dementia [VaD] and extrapyramidal [EP]-related dementia) show executive dysfunctions in their clinical presentation; and these cognitive deficits are not uncommon in the third one: Alzheimer's disease (AD). Methods: Nine EF tests (yielding 12 measures) were administered to 123 randomly selected community dwellers, aged 81 years and over, with the view to determine the effect of age on performance. Markers of AD, VaD, and EP-related dementia, as well as sociodemographic and psychological variables, were selected and their contribution to EF performance was investigated. Results: Multiple linear regression analyses revealed the greatest contribution to EF scores from the markers of AD and estimated IQ but not from the markers of VaD and EP-related dementia or from age. Conclusions: These findings suggest that chronological age acts as a proxy variable mediating the impact of other factors such as subclinical signs of neurodegenerative disorders and that it has little independent contribution to make. They also indicate the importance of cognitive abilities supported by posterior cortical circuits in EF problem resolution. This study demonstrates that cognitive decline is not an ineluctable process that is associated with “normal” aging but rather represents, in many cases, a byproduct of neurodegenerative disorders, albeit themselves highly age-related.

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A Preliminary Characterisation of Cognition and Social Cognition in Spinocerebellar Ataxia Types 2, 1, and 7

Behavioural Neurology ◽

10.1155/2010/395045 ◽

2010 ◽

Vol 23 (1-2) ◽

pp. 17-29 ◽

Cited By ~ 35

Author(s):

N. Sokolovsky ◽

A. Cook ◽

H. Hunt ◽

P. Giunti ◽

L. Cipolotti

Keyword(s):

Social Cognition ◽

Spinocerebellar Ataxia ◽

Social Cognitive ◽

Cognitive Impairments ◽

Preliminary Evidence ◽

Cognitive Profiles ◽

Motor Functioning ◽

Emotion Attribution ◽

The One ◽

Degree Of Heterogeneity

Over the last decade, studies have implicated the cerebellum not only in motor functioning, but also in cognition and social cognition. Although some aspects of cognition have been explored in the five most common forms of Spinocerebellar Ataxia (SCA), social cognition in these patients has rarely been examined. The present study provides a preliminary characterisation of the severity of cognitive and social cognitive impairments in patients with SCA2, SCA1 and SCA7 using an identical battery to the one previously used in SCA3 and SCA6 patients for comparison. The cognitive profiles of SCA1 and SCA7 patients were comparable to that of SCA6 patients; SCA1 patients had relatively intact profiles, while SCA7 patients demonstrated only some selective deficits. In contrast, SCA2 patients showed the greatest impairments, similarly to SCA3 patients. On tests of social cognition, SCA2 and SCA7 patients were impaired on a task of emotion attribution, whereas one SCA1 patient had a Theory of Mind deficit, which has also been documented in SCA3 and SCA6. We provide preliminary evidence that the neuropsychological profiles of SCA patients correspond well with the severity of pathological and clinical features. Moreover, these patients may also have social cognition impairments. Overall, we suggest that there is a degree of heterogeneity in the types of cognitive and social cognitive impairments in SCA patients.

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