Neuropsychiatry and Cognition in SCA3/MJD

Study Overview
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Brief Summary
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This research investigates how cognitive-affective aspects evolve during the course of SCA3/MJD. Due to COVID-19 pandemics, this study protocol was adapted for online-only consultations. Evaluations happening after March 2020 have been done by videocall with patients, and no neurological evaluation was thus performed on these patients. A scale on Activities of Daily Living was added to the online protocol to replace SARA, SCAFI and CCFS scales.

Detailed Description
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By the end of this study, the evaluated population will be composed of 144 participants: 36 ataxic SCA3/MJD carriers, 72 at 50% risk of carrying the SCA3/MJD mutation and 36 healthy controls. Ataxic subjects are invited to participate if they have an established molecular diagnosis of SCA3/MJD and have a SARA score greater than 2.5 points. At risk subjects are composed by the offspring of molecularly diagnosed SCA3/MJD subjects that have a SARA<3. Healthy controls belonging either to families living with the disease or to the general population are invited to participate according to how well they match with ataxic subjects included in the study. Subjects are invited to participate in the study and, after constentment procedures, cognitive-affective assessments and a scale on Activities of Daily Living (ADL) are performed on a videocall. At risk subjects collect a blood sample for double bilnd determination of their carrier status. Before March 2020, all procedures were performed in person and, instead of ADL, SARA, SCAFI and CCFS were obtained.

Official Title
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Neuropsychiatry and Cognition in the Context of Spinocerebellar Ataxia Type 3/Machado-Joseph Disease (SCA3/MJD)

Conditions
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Spinocerebellar Ataxia Type 3, Machado-Joseph Disease, SCA3, MJD

Intervention / Treatment
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* Diagnostic Test: SCA3/MJD molecular diagnosis
* Diagnostic Test: Cognitive Testing
* Diagnostic Test: Psychiatric Evaluation
* Diagnostic Test: Clinical Neurological Evaluation
* Diagnostic Test: Emotional Attribution Evaluation
* Diagnostic Test: Activities of Daily Living


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic: older than 18 year old; molecular diagnosis of SCA3/MJD; SARA>2.5. At 50% risk: older than 18 year old; have a parent with molecular diagnosis of SCA3/MJD; SARA<3. Healthy Controls older than 18 year old; no genetic relationship with a SCA3/MJD carrier. Exclusion Criteria: Non agreement in signing the informed consent; Healthy Controls: having any history of genetic disorders in their families or any psychiatric or neurologic disorder.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Symptomatic<br>Molecularly diagnosed SCA3/MJD Symptomatic subjects. | Diagnostic Test: Cognitive Testing<br>* Cross-sectional Cognitive evaluation with CCAS Scale Trail-Making Test parts A and B Stroop Color-Word Test<br>Diagnostic Test: Psychiatric Evaluation<br>* Cross-sectional Psychiatric evaluation with Hamilton-Anxiety and Hamilton-Depression rating scales.<br>Diagnostic Test: Clinical Neurological Evaluation<br>* Cross-sectional neurological evaluation with standardized clinical scales - SARA, SCAFI and CCFS.<br>Diagnostic Test: Emotional Attribution Evaluation<br>* Cross-sectional emotional attribution evaluation by means of the Reading the Mind in the Eyes Test (RMET).<br>Diagnostic Test: Activities of Daily Living<br>* Cross-sectional evaluation of Activities of Daily Living (ADLs) by means of Friedreich Ataxia Rating Scale Part II.<br>|
| Non-related Controls<br>Controls matched with symptomatic by age and educational level. | Diagnostic Test: Cognitive Testing<br>* Cross-sectional Cognitive evaluation with CCAS Scale Trail-Making Test parts A and B Stroop Color-Word Test<br>Diagnostic Test: Psychiatric Evaluation<br>* Cross-sectional Psychiatric evaluation with Hamilton-Anxiety and Hamilton-Depression rating scales.<br>Diagnostic Test: Emotional Attribution Evaluation<br>* Cross-sectional emotional attribution evaluation by means of the Reading the Mind in the Eyes Test (RMET).<br>|
| At 50% risk for SCA3/MJD group<br>The offspring of affected individuals with SARA<3. This group will be comprised of two subpopulations: pre-symptomatic individuals and related controls. The determination will be made upon molecular diagnosis to be done in a double-blind manner. | Diagnostic Test: SCA3/MJD molecular diagnosis<br>* Double-blind molecular diagnosis for determination of the presence of the mutation.<br>Diagnostic Test: Cognitive Testing<br>* Cross-sectional Cognitive evaluation with CCAS Scale Trail-Making Test parts A and B Stroop Color-Word Test<br>Diagnostic Test: Psychiatric Evaluation<br>* Cross-sectional Psychiatric evaluation with Hamilton-Anxiety and Hamilton-Depression rating scales.<br>Diagnostic Test: Clinical Neurological Evaluation<br>* Cross-sectional neurological evaluation with standardized clinical scales - SARA, SCAFI and CCFS.<br>Diagnostic Test: Emotional Attribution Evaluation<br>* Cross-sectional emotional attribution evaluation by means of the Reading the Mind in the Eyes Test (RMET).<br>Diagnostic Test: Activities of Daily Living<br>* Cross-sectional evaluation of Activities of Daily Living (ADLs) by means of Friedreich Ataxia Rating Scale Part II.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebellar Cognitive Affective Syndrome Scale | Study the performance on the Cerebellar Cognitive Affective Syndrome Scale of SCA3/MJD symptomatic subjects when compared to matched healthy controls and of pre-symptomatic subjects when compared to familial healthy controls. | Through study completion, an average of 1 year | 
| Trail-Making Test Part A and B | Study the performance on the Trail-Making Test Part A and B of SCA3/MJD symptomatic subjects when compared to matched healthy controls and of pre-symptomatic subjects when compared to familial healthy controls. | Through study completion, an average of 1 year | 
| Stroop Color-Word Test | Study the performance on the Stroop Color-Word Test of SCA3/MJD symptomatic subjects when compared to matched healthy controls and of pre-symptomatic subjects when compared to familial healthy controls. | Through study completion, an average of 1 year | 
| Emotion Attribution impairment in SCA3/MJD | Study the performance of symptomatic SCA3/MJD carriers in the Reading the Mind in the Eyes Test. | Through study completion, an average of 1 year | 
| Emotion Attribution in different phases of the disease | Study the performance of pre-symptomatic SCA3/MJD carriers in the Reading the Mind in the Eyes Test. | Through study completion, an average of 1 year | 
| Hamilton Anxiety Rating Scale | Study the profile of symptomatic and pre-symptomatic SCA3/MJD carriers in the Hamilton Anxiety Rating Scale. | Through study completion, an average of 1 year | 
| Hamilton Depression Rating Scale | Study the profile of symptomatic and pre-symptomatic SCA3/MJD carriers in the Hamilton Depression Rating Scale. | Through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Scale for the Assessment and Rating of Ataxia (SARA) | Correlations between primary outcomes and SARA. | Through study completion, an average of 1 year | 
| Composite Cerebellar Functional Severity Score (CCFS) | Correlations between primary outcomes and CCFS. | Through study completion, an average of 1 year | 
| SCA Functional Index | Correlations between primary outcomes and SCAFI. | Through study completion, an average of 1 year | 
| Friedreich Ataxia Rating Scale part II (FARS part II) | Correlations between primary outcomes and Activities of Daily Living from FARS part II. | Through study completion, an average of 1 year |