Working Memory Training in Huntington's Disease

Study Overview
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Brief Summary
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There is a paucity of investigation into effective interventions to enhance cognitive function and/or mitigate cognitive decline in individuals with Huntington disease (HD). This study targeted working memory (WM), which is the ability to actively hold information in the mind in order to perform complex mental tasks, given reports of WM dysfunction in patients with HD. The investigators examined the feasibility of conducting a 5-week WM training program (Cogmed). Patient adherence and treatment tolerance were assessed. In addition, preliminary evidence for the efficacy of this training program on targeted cognitive abilities was examined. Nine patients with pre-manifest or early stage HD underwent training. Patients were assessed before the intervention and one week after completion.

Detailed Description
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Huntington disease (HD) is associated with a variety of cognitive deficits, with prominent difficulties in working memory (WM). WM deficits are notably compromised in early-onset and prodromal HD patients. This study aimed to determine the feasibility of a computer-ized WM training program (Cogmed QM), novel to the HD population. Nine patients, aged 26-62, with early stage HD underwent a 25-session (5 days/week for 5 weeks) WM training program (Cogmed QM). Training exercises involved the manipulation and storage of verbal and visuospatial information, with difficulty adapted as a function of individual performance. Neuropsychological testing was conducted before and after training, and performance on criterion WM measures (Digit Span and Spatial Span) and near-transfer WM measures (Symbol Span and Auditory WM) were evaluated. Post-training inter-views about patient experience were thematically analyzed using NVivo software. Seven of nine patients demonstrated adherence to the training and completed all sessions within the recommended timeframe of 5 weeks. All adherent patients reported that they found training helpful (n=7), and almost all felt that their memory improved (n=6). Compared to baseline scores, patients showed significant improvement on the neuropsychological measures of verbal WM, including Digit Span (p = .047) and Auditory WM (p = .041). This pilot study provides support for feasibility of computerized WM training in early-stage patients with HD. Results suggest that HD patients can improve WM with intensive training, though a full-scale intervention project is needed to understand the reliability of changes over time.

Official Title
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Working Memory Training in Individuals With Huntington's Disease: A Pilot Project

Conditions
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Huntington's Disease

Intervention / Treatment
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* Behavioral: Cogmed QM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Laboratory-confirmed gene expansion of at least 36 CAG repeats Reported working memory difficulties on the Patient-Reported Outcomes in Cognitive Impairment (PROCOG) questionnaire Total Functional Capacity (TFC) score of at least 3, taken from the UHDRS Montreal Cognitive Assessment (MOCA) score of 19 or greater Exclusion Criteria: History of head trauma/neurological event such as stroke Untreated psychiatric symptoms or substance abuse Visual or motor symptoms that would impede ability to complete the program and/or neuropsychological testing Nonfluency in English

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cognitive training<br>Participants will undergo five weeks of cognitive training using the Cogmed QM program. All patients complete the same intervention. | Behavioral: Cogmed QM<br>* The intervention consisted of 25 Cogmed sessions, typically completed over a five week period (i.e. 5 days per week), with each session lasting between 40-50 minutes per day. The program consists of 12 exercises that target visuo-spatial or verbal working memory. At each training session, participants completed 8 of the 12 exercises (order selected by the user), with 15 trials per exercise. Cogmed QM is an adaptive program, wherein task difficulty is adjusted to performance on each trial. The level of difficulty adjusts continuously and automatically, ensuring that each session provides an engaging, challenging level of WM capacity. Breaks were permitted, and encouraged, at the participants' discretion throughout the session.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adherence to training (defined by completing the intervention within the recommended time frame) | Adherence was defined as completion of at least 80% of the total 25 training sessions within 40 calendar days or less | 40 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Digit Span subtest from the Wechsler Memory Scales - third edition | This test is used as a criterion measure (i.e. measure that closely resembles tasks in the Cogmed program). Scores will be reported in raw score units as the total correct responses. | Baseline (time 0) versus Post-intervention test score (up to 45 days post-baseline) | 
| Spatial Span subtest from the Wechsler Memory Scales - third edition | This test is used as a criterion measure (i.e. measure that closely resembles tasks in the Cogmed program). Scores will be reported in raw score units as the total correct responses. | Baseline (time 0) versus Post-intervention test score (up to 45 days post-baseline) | 
| Auditory Working Memory from the Woodcock Johnson Tests of Cognitive Ability - third edition | This test is used as a near transfer measure (i.e. test of verbal or visuospatial working memory that include stimuli that are similar to trained tasks). Scores will be reported in raw score units (total correct responses) | Baseline (time 0) versus Post-intervention test score (up to 45 days post-baseline) | 
| Symbol span subtest from the Wechsler Memory Scales - fourth edition, reported in raw score units (total correct responses) | This test is used as a near transfer measure (i.e. test of verbal or visuospatial working memory that include stimuli that are similar to trained tasks). Scores will be reported in raw score units (total correct responses) | Baseline (time 0) versus Post-intervention test score (up to 45 days post-baseline) | 
| Verbal Fluency subtest from the Delis-Kaplan Executive Function System | This tests is used as a control task (i.e tests that do not directly assess working memory). Score will be reported in raw score units (total words produced) | Baseline (time 0) versus Post-intervention test score (up to 45 days post-baseline) | 
| Symbol Digits Modalities Test (oral administration) | This tests is used as a control task (i.e tests that do not directly assess working memory). Score will be reported in raw score units (total words produced) | Baseline (time 0) versus Post-intervention test score (up to 45 days post-baseline) | 
| Word List Learning from the Hopkins Verbal Learning Test -Revised | This tests is used as a control task (i.e tests that do not directly assess working memory). Score will be reported in raw score units (total words learned) | Baseline (time 0) versus Post-intervention test score (up to 45 days post-baseline) | 
| Trail Making Test - Parts A and B | This tests is used as a control task (i.e tests that do not directly assess working memory). Score will be reported in raw score units (total time in seconds) | Baseline (time 0) versus Post-intervention test score (up to 45 days post-baseline) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Huntington disease, cognitive rehabilitation, cognitive dysfunction