Working Memory Training in Huntington's Disease

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

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.

Study Overview

• Status: Completed
• Conditions: Huntington's Disease
• Intervention / Treatment: Behavioral: Cogmed QM

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M2K 1E1
      • North York General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Laboratory-confirmed gene expansion of at least 36 CAG repeats
2. Reported working memory difficulties on the Patient-Reported Outcomes in Cognitive Impairment (PROCOG) questionnaire
3. Total Functional Capacity (TFC) score of at least 3, taken from the UHDRS
4. Montreal Cognitive Assessment (MOCA) score of 19 or greater

Exclusion Criteria:

1. History of head trauma/neurological event such as stroke
2. Untreated psychiatric symptoms or substance abuse
3. Visual or motor symptoms that would impede ability to complete the program and/or neuropsychological testing
4. Nonfluency in English

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cognitive training; Participants will undergo five weeks of cognitive training using the Cogmed QM program. All patients complete the same intervention.

Behavioral: Cogmed QM; 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.

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Qualitative experiences of training program as reported by the patient	Keywords were used to elicit themes that were indicative of participant attitude and motivation for training	Post-interview follow-up, up to 45 days following baseline visit
Tolerance (ratio of training time to breaks per day)	To assess tolerance, the ratio of active training time to breaks per day was examined (Cogmed guidelines suggest at most a 2:1 ratio of active training time and breaks per sessions).	Per session and through completion of training program, up to 40 days
Cogmed Improvement Index	The Improvement Index represents average improvement over the course of the training. It is calculated automatically by the program by subtracting the Start Index (score on third day of training) from the Max Index (best score throughout training).	Through completion of training program, up to 40 days

Collaborators and Investigators

• Sponsor: York University
• Collaborators: North York General Hospital
• Investigators: Principal Investigator: Christine Till, PhD, York University

Publications and helpful links

General Publications

• Sadeghi M, Barlow-Krelina E, Gibbons C, Shaikh KT, Fung WLA, Meschino WS, Till C. Feasibility of computerized working memory training in individuals with Huntington disease. PLoS One. 2017 Apr 28;12(4):e0176429. doi: 10.1371/journal.pone.0176429. eCollection 2017.

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: September 30, 2016
• First Submitted That Met QC Criteria: October 4, 2016
• First Posted (Estimate): October 6, 2016

Study Record Updates

• Last Update Posted (Estimate): October 10, 2016
• Last Update Submitted That Met QC Criteria: October 7, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Huntington disease; cognitive rehabilitation; cognitive dysfunction
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Cognition Disorders; Chorea; Huntington Disease
• Other Study ID Numbers: NYGH 15-0001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Study Data/Documents

1. Study Protocol
   Information comments: The lead investigator, Dr. Christine Till, can be contacted by email (ctill@yorku.ca) for a copy of the Informed Consent Form or study protocol.