Memory training points to new directions for treatment of Huntington disease

Huntington disease is a progressive disorder that causes brain cell degeneration resulting in the gradual onset of motor, cognitive and psychiatric symptoms. Psychology Professor Christine Till wanted to know if working memory (WM) training could help early-stage patients with the disease. WM refers to a mental work space that allows information to be temporarily stored while carrying out a goal.

In collaboration with the funder, North York General Hospital (NYGH), she led a study where nine patients received intensive WM training. The results, published in the journal PLoS ONE, were quite promising: Seven out of the nine patients successfully completed the intervention and perceived benefits from this treatment.

“Our study provided evidence that individual factors, such as attitude towards training, influence adherence and performance,” Till says. “This research is very useful in determining new directions for treatment,” she adds.

Huntington disease, as mentioned, is a genetic brain disorder characterized by cognitive decline. It is often accompanied by mood changes such as uncharacteristic anger, depression and anxiety (Alzheimer’s Association). Symptoms usually start when the patient is between 30 and 50 years of age.

In 2013, the Toronto Star reported that approximately 21,000 Canadians are living with Huntington or have the genetic mutation. However, there is debate around this number because many people with risk factors decline genetic testing – some, for fear of rising insurance rates, although Bill S-201 (2017) made genetic discrimination illegal.

Study recruited patients from hospital

Till chose a pilot study to launch the investigation. This is a small-scale preliminary study designed to figure out the feasibility, time and costs of doing a more comprehensive study. This affords the researchers the possibility of making improvements to the design of the study.

Previous studies of early-to-moderate stage Huntington disease had focused on improving motor functions like gait and balance. Till was particularly encouraged by studies that illustrated how mice, characterized as having genetic mutations that mimic Huntington disease, had benefited from environmental enrichment. These mouse models showed that an enriched environment could enhance motor activity and reduce brain loss.

Building on this earlier research, Till began to consider home-based computerized training programs, designed to enhance mental activity in patients. She wondered whether intensive rehabilitation based on the “use-it-or-lose-it” environmental enrichment principle might have a positive impact on patients with Huntington disease.

Between April 2015 and January 2016, 98 patients with Huntington disease from NYGH were approached by Till’s research team and considered eligible for participation in the study. Of these, 13 patients expressed interest, and nine were enrolled to participate  ̶  three females and six males. The average age was 44.

Training sessions on participants’ home computers

Participants underwent neuropsychological testing at NYGH or York University twice – once, at the start of the study, and once one week after the completion of the training. This testing was comprised of 90 minutes of questionnaires and neurocognitive assessments.

The training itself involved 25 sessions that were run through the internet and each lasted 40 to 50 minutes. Training was typically completed over a five-week period (five days a week in most cases) using the patients’ home computers.

The program consisted of 12 exercises that target:

• Visual spatial WM – such as remembering the location of previously highlighted boxes; or
• Verbal WM – such as remembering digits and repeating them backwards.

Importantly, task difficulty was taken into consideration on each trial. “The level of difficulty adjusts continuously and automatically, ensuring that each session provides an engaging, challenging level of WM capacity,” Till explains.

“Way to Go!” Support key component to training sessions

A training coach called the participants weekly to inquire about their experience with the program, and to provide motivational support and note any changes in health. Additionally, the training program provided feedback to the participant after each trial was completed. It did this by showing comparisons of previous scores and high scores, and providing auditory comments such as “Way to go!” when the participant’s response was correct. Daily performance on the training program was tracked by the computer.

Participants underwent neuropsychological tests and questionnaires

Participants took a series of performance-based neuropsychological tests. Some of the tests were similar to the skills that were trained by the intervention. Other tests measured skills that were not trained by the computer program, such as visual scanning speed, which was assessed using the Trail Making Test.  Baseline results were compared against scores at the end of the training period.

Participants also completed questionnaires to gain information about day-to-day functioning, including:

• Executive functioning and self-regulation in daily life (Behaviour Rating Inventory of Executive Function);
• Health-related quality of life (Huntington Disease Quality of Life questionnaire); and
• Psychological well-being and mood (Brief Symptom Inventory).

Individual’s attitude toward training influences performance

Exit interviews provided important insights: All participants who completed the program reported that it was helpful, and viewed the feedback and instructions in the program positively.

This work underscores the idea that an individual’s attitude toward an intensive intervention influences performance. “Almost all participants responded well to the feedback they received. It is likely that individualized attention given to the individuals served as motivation to continue training,” Till explains.

The article, “Feasibility of computerized working memory training in individuals with Huntington disease,” was published in PLoS ONE (April 2017). To learn more about Till’s research, visit her lab website.

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By Megan Mueller, manager, research communications, Office of the Vice-President Research & Innovation, York University, muellerm@yorku.ca