1 in 3 Parkinson’s Patients Struggle to Learn New Tasks

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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One in three people with early to mid-stage Parkinson’s disease were found to have difficulties in learning a new task by following instructions.

The deficits were more prone during the early stages of learning, when new memories are being made, and were linked to poorer activation of certain brain regions important for instruction-based learning, a new study suggests.

But, notably, the study showed that patients did not have issues with forgetting once memories are made.

These findings may help identify patients at early stages of cognitive decline, the researchers said, noting that problems in instruction-based learning are “likely to interfere with other clinical assessments of mental functioning.”

“We recommend the assessment of instruction-based learning as an important first step before other neuropsychological assessments are undertaken,” Beth Parkin, senior lecturer in psychology from the cognitive neuroscience group at the University of Westminster, in London, and the study’s first author, said in a university press release.

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The study, “Dissociable effects of age and Parkinson’s disease on instruction-based learning,” was published in the journal Brain Communications.

Parkinson’s disease is known to affect several cognitive functions. Deficits in executive and memory functioning are common, but do not necessarily occur at the same time.

“Understanding this variability is important as these cognitive deficits impact the patient’s ability to lead a full and independent life,” the researchers wrote, adding that “problems of memory and cognition have been consistently highlighted as a prominent concern for people with Parkinson’s.”

Such problems also make it difficult for clinicians to assess patients and develop “personally tailored treatment approaches, with multi-armed therapies targeting the specific neural systems that are disrupted.”

To address this issue, researchers at the University of Westminster and Imperial College London, in the U.K., evaluated the ability of 17 Parkinson’s patients to learn new tasks based on explicit instructions — an approach called instruction-based learning.

This learning process uses two brain systems — specifically the frontoparietal and front striatal — that are commonly affected in people with Parkinson’s disease.

The study included eight men and nine women with mild to moderate disease, recruited at the Imperial College London NHS trust. The participants had a mean age of 61.3. Nine patients were being treated with dopamine-replacing therapies, but were instructed to withdraw the medication before enrolling.

To serve as controls, 38 healthy adults also were recruited for the study. A total of 18 served as age-matched controls for older Parkinson’s patients (mean age 61.3 years) and 20 for younger patients (mean age 26.7 years).

All of the participants were asked to sort objects with different colors and shapes according to specific and detailed rules. They had 16 seconds to memorize the rule and then categorize the objects. This task was repeated four times, with four different rules. The instructions were explicit, leaving no room for ambiguity.

The researchers compared the performance of each group and analyzed their brain activity by functional magnetic resonance imaging, or fMRI, and magnetic resonance spectroscopy, known as MRS. fMRI shows where blood flows in the brain, while MRS shows the chemical composition of the brain.

As expected, young adults performed the learning experiment significantly faster than both older adults and Parkinson’s disease patients. No differences were seen in speed between those with Parkinson’s and older adults. Participants across all groups became faster as the rules were practiced.

However, when considering the errors that occurred in conducting the task, the results showed that a third of Parkinson’s patients made significantly more errors than older and younger adults (no differences were seen between these two age groups).

The investigators found a link between the error rate and the learning stage, specifically that Parkinson’s patients made significantly more errors during the initial learning stages, when new memories are being made.

Overall, all groups conducted their task with a high level of accuracy: mean of 97.6% for young adults, 96.3% for older adults, and 88.0% for people with Parkinson’s.

A subset of six patients (33%) had error rates four times higher than the standard error of the worst-performing young adult.

Brain imaging using fMRI showed that younger participants had a higher level of activation compared with older adults and people with Parkinson’s. The results showed a negative association between error rate and frontoparietal cortex activation during rule practicing. That means that more errors were made upon a lower activation of this brain area.

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Despite this, researchers detected that both older adults and people with Parkinson’s were able to balance the activity of the brain regions needed to perform tasks based on explicit instructions.

The results of the MRS analysis suggested that Parkinson’s disease patients had lower levels of the GABA neurotransmitter, the main inhibitory neurotransmitter in the brain. Of note, neurotransmitters are substances produced in response to nerve signals that act as chemical messengers.

“Our results support that a substantial proportion of early-to-mid stage people with Parkinson’s have deficits in IBL [instruction-based learning], with implications for patient assessment and daily function,” the researchers wrote.

“This deficit is concomitant [or naturally occurring] with abnormal activity and reduced GABA levels within areas of the brain that are associated with working memory,” they wrote.

The team believes that this research may help improve and personalize treatment for Parkinson’s patients.

“These findings not only tell us about the brain mechanisms underpinning the cognitive problems experienced in people with Parkinson’s, but they also have clinical implications,” Parkin said.

“In particular, the problems detected here are likely to interfere with other clinical assessments of mental functioning, as they all rely on the patient’s ability to learn from instructions,” she added.

Thus, the researchers suggested that a brief instruction-based learning test should be included “when assessing behavioural deficits in Parkinson’s disease, to ensure that the results are not confounded,” they wrote.

This new information also should be used in developing therapies for patients to use at home, the researchers said.

“These results demonstrate, for the first time, that a subset of early-to-mid stage people with Parkinson’s show substantial deficits when binding new task rules in working memory. Given the ubiquity of instruction-based learning, these deficits are likely to impede daily living,” they said, noting that the errors were “highly consistent.”

Overall, these findings “support our hypothesis that the ability to learn new task rules from explicit instructions is substantially disrupted, with approximately one-third of our early-to-mid stage Parkinson’s disease group exhibiting an abnormally high error rate,” the team concluded.