Cognitive Training in Parkinson's Disease, the iPARK Study

The aim of the iPARK-study is to investigate the effects of a process-based cognitive training program with focus on working memory in patients with Parkinson's Disease (PD). The study is a double blinded, randomized controlled trial with a parallel group design that aim to recruit 80 persons with PD. All patients will undergo 30 sessions (6-7 weeks) of web-based cognitive training performed at home. The working memory training is a process-based training program focusing specific on updating. The placebo program is a low dose short term memory paradigm without updating. A battery of neuropsychological tests (working memory, attention, episodic memory, inhibition control, risk taking and motoric speed) and questionnaires (everyday functioning and psychological health) will be performed before training and directly after training and after 16 weeks. Patient expectation and measures of adherence (motivation and results during training) will be controlled for.

The iPARK trial is expected to provide novel and clinical useful information whether updating training is an effective training paradigm in PD. Further it will hopefully contribute to a better understanding of cognitive function in PD.

Parkinson's Disease (PD) is after Alzheimers disease (AD) the most common neurodegenerative disease with a prevalence of 1% of the population over 60 years of age. The cardinal symptoms are motoric and are believed to be caused by depletion of dopamine in the brain with severe depletion in the striatum. In addition to the motor impairments, there are several non-motor functions also affected, where cognitive decline and dementia are among the most common problems. Some claim that up to 75% of the total PD population will eventually develop dementia. Prior to dementia, milder cognitive problems are common and already at the time of diagnosis up to 42.5% of patients with PD are affected by decline in different cognitive functions. Early cognitive deficits seen is inhibition, shifting, working memory and planning, but a cognitive profile of visuospatial decline, semantic fluency and episodic memory has been connected to Parkinson's Disease Dementia (PDD). The occurrence of Lewy-bodies and Alzheimer type brain pathology is common in PDD but dopamine depletion has also been connected to cognitive decline in healthy elderly and in PD.

Although prescription of dementia medication in PD most likely has increased during the last decade there are limited evidence of treatment effects . This particular patient group is already burdened by polypharmacy and therefore investigating non-pharmacological interventions is of crucial importance. A recent systematic review of cognitive intervention studies in PD suggests that there is evidence of clinically meaningful improvements in overall cognition and moderate to large effect sizes on measures of working memory, processing speed and executive functions. Another review on the topic suggested that the results are promising, at least in the immediate or short term for some cognitive domains, but due to inconsistencies between studies and lack of methodological salience there are still a lot of questions unanswered. Baseline factors such as cognitive functioning, Hoehn and Yahr stage, premorbid intelligence all can have contributing effects on individual differences in training gain. Therefore it is important to thoroughly investigate baseline characteristics.

In the future, studies need to include more participants, be hypothesis driven and include more detail of the cognitive profile, training intervention and outcome measures.

One approach to cognitive training that has received a lot of attention and critique is process-based cognitive training, such as training focusing on working memory (WM) and executive functions (EF). The purpose of the process based approach is to strengthen general cognitive processes important to global cognitive functioning. WM and EF play central roles in several different functions such as episodic memory, reading comprehension and problem solving to mention a few. Research has also shown that WM and EF is negatively affected both in normal and pathological aging, such as PD.

Training of executive functioning and working memory have gained some promising results in healthy adults, showing improvements in working memory and executive functioning but there is also an indication of broader generalizations of training gain. Previously the effect of process-based updating training in healthy young and older individuals has been studied. Results showed that a period of updating training increased Blood Oxygen Level Dependent (BOLD) activity in striatum related to increased cognitive performance in both groups. Also a corresponding effect of training on dopaminergic neurotransmission was detected.

In the light of the dopamine dysfunction in PD, with negative effects on both motoric and cognitive function it is of interest to study if a non-invasive, non-pharmacological intervention can lead to better updating function with increased dopamine levels in patients with PD. The iPARK study is a double blinded randomized controlled trial that will examine the effect of a web-based cognitive training program with focus on updating training.

The primary question asked will be if updating training will improve the ability to update contents in working memory and also if there will be improvements in other cognitive functions such as psychomotor speed, working memory, executive functions and episodic memory. Further the aim is to investigate if there will be improvements in self-perceived everyday cognitive function and psychological health as well as if the effects seen will be sustained over a period of four months. Baseline factors will be investigated to see if they have a modulating effect on training. Further the iPARK trial will determine if a web-based training performed at home without active supervision is a feasible approach in this particular patient group. Compliance, adherence and expectations will be measured systematically.

Eligibility Criteria:
Inclusion Criteria:

1. Diagnosis of Parkinson's Disease according to United Kingdom Parkinson's Disease Brain Bank (UKPDSBB) criteria
2. Hoehn and Yahr stage I-III
3. Pathological dat scan
4. A score of 24 or over on the MMSE AND be without Dementia
5. Stable medication over the past three months
6. Owns and is able to use a home based computer or tablet with internet connection.

Exclusion Criteria:

1. Unstable medication
2. Ongoing cognitive training
3. Diagnosis of PDD
4. Drug or alcohol abuse