Cognitive Training in Parkinson Study
- Conditions
- Alteration in CognitionParkinson DiseaseImpaired Cognition
- Interventions
- Behavioral: Online cognitive training 1Behavioral: Online cognitive training 2
- Registration Number
- NCT02920632
- Lead Sponsor
- Amsterdam UMC, location VUmc
- Brief Summary
This study evaluates the efficacy of an eight-week online cognitive training program on objective and subjective cognitive functions in Parkinson's disease. Moreover, we intend to map the effect on brain network function, and if cognitive training can prevent the development of PD-MCI/PD-D after one- and two-year follow-up. In this study, two training groups will be compared (N: 70 vs 70). In a part of the participants MRI will be assessed (N: 40 vs. 40). We expect cognitive training to improve cognitive functions, and to improve the efficiency of brain network function. Moreover, we expect that cognitive training can decrease the risk of PD-MCI/PD-D at one- and two-year follow-up.
- Detailed Description
BACKGROUND In Parkinson's disease (PD), cognitive dysfunction is frequently reported - approximately 50% of PD patients experience cognitive impairment (Litvan et al., 2011). Of these impairments, executive dysfunction is most frequently reported early in the disease trajectory (Bosboom, Stoffers, \& Wolters, 2004; Muslimovic, Post, Speelman, \& Schmand, 2005), while impairments in other cognitive domains (i.e. attention, episodic memory, visuospatial functions) are also highly prevalent (Bosboom et al., 2004). The majority of PD patients ultimately develops PD dementia (PD-D; Aarsland, Andersen, Larsen, Lolk, \& Kragh-Sorensen, 2003; Hely, Reid, Adena, Halliday, \& Morris, 2008). Moreover, about 10% of the PD patients develops PD-D every year (Aarsland \& Kurz, 2010). Cognitive dysfunctions in PD have a significant negative influence on the quality of life (Klepac, Trkulja, Relja, \& Babic, 2008), while treatment of these dysfunctions is in its infancy.
Cognitive training may provide a new intervention for reducing cognitive complaints and delaying the onset of mild cognitive impairment (MCI) or PD-D. This intervention has been widely studied in other diseases (Cicerone et al., 2011; Olazaran et al., 2010). Moreover, studies have provided evidence not only for behavioral influences, but also for brain connectivity and activity effects of cognitive training (Chapman et al., 2015; Castellanos et al., 2010; Subramaniam et al., 2012; Subramaniam et al., 2014; Belleville et al., 2011; Rosen, Sugiura, Kramer, Whitfield-Gabrieli, \& Gabrieli, 2011). This suggests a restorative effect of cognitive training on disrupted brain networks.
In PD, cognitive dysfunction - mainly executive dysfunction - is associated with disruption of the cortico-striato-thalamo-corticale circuits by depletion of dopamine. Dysfunction of these circuits seems to disrupt several cognitive networks, which leads to cognitive dysfunction (Baggio et al., 2014). Cognitive training could counteract these disruptions by normalising activity and connectivity, and ultimately lead to a reduction of impairment. Since earlier studies in different patient populations have shown that cognitive training has lasting effects (Petrelli et al., 2015), normalising disruptions underlying cognitive impairment could prevent cognitive deterioration and therefore prevent or delay the development of PD-D.
Few studies in PD have focused on cognitive training and its neural correlates. A meta-analysis by Leung et al. (2015) showed positive effects of cognitive training on mainly 'frontal' cognitive functions (i.e. working memory, executive functions, processing speed). In addition, earlier research has described a neuroprotective effect of cognitive training on the development of MCI in PD (odds ratio: 3; Petrelli et al., 2015). Until now, however, studies have been relatively small and mainly without a controlled design - consequently, there is a need for large randomized controlled studies (Hindle, Petrelli, Clare, \& Kalbe, 2013; Leung et al., 2015). Moreover, neural effects of cognitive training are largely unknown in PD. Furthermore, it is important to study the improvement of patients on daily functioning after cognitive training, rather than solely focusing on cognitive tasks and neural measures. Finally, cognitive training has been performed mainly in hospital settings, while PD patients have mobility problems - a training method suitable to perform from home is therefore needed for this population.
OBJECTIVES The study objective is primarily to measure the effect of an online cognitive training in patients with mild cognitive complaints in PD. An online training, specifically altered for PD patients (BrainGymmer) will be compared with an active comparator. In both conditions, participants will train eight weeks, three times a week during 45 minutes.
Primary objective:
- To measure the effect of an online cognitive training (as compared to the active comparator), eight weeks, three times a week, on executive functions in patients with mild cognitive complaints in PD.
Secondary objectives:
* To measure the effect of online cognitive training on daily functioning.
* To measure the endurance of the training effect after six months, one and two years.
* To assess the reduced risk of MCI and PD-D development by cognitive training.
* To assess the effect of cognitive training on brain network efficiency and connectivity.
* To assess the effect of cognitive training on brain network topology and connectivity, and cognition, relative to those of matched healthy control participants.
* To assess the difference in brain network topology and connectivity, and cognition, between Parkinson's disease patients with or without cognitive impairment and healthy control participants.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 170
- Subjective cognitive complaints, measured by the Parkinson's Disease Cognitive Functional Rating Scale score > 3 (PD-CFRS). A score above 3 indicates significant cognitive complaints, that are milder than complaints associated with Parkinson's disease dementia. This questionnaire is filled in by the patient.
- Participants' Hoehn & Yahr stage is lower than 4. Patients are stable on dopaminergic medication at least a month before starting the intervention. During the intervention, patient and neurologist will be asked to keep the dopaminergic medication dosage as stable as possible.
- Participants have access to a computer or tablet, with access to the Internet. If the participant uses a computer, he or she is capable of using a keyboard and computer mouse.
- Participants are willing to sign informed consent.
General criteria:
- Indications for a dementia syndrome, measured by the Self-administered Gerocognitive Examination score < 14 or the Montreal Cognitive Assessment score < 22.
- Current drug- or alcohol abuse, measured by a score > 1 on the four CAGE AID-questions (according to the Trimbos guidelines).
- The inability to undergo extensive neuropsychological assessment, or eight weeks of intervention.
- Moderate to severe depressive symptoms, as defined by the Beck Depression Inventory score > 18.
- An impulse control disorder, including internet addiction, screened by the impulse control disorder criteria interview.
- Psychotic symptoms, screened by the Questionnaire for Psychotic Experiences. Benign hallucinations with insight are not contraindicated.
- Traumatic brain injury, only in case of a contusio cerebri with 1) loss of consciousness for > 15 minutes and 2) posttraumatic amnesia > 1 hour.
- A space occupying lesion defined by a radiologist, or significant vascular abnormalities (Fazekas > 1).
For participation in MRI research:
-
Severe claustrophobia
-
Metal in the body (for example, deep brain stimulator or pacemaker)
-
Pregnancy
-
Problems with or shortness of breath during 60 minutes of lying still.
- Healthy control subjects ---
Inclusion criteria:
- Participants are willing to sign informed consent.
Exclusion criteria:
- Indications for a neurological disease, such as Parkinson's disease, Alzheimer's disease, mild cognitive impairment, multiple sclerosis or Huntington's disease;
- Indications for a dementia syndrome, measured by the Montreal Cognitive Assessment score < 22.
- Indications for a current stroke or CVA, or in the past.
- Indications for the presence of a psychotic or depressive disorder, measured with a positive screening on the SAPS-PD (benign hallucinations with insight are not contraindicated) and a BDI > 18 respectively.
- Current drug- or alcohol abuse, measured by a score > 1 on the four CAGE AID-questions (according to the Trimbos guidelines).
- The inability to undergo extensive neuropsychological assessment, or eight weeks of intervention.
- Traumatic brain injury, only in case of a contusio cerebri with 1) loss of conciousness for > 15 minutes and 2) posttraumatic amnesia > 1 hour.
- A space occupying lesion defined by a radiologist, or significant vascular abnormalities (Fazekas > 1).
- Contra-indications for participation in MRI scanning (see above)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Online cognitive training 1 Online cognitive training 1 Eight-week, three times a week during 45 minutes cognitive training Online cognitive training 2 Online cognitive training 2 Eight-week, three times a week during 45 minutes cognitive activities
- Primary Outcome Measures
Name Time Method Accuracy on the Tower of London Task Baseline (T0, "Pre-intervention") to eight weeks (T1, "Post-intervention") Change in executive function after eight weeks of cognitive training as measured by percentage correct on the Tower of London task. Accuracy is measured in percentage correct (%, range 0-100, higher is considered better).
- Secondary Outcome Measures
Name Time Method Total Score on Parkinson's Disease Cognitive Functional Rating Scale Baseline (T0, "Pre-intervention") to eight weeks (T1, "Post-intervention") Score on subjective cognitive complaints after eight weeks of cognitive training, measured with the Parkinson's disease Cognitive Functional Rating Scale (PD-CFRS), with score range \[0-24\], where higher scores indicate more severe subjective cognitive complaints.
Total Score on Cognitive Failures Questionnaire Baseline (T0, "Pre-intervention") to eight weeks (T1, "Post-intervention") Score on subjective cognitive complaints after eight weeks of cognitive training (T0 to T1), measured by the Cognitive failures questionnaire (CFQ), a questionnaire with range \[0-100\] where a higher score indicates more severe subjective cognitive complaints.
Reaction Time on the Tower of London Task Baseline (T0, "Pre-intervention") to eight weeks (T1, "Post-intervention") Change on Executive function from T0 to T1, measured with the average reaction time on the Tower of London task over all trials. Reaction time is measured in seconds, where higher reaction time is considered worse.
Performance on the Controlled Oral Word Association Test Baseline (T0, "Pre-intervention") to eight weeks (T1, "Post-intervention") Executive functions CHANGE after eight weeks of cognitive training (T0 to T1), measured with the Controlled Oral Word Association Test (Letter fluency). Minimum score: 0, there is no maximum score. A higher score indicates better performance.
Performance on Tower of London Accuracy at Six-months Follow-up Six months after training completion (T2) Persistence of cognitive training effect on executive functions measured with the accuracy on the Tower of London task six-month after completion of the intervention. Accuracy is measured with mean percentage correct over 100 trials, where a higher percentage correct reflects better cognitive function.
Performance on Tower of London Accuracy at One-year Follow-up One year after completion of intervention (T3, "Follow-up 2") Persistence of cognitive training effect on executive functions measured with the accuracy on the Tower of London task one year after completion of the intervention. Accuracy is measured with mean percentage correct over 100 trials, where a higher percentage correct reflects better cognitive function.
Performance on Tower of London Accuracy at Two-year Follow-up Two years after completion of the intervention (T4) Persistence of cognitive training effect on executive functions measured with the accuracy on the Tower of London task two year after completion of the intervention. Accuracy is measured with mean percentage correct over 100 trials, where a higher percentage correct reflects better cognitive function.
Conversion to Mild Cognitive Impairment or Dementia at One-year Follow-up One year after completion of the intervention (T3) Incidence of conversion of cognitive status at one-year follow-up with respect to the cognitive status at baseline (T0). Cognitive status is defined as cognitively normal (NC), mild cognitive impairment (MCI, according to cognitive aspects of level II MDS criteria), or dementia (according to cognitive aspects of MDS criteria for probable PD dementia). Conversion was defined as -1: conversion to a worse classification (ie, NC to MCI, NC to dementia or MCI to dementia), 0: no change, or 1: conversion to a better classification (ie, dementia to NC, MCI to NC, dementia to MCI).
Performance on the Stroop Color-Word Test, Card I Baseline (T0, "Pre-intervention") to eight weeks (T1, "Post-intervention") Processing speed change after eight weeks of cognitive training, measured with the Stroop Color Word Test (word-reading), where a higher time to completion indicates worse cognitive function.
Performance on the Stroop Color-Word Test, Card III Baseline (T0, "Pre-intervention") to eight weeks (T1, "Post-intervention") Executive function CHANGE after eight weeks of cognitive training, measured with the Stroop Color Word Test (card III, color-word interference), where a higher time to completion indicates worse cognitive function.
Conversion of Cognitive Status at Two-year Follow-up Two year after completion of the intervention (T3) Count of conversion of cognitive status at two-year follow-up with respect to the cognitive status at baseline (T0). Cognitive status is defined as cognitively normal (NC), mild cognitive impairment (MCI, according to cognitive aspects of level II MDS criteria), or dementia (according to cognitive aspects of MDS criteria for probable PD dementia). Conversion was defined as -1: conversion to a worse classification (ie, NC to MCI, NC to dementia or MCI to dementia), 0: no change, or 1: conversion to a better classification (ie, dementia to NC, MCI to NC, dementia to MCI).
Trial Locations
- Locations (1)
VU University Medical Center
🇳🇱Amsterdam, Noord-Holland, Netherlands