Alteration in Cognition, Impaired Cognition, Parkinson Disease
Conditions
Keywords
Parkinson, Cognitive training, Cognitive rehabilitation, Brain networks
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.
Interventions
BEHAVIORALOnline cognitive training 1
Eight-week online cognitive training program, three times a week for 45 minutes. The training contains several games that are designed to train cognitive functions.
BEHAVIORALOnline cognitive training 2
Eight-week online active comparator program, three times a week for 45 minutes. The training contains several games.
Sponsors
Dutch Parkinson Patient Association
Amsterdam UMC, location VUmc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
\--- Parkinson's disease patients --- Inclusion Criteria: * 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.
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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). |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Depressive Symptom Severity | Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4) | Psychiatric symptom severity, depression (Beck Depression Inventory). |
| Anxiety Symptom Severity | Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4) | Psychiatric symptom severity, including anxiety (Parkinson Anxiety Scale). |
| Impulse Control Disorder Symptom Severity | Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4) | Psychiatric symptom severity, including impulse control disorders (QUIP-RS). |
| Psychotic Symptom Severity | Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4) | Psychiatric symptom severity, including psychotic symptoms (Questionnaire for psychotic events). |
| Apathy Symptom Severity | Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4) | Psychiatric symptom severity, including apathy (Apathy Scale). |
| Expectations of the Intervention | Pre-intervention (T0) | Participants' expectation prior the intervention, measured by the credibility/expectancy questionnaire. |
| Global Cognitive Functioning (1) | Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4) | Global cognitive functioning assessed by the Montreal Cognitive Assessment (MoCA). |
| Global Cognitive Functioning (2) | Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4) | Global cognitive functioning assessed by the Pentagon copy test, which is predictive of cognitive deterioration. |
| Specific Cognitive Functioning: Attention/Working Memory (1) | Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4) | Attention function, measured by the Stroop task part I: word naming. |
| Specific Cognitive Functioning: Attention/Working Memory (2) | Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4) | Working memory function, measured by the backwards digit span test of the Wechsler adult intelligence test (WAIS)-III. |
| Specific Cognitive Functioning: Episodic Memory (1) | Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4) | Episodic memory function, measured by the Dutch version of the Auditory verbal learning test (RAVLT). |
| Specific Cognitive Functioning: Episodic Memory (2) | Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4) | Episodic memory function, measured by the Location learning task. |
| Specific Cognitive Functioning: Language (1) | Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4) | Language function, measured by the Boston naming task. |
| Specific Cognitive Functioning: Language (2) | Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4) | Language function, measured by the category fluency task. |
| Medication Use | Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4) | Disease characteristic: medication use. |
| Specific Cognitive Functioning: Visuospatial/Visuoconstructive Function (2) | Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4) | Visuospatial function, measured by the Rey complex figure task. |
| Physical Activity | Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4) | Amount of estimated physical activity that a person performs, measured by the New Zealand Physical Activity Questionnaire |
| Cognitive Reserve | Two years (T4) | Estimation of cognitive reserve measured with the Cognitive Reserve Index questionnaire |
| Specific Cognitive Functioning: Visuospatial/Visuoconstructive Function (1) | Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4) | Visuospatial function, measured by the Benton visual form discrimination task. |
| Motor Symptoms | Pre-intervention (T0), one year (T3), two years (T4) | Motor symptoms assessed by the Unified Parkinson's Disease Rating Scale - III |
| Difference Between Parkinson's Disease Patients' Brain Network Topology With or Without Cognitive Impairment, and Healthy Control Subjects. | Pre-intervention (T0) | Participants will be classified to cognitive impairment or no cognitive impairment, and their brain network topology will be compared with healthy subjects. |
| Online Cognitive Training Effect on Brain Network Topology Relative to Healthy Control Group | Eight weeks (T1) | The effect of online cognitive training on brain network topology using resting state fMRI compared with brain network topology of healthy subjects. Healthy subjects will undergo (functional) MRI scanning once. |
| Online Cognitive Training Effect on Brain Activity Measured by Resting State fMRI | Eight weeks (T1) | The effect of online cognitive training on brain activity using resting state fMRI. Regional activity and functional connectivity changes will be assessed after eight weeks of training (T1). |
| Online Cognitive Training Effect on Structural Brain Connectivity Measured by DTI | Eight weeks (T1) | The effect of online cognitive training on structural brain connectivity using DTI. Structural changes will be assessed after eight weeks of training (T1). |
| Online Cognitive Training Effect on Brain Morphology Measured by MRI | Eight weeks (T1) | The effect of online cognitive training on brain morphology using MRI. Structural changes will be assessed after eight weeks of training (T1). |
| Age | Pre-intervention (T0) | Demographic characteristic: age at baseline. |
| Sex | Pre-intervention (T0) | Demographic characteristic: sex. |
| Educational Level | Pre-intervention (T0) | Demographic characteristic: educational level. |
| Disease Duration | Pre-intervention (T0) | Disease characteristic: disease duration. |
| Disease Stage | Pre-intervention (T0), one year (T3), two years (T4) | Disease characteristic: disease stage (Hoehn and Yahr stage). |
Countries
Netherlands
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Online Cognitive Training 1 (N=68) Eight-week, three times a week during 45 minutes cognitive training
Online cognitive training 1: Eight-week online cognitive training program, three times a week for 45 minutes. The training contains several games that are designed to train cognitive functions. | 68 |
| Online Cognitive Training 2 (N=68) Eight-week, three times a week during 45 minutes cognitive activities
Online cognitive training 2: Eight-week online active comparator program, three times a week for 45 minutes. The training contains several games. | 68 |
| Healthy Control Subjects (N=31) Reference group to compare cognitive training effects to | 29 |
| Total | 165 |
Baseline characteristics
| Characteristic | Online Cognitive Training 1 (N=68) | Online Cognitive Training 2 (N=68) | Healthy Control Subjects (N=31) | Total |
|---|---|---|---|---|
| Age, Continuous | 62.9 years STANDARD_DEVIATION 8.1 | 62.9 years STANDARD_DEVIATION 7 | 62.3 years STANDARD_DEVIATION 9.8 | 62.8 years STANDARD_DEVIATION 8 |
| Beck Depression Inventory (BDI) | 8.2 units on the BDI scale STANDARD_DEVIATION 4 | 7.9 units on the BDI scale STANDARD_DEVIATION 4.1 | 4.3 units on the BDI scale STANDARD_DEVIATION 4.2 | 7.3 units on the BDI scale STANDARD_DEVIATION 4.3 |
| Montreal Cognitive Assessment (MoCA) | 26.3 units on the MoCA scale STANDARD_DEVIATION 2 | 25.9 units on the MoCA scale STANDARD_DEVIATION 2.3 | 28.2 units on the MoCA scale STANDARD_DEVIATION 1.5 | 26.5 units on the MoCA scale STANDARD_DEVIATION 2.2 |
| Race and Ethnicity Not Collected | — | — | — | 0 Participants |
| Sex: Female, Male Female | 33 Participants | 21 Participants | 12 Participants | 66 Participants |
| Sex: Female, Male Male | 35 Participants | 47 Participants | 17 Participants | 99 Participants |
| Unified PD Rating Scale-III - motor score (UPDRS-III) | 20.2 units on the motor score scale STANDARD_DEVIATION 8.3 | 21.0 units on the motor score scale STANDARD_DEVIATION 9.5 | — | 20.6 units on the motor score scale STANDARD_DEVIATION 8.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 68 | 0 / 68 | 0 / 31 |
| other Total, other adverse events | 9 / 68 | 10 / 68 | 0 / 31 |
| serious Total, serious adverse events | 0 / 68 | 1 / 68 | 0 / 31 |
Outcome results
Primary
Accuracy on the Tower of London Task
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).
Time frame: Baseline (T0, Pre-intervention) to eight weeks (T1, Post-intervention)
Population: Number analyzed lower due to difficulty understanding the task, or no follow-up assessment in PD group and difficulty understanding the task (n=1) in healthy control group. Healthy control subjects did not undergo an intervention and T1 measurement and scores at T1 are therefore not supplied for this subgroup.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Online Cognitive Training 1 | Accuracy on the Tower of London Task | Baseline - T0 | 81.2 percentage of correct responses | Standard Deviation 9.1 |
| Online Cognitive Training 1 | Accuracy on the Tower of London Task | eight weeks - T1 | 84.0 percentage of correct responses | Standard Deviation 10.4 |
| Online Cognitive Training 2 | Accuracy on the Tower of London Task | Baseline - T0 | 82.3 percentage of correct responses | Standard Deviation 7.9 |
| Online Cognitive Training 2 | Accuracy on the Tower of London Task | eight weeks - T1 | 84.9 percentage of correct responses | Standard Deviation 8.2 |
| Healthy Control Subjects | Accuracy on the Tower of London Task | Baseline - T0 | 88.1 percentage of correct responses | Standard Deviation 5.8 |
Secondary
Conversion of Cognitive Status at Two-year Follow-up
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).
Time frame: Two year after completion of the intervention (T3)
Population: Healthy control subjects did not undergo follow-up assessments. Number of participants analyzed differs from total population due to drop-out and missed assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Online Cognitive Training 1 | Conversion of Cognitive Status at Two-year Follow-up | -1: Conversion to worse classification | 13 participants |
| Online Cognitive Training 1 | Conversion of Cognitive Status at Two-year Follow-up | 0: No change | 25 participants |
| Online Cognitive Training 1 | Conversion of Cognitive Status at Two-year Follow-up | 1: Conversion to better classification | 15 participants |
| Online Cognitive Training 2 | Conversion of Cognitive Status at Two-year Follow-up | -1: Conversion to worse classification | 14 participants |
| Online Cognitive Training 2 | Conversion of Cognitive Status at Two-year Follow-up | 0: No change | 27 participants |
| Online Cognitive Training 2 | Conversion of Cognitive Status at Two-year Follow-up | 1: Conversion to better classification | 10 participants |
Secondary
Conversion to Mild Cognitive Impairment or Dementia at One-year Follow-up
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).
Time frame: One year after completion of the intervention (T3)
Population: Healthy control subjects did not undergo follow-up assessments. Number of participants analyzed differs from total population due to drop-out and missed assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Online Cognitive Training 1 | Conversion to Mild Cognitive Impairment or Dementia at One-year Follow-up | -1: Conversion to worse classification | 12 participants |
| Online Cognitive Training 1 | Conversion to Mild Cognitive Impairment or Dementia at One-year Follow-up | 0: No change | 28 participants |
| Online Cognitive Training 1 | Conversion to Mild Cognitive Impairment or Dementia at One-year Follow-up | 1: Conversion to better classification | 16 participants |
| Online Cognitive Training 2 | Conversion to Mild Cognitive Impairment or Dementia at One-year Follow-up | -1: Conversion to worse classification | 11 participants |
| Online Cognitive Training 2 | Conversion to Mild Cognitive Impairment or Dementia at One-year Follow-up | 0: No change | 27 participants |
| Online Cognitive Training 2 | Conversion to Mild Cognitive Impairment or Dementia at One-year Follow-up | 1: Conversion to better classification | 15 participants |
Secondary
Performance on the Controlled Oral Word Association Test
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.
Time frame: Baseline (T0, Pre-intervention) to eight weeks (T1, Post-intervention)
Population: Three participants dropped out of the study and did not perform the T1 measurement and were subsequently removed from analyses. Healthy control subjects did not perform the second assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Online Cognitive Training 1 | Performance on the Controlled Oral Word Association Test | Baseline (T0) | 38.0 total number of words produced | Standard Deviation 10.6 |
| Online Cognitive Training 1 | Performance on the Controlled Oral Word Association Test | Eight weeks (T1) | 42.5 total number of words produced | Standard Deviation 12.7 |
| Online Cognitive Training 2 | Performance on the Controlled Oral Word Association Test | Baseline (T0) | 38.8 total number of words produced | Standard Deviation 11.9 |
| Online Cognitive Training 2 | Performance on the Controlled Oral Word Association Test | Eight weeks (T1) | 42.6 total number of words produced | Standard Deviation 12.5 |
| Healthy Control Subjects | Performance on the Controlled Oral Word Association Test | Baseline (T0) | 43.7 total number of words produced | Standard Deviation 9.7 |
Secondary
Performance on the Stroop Color-Word Test, Card I
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.
Time frame: Baseline (T0, Pre-intervention) to eight weeks (T1, Post-intervention)
Population: Three participants dropped out of the study and did not perform the T1 measurement and were subsequently removed from analyses. Healthy control subjects did not perform the second assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Online Cognitive Training 1 | Performance on the Stroop Color-Word Test, Card I | Baseline (T0) | 54.1 time in seconds | Standard Deviation 10.7 |
| Online Cognitive Training 1 | Performance on the Stroop Color-Word Test, Card I | Eight weeks (T1) | 50.8 time in seconds | Standard Deviation 9.1 |
| Online Cognitive Training 2 | Performance on the Stroop Color-Word Test, Card I | Baseline (T0) | 56.3 time in seconds | Standard Deviation 15.1 |
| Online Cognitive Training 2 | Performance on the Stroop Color-Word Test, Card I | Eight weeks (T1) | 54.3 time in seconds | Standard Deviation 13.2 |
| Healthy Control Subjects | Performance on the Stroop Color-Word Test, Card I | Baseline (T0) | 49.2 time in seconds | Standard Deviation 9.4 |
Secondary
Performance on the Stroop Color-Word Test, Card III
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.
Time frame: Baseline (T0, Pre-intervention) to eight weeks (T1, Post-intervention)
Population: Three participants dropped out of the study and did not perform the T1 measurement and one participant did not undergo card III of the Stroop color word test at T1; these participants were subsequently removed from analyses. Healthy control subjects did not perform the second assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Online Cognitive Training 1 | Performance on the Stroop Color-Word Test, Card III | Baseline (T0) | 114.9 time in seconds | Standard Deviation 49.3 |
| Online Cognitive Training 1 | Performance on the Stroop Color-Word Test, Card III | Eight weeks (T1) | 101.7 time in seconds | Standard Deviation 28.6 |
| Online Cognitive Training 2 | Performance on the Stroop Color-Word Test, Card III | Baseline (T0) | 106.9 time in seconds | Standard Deviation 33.9 |
| Online Cognitive Training 2 | Performance on the Stroop Color-Word Test, Card III | Eight weeks (T1) | 103.4 time in seconds | Standard Deviation 30.7 |
| Healthy Control Subjects | Performance on the Stroop Color-Word Test, Card III | Baseline (T0) | 85.9 time in seconds | Standard Deviation 19 |
Secondary
Performance on Tower of London Accuracy at One-year Follow-up
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.
Time frame: One year after completion of intervention (T3, Follow-up 2)
Population: Healthy control subjects did not undergo follow-up assessments. Number of participants analyzed differs from total sample due to drop-out (n=12), missed assessment (n=15) and difficulty understanding the task (n=2).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Online Cognitive Training 1 | Performance on Tower of London Accuracy at One-year Follow-up | 83.3 percentage of correct responses | Standard Deviation 14 |
| Online Cognitive Training 2 | Performance on Tower of London Accuracy at One-year Follow-up | 84.7 percentage of correct responses | Standard Deviation 10.5 |
Secondary
Performance on Tower of London Accuracy at Six-months Follow-up
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.
Time frame: Six months after training completion (T2)
Population: Healthy control subjects did not undergo follow-up assessment. Number of participants analyzed lower than total population due to drop-out at T2 (n=8) and difficulty understanding the task at one of the time-points (n=11)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Online Cognitive Training 1 | Performance on Tower of London Accuracy at Six-months Follow-up | 84.3 percentage of correct responses | Standard Deviation 10.4 |
| Online Cognitive Training 2 | Performance on Tower of London Accuracy at Six-months Follow-up | 84.5 percentage of correct responses | Standard Deviation 9.1 |
Secondary
Performance on Tower of London Accuracy at Two-year Follow-up
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.
Time frame: Two years after completion of the intervention (T4)
Population: Healthy control subjects did not undergo follow-up assessemnts. Number of participants analyzed differs from total sample due to drop-out (n=12), missed assessment (n=21) and difficulty understanding the task.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Online Cognitive Training 1 | Performance on Tower of London Accuracy at Two-year Follow-up | 82.7 percentage of correct responses | Standard Deviation 11.7 |
| Online Cognitive Training 2 | Performance on Tower of London Accuracy at Two-year Follow-up | 82.1 percentage of correct responses | Standard Deviation 10.6 |
Secondary
Reaction Time on the Tower of London Task
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.
Time frame: Baseline (T0, Pre-intervention) to eight weeks (T1, Post-intervention)
Population: Number analyzed lower due to difficulty understanding the task (n=7), or no follow-up assessment (n=3) in PD group and difficulty understanding the task (n=1) in healthy control group. Healthy control subjects did not undergo an intervention and T1 measurement and scores at post-intervention are therefore not supplied.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Online Cognitive Training 1 | Reaction Time on the Tower of London Task | Baseline - T0 | 12.4 seconds | Standard Deviation 3.2 |
| Online Cognitive Training 1 | Reaction Time on the Tower of London Task | Eight weeks - T1 | 11.4 seconds | Standard Deviation 2.9 |
| Online Cognitive Training 2 | Reaction Time on the Tower of London Task | Baseline - T0 | 12.7 seconds | Standard Deviation 2.7 |
| Online Cognitive Training 2 | Reaction Time on the Tower of London Task | Eight weeks - T1 | 12.1 seconds | Standard Deviation 2.9 |
| Healthy Control Subjects | Reaction Time on the Tower of London Task | Baseline - T0 | 11.2 seconds | Standard Deviation 2.2 |
Secondary
Total Score on Cognitive Failures Questionnaire
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.
Time frame: Baseline (T0, Pre-intervention) to eight weeks (T1, Post-intervention)
Population: One participant in Online cognitive training 1 did not fill out the questionnaires.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Online Cognitive Training 1 | Total Score on Cognitive Failures Questionnaire | Baseline - T0 | 38.2 scores on a scale | Standard Deviation 10.6 |
| Online Cognitive Training 1 | Total Score on Cognitive Failures Questionnaire | Eight week - T1 | 36.9 scores on a scale | Standard Deviation 10.5 |
| Online Cognitive Training 2 | Total Score on Cognitive Failures Questionnaire | Baseline - T0 | 38.5 scores on a scale | Standard Deviation 11.5 |
| Online Cognitive Training 2 | Total Score on Cognitive Failures Questionnaire | Eight week - T1 | 38.0 scores on a scale | Standard Deviation 12.7 |
Secondary
Total Score on Parkinson's Disease Cognitive Functional Rating Scale
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.
Time frame: Baseline (T0, Pre-intervention) to eight weeks (T1, Post-intervention)
Population: Questionnaire not taken in healthy control group
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Online Cognitive Training 1 | Total Score on Parkinson's Disease Cognitive Functional Rating Scale | Baseline - T0 | 8.0 score on a scale | Standard Deviation 4 |
| Online Cognitive Training 1 | Total Score on Parkinson's Disease Cognitive Functional Rating Scale | Eight week - T1 | 6.9 score on a scale | Standard Deviation 4.3 |
| Online Cognitive Training 2 | Total Score on Parkinson's Disease Cognitive Functional Rating Scale | Baseline - T0 | 9.7 score on a scale | Standard Deviation 4.7 |
| Online Cognitive Training 2 | Total Score on Parkinson's Disease Cognitive Functional Rating Scale | Eight week - T1 | 8.0 score on a scale | Standard Deviation 5.1 |
Other Pre-specified
Age
Demographic characteristic: age at baseline.
Time frame: Pre-intervention (T0)
Other Pre-specified
Anxiety Symptom Severity
Psychiatric symptom severity, including anxiety (Parkinson Anxiety Scale).
Time frame: Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other Pre-specified
Apathy Symptom Severity
Psychiatric symptom severity, including apathy (Apathy Scale).
Time frame: Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other Pre-specified
Cognitive Reserve
Estimation of cognitive reserve measured with the Cognitive Reserve Index questionnaire
Time frame: Two years (T4)
Other Pre-specified
Depressive Symptom Severity
Psychiatric symptom severity, depression (Beck Depression Inventory).
Time frame: Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other Pre-specified
Difference Between Parkinson's Disease Patients' Brain Network Topology With or Without Cognitive Impairment, and Healthy Control Subjects.
Participants will be classified to cognitive impairment or no cognitive impairment, and their brain network topology will be compared with healthy subjects.
Time frame: Pre-intervention (T0)
Other Pre-specified
Disease Duration
Disease characteristic: disease duration.
Time frame: Pre-intervention (T0)
Other Pre-specified
Disease Stage
Disease characteristic: disease stage (Hoehn and Yahr stage).
Time frame: Pre-intervention (T0), one year (T3), two years (T4)
Other Pre-specified
Educational Level
Demographic characteristic: educational level.
Time frame: Pre-intervention (T0)
Other Pre-specified
Expectations of the Intervention
Participants' expectation prior the intervention, measured by the credibility/expectancy questionnaire.
Time frame: Pre-intervention (T0)
Other Pre-specified
Global Cognitive Functioning (1)
Global cognitive functioning assessed by the Montreal Cognitive Assessment (MoCA).
Time frame: Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other Pre-specified
Global Cognitive Functioning (2)
Global cognitive functioning assessed by the Pentagon copy test, which is predictive of cognitive deterioration.
Time frame: Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other Pre-specified
Impulse Control Disorder Symptom Severity
Psychiatric symptom severity, including impulse control disorders (QUIP-RS).
Time frame: Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other Pre-specified
Medication Use
Disease characteristic: medication use.
Time frame: Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other Pre-specified
Motor Symptoms
Motor symptoms assessed by the Unified Parkinson's Disease Rating Scale - III
Time frame: Pre-intervention (T0), one year (T3), two years (T4)
Other Pre-specified
Online Cognitive Training Effect on Brain Activity Measured by Resting State fMRI
The effect of online cognitive training on brain activity using resting state fMRI. Regional activity and functional connectivity changes will be assessed after eight weeks of training (T1).
Time frame: Eight weeks (T1)
Other Pre-specified
Online Cognitive Training Effect on Brain Morphology Measured by MRI
The effect of online cognitive training on brain morphology using MRI. Structural changes will be assessed after eight weeks of training (T1).
Time frame: Eight weeks (T1)
Other Pre-specified
Online Cognitive Training Effect on Brain Network Topology Relative to Healthy Control Group
The effect of online cognitive training on brain network topology using resting state fMRI compared with brain network topology of healthy subjects. Healthy subjects will undergo (functional) MRI scanning once.
Time frame: Eight weeks (T1)
Other Pre-specified
Online Cognitive Training Effect on Structural Brain Connectivity Measured by DTI
The effect of online cognitive training on structural brain connectivity using DTI. Structural changes will be assessed after eight weeks of training (T1).
Time frame: Eight weeks (T1)
Other Pre-specified
Physical Activity
Amount of estimated physical activity that a person performs, measured by the New Zealand Physical Activity Questionnaire
Time frame: Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other Pre-specified
Psychotic Symptom Severity
Psychiatric symptom severity, including psychotic symptoms (Questionnaire for psychotic events).
Time frame: Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other Pre-specified
Sex
Demographic characteristic: sex.
Time frame: Pre-intervention (T0)
Other Pre-specified
Specific Cognitive Functioning: Attention/Working Memory (1)
Attention function, measured by the Stroop task part I: word naming.
Time frame: Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other Pre-specified
Specific Cognitive Functioning: Attention/Working Memory (2)
Working memory function, measured by the backwards digit span test of the Wechsler adult intelligence test (WAIS)-III.
Time frame: Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other Pre-specified
Specific Cognitive Functioning: Episodic Memory (1)
Episodic memory function, measured by the Dutch version of the Auditory verbal learning test (RAVLT).
Time frame: Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other Pre-specified
Specific Cognitive Functioning: Episodic Memory (2)
Episodic memory function, measured by the Location learning task.
Time frame: Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other Pre-specified
Specific Cognitive Functioning: Language (1)
Language function, measured by the Boston naming task.
Time frame: Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other Pre-specified
Specific Cognitive Functioning: Language (2)
Language function, measured by the category fluency task.
Time frame: Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other Pre-specified
Specific Cognitive Functioning: Visuospatial/Visuoconstructive Function (1)
Visuospatial function, measured by the Benton visual form discrimination task.
Time frame: Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other Pre-specified
Specific Cognitive Functioning: Visuospatial/Visuoconstructive Function (2)
Visuospatial function, measured by the Rey complex figure task.
Time frame: Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)