Parkinson DiseasecogtipsNCT02920632
Cognitive Training in Parkinson Study
A study testing Online cognitive training 1 and Online cognitive training 2 in people with Parkinson Disease and Impaired Cognition, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial 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… Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Parkinson Disease, Impaired Cognition, Alteration in Cognition
- What is being tested?
- Online cognitive training 1 and Online cognitive training 2
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 167 participants
- Where
- 1 siteNetherlands
- Study dates
- 15 Sep 2017to 9 Aug 2021
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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.
- Participants are willing to sign informed consent.
Who cannot join
- 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.
Show all 24Show fewer
- 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 ---
- 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)
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
VU University Medical Center
Amsterdam, North Holland, 1081HV
About this study
Official title: COGTIPS (COGnitive Training In Parkinson Study): The Effect of Online Cognitive Training on Cognition and Brain Networks in Parkinson's Disease
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.
Read the 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.
- Being tested
- Online cognitive training 1, Online cognitive training 2
- Keywords
- Parkinson, Cognitive training, Cognitive rehabilitation, Brain networks
- Medical subject headings
- Parkinson Disease, Cognition Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Online cognitive training 1Behavioural
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.
Online cognitive training 2Behavioural
Eight-week online active comparator program, three times a week for 45 minutes. The training contains several games.
| Study group | Role | What they receive |
|---|---|---|
| Online cognitive training 1 | Experimental | Eight-week, three times a week during 45 minutes cognitive training Receives: Behavioral: Online cognitive training 1 |
| Online cognitive training 2 | Active comparator | Eight-week, three times a week during 45 minutes cognitive activities Receives: Behavioral: Online cognitive training 2 |
| Healthy control subjects | No intervention | Reference group to compare cognitive training effects to |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline (T0, "Pre-intervention") to eight weeks (T1, "Post-intervention")
Secondary outcomes (11)
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.
Measured: Baseline (T0, "Pre-intervention") to eight weeks (T1, "Post-intervention")
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.
Measured: Baseline (T0, "Pre-intervention") to eight weeks (T1, "Post-intervention")
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.
Measured: Baseline (T0, "Pre-intervention") to eight weeks (T1, "Post-intervention")
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.
Measured: Baseline (T0, "Pre-intervention") to eight weeks (T1, "Post-intervention")
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.
Measured: Six months after training completion (T2)
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.
Measured: One year after completion of intervention (T3, "Follow-up 2")
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.
Measured: Two years after completion of the intervention (T4)
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).
Measured: One year after completion of the intervention (T3)
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.
Measured: Baseline (T0, "Pre-intervention") to eight weeks (T1, "Post-intervention")
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.
Measured: Baseline (T0, "Pre-intervention") to eight weeks (T1, "Post-intervention")
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).
Measured: Two year after completion of the intervention (T3)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2016 (estimated)
- Study start15 Sep 2017
- Primary completion17 Jul 2019
- Study completion9 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 167 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Collaborators
- Dutch Parkinson Patient Association
- Responsible party
- Principal investigator, Chris Vriend, PhD, Amsterdam UMC, location VUmc
- Investigators
- Chris Vriend, PhD., Principal investigator, Amsterdam UMC, location VUmcOdile A Van den Heuvel, MD PhD., Principal investigator, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02920632
- Sponsor's protocol ID
- CWO/16-10
- Acronym
- cogtips
- Status last verified
- May 2024
- First submitted
- 30 Aug 2016
- Last updated
- 19 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Litvan I, Aarsland D, Adler CH, Goldman JG, Kulisevsky J, Mollenhauer B, Rodriguez-Oroz MC, Troster AI, Weintraub D. MDS Task Force on mild cognitive impairment in Parkinson's disease: critical review of PD-MCI. Mov Disord. 2011 Aug 15;26(10):1814-24. doi: 10.1002/mds.23823. Epub 2011 Jun 9.
PubMed 21661055Bosboom JL, Stoffers D, Wolters ECh. Cognitive dysfunction and dementia in Parkinson's disease. J Neural Transm (Vienna). 2004 Oct;111(10-11):1303-15. doi: 10.1007/s00702-004-0168-1. Epub 2004 Jun 30.
PubMed 15480840Muslimovic D, Post B, Speelman JD, Schmand B. Cognitive profile of patients with newly diagnosed Parkinson disease. Neurology. 2005 Oct 25;65(8):1239-45. doi: 10.1212/01.wnl.0000180516.69442.95.
PubMed 16247051Aarsland D, Andersen K, Larsen JP, Lolk A, Kragh-Sorensen P. Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study. Arch Neurol. 2003 Mar;60(3):387-92. doi: 10.1001/archneur.60.3.387.
PubMed 12633150Hely MA, Reid WG, Adena MA, Halliday GM, Morris JG. The Sydney multicenter study of Parkinson's disease: the inevitability of dementia at 20 years. Mov Disord. 2008 Apr 30;23(6):837-44. doi: 10.1002/mds.21956.
PubMed 18307261Aarsland D, Kurz MW. The epidemiology of dementia associated with Parkinson disease. J Neurol Sci. 2010 Feb 15;289(1-2):18-22. doi: 10.1016/j.jns.2009.08.034. Epub 2009 Sep 4.
PubMed 19733364Klepac N, Trkulja V, Relja M, Babic T. Is quality of life in non-demented Parkinson's disease patients related to cognitive performance? A clinic-based cross-sectional study. Eur J Neurol. 2008 Feb;15(2):128-33. doi: 10.1111/j.1468-1331.2007.02011.x.
PubMed 18217883Cicerone KD, Langenbahn DM, Braden C, Malec JF, Kalmar K, Fraas M, Felicetti T, Laatsch L, Harley JP, Bergquist T, Azulay J, Cantor J, Ashman T. Evidence-based cognitive rehabilitation: updated review of the literature from 2003 through 2008. Arch Phys Med Rehabil. 2011 Apr;92(4):519-30. doi: 10.1016/j.apmr.2010.11.015.
PubMed 21440699Olazaran J, Reisberg B, Clare L, Cruz I, Pena-Casanova J, Del Ser T, Woods B, Beck C, Auer S, Lai C, Spector A, Fazio S, Bond J, Kivipelto M, Brodaty H, Rojo JM, Collins H, Teri L, Mittelman M, Orrell M, Feldman HH, Muniz R. Nonpharmacological therapies in Alzheimer's disease: a systematic review of efficacy. Dement Geriatr Cogn Disord. 2010;30(2):161-78. doi: 10.1159/000316119. Epub 2010 Sep 10.
PubMed 20838046Chapman SB, Aslan S, Spence JS, Hart JJ Jr, Bartz EK, Didehbani N, Keebler MW, Gardner CM, Strain JF, DeFina LF, Lu H. Neural mechanisms of brain plasticity with complex cognitive training in healthy seniors. Cereb Cortex. 2015 Feb;25(2):396-405. doi: 10.1093/cercor/bht234. Epub 2013 Aug 28.
PubMed 23985135Castellanos NP, Paul N, Ordonez VE, Demuynck O, Bajo R, Campo P, Bilbao A, Ortiz T, del-Pozo F, Maestu F. Reorganization of functional connectivity as a correlate of cognitive recovery in acquired brain injury. Brain. 2010 Aug;133(Pt 8):2365-81. doi: 10.1093/brain/awq174.
PubMed 20826433Subramaniam K, Luks TL, Fisher M, Simpson GV, Nagarajan S, Vinogradov S. Computerized cognitive training restores neural activity within the reality monitoring network in schizophrenia. Neuron. 2012 Feb 23;73(4):842-53. doi: 10.1016/j.neuron.2011.12.024.
PubMed 22365555Subramaniam K, Luks TL, Garrett C, Chung C, Fisher M, Nagarajan S, Vinogradov S. Intensive cognitive training in schizophrenia enhances working memory and associated prefrontal cortical efficiency in a manner that drives long-term functional gains. Neuroimage. 2014 Oct 1;99:281-92. doi: 10.1016/j.neuroimage.2014.05.057. Epub 2014 May 24.
PubMed 24867353Belleville S, Clement F, Mellah S, Gilbert B, Fontaine F, Gauthier S. Training-related brain plasticity in subjects at risk of developing Alzheimer's disease. Brain. 2011 Jun;134(Pt 6):1623-34. doi: 10.1093/brain/awr037. Epub 2011 Mar 22.
PubMed 21427462Rosen AC, Sugiura L, Kramer JH, Whitfield-Gabrieli S, Gabrieli JD. Cognitive training changes hippocampal function in mild cognitive impairment: a pilot study. J Alzheimers Dis. 2011;26 Suppl 3(Suppl 3):349-57. doi: 10.3233/JAD-2011-0009.
PubMed 21971474
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- COGTIPS (COGnitive Training In Parkinson Study): The Effect of Online Cognitive Training on Cognition and Brain Networks in Parkinson's Disease
- ClinicalTrials.gov ID
- NCT02920632
- Acronym / sponsor ID
- cogtips / CWO/16-10
- Keywords
- Parkinson, Cognitive training, Cognitive rehabilitation, Brain networks
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 167 participants (actual)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Collaborators
- Dutch Parkinson Patient Association
- Study start
- 15 Sep 2017 (actual)
- Primary completion
- 17 Jul 2019 (actual)
- Study completion
- 9 Aug 2021 (actual)
- First posted
- 30 Sep 2016 (estimated)
- Results
- Posted 19 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Online cognitive training 1 | Experimental | Behavioral: Online cognitive training 1Eight-week, three times a week during 45 minutes cognitive training |
| Online cognitive training 2 | Active comparator | Behavioral: Online cognitive training 2Eight-week, three times a week during 45 minutes cognitive activities |
| Healthy control subjects | No intervention | –Reference group to compare cognitive training effects to |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
- Participants are willing to sign informed consent.
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Online cognitive training 1Eight-week online cognitive training program, three times a week for 45 minutes. The training contains several games that are designed to train cognitive functions. | Behavioural | Online cognitive training 1 |
| Online cognitive training 2Eight-week online active comparator program, three times a week for 45 minutes. The training contains several games. | Behavioural | Online cognitive training 2 |
Primary outcome
Accuracy on the Tower of London Task
Time frame: 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).
11 secondary outcomes
Total Score on Parkinson's Disease Cognitive Functional Rating Scale
Time frame: Baseline (T0, "Pre-intervention") to eight weeks (T1, "Post-intervention")
Total Score on Cognitive Failures Questionnaire
Time frame: Baseline (T0, "Pre-intervention") to eight weeks (T1, "Post-intervention")
Reaction Time on the Tower of London Task
Time frame: Baseline (T0, "Pre-intervention") to eight weeks (T1, "Post-intervention")
Performance on the Controlled Oral Word Association Test
Time frame: Baseline (T0, "Pre-intervention") to eight weeks (T1, "Post-intervention")
Performance on Tower of London Accuracy at Six-months Follow-up
Time frame: Six months after training completion (T2)
Performance on Tower of London Accuracy at One-year Follow-up
Time frame: One year after completion of intervention (T3, "Follow-up 2")
Performance on Tower of London Accuracy at Two-year Follow-up
Time frame: Two years after completion of the intervention (T4)
Conversion to Mild Cognitive Impairment or Dementia at One-year Follow-up
Time frame: One year after completion of the intervention (T3)
Performance on the Stroop Color-Word Test, Card I
Time frame: Baseline (T0, "Pre-intervention") to eight weeks (T1, "Post-intervention")
Performance on the Stroop Color-Word Test, Card III
Time frame: Baseline (T0, "Pre-intervention") to eight weeks (T1, "Post-intervention")
Conversion of Cognitive Status at Two-year Follow-up
Time frame: Two year after completion of the intervention (T3)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21661055Litvan I, Aarsland D, Adler CH, Goldman JG, Kulisevsky J, Mollenhauer B, Rodriguez-Oroz MC, Troster AI, Weintraub D. MDS Task Force on mild cognitive impairment in Parkinson's disease: critical review of PD-MCI. Mov Disord. 2011 Aug 15;26(10):1814-24. doi: 10.1002/mds.23823. Epub 2011 Jun 9.
- Background: PubMed 15480840Bosboom JL, Stoffers D, Wolters ECh. Cognitive dysfunction and dementia in Parkinson's disease. J Neural Transm (Vienna). 2004 Oct;111(10-11):1303-15. doi: 10.1007/s00702-004-0168-1. Epub 2004 Jun 30.
- Background: PubMed 16247051Muslimovic D, Post B, Speelman JD, Schmand B. Cognitive profile of patients with newly diagnosed Parkinson disease. Neurology. 2005 Oct 25;65(8):1239-45. doi: 10.1212/01.wnl.0000180516.69442.95.
- Background: PubMed 12633150Aarsland D, Andersen K, Larsen JP, Lolk A, Kragh-Sorensen P. Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study. Arch Neurol. 2003 Mar;60(3):387-92. doi: 10.1001/archneur.60.3.387.
- Background: PubMed 18307261Hely MA, Reid WG, Adena MA, Halliday GM, Morris JG. The Sydney multicenter study of Parkinson's disease: the inevitability of dementia at 20 years. Mov Disord. 2008 Apr 30;23(6):837-44. doi: 10.1002/mds.21956.
- Background: PubMed 19733364Aarsland D, Kurz MW. The epidemiology of dementia associated with Parkinson disease. J Neurol Sci. 2010 Feb 15;289(1-2):18-22. doi: 10.1016/j.jns.2009.08.034. Epub 2009 Sep 4.
- Background: PubMed 18217883Klepac N, Trkulja V, Relja M, Babic T. Is quality of life in non-demented Parkinson's disease patients related to cognitive performance? A clinic-based cross-sectional study. Eur J Neurol. 2008 Feb;15(2):128-33. doi: 10.1111/j.1468-1331.2007.02011.x.
- Background: PubMed 21440699Cicerone KD, Langenbahn DM, Braden C, Malec JF, Kalmar K, Fraas M, Felicetti T, Laatsch L, Harley JP, Bergquist T, Azulay J, Cantor J, Ashman T. Evidence-based cognitive rehabilitation: updated review of the literature from 2003 through 2008. Arch Phys Med Rehabil. 2011 Apr;92(4):519-30. doi: 10.1016/j.apmr.2010.11.015.
- Background: PubMed 20838046Olazaran J, Reisberg B, Clare L, Cruz I, Pena-Casanova J, Del Ser T, Woods B, Beck C, Auer S, Lai C, Spector A, Fazio S, Bond J, Kivipelto M, Brodaty H, Rojo JM, Collins H, Teri L, Mittelman M, Orrell M, Feldman HH, Muniz R. Nonpharmacological therapies in Alzheimer's disease: a systematic review of efficacy. Dement Geriatr Cogn Disord. 2010;30(2):161-78. doi: 10.1159/000316119. Epub 2010 Sep 10.
- Background: PubMed 23985135Chapman SB, Aslan S, Spence JS, Hart JJ Jr, Bartz EK, Didehbani N, Keebler MW, Gardner CM, Strain JF, DeFina LF, Lu H. Neural mechanisms of brain plasticity with complex cognitive training in healthy seniors. Cereb Cortex. 2015 Feb;25(2):396-405. doi: 10.1093/cercor/bht234. Epub 2013 Aug 28.
- Background: PubMed 20826433Castellanos NP, Paul N, Ordonez VE, Demuynck O, Bajo R, Campo P, Bilbao A, Ortiz T, del-Pozo F, Maestu F. Reorganization of functional connectivity as a correlate of cognitive recovery in acquired brain injury. Brain. 2010 Aug;133(Pt 8):2365-81. doi: 10.1093/brain/awq174.
- Background: PubMed 22365555Subramaniam K, Luks TL, Fisher M, Simpson GV, Nagarajan S, Vinogradov S. Computerized cognitive training restores neural activity within the reality monitoring network in schizophrenia. Neuron. 2012 Feb 23;73(4):842-53. doi: 10.1016/j.neuron.2011.12.024.
- COGTIPS methodology articleLink provided by the sponsor.
- COGTIPS DWI results articleLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chris Vriend, PhD. principal investigator
Amsterdam UMC, location VUmc
Odile A Van den Heuvel, MD PhD. principal investigator
Amsterdam UMC, location VUmc
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Online cognitive training 1 and Online cognitive training 2 in people with Parkinson Disease and Impaired Cognition, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Accuracy on the Tower of London Task (time frame: Baseline (T0, "Pre-intervention") to eight weeks (T1, "Post-intervention")). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02920632, which also lists 20 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.