Cognitive Training in Parkinson Study

Parkinson Disease Clinical Trial

— cogtips  

Official title:

COGTIPS (COGnitive Training In Parkinson Study): The Effect of Online Cognitive Training on Cognition and Brain Networks in Parkinson's Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02920632
• Other study ID #: CWO/16-10
• Status: Active, not recruiting
• Phase: N/A
• Start date: September 15, 2017
• Est. completion date: September 2021

Study information

• Verified date: October 2020
• Source: VU University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 170
• Est. completion date: September 2021
• Est. primary completion date: July 17, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

--- 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.

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)

Related Conditions & MeSH terms

• Alteration in Cognition
• Cognitive Dysfunction
• Impaired Cognition
• Parkinson Disease

Intervention

Behavioral:
• 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.
• Online cognitive training 2
Eight-week online active comparator program, three times a week for 45 minutes. The training contains several games.

Locations

Country	Name	City	State
Netherlands	VU University Medical Center	Amsterdam	Noord-Holland

Sponsors (2)

Lead Sponsor	Collaborator
VU University Medical Center	Dutch Parkinson Patient Association

Country where clinical trial is conducted

Netherlands, 

References & Publications (19)

Aarsland D, Andersen K, Larsen JP, Lolk A, Kragh-Sørensen P. Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study. Arch Neurol. 2003 Mar;60(3):387-92. — View Citation

Aarsland 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. Review. — View Citation

Baggio HC, Sala-Llonch R, Segura B, Marti MJ, Valldeoriola F, Compta Y, Tolosa E, Junqué C. Functional brain networks and cognitive deficits in Parkinson's disease. Hum Brain Mapp. 2014 Sep;35(9):4620-34. doi: 10.1002/hbm.22499. Epub 2014 Mar 17. — View Citation

Belleville S, Clément 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. — View Citation

Bosboom JL, Stoffers D, Wolters ECh. Cognitive dysfunction and dementia in Parkinson's disease. J Neural Transm (Vienna). 2004 Oct;111(10-11):1303-15. Epub 2004 Jun 30. Review. — View Citation

Castellanos NP, Paúl N, Ordóñez VE, Demuynck O, Bajo R, Campo P, Bilbao A, Ortiz T, del-Pozo F, Maestú 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. — View Citation

Chapman 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. — View Citation

Cicerone 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. Review. — View Citation

Hely 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. — View Citation

Hindle JV, Petrelli A, Clare L, Kalbe E. Nonpharmacological enhancement of cognitive function in Parkinson's disease: a systematic review. Mov Disord. 2013 Jul;28(8):1034-49. doi: 10.1002/mds.25377. Epub 2013 Feb 20. Review. — View Citation

Klepac 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. — View Citation

Leung IH, Walton CC, Hallock H, Lewis SJ, Valenzuela M, Lampit A. Cognitive training in Parkinson disease: A systematic review and meta-analysis. Neurology. 2015 Nov 24;85(21):1843-51. doi: 10.1212/WNL.0000000000002145. Epub 2015 Oct 30. Review. — View Citation

Litvan I, Aarsland D, Adler CH, Goldman JG, Kulisevsky J, Mollenhauer B, Rodriguez-Oroz MC, Tröster 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. Review. — View Citation

Muslimovic D, Post B, Speelman JD, Schmand B. Cognitive profile of patients with newly diagnosed Parkinson disease. Neurology. 2005 Oct 25;65(8):1239-45. — View Citation

Olazarán J, Reisberg B, Clare L, Cruz I, Peña-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, Muñiz 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. Review. — View Citation

Petrelli A, Kaesberg S, Barbe MT, Timmermann L, Rosen JB, Fink GR, Kessler J, Kalbe E. Cognitive training in Parkinson's disease reduces cognitive decline in the long term. Eur J Neurol. 2015 Apr;22(4):640-7. doi: 10.1111/ene.12621. Epub 2014 Dec 22. — View Citation

Rosen 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 3:349-57. doi: 10.3233/JAD-2011-0009. — View Citation

Subramaniam 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. — View Citation

Subramaniam 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. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Age	Demographic characteristic: age at baseline.	Pre-intervention (T0)
Other	Sex	Demographic characteristic: sex.	Pre-intervention (T0)
Other	Educational level	Demographic characteristic: educational level.	Pre-intervention (T0)
Other	Disease duration	Disease characteristic: disease duration.	Pre-intervention (T0)
Other	Disease stage	Disease characteristic: disease stage (Hoehn and Yahr stage).	Pre-intervention (T0), one year (T3), two years (T4)
Other	Medication use	Disease characteristic: medication use.	Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other	Motor symptoms	Motor symptoms assessed by the Unified Parkinson's Disease Rating Scale - III	Pre-intervention (T0), one year (T3), two years (T4)
Other	Depressive symptom severity	Psychiatric symptom severity, depression (Beck Depression Inventory).	Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other	Anxiety symptom severity	Psychiatric symptom severity, including anxiety (Parkinson Anxiety Scale).	Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other	Impulse control disorder symptom severity	Psychiatric symptom severity, including impulse control disorders (QUIP-RS).	Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other	Psychotic symptom severity	Psychiatric symptom severity, including psychotic symptoms (Questionnaire for psychotic events).	Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other	Apathy symptom severity	Psychiatric symptom severity, including apathy (Apathy Scale).	Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other	Expectations of the intervention	Participants' expectation prior the intervention, measured by the credibility/expectancy questionnaire.	Pre-intervention (T0)
Other	Global cognitive functioning (1)	Global cognitive functioning assessed by the Montreal Cognitive Assessment (MoCA).	Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other	Global cognitive functioning (2)	Global cognitive functioning assessed by the Pentagon copy test, which is predictive of cognitive detoriation.	Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other	Specific cognitive functioning: attention/working memory (1)	Attention function, measured by the Stroop task part I: word naming.	Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other	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.	Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other	Specific cognitive functioning: episodic memory (1)	Episodic memory function, measured by the Dutch version of the Auditory verbal learning test (RAVLT).	Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other	Specific cognitive functioning: episodic memory (2)	Episodic memory function, measured by the Location learning task.	Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other	Specific cognitive functioning: language (1)	Language function, measured by the Boston naming task.	Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other	Specific cognitive functioning: language (2)	Language function, measured by the category fluency task.	Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other	Specific cognitive functioning: visuospatial/visuoconstructive function (1)	Visuospatial function, measured by the Benton visual form discrimination task.	Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other	Specific cognitive functioning: visuospatial/visuoconstructive function (2)	Visuospatial function, measured by the Rey complex figure task.	Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other	Physical activity	Amount of estimated physical activity that a person performes, measured by the New Zealand Physical Activity Questionnaire	Pre-intervention (T0), eight weeks (T1), six months (T2), one year (T3), two years (T4)
Other	Cognitive reserve	Estimation of cognitive reserve measured with the Cognitive Reserve Index questionnaire	Two years (T4)
Primary	Efficacy of the online cognitive training on executive function (1)	Improvement in executive function after eight weeks of cognitive training as measured by the Tower of London	Eight weeks (T1)
Secondary	Efficacy of the online cognitive training on subjective cognitive complaints (1)	Improvement on subjective cognitive complaints after eight weeks of cognitive training, measured by the Parkinson's disease Cognitive Functional Rating Scale (PD-CFRS).	Eight weeks (T1)
Secondary	Efficacy of the online cognitive training on subjective cognitive complaints (2)	Improvement on subjective cognitive complaints after eight weeks of cognitive training, measured by the Cognitive failures questionnaire (CFQ).	Eight weeks (T1)
Secondary	Efficacy of the online cognitive training on executive cognitive functions (2)	Improvement on executive cognitive functions after eight weeks of cognitive training, measured by the Stroop color-word task. The color-word card (card III) will be corrected for color naming speed (measured by card II).	Eight weeks (T1)
Secondary	Efficacy of the online cognitive training on executive cognitive functions (3)	Improvement on executive cognitive functions after eight weeks of cognitive training, measured by the Letter fluency task.	Eight weeks (T1)
Secondary	Persistence of cognitive training effect on executive functions at six-month follow-up	Persistence of cognitive training effect on executive functions measured by the Tower of London task at six-month follow-up of no cognitive training.	Six months (T2)
Secondary	Persistence of cognitive training effect on executive functions at one-year follow-up	Persistence of cognitive training effect on executive functions measured by the Tower of London task at one-year follow-up of no cognitive training.	One year (T3)
Secondary	Persistence of cognitive training effect on executive functions at two-year follow-up	Persistence of cognitive training effect on executive functions measured by the Tower of London task at one-year follow-up of no cognitive training.	Two years (T4)
Secondary	Risk reduction of PD-MCI/PD-D development at follow-up	The reduction of the risk on developing PD-MCI or PD-D at six months and one year follow-up. Diagnostic criteria for Level II PD-MCI and probable PD-D will be used.	Six months (T2), one year (T3), two years (T4)
Secondary	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).	Eight weeks (T1)
Secondary	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).	Eight weeks (T1)
Secondary	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).	Eight weeks (T1)
Secondary	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.	Eight weeks (T1)
Secondary	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.	Pre-intervention (T0)

External Links

•   Website of the trial