- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02637089
Longitudinal Study of Mild Cognitive Impairment in Parkinson's Disease (PD-MCI)
Longitudinal Comparison of the Nature and Evolution of Mild Cognitive Impairment in Individuals With and Without Parkinson's Disease Characterized by Neuroimaging, Clinical Assessments and Genotyping
Study Overview
Status
Conditions
Detailed Description
Parkinson's disease (PD) is the second most frequent chronic neurodegenerative disorder, affecting up to 2% among persons older than 65 years of age and nearly 10% of people over 80. The cardinal symptoms of PD include tremor, rigidity and bradykinesia originating from the loss of dopaminergic neurons in the striatum. It has recently been shown that the non-motor symptoms in PD such as cognitive and behavioural impairment are highly prevalent and have a severe and direct negative effect on health-related and perceived quality of life. It is now well established that 25 to 40% of persons with PD will develop cognitive deficits early in the disease. Moreover, the risk of developing dementia is almost six times higher in PD patients than in age-matched controls. The nature and evolution of cognitive deficits in PD remain poorly understood, so is their relationship with neuropsychiatric features often observed in the disease including depression, anxiety and apathy. Furthermore, the medication treatment of cognitive deficits in PD yields very modest results. PD neuropathology is associated with alpha-synuclein-containing Lewy-Bodies whereas that of Alzheimer's disease (AD) is usually associated with Aß-amyloid plaques and tau-containing neurofibrillary lesions. However, recent post-mortem studies suggest that between 30 and 45% of PD patients with dementia also meet neuropathologic diagnostic criteria for AD. With such a high proportion of demented PD patients with concurrent AD, it would be valuable, from a therapeutic standpoint, to identify those with AD earlier. In the context of the present proposal the investigators will be able to follow different groups of PD patients longitudinally and compare them to non-PD patients with mild cognitive impairment who are at risk of developing a medio-temporal lobe dementia such as Alzheimer's disease.
The three major aims for this longitudinal study are:
- Identify anatomical and functional neuroimaging, neuropsychological and neuropsychiatric profiles that can serve as markers for the early prediction of dementia in PD.
- Uncover the cognitive and neural characteristics that are specific to PD-MCI subjects vs. characteristics shared by all MCI subjects whether due to PD or other aetiology such as Alzheimer's disease.
- Identify the effect of specific genotypes that can influence the cognitive profile and evolution in PD.
The investigators will recruit 100 PD and 100 non-PD individuals. None of them will have dementia. Participants will be selected in order to obtain about 65% MCI and 35% cognitively intact individuals in each cohort (PD, non-PD). At study start they will be asked to consent to a blood draw for genotyping purposes. At each time point, they will receive a neuropsychological evaluation to determine whether and which domain(s) of cognition is (are) affected and whether the participant meets the criteria for dementia. Neuropsychiatric symptoms which are often present before the onset of cognitive symptoms will be assessed at each time point using the Mild Behavioural Impairment-Checklist (MBI-C). At Time points 1 and 2 they will also undergo two MRI sessions containing anatomical acquisitions as well as BOLD functional series while performing an executive (set-shifting) task that the investigators have shown to rely on fronto-striatal regions and an (associative) memory task that solicits the medial temporal lobe. At Time point 3 they will undergo just one MRI session not containing any task. This will allow the investigators to identify markers that can distinguish subgroups with respect to their possible evolution towards dementia. This multi-faceted, longitudinal project promises to enhance the understanding of the nature and evolution of cognitive dysfunction in PD relative to general aging. To the investigators' knowledge, this is the first time that PD and non-PD patients stratified according to cognitive profile will be studied longitudinally using neuropsychological evaluation, anatomical and functional neuroimaging measures as well as genotyping. This information has the potential to yield markers that can be used in clinics to determine the diagnosis and prognosis of cognitive dysfunction in PD, allowing for an early prediction of dementia in the disease. This will ultimately yield intervention and treatment strategies tailored to different patient subtypes, aimed at improving cognitive deficits and decelerating the decline.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Iris Kathol, PhD
- Phone Number: 1-403-210-6830
- Email: ikathol@ucalgary.ca
Study Contact Backup
- Name: Lorelei Tainsh, RN, CRC
- Phone Number: 1-403-220-8413
- Email: derwent@ucalgary.ca
Study Locations
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Alberta
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Calgary, Alberta, Canada, T2N 4N1
- Recruiting
- University of Calgary, Department of Clinical Neurosciences
-
Contact:
- Iris Kathol, PhD
- Phone Number: 1-403-210-6830
- Email: ikathol@ucalgary.ca
-
Contact:
- Nadia Maarouf, PhD
- Phone Number: 1-403-210-8519
- Email: nmaarouf@ucalgary.ca
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Principal Investigator:
- Oury Monchi, PhD
-
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
Cases:
- Non-demented PD patients at stages II or III of Hoehn and Yahr at Time point 1 with or without MCI
- MCI patients
- Willing and able to provide written informed consent
- Willing to provide blood sample, willing to participate in all clinical assessments, willing to have brain MRIs
Controls:
- Community volunteers, with no history of PD or cognitive or memory complaints
- Willing and able to provide written informed consent
- Willing to provide blood sample, willing to participate in all clinical assessments, willing to have brain MRIs
- Screen negative for MCI
Exclusion Criteria:
•All participants who meet the diagnosis of dementia at Time point 1 as indicated by Mini-Mental State Evaluation (MMSE) of 20 or less and indicated through the clinical testing.
(The neuropsychological evaluation will always take place before the imaging sessions, in case participants must be excluded based on their cognitive profile.)
- All participants taking benzodiazepines will be excluded as these can severely impair performance of cognitive tasks.
- Participants with metallic objects in their bodies will not be eligible for the study because the strong magnetic field in the scanner could cause these objects to change position and may cause injury.
The following criteria will also be used as grounds for exclusion, as they have severe impact on cognitive function:
- Alcohol-dependency
- Presence or history of severe psychiatric disorder, neurological disorder or stroke
- General anaesthesia in the past six months
- History of cerebrovascular disorders
Study Plan
How is the study designed?
Design Details
- Observational Models: Case-Control
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
---|
PD-non-MCI
Patients with Parkinson's disease, no mild cognitive impairment
|
PD-MCI
Patients with Parkinson's disease with mild cognitive impairment
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MCI (non-PD-MCI)
Patients with mild cognitive impairment, no Parkinson's disease
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HC (non-PD-non-MCI)
Healthy Controls (age-matched to patients)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Identify which structures in the brain exhibit the highest structural changes and / or BOLD changes correlated to the Z-scores of the neuropsychological assessments
Time Frame: Baseline, 18 months, 36 months
|
Structural changes and changes in BOLD fMRI sequence will be measured at each of the three time points.
These measurements will be correlated to the Z-scores of the neuropsychological assessments at each time point.
|
Baseline, 18 months, 36 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change from baseline in Z-scores of different neuropsychological assessments
Time Frame: Baseline, 18 months, 36 months
|
Executive, Attention, Visio-spatial and Visio-perceptual, Language, Verbal and Episodic Memory and Global Cognition |
Baseline, 18 months, 36 months
|
Change in Cognitive Ability measured as BOLD fMRI sequence
Time Frame: Baseline, 18 months, 36 months
|
Establish an episodic imaging memory task to be performed in the scanner to measure the level of medial temporal lobe activation via BOLD fMRI sequence (blood-oxygen-level-dependent contrast imaging)
|
Baseline, 18 months, 36 months
|
Change in Executive Functioning measured as BOLD fMRI sequence
Time Frame: Baseline, 18 months, 36 months
|
Establish an executive task to be performed in the scanner to measure the level of activation in the basal ganglia and the prefrontal cortex via BOLD fMRI sequence (blood-oxygen-level-dependent contrast imaging)
|
Baseline, 18 months, 36 months
|
Measure changes in the volume of subcortical structures in the brain
Time Frame: Baseline, 18 months, 36 months
|
Volume of subcortical structures (mm3)
|
Baseline, 18 months, 36 months
|
Measure changes in cortical thickness in the brain
Time Frame: Baseline, 18 months, 36 months
|
Cortical thickness (mm)
|
Baseline, 18 months, 36 months
|
Measure structural changes in the brain
Time Frame: Baseline, 18 months, 36 months
|
Rate of change in cortical thickness (mm/year)
|
Baseline, 18 months, 36 months
|
Analyze DNA for following genes: COMT, DAT1, MAPT, ApoE, GBA, CHNRA4
Time Frame: Baseline
|
Genotyping
|
Baseline
|
Measure level of biomarkers: Aß-amyloid in blood through fluorescence spectroscopy
Time Frame: Baseline
|
Increase or decrease in fluorescence can be determined visually by looking at spectral fluorescence images.
Increased fluorescence can be quantified in % compared to blood from a participant who has no disease associated with abnormal protein aggregation.
|
Baseline
|
Measure psychiatric changes with the Mild Behavioural Impairment-Checklist (MBI-C)
Time Frame: Baseline, 18 months, 36 months
|
Changes in scores per domain
|
Baseline, 18 months, 36 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Oury Monchi, PhD, University of Calgary, Cumming School of Medicine, Department of Clinical Neurosciences
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- REB14-2463
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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