Electrophysiological Signature of Mild Cognitive Impairment and Its Relationship with Parkinson's Disease: a High-density EEG Investigation (MMCI)

October 11, 2024 updated by: IRCCS San Camillo, Venezia, Italy
The study aims to investigate neural correlate of Mild Cognitive Impairment (MCI) in Parkinson's disease (PD) and to identify a link between functional impairment (in both cognitive and motor domains) and electrophysiological cortical sing of MCI in PD. A sample of 42 subjects will be divide into three subgroup: healthy control, PD with MCI (PD-MCI) and PD without MCI (PD-ctrl). Those subjects will undergo a specific neuropsychological evaluation and, to measure the electro-cortical activity, high-density electroencephalography (hdEEG) will be record during both resting state and cognitive tasks. Furthermore, hdEEG data will be combine with structural magnetic resonance to obtain information about network connectivity.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Parkinson's disease (PD) is a neurodegenerative disorder, characterized by a degeneration of dopaminergic neurons at the level of the pars compacta of the substantia nigra, which results in impaired control of the nigrostriatal pathway. This degeneration is manifested by both motor and non-motor symptoms such bradykinesia, tremor, rigidity, and cognitive disorders. Particularly, patients with PD might be affected by Mild Cognitive Impairment (MCI), dementia, and related behavioral disorders including apathy and depressive syndromes. However, while motor disturbances are more evident, it is difficult to evaluate the onset of cognitive symptoms, especially in the prodromal phases of the disease. Indeed, it seems that the onset of cognitive deficits in PD occurs in a high prevalence in the earlier stages of the disease. PD patients can often be associated with MCI, a preclinical condition characterized by the presence of deficits in memory and executive functions as well as, to a lesser extent, in language- and visuospatial- related functions.

Dual-syndrome hypothesis posit the existence of two subtypes of MCI one fronto-striatal, characterised by executive and attentional deficits, and a posterior cortical one, characterised by deficits in memory visuo-spatial and language deficits. Recent studies described alterations in brain rhythm, measured with high-density EEG (HDEEG) in terms of frequency domain analysis, at the level of fronto-striatal regions only in patients with the fronto-striatal subtype. Moreover, fMRI studies have shown that the presence of MCI in PD causes a reduction in activity at the level of the cognitive cortico-striatal loop, which includes the caudate nucleus (CN) and prefrontal cortex (PFC).

Although the use of neurophysiological and neuroimaging techniques have substantially grown, the available data highlight the lack of detailed descriptions of functional connectivity in relation whit the onset and extent of the cognitive deficit itself. Therefore, the aim of the present study is to characterise MCI in PD from a neurophysiological and clinical point of view. First, all patients undergo a neuropsychological assessment to identify PD patients with MCI (PD-MCI) and those without MCI (PD-nMCI). Then, to investigate the functional connectivity of cortical areas underpinning cognitive decline, HDEEG will be record, during both resting state and cognitive tasks. Furthermore, for each participant will be collect MRI (Magnetic resonance imaging), to combine structural data with electrodes position over the scalp. This would allow obtaining a realistic model of the head for source analysis.

Identification of alterations in functional connectivity between specific cortical areas in MCI-PD patients, and a possible direct relationship between these and clinical impairment, could lead to improve therapeutic interventions and prevent cognitive disorders in PD patients.

Study Type

Observational

Enrollment (Estimated)

42

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Parkinson's patients will be recruited in the IRCCS San Camillo Hospital or through collaborators of the responsible researchers.

Healty controls will be enrolled voluntarily.

Description

Inclusion Criteria:

  • Upper score >24 MMSE or >15.5 Moca
  • If taking medications, taking stable doses for at least 4 weeks prior to the inclusion visit - of anticholinesterase drugs (donepezil, memantine, rivastigmine, ...) or antidepressants (SSRIs, tricyclics, SNARI, ...) or Levodopa.
  • Having signed the informed consent

Exclusion Criteria:

  • Subjects with severe dementia ( MMSE < 24 )
  • Lower score <15.5 Moca
  • Subjects on antipsychotic treatment for less than 3 months
  • Subjects with uncontrolled comorbidities
  • Subjects with metal prostheses or dentures and in general conditions for which MRI examinations are prevented.
  • Subjects with an inability to walk independently.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
PD-MCI
Parkinson's disease with Mild Cognitive Impairment
Diagnostic test: Hd-EEG
Subjects undergo a clinical and neuropsychological assesment, then a Hd-EEG both during resting state and execution of tasks, and structural Magnetic Resonance Imaging
Other Names:
  • MRI
PD-nMCI
Parkinson's disease without Mild Cognitive Impairment
Diagnostic test: Hd-EEG
Subjects undergo a clinical and neuropsychological assesment, then a Hd-EEG both during resting state and execution of tasks, and structural Magnetic Resonance Imaging
Other Names:
  • MRI
Healthy control
Healthy participants matched for age and gender with the experimental groups
Diagnostic test: Hd-EEG
Subjects undergo a clinical and neuropsychological assesment, then a Hd-EEG both during resting state and execution of tasks, and structural Magnetic Resonance Imaging
Other Names:
  • MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Power Spectrum Density Analysis profile for hdEEG resting state data
Time Frame: at baseline
For all the groups, starting from the hdEEG data, brain oscillation will be studied by performing the Power Spectral Analysis (PSD). The PSD aims to investigate the spectral properties in the delta (1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), beta (13-30 Hz), and gamma (>30Hz) frequencies bands. PSD will be performed for each electrode, for each subject, and then averaged across subjects, obtaining a value of PSD for each electrode, separately for each group (PD-ctrl vs PD-MCI). Then the PSD value will be displayed over the scalp with a topological representation.
at baseline
Power Spectrum Density Analysis profile for hdEEG during cognitive task data
Time Frame: at baseline
For all the groups, starting from the hdEEG data, brain oscillation will be studied by performing the Power Spectral Analysis (PSD). The PSD aims to investigate the spectral properties in the delta (1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), beta (13-30 Hz), and gamma (>30 Hz) frequencies bands. PSD will be performed for each electrode, for each subject, and then averaged across subject obtaining value of PSD for each electrode, separately for each group (PD-ctrl vs PD-MCI). Then the PSD value will be displayed over the scalp with a topological representation.
at baseline
Functional connectivity - seed based analysis for hdEEG resting state data
Time Frame: at baseline
To study the temporal correlation of cortical signals generated in spatially distributed regions of interest (ROI), the collected hdEEG data will be analyzed using the seed-based functional connectivity analysis (FC-SBA). FC-SBA will measures the time course activation of specific resting state networks (RSNs). Specifically, the DMN (default mode network), SN (Salience Network), FPN1 and FNP2 (Fronto-parietal Network). This approach allows to obtain the functional connectivity matrices that will show the activation pattern of different RSNs and frequency bands (delta 1-4Hz; theta 4-8Hz; alpha 8-13 Hz, beta 13-30Hz; gamma >30Hz).
at baseline
Functional connectivity - seed based analysis for hdEEG during cognitive task data
Time Frame: at baseline
To study the temporal correlation of cortical signals generated in spatially distributed regions of interest (ROI), the collected hdEEG data will be analyzed using the seed-based functional connectivity analysis (FC-SBA). FC-SBA will measures the time course activation of specific resting state networks (RSNs). Specifically, the DMN (default mode network), SN (Salience Network), FPN1 and FNP2 (Fronto-parietal Network). This approach allows to obtain the functional connectivity matrices that will show the activation pattern of different RSNs and frequency bands (delta 1-4Hz; theta 4-8Hz; alpha 8-13 Hz, beta 13-30Hz; gamma >30Hz).
at baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Performances at neuropsychological evaluation
Time Frame: at baseline

Cognitive performances will be assessed before hdEEG by a neuropsychological battery encompassing the main cognitive domains. Specific neuropsychological tests will be administered according to the specific guideline for the cognitive evaluation in Parkinson's Disease, defined by the MDS Task Force.

Raw scores at each test will be converted in z-scores based on each test normative data. Z-scores will be averaged to calculate composite scores for each cognitive domain. The composite scores will be the following: general cognitive functioning, attention, executive function, short-term memory, long-term memory, visuospatial abilities, language.
at baseline
Fraility assessment
Time Frame: at baseline
FRIED PHENOTYPE (PASE) analyzes 5 dimensions: presence of fatigue, grip strength, walking speed, unintentional weight loss, and level of activity. If at least 3 of these dimensions are deficient, then the patient is classified as frail; if 2 are deficient, the patient is pre-frail; if none are deficient, the patient is robust.
at baseline
Accuracy during cognitive task
Time Frame: at baseline
Accuracy during cognitive task will be extracted from the behavioral responses of each participant as the percentage of the correct responses. The accuracy at the task will be used as an additional parameter for analysis of the primary outcomes.
at baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS San Camillo, Venezia, Italy

Investigators

  • Principal Investigator: francesca burgio, phd, San Camillo IRCCS

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 18, 2023

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

May 1, 2025

Study Registration Dates

First Submitted

February 8, 2024

First Submitted That Met QC Criteria

October 11, 2024

First Posted (Actual)

October 15, 2024

Study Record Updates

Last Update Posted (Actual)

October 15, 2024

Last Update Submitted That Met QC Criteria

October 11, 2024

Last Verified

October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023.06

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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