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

Обзор

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.

Подробное описание

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.

Вмешательства

• Диагностический тест 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

Первичные конечные точки

• Power Spectrum Density Analysis profile for hdEEG resting state data [Срок оценки: at baseline]
• Power Spectrum Density Analysis profile for hdEEG during cognitive task data [Срок оценки: at baseline]
• Functional connectivity - seed based analysis for hdEEG resting state data [Срок оценки: at baseline]
• Functional connectivity - seed based analysis for hdEEG during cognitive task data [Срок оценки: at baseline]

Вторичные конечные точки (3)

• Performances at neuropsychological evaluation [Срок оценки: at baseline]
• Fraility assessment [Срок оценки: at baseline]
• Accuracy during cognitive task [Срок оценки: at baseline]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Италия · 1 центр

• IRCCS San Camillo S.R.L — Lido

Публикации

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Идентификаторы

NCT: NCT06640673 · 2023.06

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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