29 research outputs found
Troubles du comportement en sommeil paradoxal idiopathiques et associés à la maladie de Parkinson : analyse comportementale et neurophysiologique du traitement des informations visuelles
Rapid eye movement sleep behavior disorder (RBD) has been recognized formally as a parasomnia in 1986 by Carlos Schenck. RBD is characterized by loss of normal muscle atonia during rapid eye movement sleep, associated with motor activity from simple jerks to elaborate, often violent, behaviors. This motor activity occurs while dreaming, and has been described as âacting out dreamsâ. RBD are frequent in Parkinsonâs disease (PD). PD patients with RBD show more severe cognitive disorders and have a higher risk of developing dementia than patients without RBD. When isolated and with no identified pathological etiology, RBD are considered as âidiopathicâ (iRBD). This âidiopathicâ form has been questioned due to the presence of markers of neurodegeneration (cognitive disorders, structural and functional cerebral abnormalities) in iRBD patients. A quite large number of iRBD patients will eventually develop parkinsonism and/or dementia after several years. A recent study reports a delayed emergence of parkinsonism/dementia in 81 % of iRBD patients with a mean interval of 14 years from onset of RBD. These data has leaded to consider RBD as a symptom of the PD âpre-motorâ stage. This classic progression of PD staging (pre-clinic, pre-motor, motor, dementia) is not found in every PD patient. It would rather reveal a specific PD sub-type characterized by many non-motor symptoms preceding parkinsonism and with a higher risk of early dementia. Cognitive disorders would be one of these non-motor symptoms, especially affecting visual perception. The goal of this doctoral dissertation was to study the relationship between RBD, visual perception disorders and PD. The first study aimed at identifying the nature of visual perception disorders in iRBD patients, based on specific assessments of visuo-spatial functions. The results showed a deficit of the intermediate stage of visual perception in iRBD patients. PD patients had a similar deficit which was more severe when associated with RBD. The second study focused on the analysis of the possible cerebral dysfunction underlying this visual perception deficit in iRBD patients. This study was based on the recording of the Ncl (negativity associated with closure), a cognitive event-related potential indexing the ability to recognize an object even partially occulted, mainly based on the intermediate stage of object processing. The results showed no Ncl component in iRBD patients. This is in line with a cerebral dysfunction located in the lateral occipital complex (LOC), a region belonging to the ventral visual pathway. The third study examined the cognitive profile of treatment-naĂŻve PD patients, first at the time of diagnosis and then one year later. Previous published data demonstrated that the presence of RBD is associated with more severe cognitive disorders in treated PD patients. Based on the first assessments of our group of treatment-naĂŻve patients, we examined whether these differences already exist at the time of diagnosis. The objective of the second evaluation session was to determine whether PD patients with RBD had a higher risk of early severe cognitive impairments than non-RBD patients. At the first session, 17 of the 57 patients (30%) met the criteria for RBD. At that time, RBD was not found to be associated with cognitive decline. We did not find clinical differences related to PD or others sleep disorders between RBD and non-RBD PD patients. Some yet isolated results might reflect a trend towards a potential decline in RBD patients. At the second session, only RBD patients but not non-RBD patients showed a cognitive slowing. RBD patients may also have a trend toward apathy. A longer follow-up study is needed to confirm this trend. [...]Les troubles du comportement en sommeil paradoxal (TCSP) ont Ă©tĂ© individualisĂ©s comme un type de parasomnie par Carlos Schenck en 1986. Il sâagit dâune parasomnie caractĂ©risĂ©e par lâabsence dâatonie musculaire pendant le sommeil paradoxal associĂ©e Ă lâapparition de mouvements anormaux allant de simples secousses Ă des comportements Ă©laborĂ©s souvent violents. Ces comportements dĂ©pendent de lâactivitĂ© onirique et sont dĂ©crits comme une « mise en acte des rĂȘves ». Les TCSP sont frĂ©quents dans la maladie de Parkinson. Les patients parkinsoniens ayant des TCSP ont des troubles cognitifs plus importants et ont un risque de dĂ©mence plus important que les autres patients. Les TCSP peuvent Ă©galement se prĂ©senter de maniĂšre isolĂ©e, sans aucune cause pathologique apparente. Ils sont alors considĂ©rĂ©s comme « idiopathiques » (TCSPi). Ce terme « idiopathique » a nĂ©anmoins Ă©tĂ© remis en cause du fait de la prĂ©sence de nombreux signes Ă©vocateurs dâune synuclĂ©inopathie chez ces patients (affaiblissement des performances cognitives, anomalies cĂ©rĂ©brales structurales et fonctionnelles). De nombreux patients ayant des TCSP initialement considĂ©rĂ©s comme idiopathiques, vont dĂ©velopper un syndrome parkinsonien et/ou une dĂ©mence aprĂšs plusieurs annĂ©es dâĂ©volution. Une Ă©tude rĂ©cente rapporte que cela concerne 81 % des patients aprĂšs 16 ans de suivi. Ces donnĂ©es ont conduit Ă lâhypothĂšse selon laquelle les TCSP seraient un symptĂŽme rĂ©vĂ©lant les stades prĂ©coces « non-moteurs » de la MP. Les agrĂ©gats pathologiques dâalpha-synuclĂ©ine touchant les structures du tronc cĂ©rĂ©bral seraient Ă lâorigine de lâapparition de TCSP avant mĂȘme le syndrome parkinsonien. Cette chronologie dans les stades dâĂ©volution de la MP (prĂ©-clinique, prĂ©-moteur, moteur, dĂ©mence) ne semble nĂ©anmoins pas ĂȘtre retrouvĂ©e chez tous les patients parkinsoniens. Elle rĂ©vĂšlerait plutĂŽt un certain sous-type de MP, caractĂ©risĂ©e par de nombreux symptĂŽmes non-moteurs prĂ©cĂ©dant le syndrome parkinsonien et par un risque accru de dĂ©mence prĂ©coce. Parmi ces symptĂŽmes non moteurs, les troubles cognitifs seraient importants et toucheraient notamment le fonctionnement visuo-perceptif. Ce travail a eu pour objectif dâĂ©tudier le lien entre les TCSP, les troubles visuo-perceptifs et la maladie de Parkinson. Dans une premiĂšre Ă©tude, des Ă©valuations spĂ©cifiques des fonctions visuo-spatiales ont permis de mettre en Ă©vidence des troubles visuo-perceptifs chez les patients ayant des TCSPi. Les patients parkinsoniens ayant des TCSP avaient des troubles visuo-perceptifs plus marquĂ©s que ceux nâayant pas de TCSP. Les rĂ©sultats ont Ă©galement permis dâidentifier la nature des troubles visuo-perceptifs. Les processus intermĂ©diaires de traitement de lâinformation visuelle semblent spĂ©cifiquement touchĂ©s dans ces groupes de patients.La deuxiĂšme partie de notre travail a Ă©tĂ© consacrĂ©e Ă lâexploration des corrĂ©lats neurophysiologiques de cette atteinte perceptive chez les patients ayant des TCSPi. Cette Ă©tude Ă©tait basĂ©e sur lâanalyse dâun potentiel Ă©voquĂ© cognitif : la Ncl (negativity associated with closure) dĂ©crite comme un marqueur de notre capacitĂ© Ă reconnaĂźtre des objets partiellement occultĂ©s ; autrement dit, une composante gĂ©nĂ©rĂ©e par la mise en jeu des processus intermĂ©diaires de traitement de lâinformation visuelle. Lâabsence de Ncl observĂ©e chez les patients ayant des TCSPi est compatible avec lâhypothĂšse dâun dysfonctionnement des rĂ©gions du Lateral occipital complex (LOC) situĂ©es sur la voie ventrale de traitement de lâinformation visuelle. [...
Rapid eye movement sleep behavior disorder idiopathic and associated with Parkinson's disease : behavioral and neurophysiological analysis of visual information processing
Les troubles du comportement en sommeil paradoxal (TCSP) ont Ă©tĂ© individualisĂ©s comme un type de parasomnie par Carlos Schenck en 1986. Il sâagit dâune parasomnie caractĂ©risĂ©e par lâabsence dâatonie musculaire pendant le sommeil paradoxal associĂ©e Ă lâapparition de mouvements anormaux allant de simples secousses Ă des comportements Ă©laborĂ©s souvent violents. Ces comportements dĂ©pendent de lâactivitĂ© onirique et sont dĂ©crits comme une « mise en acte des rĂȘves ». Les TCSP sont frĂ©quents dans la maladie de Parkinson. Les patients parkinsoniens ayant des TCSP ont des troubles cognitifs plus importants et ont un risque de dĂ©mence plus important que les autres patients. Les TCSP peuvent Ă©galement se prĂ©senter de maniĂšre isolĂ©e, sans aucune cause pathologique apparente. Ils sont alors considĂ©rĂ©s comme « idiopathiques » (TCSPi). Ce terme « idiopathique » a nĂ©anmoins Ă©tĂ© remis en cause du fait de la prĂ©sence de nombreux signes Ă©vocateurs dâune synuclĂ©inopathie chez ces patients (affaiblissement des performances cognitives, anomalies cĂ©rĂ©brales structurales et fonctionnelles). De nombreux patients ayant des TCSP initialement considĂ©rĂ©s comme idiopathiques, vont dĂ©velopper un syndrome parkinsonien et/ou une dĂ©mence aprĂšs plusieurs annĂ©es dâĂ©volution. Une Ă©tude rĂ©cente rapporte que cela concerne 81 % des patients aprĂšs 16 ans de suivi. Ces donnĂ©es ont conduit Ă lâhypothĂšse selon laquelle les TCSP seraient un symptĂŽme rĂ©vĂ©lant les stades prĂ©coces « non-moteurs » de la MP. Les agrĂ©gats pathologiques dâalpha-synuclĂ©ine touchant les structures du tronc cĂ©rĂ©bral seraient Ă lâorigine de lâapparition de TCSP avant mĂȘme le syndrome parkinsonien. Cette chronologie dans les stades dâĂ©volution de la MP (prĂ©-clinique, prĂ©-moteur, moteur, dĂ©mence) ne semble nĂ©anmoins pas ĂȘtre retrouvĂ©e chez tous les patients parkinsoniens. Elle rĂ©vĂšlerait plutĂŽt un certain sous-type de MP, caractĂ©risĂ©e par de nombreux symptĂŽmes non-moteurs prĂ©cĂ©dant le syndrome parkinsonien et par un risque accru de dĂ©mence prĂ©coce. Parmi ces symptĂŽmes non moteurs, les troubles cognitifs seraient importants et toucheraient notamment le fonctionnement visuo-perceptif. Ce travail a eu pour objectif dâĂ©tudier le lien entre les TCSP, les troubles visuo-perceptifs et la maladie de Parkinson. Dans une premiĂšre Ă©tude, des Ă©valuations spĂ©cifiques des fonctions visuo-spatiales ont permis de mettre en Ă©vidence des troubles visuo-perceptifs chez les patients ayant des TCSPi. Les patients parkinsoniens ayant des TCSP avaient des troubles visuo-perceptifs plus marquĂ©s que ceux nâayant pas de TCSP. Les rĂ©sultats ont Ă©galement permis dâidentifier la nature des troubles visuo-perceptifs. Les processus intermĂ©diaires de traitement de lâinformation visuelle semblent spĂ©cifiquement touchĂ©s dans ces groupes de patients.La deuxiĂšme partie de notre travail a Ă©tĂ© consacrĂ©e Ă lâexploration des corrĂ©lats neurophysiologiques de cette atteinte perceptive chez les patients ayant des TCSPi. Cette Ă©tude Ă©tait basĂ©e sur lâanalyse dâun potentiel Ă©voquĂ© cognitif : la Ncl (negativity associated with closure) dĂ©crite comme un marqueur de notre capacitĂ© Ă reconnaĂźtre des objets partiellement occultĂ©s ; autrement dit, une composante gĂ©nĂ©rĂ©e par la mise en jeu des processus intermĂ©diaires de traitement de lâinformation visuelle. Lâabsence de Ncl observĂ©e chez les patients ayant des TCSPi est compatible avec lâhypothĂšse dâun dysfonctionnement des rĂ©gions du Lateral occipital complex (LOC) situĂ©es sur la voie ventrale de traitement de lâinformation visuelle. [...]Rapid eye movement sleep behavior disorder (RBD) has been recognized formally as a parasomnia in 1986 by Carlos Schenck. RBD is characterized by loss of normal muscle atonia during rapid eye movement sleep, associated with motor activity from simple jerks to elaborate, often violent, behaviors. This motor activity occurs while dreaming, and has been described as âacting out dreamsâ. RBD are frequent in Parkinsonâs disease (PD). PD patients with RBD show more severe cognitive disorders and have a higher risk of developing dementia than patients without RBD. When isolated and with no identified pathological etiology, RBD are considered as âidiopathicâ (iRBD). This âidiopathicâ form has been questioned due to the presence of markers of neurodegeneration (cognitive disorders, structural and functional cerebral abnormalities) in iRBD patients. A quite large number of iRBD patients will eventually develop parkinsonism and/or dementia after several years. A recent study reports a delayed emergence of parkinsonism/dementia in 81 % of iRBD patients with a mean interval of 14 years from onset of RBD. These data has leaded to consider RBD as a symptom of the PD âpre-motorâ stage. This classic progression of PD staging (pre-clinic, pre-motor, motor, dementia) is not found in every PD patient. It would rather reveal a specific PD sub-type characterized by many non-motor symptoms preceding parkinsonism and with a higher risk of early dementia. Cognitive disorders would be one of these non-motor symptoms, especially affecting visual perception. The goal of this doctoral dissertation was to study the relationship between RBD, visual perception disorders and PD. The first study aimed at identifying the nature of visual perception disorders in iRBD patients, based on specific assessments of visuo-spatial functions. The results showed a deficit of the intermediate stage of visual perception in iRBD patients. PD patients had a similar deficit which was more severe when associated with RBD. The second study focused on the analysis of the possible cerebral dysfunction underlying this visual perception deficit in iRBD patients. This study was based on the recording of the Ncl (negativity associated with closure), a cognitive event-related potential indexing the ability to recognize an object even partially occulted, mainly based on the intermediate stage of object processing. The results showed no Ncl component in iRBD patients. This is in line with a cerebral dysfunction located in the lateral occipital complex (LOC), a region belonging to the ventral visual pathway. The third study examined the cognitive profile of treatment-naĂŻve PD patients, first at the time of diagnosis and then one year later. Previous published data demonstrated that the presence of RBD is associated with more severe cognitive disorders in treated PD patients. Based on the first assessments of our group of treatment-naĂŻve patients, we examined whether these differences already exist at the time of diagnosis. The objective of the second evaluation session was to determine whether PD patients with RBD had a higher risk of early severe cognitive impairments than non-RBD patients. At the first session, 17 of the 57 patients (30%) met the criteria for RBD. At that time, RBD was not found to be associated with cognitive decline. We did not find clinical differences related to PD or others sleep disorders between RBD and non-RBD PD patients. Some yet isolated results might reflect a trend towards a potential decline in RBD patients. At the second session, only RBD patients but not non-RBD patients showed a cognitive slowing. RBD patients may also have a trend toward apathy. A longer follow-up study is needed to confirm this trend. [...
Hallucinations and conscious access to visual inputs in Parkinson's disease
The pathophysiology of visual hallucinations in Parkinson's disease has yet to be characterized. Although stimulus-driven ("bottom-up") processes are known to be impaired, the role of "top-down" processes remains to be determined. Distinguishing between conscious and non-conscious detections (i.e. access to consciousness) may be a valuable way of monitoring top-down processes. Conscious access to visual inputs was investigated to identify the neural substrates underlying susceptibility to hallucinations in Parkinson's disease. Seventeen healthy controls, 18 Parkinson's disease patients with minor visual hallucinations and 16 without were enrolled in the study. During functional magnetic resonance imaging, the participants performed a visual detection task. The detection threshold was significantly higher in each patient group than in healthy controls while the two groups of patients did not differ significantly. Compared with hallucination-free patients, patients with minor hallucinations displayed hyperactivation of prefrontal and right occipital cortices, and hypoactivation of the left cingulate, temporal and occipital cortices. During conscious access to visual inputs, the functional network in patients with visual hallucinations differed from that seen in patients without visual hallucinations. This suggests that the supremacy of top-down processes in visual information processing may enhance susceptibility to hallucinations in Parkinson's disease
Cognitive disorders in parkinson's disease: confirmation of a spectrum of severity
International audienceBACKGROUND: Clinical presentation and progression of cognitive disorders in Parkinson's disease (PD) is heterogeneous. Our objective was to confirm prospectively a previous exploratory cluster analysis based on retrospective data that identified five cognitive phenotypes in PD.METHODS: A model-based confirmatory cluster analysis was conducted on the results of neuropsychological tests administered in 156 PD patients from two European movement disorder centers (Lille, n = 81; Maastricht, n = 75). The number of clusters was determined on the basis of statistical criteria as well as clinical plausibility. A factorial discriminant analysis assessed the quality of the clusters' separation.RESULTS: A five-cluster model was statistically superior and clinically the most relevant. These clusters can be described as follows: 1) cognitively intact patients with high level of performance in all cognitive domains (25.64%), 2) cognitively intact patients slightly slower than those in cluster 1 (26.92%), 3) patients with deficits in executive functions (37.18%), 4) patients with severe deficits in all cognitive domains, particularly executive functions (3.20%), 5) patients with severe deficits in all cognitive domains, particularly working memory and recall in verbal episodic memory (7.05%). The groups differed in terms of age, apathy and frequency of hallucinations that were all higher in the clusters with cognitive deficits, and the duration of formal education was lower in those groups.CONCLUSIONS: We confirm our previous exploratory analysis. Cognitive disorders in PD patients are heterogeneous and can be separated in five clusters ranging from patients with performance in the normal range to patients with severe disorders in all cognitive domains
Functional connectivity disruptions correlate with cognitive phenotypes in Parkinson's disease
International audienceCognitive deficits in Parkinson's disease are thought to be related to altered functional brain connectivity. To date, cognitive-related changes in Parkinson's disease have never been explored with dense-EEG with the aim of establishing a relationship between the degree of cognitive impairment, on the one hand, and alterations in the functional connectivity of brain networks, on the other hand. This study was aimed at identifying altered brain networks associated with cognitive phenotypes in Parkinson's disease using dense-EEG data recorded during rest with eyes closed. Three groups of Parkinson's disease patients (N = 124) with different cognitive phenotypes coming from a data-driven cluster analysis, were studied: G1) cognitively intact patients (63), G2) patients with mild cognitive deficits (46) and G3) patients with severe cognitive deficits (15). Functional brain networks were identified using a dense-EEG source connectivity method. Pairwise functional connectivity was computed for 68 brain regions in different EEG frequency bands. Network statistics were assessed at both global (network topology) and local (inter-regional connections) level. Results revealed progressive disruptions in functional connectivity between the three patient groups, typically in the alpha band. Differences between G1 and G2 (p < 0.001, corrected using permutation test) were mainly frontotemporal alterations. A statistically significant correlation (Ï = 0.49, p < 0.001) was also obtained between a proposed network-based index and the patients' cognitive score. Global properties of network topology in patients were relatively intact. These findings indicate that functional connectivity decreases with the worsening of cognitive performance and loss of frontotemporal connectivity may be a promising neuromarker of cognitive impairment in Parkinson's disease
A 15-day course of donepezil modulates spectral EEG dynamics related to target auditory stimuli in young, healthy adult volunteers
To identify possible electroencephalographic (EEG) markers of donepezil's effect on cortical activity in young, healthy adult volunteers at the group level.
METHODS:
Thirty subjects were administered a daily dose of either 5mg donepezil or placebo for 15days in a double-blind, randomized, cross-over trial. The electroencephalogram during an auditory oddball paradigm was recorded from 58 scalp electrodes. Current source density (CSD) transformations were applied to EEG epochs. The event-related potential (ERP), inter-trial coherence (ITC: the phase consistency of the EEG spectrum) and event-related spectral perturbation (ERSP: the EEG power spectrum relative to the baseline) were calculated for the target (oddball) stimuli.
RESULTS:
The donepezil and placebo conditions differed in terms of the changes in delta/theta/alpha/beta ITC and ERSP in various regions of the scalp (especially the frontal electrodes) but not in terms of latency and amplitude of the P300-ERP component.
CONCLUSION:
Our results suggest that ITC and ERSP analyses can provide EEG markers of donepezil's effects in young, healthy, adult volunteers at a group level.
SIGNIFICANCE:
Novel EEG markers could be useful to assess the therapeutic potential of drug candidates in Alzheimer's disease in healthy volunteers prior to the initiation of Phase II/III clinical studies in patients
A 15-day course of donepezil modulates spectral EEG dynamics related to target auditory stimuli in young, healthy adult volunteers
Objective: To identify possible electroencephalographic (EEG) markers of donepezil's effect on cortical activity in young, healthy adult volunteers at the group level. Methods: Thirty subjects were administered a daily dose of either 5. mg donepezil or placebo for 15. days in a double-blind, randomized, cross-over trial. The electroencephalogram during an auditory oddball paradigm was recorded from 58 scalp electrodes. Current source density (CSD) transformations were applied to EEG epochs. The event-related potential (ERP), inter-trial coherence (ITC: the phase consistency of the EEG spectrum) and event-related spectral perturbation (ERSP: the EEG power spectrum relative to the baseline) were calculated for the target (oddball) stimuli. Results: The donepezil and placebo conditions differed in terms of the changes in delta/theta/alpha/beta ITC and ERSP in various regions of the scalp (especially the frontal electrodes) but not in terms of latency and amplitude of the P300-ERP component. Conclusion: Our results suggest that ITC and ERSP analyses can provide EEG markers of donepezil's effects in young, healthy, adult volunteers at a group level. Significance: Novel EEG markers could be useful to assess the therapeutic potential of drug candidates in Alzheimer's disease in healthy volunteers prior to the initiation of Phase II/III clinical studies in patients