Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions.

The medial temporal lobe (MTL) is a nidus for neurodegenerative pathologies and therefore an important region in which to study polypathology. We investigated associations between neurodegenerative pathologies and the thickness of different MTL subregions measured using high-resolution post-mortem MRI. Tau, TAR DNA-binding protein 43 (TDP-43), amyloid-ß and α-synuclein pathology were rated on a scale of 0 (absent)-3 (severe) in the hippocampus and entorhinal cortex (ERC) of 58 individuals with and without neurodegenerative diseases (median age 75.0 years, 60.3% male). Thickness measurements in ERC, Brodmann Area (BA) 35 and 36, parahippocampal cortex, subiculum, cornu ammonis (CA)1 and the stratum radiatum lacunosum moleculare (SRLM) were derived from 0.2 × 0.2 × 0.2 mm3 post-mortem MRI scans of excised MTL specimens from the contralateral hemisphere using a semi-automated approach. Spearman's rank correlations were performed between neurodegenerative pathologies and thickness, correcting for age, sex and hemisphere, including all four proteinopathies in the model. We found significant associations of (1) TDP-43 with thickness in all subregions (r = - 0.27 to r = - 0.46), and (2) tau with BA35 (r = - 0.31) and SRLM thickness (r = - 0.33). In amyloid-ß and TDP-43 negative cases, we found strong significant associations of tau with ERC (r = - 0.40), BA35 (r = - 0.55), subiculum (r = - 0.42) and CA1 thickness (r = - 0.47). This unique dataset shows widespread MTL atrophy in relation to TDP-43 pathology and atrophy in regions affected early in Braak stageing and tau pathology. Moreover, the strong association of tau with thickness in early Braak regions in the absence of amyloid-ß suggests a role of Primary Age-Related Tauopathy in neurodegeneration.

Resuming elective hip and knee arthroplasty after the first phase of the SARS-CoV-2 pandemic: the European Hip Society and European Knee Associates recommendations.

PURPOSE: The Covid-19 pandemic has disrupted health care systems all over the world. Elective surgical procedures have been postponed and/or cancelled. Consensus is, therefore, required related to the factors that need to be in place before elective surgery, including hip and knee replacement surgery, which is restarted. Entirely new pathways and protocols need to be worked out. METHODS: A panel of experts from the European Hip Society and European Knee Association have agreed to a consensus statement on how to reintroduce elective arthroplasty surgery safely. The recommendations are based on the best available evidence and have been validated in a separate survey. RESULTS: The guidelines are based on five themes: modification and/or reorganisation of hospital wards. Restrictions on orthopaedic wards and in operation suite(s). Additional disinfection of the environment. The role of ultra-clean operation theatres. Personal protective equipment enhancement. CONCLUSION: Apart from the following national and local guidance, protocols need to be put in place in the patient pathway for primary arthroplasty to allow for a safe return.

Recommendations for resuming elective hip and knee arthroplasty in the setting of the SARS-CoV-2 pandemic: the European Hip Society and European Knee Associates Survey of Members.

PURPOSE: The COVID-19 pandemic has disrupted the health care system around the entire globe. A consensus is needed about resuming total hip and knee procedures. The European Hip Society (EHS) and the European Knee Association (EKA) formed a panel of experts that have produced a consensus statement on how the safe re-introduction of elective hip and knee arthroplasty should be undertaken. METHODS: A prospective online survey was done among members of EHS and EKA. The survey consisted of 27 questions. It includes basic information on demographics and details the participant's agreement with each recommendation. The participant could choose among three options (agree, disagree, abstain). Recommendations focussed on pre-operative, peri-operative, and post-operative handling of patients and precautions. RESULTS: A total of 681 arthroplasty surgeons participated in the survey, with 479 fully completing the survey. The participants were from 44 countries and 6 continents. Apart from adhering to National and Local Guidelines, the recommendations concerned how to make elective arthroplasty safe for patients and staff. CONCLUSION: The survey has shown good-to-excellent agreement of the participants with regards to the statements made in the recommendations for the safe return to elective arthroplasty following the first wave of the COVID-19 pandemic.

Driving safety improves after individualized training: An RCT involving older drivers in an urban area.

Objective: This study aimed to reproduce the results of a previous investigation on the safety benefits of individualized training for older drivers. We modified our method to address validity and generalizability issues. Methods: Older drivers were randomly assigned to one of the 3 arms: (1) education alone, (2) education + on road training, and (3) education + on road + simulator training. Older drivers were recruited from a larger urban community. At the pre- and posttests (separated by 4 to 8 weeks) participants followed driving directions using a Global Positioning System (GPS) navigation system. Results: Our findings support the positive influence of individualized on-road training for urban-dwelling older drivers. Overall, driving safety improved among drivers who received on-road training over those who were only exposed to an education session, F(1, 40) = 11.66, P = .001 (26% reduction in total unsafe driving actions [UDAs]). Statistically significant improvements were observed on observation UDAs (e.g., scanning at intersections, etc.), compliance UDAs (e.g., incomplete stop), and procedural UDAs (e.g., position in lane). Conclusion: This study adds to the growing evidence base in support of individualized older driver training to optimize older drivers' safety and promote continued safe driving.

Quantification of brain cholinergic denervation in Alzheimer's disease using PET imaging with [18F]-FEOBV.

18F-fluoroethoxybenzovesamicol (FEOBV) is a new PET radiotracer that binds to the vesicular acetylcholine transporter. In both animals and healthy humans, FEOBV was found sensitive and reliable to characterize presynaptic cholinergic nerve terminals in the brain. It has been used here for we believe the first time in patients with Alzheimer's disease (AD) to quantify brain cholinergic losses. The sample included 12 participants evenly divided in healthy subjects and patients with AD, all assessed with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) cognitive scales. Every participant underwent three consecutive PET imaging sessions with (1) the FEOBV as a tracer of the cholinergic terminals, (2) the 18F-NAV4694 (NAV) as an amyloid-beta tracer, and (3) the 18F-Fluorodeoxyglucose (FDG) as a brain metabolism agent. Standardized uptake value ratios (SUVRs) were computed for each tracer, and compared between the two groups using voxel wise t-tests. Correlations were also computed between each tracer and the cognitive scales, as well as between FEOBV and the two other radiotracers. Results showed major reductions of FEOBV uptake in multiple cortical areas that were evident in each AD subject, and in the AD group as a whole when compared to the control group. FDG and NAV were also able to distinguish the two groups, but with lower sensitivity than FEOBV. FEOBV uptake values were positively correlated with FDG in numerous cortical areas, and negatively correlated with NAV in some restricted areas. The MMSE and MoCA cognitive scales were found to correlate significantly with FEOBV and with FDG, but not with NAV. We concluded that PET imaging with FEOBV is more sensitive than either FDG or NAV to distinguish AD patients from control subjects, and may be useful to quantify disease severity. FEOBV can be used to assess cholinergic degeneration in human, and may represent an excellent biomarker for AD.

Bilateral distal fibula fractures in a woman on long-term bisphosphonate therapy.

We report the case of a 53-year-old female, treated by bisphosphonate for 12 years, who presented atraumatic fractures of both fibulas. Her X-rays showed bilateral distal fibula fractures with radiological features similar to atypical femur fractures. The distal fibula should be considered as a potential site for stress fractures in bisphosphonate users. Bisphosphonates are the most widely used drugs in the treatment of osteoporosis. During the last decade, the occurrence of atypical fractures, mostly subtrochanteric and diaphyseal femoral fractures, has been acknowledged in patients with long-term use of bisphosphonates. We report the case of a 53-year-old female on alendronate therapy for the past 12 years who presented with a few months history of atraumatic right, and subsequently left, lateral ankle pain. Her X-rays showed bilateral distal fibula fractures with radiological features similar to atypical femur fractures. She had been treated conservatively with walking boots and her treatment with bisphosphonate had been stopped 5 months prior to the fractures. Callus was progressively seen on serial follow-up X-rays, and both fractures healed completely within a reasonable period of 1 year. Investigations did not reveal any secondary causes of osteoporosis or metabolic bone disorders. To our knowledge, this is the first reported case of bilateral distal fibula fractures in a patient on long-term bisphosphonate therapy.

An international study of the quality of national-level guidelines on driving with medical illness.

BACKGROUND: Medical illnesses are associated with a modest increase in crash risk, although many individuals with acute or chronic conditions may remain safe to drive, or pose only temporary risks. Despite the extensive use of national guidelines about driving with medical illness, the quality of these guidelines has not been formally appraised. AIM: To systematically evaluate the quality of selected national guidelines about driving with medical illness. DESIGN: A literature search of bibliographic databases and Internet resources was conducted to identify the guidelines, each of which was formally appraised. METHODS: Eighteen physicians or researchers from Canada, Australia, Ireland, USA and UK appraised nine national guidelines, applying the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. RESULTS: Relative strengths were found in AGREE II scores for the domains of scope and purpose, stakeholder involvement and clarity of presentation. However, all guidelines were given low ratings on rigour of development, applicability and documentation of editorial independence. Overall quality ratings ranged from 2.25 to 5.00 out of 7.00, with modifications recommended for 7 of the guidelines. Intra-class coefficients demonstrated fair to excellent appraiser agreement (0.57-0.79). CONCLUSIONS: This study represents the first systematic evaluation of national-level guidelines for determining medical fitness to drive. There is substantive variability in the quality of these guidelines, and rigour of development was a relative weakness. There is a need for rigorous, empirically derived guidance for physicians and licensing authorities when assessing driving in the medically ill.

The influences of psychotic symptoms on the activities of daily living of individuals with Alzheimer disease: a longitudinal analysis.

OBJECTIVES: Psychotic symptoms associated with Alzheimer Disease (AD) contribute to excess functional dependence. Longitudinal studies have generally examined the association between rates of functional decline and the occurrence of psychotic symptoms from either a single evaluation or from multiple evaluations rather than through changes in frequency and severity of symptoms. Although the presence or absence of psychotic symptoms at initial or follow-up examinations may be associated with changes in functional status, the nature of the relationship between changes in these domains cannot be inferred. We examine the association between changes in the frequency of psychotic symptoms and changes in dependence in activities of daily living (ADL) over a period ranging from 1 to 74 months (median = 17.7). METHOD: Data from a cohort of 234 individuals referred to a memory clinic were analyzed using multilevel linear regression. Information on ADL, behavioral and psychological symptoms, depression, and cognition was collected. RESULTS: An increase in the frequency of psychotic symptoms had a unique influence on the deterioration of basic ADL, after controlling for demographic variables, changes in cognition, depression, and other behavioral and psychological symptoms (B = -.017, p = .003). However, changes in psychotic symptoms did not significantly contribute to declines in the ability to perform instrumental ADL (B = -.008, p = .439). CONCLUSION: Changes in psychotic symptoms may influence basic but not instrumental ADL over time. These findings may have ramifications for studies and treatment plans for individuals with AD who demonstrate psychotic symptoms.

Tiotropium improves walking endurance in COPD.

The primary objective of this study was to evaluate the effects of a 3-week treatment with tiotropium on walking capacity in chronic obstructive pulmonary disease (COPD). After familiarisation with study procedures, 36 patients were randomised to receive tiotropium 18 µg once daily or a matching placebo in a double-blind, parallel-group study. Pre- (trough) and 2-h post-dose pulmonary function was measured. An endurance shuttle walk was then completed. The same procedures were repeated after 3 weeks of treatment. Ventilatory parameters were monitored during exercise. At 3 weeks, tiotropium significantly improved walking endurance time in comparison with placebo, with a mean±sd between-group difference of 128±141 s (p=0.017). At 3 weeks, trough values for forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC) were significantly improved with tiotropium in comparison with placebo. The post-dose response to tiotropium was statistically superior to placebo after the first dose and after 3 weeks of treatment for FEV(1), FVC and inspiratory capacity. Ventilation and tidal volume at the end of walking were significantly improved with tiotropium. 3 weeks of tiotropium resulted in a greater walking endurance in patients with COPD. Improvements in FEV(1), maximal ventilation and tidal volume may contribute to this enhanced exercise capacity.

Photoactivated release of cargo from the cavity of polyelectrolyte capsules to the cytosol of cells.

Polyelectrolyte capsules with metal nanoparticles in their walls and fluorescently labeled polymers as cargo inside their cavity were prepared. Capsules were ingested by living cells with no uncontrolled release of the cargo upon the incorporation process. Photoinduced heating of the metal nanoparticles in the capsule walls lead to rupture of the capsule walls, and the polymeric cargo was released to the whole cytosol. Viability tests demonstrate that opening of capsules at moderate light intensities does not impair the cellular metabolism, whereas capsule opening at high light intensities ultimately leads to cell death.

Sensorimotor adaptation in Parkinson's disease: evidence for a dopamine dependent remapping disturbance.

Sensorimotor adaptation is thought to involve a remapping of the kinematic and kinetic parameters associated with movements performed within a changing environment. Patients with Parkinson's disease (PD) are known to be affected on this type of learning process, although the specific role of dopamine depletion in these deficits has not yet been elucidated. The present study was an attempt to clarify whether dopamine depletion in PD may directly affect the capacity to internally reorganize the visuomotor remapping of a distorted environment. Fourteen PD patients were tested twice, while they were treated and while they were withdrawn from their regular levodopa treatment. Fourteen control subjects were also enrolled and tested twice. Two parallel forms of the Computed Mirror Pointing Task (CMPT), requiring making a reaching movement in a visually transformed environment (mirror inversion), were administered to each participant. Each of them had to perform 40 trials at each of the 2 testing sessions. At each trial, sensorimotor adaptation was evaluated by the initial direction angle (IDA), which reflects the direction of movement before any visually guided readjustment. Results revealed no IDA difference at baseline, between control subject and PD patients, whether they were treated or not. In all group, IDA values at that time were large, reflecting a tendency to make movements according to the real life visuomotor mapping (based on the natural direct vision). However, striking differences appeared during sensorimotor learning, in that IDA reduction along trials was poorer in patient not treated with levodopa than both control subjects and the same PD patient treated with levodopa. No difference was observed between the treated PD patients and control subjects. Given that IDA is thought to reflect the internal representation of the visuomotor mapping, it is concluded that dopamine depletion in PD would affects sensorimotor adaptation, in that it facilitates old and poorly adapted movements (real life mapping), instead of new and more adapted ones (mirror transformed mapping).

Raclopride-induced motor consolidation impairment in primates: role of the dopamine type-2 receptor in movement chunking into integrated sequences.

Results obtained in patients with schizophrenia have shown that antipsychotic drugs may induce motor learning deficits correlated with the striatal type-2 dopamine receptors (D(2)R) occupancy. Other findings suggest that the role of the striatum in motor learning could be related to a process of "chunking" discrete movements into motor sequences. We therefore hypothesized that a D(2)R blocking substance, such as raclopride, would affect motor learning by specifically disrupting the grouping of movements into sequences. Two monkeys were first trained to perform a baseline-overlearned sequence (Seq. A) drug free. Then, a new sequence was learned (Seq. B) and the overlearned sequence was recalled OFF-drug (Seq. A recall OFF-drug). The effect of raclopride was then assessed on the learning of a third sequence (Seq. C), and on the recall of the overlearned sequence (Seq. A recall ON-drug). Results showed that performance related to the overlearned sequence remained the same in the three experimental conditions (Seq. A, Seq. A recall OFF-drug, Seq. A recall ON-drug), whether the primates received raclopride or not. On the other hand, new sequence learning was significantly affected during raclopride treatment (Seq. C), when compared with new sequence learning without the effect of any drug (Seq. B). Raclopride-induced disturbances consisted in performance fluctuations, which persisted even after many days of trials, and prevented the monkeys from reaching a stable level of performance. Further analyses also showed that these fluctuations appeared to be related to monkeys' inability to group movements into single flowing motor sequences. The results of our study suggest that dopamine is involved in the stabilization or consolidation of motor performances, and that this function would involve a chunking of movements into well-integrated sequences.

Congenital hepatic arteriovenous malformation: an unusual cause of neonatal persistent pulmonary hypertension.

Congenital hepatic arteriovenous malformations are rare anomalies, which typically present in infancy with congestive heart failure, anemia, and hepatomegaly. Morbidity and mortality is high if the condition is not recognized and treated promptly. Hepatic arteriovenous malformation associated with persistent pulmonary hypertension of the newborn has been reported in two cases in the literature. We report a neonate who was referred for management of persistent pulmonary hypertension and was subsequently diagnosed with a large hepatic arteriovenous malformation. He underwent coil embolization following which pulmonary hypertension resolved.

Does condition of Atlantic cod (Gadus morhua) have a greater impact upon swimming performance at Ucrit or sprint speeds?

To compare the sensitivity of sprint and critical (Ucrit) swimming speeds to the condition of Atlantic cod (Gadus morhua) and to identify the best anatomic, behavioural and biochemical correlates of these types of swimming, we established two groups of cod that were fed or starved for 12 weeks. We evaluated sprint swimming and Ucrit performance as well as the speed at which repeated burst-coast movements began in the Ucrit test before measuring the metabolic capacities of red and white muscle sampled caudally, centrally and rostrally and the anatomic characteristics of the cod. White muscle lactate was measured directly after the Ucrit test. As expected, the twofold difference in Fulton's condition factor (0.5+/-0.04 for starved and 1.0+/-0.1 for fed cod) was accompanied by large differences in the anatomic and biochemical parameters measured. Despite the relative sparing of muscle aerobic capacity during starvation and despite the greater use of oxidative fibres during Ucrit compared with sprint swimming, these types of swimming differed by much the same extent between starved and fed cod. In the Ucrit tests, white muscle lactate levels and lactate accumulation per burst-coast movement were considerably higher in fed than starved cod, suggesting more intensive use of fast muscle fibres in cod in good condition. Multiple regression analysis indicated strong correlations between Ucrit, the speed at which regular burst-coasting began and the activity of pyruvate dehydrogenase (PDH) in red muscle (both caudal and central positions). PDH activity may limit the rate of oxidative ATP production by red muscle. The activity of cytochrome c oxidase in rostral white muscle was the strongest correlate of sprint swimming, suggesting that aerobic preparation of white muscle facilitates rapid contraction. The correlation between Ucrit and sprint swimming was weak, perhaps due to inter-individual differences in sensitivity during sprint tests.

Comparison between olanzapine and haloperidol on procedural learning and the relationship with striatal D2 receptor occupancy in schizophrenia.

The striatum is known to play a primary role in procedural learning. In this study, the authors simultaneously assessed the effects of two antipsychotic drugs on procedural learning and on striatal dopamine (D2) receptor occupancy. Twenty-seven patients receiving either olanzapine or haloperidol as antipsychotic medication were assessed with the Computed Visual Tracking Task (CVTT) and Single Photon Emission Computed Tomography (SPECT) following the administration of Iodine 123-IBZM (123I-IBZM), a radioligand with a high affinity and specificity for the D2 receptors. The results showed poorer procedural learning in the haloperidol-treated patients than in normal control subjects, while no difference could be found between olanzapine-treated patients and normal control subjects. In the haloperidol but not the olanzapine group, significant correlations were found between procedural learning deficits and striatal D2 receptor occupancy. However, there was no significant difference in D2 receptor occupancy between olanzapine- and haloperidol-treated patients, and this may be related to the high doses of olanzapine and low doses of haloperidol administered. The authors concluded that: 1) striatal D2 receptor blockade may alter procedural learning in humans; and 2) olanzapine may have a protective effect on procedural learning, even at doses that produce striatal D2 receptor occupancy as high as that found with haloperidol. This protective effect of olanzapine may be related to its atypical pharmacological properties.

Association between waking EEG slowing and REM sleep behavior disorder in PD without dementia.

OBJECTIVE: To compare nondemented patients with Parkinson's disease (PD) with and without REM sleep behavior disorder (RBD) to healthy controls on quantitative EEG characteristics for both wakefulness and REM sleep. METHODS: Fifteen patients with PD (7 patients with polysomnographic-confirmed RBD [PD-RBD] and 8 patients without RBD [PD-NRBD]) and 15 healthy control subjects were studied. Each subject underwent a quantitative EEG analysis of both wakefulness and REM sleep. RESULTS: During wakefulness, patients with PD-RBD showed a higher theta power in frontal, parietal, temporal, and occipital regions in comparison to patients with PD-NRBD and control subjects. Moreover, a slowing of the dominant occipital frequency was observed only in patients with PD-RBD (p < 0.02). Patients with PD-NRBD did not present any slowing of the EEG. No between-group difference in quantitative REM sleep EEG was observed. CONCLUSIONS: This study demonstrates that the EEG slowing reported during wakefulness in nondemented patients with PD is strongly related to the presence of RBD.

Caregiving and its impact on families of the terminally ill.

Changes in the health care system have meant that increasing numbers of the terminally ill receive the majority of their care at home. The purpose of this paper was to document patterns of informal and formal care provided to the terminally ill and assess the impact caregiving has on family members. One hundred and fifty-one family caregivers were recruited for interviews from two community-nursing agencies in an urban region of the province of Ontario, Canada. The majority of respondents 119 (79%) were the female spouses of the patient. The numbers of caregivers providing assistance in specific functional activities were: bathing, 133 (88%); mobility, 123 (81%); dressing and undressing, 114 (76%); toileting, 101(67%), and assistance at night 97 (64%). Sixty-two (41%) respondents reported that they had been providing some form of caregiving for over one year. They also reported that physical demands in caregiving increased substantially during the last three months of the care recipient's life. As family caregivers provided more assistance in activities of daily living they were at greater risk of reporting high caregiver burden. The results of this paper identify the types of care provided by family caregivers of the terminally ill and the impact these demands have on the family caregiver.

REM sleep behavior disorder and REM sleep without atonia in Parkinson's disease.

OBJECTIVE: To determine the frequency of REM sleep behavior disorder (RBD) among patients with PD using both history and polysomnography (PSG) recordings and to further study REM sleep muscle atonia in PD. BACKGROUND: The reported occurrence of RBD in PD varies from 15 to 47%. However, no study has estimated the frequency of RBD using PSG recordings or analyzed in detail the characteristics of REM sleep muscle atonia in a large group of unselected patients with PD. METHODS: Consecutive patients with PD (n = 33) and healthy control subjects (n = 16) were studied. Each subject underwent a structured clinical interview and PSG recording. REM sleep was scored using a method that allows the scoring of REM sleep without atonia. RESULTS: One third of patients with PD met the diagnostic criteria of RBD based on PSG recordings. Only one half of these cases would have been detected by history. Nineteen (58%) of 33 patients with PD but only 1 of 16 control subjects had REM sleep without atonia. Of these 19 patients with PD, 8 (42%) did not present with behavioral manifestations of RBD, and their cases may represent preclinical forms of RBD associated with PD. Moreover, the percentage of time spent with muscle atonia during REM sleep was lower among patients with PD than among healthy control subjects (60.1% vs 93.2%; p = 0.003). CONCLUSIONS: RBD and REM sleep without atonia are frequent in PD as shown by PSG recordings.

Behavioral disorganization in schizophrenia during a daily activity: the kitchen behavioral scoring scale.

Executive dysfunction has been extensively described in schizophrenia and has been found to correlate with the negative symptoms of the disease. However, executive dysfunction is usually assessed by cognitive tests, and these are not necessarily good predictors of an individual's daily functioning. This study aimed to discover whether executive dysfunction in schizophrenia can be measured by analyzing a daily routine such as cooking a meal. Behavior was scored on the basis of the optimal sequence of macrostructures (order of dishes) and microsteps (order of actions) that must be performed to prepare the meal in a minimum of time and with the smallest delay between the completion of the first and last dishes. The results showed that patients with schizophrenia make macrostructure but not micro-step sequencing errors. The number of repetitions and omissions and the delay between the completion of the first and last dish were all greater in patients than in control subjects. In patients with schizophrenia, but not in normal controls, these behavioral malfunctions were significantly correlated with both negative symptoms and performance on the executive tasks. Poor performance on the memory tests was not correlated with the behavioral malfunction. Therefore, daily functioning in schizophrenia may be specifically influenced by executive dysfunction in schizophrenia, and this can be quantitatively assessed with a behavioral scale of action sequences.

[Rapid-eye-movement sleep disorders in Parkinson's disease]. / Les troubles du sommeil paradoxal dans la maladie de Parkinson.

During the past 10 years, there has been an increasing interest in the study of rapid-eye-movement (REM) sleep in neurodegenerative diseases and more particulary in Parkinson's disease (PD). This interest is justified by the strong association observed between these diseases and REM sleep behavior disorder (RBD). In the first section of this paper, a critical review of the literature on the presence of REM sleep disorders in PD is presented. Studies that show an association between PD and RBD are reviewed. Studies that report the presence of other REM sleep disorders in PD (short latency, abnormal length and/or proportion of REM sleep, increasing occurrence of hallucinations) are then discussed. Limitations of the criteria proposed by Rechtschaffen et Kales (1968) for the quantification of REM sleep are also presented. Some authors believe that dopaminergic (DA) agents used in the treatment of PD (levodopa, bromocriptine, pergolide, pramipexole and selegiline) could be a responsable factor for the occurence of REM sleep disorders observed in this disease. The literature concerning the impact of these DA agents on human REM sleep is therefore critically reviewed. It is concluded that DA agents cannot explain on their own the presence of REM sleep disorders in PD. Other causes, among which the disturbance of some neurochemical systems linked to the neuropathological process of the disease, must be considered in order to explain these REM sleep disorders. In the second section of this paper, we present the different pathophysiological hypotheses proposed to explain REM sleep disorders in PD, such as a dysfunction of the cholinergic, noradrenergic, serotonergic, dopaminergic or GABAergic neurons. Emphasis is placed on the role of cholinergic neurons of the pedunculopontine and laterodorsal tegmental nuclei, structures shown to be particularly impaired in PD. Neurophysiological, neuroanatomical and neuropharmacological studies demonstrate that these neurons are strongly implicated in the different REM sleep parameters (muscular atonia, electroencephalographic desynchronisation, ponto-geniculo-occipital spikes). Finally, future research directions are proposed.