Marie Delliaux

Characteristics of apathy in Parkinson's disease

The objective of this study was to use the Lille Apathy Rating Scale to assess apathy in a large population of Parkinsons disease (PD) patients and identify several different apathy profiles. One hundred fifty‐nine patients with probable PD and 58 healthy controls participated in the study. Apathy was assessed using the Lille Apathy Rating Scale. Motor, cognitive, and depressive symptoms were rated on standardized scales. Data were analyzed using linear regression and multivariate analyses of variance. Thirty‐two percent of the PD patients were classified as apathetic. Apathy was more frequent in patients with dementia. The four apathy dimensions contributed differently to the overall severity of the apathetic condition. Action initiation and intellectual curiosity had a marked influence. Linear regression analysis revealed that the apathy level was mainly determined by cognitive impairment, not associated with the severity of motor symptoms, and only associated with the apathy subcomponent of the Montgomery and Asberg Depression Rating Scale. Apathy is highly prevalent in PD patients. Apathy profiles vary according to the clinical presentation of PD. The high prevalence of apathy in PD suggests the involvement of frontal–subcortical circuits. Although the neurochemical substrate of apathy remains poorly characterized, the strong link between apathy and cognitive impairment observed in several studies suggests the participation of nondopaminergic circuits.

Rivastigmine in apathetic but dementia and depression-free patients with Parkinson's disease: a double-blind, placebo-controlled, randomised clinical trial

Background Even with optimal dopaminergic treatments, many patients with Parkinsons disease (PD) are frequently incapacitated by apathy prior to the development of dementia. We sought to establish whether rivastigmines ability to inhibit acetyl- and butyrylcholinesterases could relieve the symptoms of apathy in dementia-free, non-depressed patients with advanced PD. Methods We performed a multicentre, parallel, double-blind, placebo-controlled, randomised clinical trial (Protocol ID: 2008-002578-36; clinicaltrials.gov reference: NCT00767091) in patients with PD with moderate to severe apathy (despite optimised dopaminergic treatment) and without dementia. Patients from five French university hospitals were randomly assigned 1:1 to rivastigmine (transdermal patch of 9.5 mg/day) or placebo for 6 months. The primary efficacy criterion was the change over time in the Lille Apathy Rating Scale (LARS) score. Finding 101 consecutive patients were screened, 31 were eligible and 16 and 14 participants were randomised into the rivastigmine and placebo groups, respectively. Compared with placebo, rivastigmine improved the LARS score (from −11.5 (−15/−7) at baseline to −20 (−25/−12) after treatment; F(1, 25)=5.2; p=0.031; adjusted size effect: −0.9). Rivastigmine also improved the caregiver burden and instrumental activities of daily living but failed to improve quality of life. No severe adverse events occurred in the rivastigmine group. Interpretation Rivastigmine may represent a new therapeutic option for moderate to severe apathy in advanced PD patients with optimised dopaminergic treatment and without depression dementia. These findings require confirmation in a larger clinical trial. Our results also confirmed that the presence of apathy can herald a pre-dementia state in PD. Registration Clinicaltrials.gov reference: NCT00767091.

The Lille Apathy Rating Scale: Validation of a caregiver-based version

Apathy is reported in 16.5% to 70% of Parkinsons disease (PD) patients. Our recently developed Lille Apathy Rating Scale (LARS) has been specifically validated for patient‐based assessment of apathy in PD. The aim of the present study was to validate a caregiver‐based version of the LARS. Sixty consecutive PD patients and their respective caregivers participated in the study. An informant‐based version of the LARS (LARS‐i) was developed to rate apathy via a caregiver‐based structured interview. Apathy was also assessed in a patient‐based interview using the LARS and the informant‐ and clinician‐rated versions of the Apathy Evaluation Scale (AES). Cronbachs alpha and standardized alpha coefficients were 0.872 and 0.877, respectively, and the split‐half reliability was 0.901 (revealing good internal consistency). The test‐retest and inter‐rater reliability values were 0.960 and 0.996, respectively. Criterion‐related validity (according to an independent, expert diagnosis) was good. Scores on the LARS and the LARS‐i were highly correlated. However, apathy was rated significantly more severely by the caregiver than by the patient. This difference was significantly higher for demented than nondemented PD patients. The LARS‐i was seen to have excellent psychometric properties and appears to be valid for use in PD with respect to the patient‐based LARS and the informant‐ and clinician‐rated versions of the AES.

Apathy in untreated early‐stage Parkinson disease: Relationship with other non‐motor symptoms

Apathy is a frequent and disabling behavioral disorder in patients with Parkinsons disease (PD). Its prevalence in treatment‐naive patients with early‐stage PD has not been extensively investigated. Moreover, whether apathy is related to other non‐motor symptoms in early‐stage PD is unknown. Our objective was to determine the prevalence and features of apathy and associated factors in a group of treatment‐naive patients with early‐stage PD. Ninety‐five treatment‐naive patients with early‐stage PD participated in the study. Apathy, depression, motor symptoms, and overall cognitive efficiency were assessed. The presence of the main non‐motor symptoms was checked during a detailed clinical interview. Group comparisons were carried out to investigate the association with apathy. Eighteen patients (18.95%) were diagnosed as apathetic, and five of the latter had concomitant depression. Apathetic patients had significantly more severe motor symptoms (P < 0.001) and a lower cognitive status (P = 0.032) than non‐apathetic patients. When considering non‐motor symptoms, apathy was significantly associated only with fatigue (P = 0.007) and anhedonia (P = 0.010), both of which were more prevalent in apathetic patients than in non‐apathetic patients. In treatment‐naive patients with early‐stage PD, apathy was significantly associated with more severe motor symptoms and a lower cognitive status. After adjustment for these factors, apathy appeared to be a relatively isolated, independent symptom because the only other associated non‐motor symptoms were fatigue and anhedonia.

Rapid eye movement sleep behavior disorder in treatment-naïve Parkinson disease patients

OBJECTIVE Rapid eye movement (REM) sleep behavior disorder (RBD) is a risk factor for dementia in Parkinson disease (PD) patients. The objectives of our study were to prospectively evaluate the frequency of RBD in a sample of treatment-naïve, newly diagnosed PD patients and compare sleep characteristics and cognition in RBD and non-RBD groups. METHODS Fifty-seven newly diagnosed PD patients were consecutively recruited in a university medical center. All patients underwent two overnight polysomnography (PSG) sessions and were diagnosed with RBD according to the International Classification of Sleep Disorders, Second Revision criteria. Daytime sleepiness was measured in a multiple sleep latency test (MSLT). Cognition was assessed in a standard neuropsychologic examination. RESULTS Seventeen PD patients (30%) met the criteria for RBD. The RBD patients and non-RBD patients did not significantly differ in mean age, gender ratio, disease duration, motor symptom subtype and severity, total sleep time, percentage of REM sleep, apnea-hypopnea index, mean oxygen saturation, and importantly cognitive performance. However, non-RBD patients had a significantly shorter mean daytime sleep latency than RBD patients (15 vs. 18 min, respectively; P=.014). CONCLUSION A high frequency of RBD was found in our sample of 57 newly diagnosed PD patients. At this stage in the disease, RBD was not found to be associated with other sleep disorders or cognitive decline. Follow-up is needed to assess the risk for developing dementia in early-stage PD patients with RBD.

External globus pallidus stimulation modulates brain connectivity in Huntington's disease.

Positron emission tomography with O-15-labeled water was used to study at rest the neurophysiological effects of bilateral external globus pallidus (GPe) deep brain stimulation in patients with Huntingtons disease (HD). Five patients were compared with a control group in the on and off states of the stimulator. External globus pallidus stimulation decreased neuronal activity and modulated cerebral connectivity within the basal ganglia-thalamocortical circuitry, the sensorimotor, and the default-mode networks. These data indicate that GPe stimulation modulates functional integration in HD patients in accordance with the basal ganglia-thalamocortical circuit model.

REM sleep behaviour disorder and visuoperceptive dysfunction: a disorder of the ventral visual stream?

In idiopathic rapid eye movement sleep behaviour disorder (RBD), an association with visuoperceptive disorders has been described. However, such an association has not been clearly established in RBD secondary to Parkinson’s disease (PD). We compared visuoperceptive function in four groups of non-demented patients (parkinsonian patients with or without RBD, patients with idiopathic RBD and control participants) via a procedure enabling the analysis of the various components of visual information processing and in order to answer the following question: is RBD associated with visuoperceptive and/or attentional disorders in PD and, if so, where is the dysfunction located along the visual pathway? Sensorial aspects of visual information were evaluated using a contrast sensitivity test, perceptual aspects were assessed using a contour-based object identification test and visual attention was measured in an attentional capture paradigm. The diagnosis of RBD was confirmed by polysomnography. We observed a higher object identification threshold (OIT) (1) in PD patients with RBD compared with PD patients without RBD and with controls and (2) in idiopathic RBD patients compared with controls. There were no significant OIT differences between PD patients with RBD and idiopathic RBD patients or between PD patients without RBD and controls. We did not find any significant inter-group differences in any of the other visuoperceptive tests. RBD, idiopathic or secondary to PD, is associated with perceptual closure dysfunction. Our results suggest that this perceptual dysfunction is specifically associated with RBD and may be related to a non-dopaminergic impairment.

Role of attentional resources on gait performance in Huntington's disease.

Patients with Huntingtons disease (HD) suffer from cognitive deficits with impaired executive functions, including limited attentional resources. We sought to use a dual‐task paradigm to evaluate attentional demands and the ability of patients with HD to concentrate on two tasks simultaneously. We analyzed the interference effects of cognitive and motor tasks on walking in HD and the contribution of clinical symptoms to gait disturbances. Patients and controls were asked to perform either a motor task (carrying a tray with four glasses), a cognitive task (counting backwards), or no task at all while walking at their preferred speed. Kinematic spatial parameters, temporal parameters, and angular parameters related to gait were recorded in 15 patients and 15 controls by means of a videomotion analysis system. Gait instability was assessed using the stride‐to‐stride variability of the various gait parameters. For patients with HD, performing a concurrent cognitive task resulted in a lower gait speed (compared with free walking), with decreased cadence and stride length. However, this effect was not observed in controls. Performing a motor task did not change any kinematic gait parameters in either HD or control subjects. We found correlations between gait speed in the dual cognitive/walking task on one hand and the motor UHDRS score, cognitive status and executive function on the other. Patients with HD had greater difficulty walking while performing a concurrent cognitive task; the drain on attentional resources deteriorated walking performance.

Effect of external cueing on gait in Huntington's disease

In Huntingtons disease (HD) patients, gait is characterized by a timing disorder with marked intraindividual variability in temporal gait parameters (caused by the presence of both hyperkinetic and hypokinetic features). We sought to determine the influence of use of a metronome on gait parameters in patients simultaneously performing motor or cognitive tasks that required attentional resources. The objective is to evaluate the influence of rhythmic cues on gait interference during self‐regulated walking and a dual task paradigm in HD. Fifteen HD patients and 15 paired controls were asked to walk and simultaneously perform another motor task (carrying a tray with four full glasses) or a cognitive task (counting backwards). We evaluated the effect of a metronome (set at 100% and 120% of the subjects self‐determined cadence) in three different task conditions (gait alone, gait + motor task, gait + cognitive task). The use of auditory cues during free gait and dual tasks did not improve kinematic parameters in HD patients, in contrast to the situation for control subjects (improvement in gait speed and cadence but not stride length when the metronome was set at 120% in all conditions). HD patients have difficulty in synchronizing their footsteps with a metronome, mainly due to attentional deficits.

Cognitive complaints in Parkinson’s disease: its relationship with objective cognitive decline

Cognitive complaint interviews (CCI) have been shown to be useful in the early detection of dementia in elderly people. Surprisingly, CCIs are rarely used in Parkinson’s disease (PD), despite a six-fold higher risk of dementia than in healthy subjects. The present study sought to determine whether a structured CCI could detect cognitive decline in PD. A validated CCI was added to the usual clinical interview for 180 PD patients. Objective cognitive status was assessed by the Mattis dementia rating scale score. The CCIs ability to detect cognitive decline in PD patients was determined using a receiver operating characteristic (ROC) curve. 58 (32.22%) patients had a significant, subjective cognitive complaint (CCI score >3). Of these, 48.27% had objective cognitive decline. Objective cognitive decline was significantly more frequent in the patients with subjective cognitive complaint. However, the ROC curve for discriminating between patients with and without objective cognitive deficits as a function of their subjective cognitive complaint had low sensitivity (0.50, 95% CI: 0.36–0.64) and moderate specificity (0.74, 95% CI: 0.69–0.84). Logistic regression incorporating the main demographical and clinical variables showed that the CCI score’s discriminant power was improved by adding age and the number of years in education to the predictive model. Objective cognitive decline and dementia are more frequent among PD patients reporting a cognitive complaint than among patients not reporting a complaint. However, the CCI does not enable more accurate screening for PD-associated dementia.