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Apathy is commonly defined as a loss of motivation leading to a reduction in goal-directed behaviors. This multidimensional syndrome, which includes cognitive, emotional and behavioral components, is one of the most prevalent neuropsychiatric features of Parkinson’s disease (PD). It has been established that the prevalence of apathy increases as PD progresses. However, the pathophysiology and anatomic substrate of this syndrome remain unclear. Apathy seems to be underpinned by impaired anatomical structures that link the prefrontal cortex with the limbic system. It can be encountered in the prodromal stage of the disease and in fluctuating PD patients receiving bilateral chronic subthalamic nucleus stimulation. In these stages, apathy may be considered as a disorder of motivation that embodies amotivational behavioral syndrome, is underpinned by combined dopaminergic and serotonergic denervation and is dopa-responsive. In contrast, in advanced PD patients, apathy may be considered as cognitive apathy that announces cognitive decline and PD dementia, is underpinned by diffuse neurotransmitter system dysfunction and Lewy pathology spreading and is no longer dopa-responsive. In this review, we discuss the clinical patterns of apathy and their treatment, the neurobiological basis of apathy, the potential role of the anatomical structures involved and the pathways in motivational and cognitive apathy.

Apathy and impulsivity are multidimensional constructs that shape goal-directed behavior. Although the motivational dopaminergic spectrum hypothesis frames them as opposing ends of a single continuum, questionnaire-based studies consistently show that they positively co-occur in both healthy and clinical populations. An emerging theoretical resolution of this paradox is that apathy and impulsivity relate to distinct components of goal-directed behavior, with co-occurrence potentially arising from domain-general factors and/or partially overlapping neurophysiological networks. Here, we examined this proposal in the domain of action control using the stop-signal task, which provides separable indices of action inhibition (stop-signal response time, SSRT) and action initiation (go response time, goRT) within the independent race model. Based on prior findings and theoretical considerations, we expected SSRT to covary with urgency-related impulsivity and goRT with action-initiation apathy. A large sample of healthy young adults (N = 144) completed a stop-signal task implemented in accordance with consensus recommendations, alongside validated multidimensional measures of impulsivity (UPPS-P impulsive behavior scale) and apathy (Lille Apathy Rating Scale). Bayesian analyses replicated a positive association between global apathy and impulsivity scores. However, SSRT was not associated with urgency, and goRT was not associated with action-initiation apathy, with moderate evidence for the null. Additional exploratory analyses provided moderate evidence against the majority of correlations between stop-signal indices and the remaining scale dimensions, including global scores. Thus, stop-signal indices did not dissociate apathy and impulsivity in action control, highlighting limits of task-based accounts of their co-occurrence.

Parkinson’s disease (PD) is affecting about 1.2 million patients in Europe with a prevalence that is expected to have an exponential increment, in the next decades. This epidemiological evolution will be challenged by the low number of neurologists able to deliver expert care for PD. As PD is better recognized, there is an increasing demand from patients for rigorous control of their symptoms and for therapeutic education. In addition, the highly variable nature of symtoms between patients and the fluctuations within the same patient requires innovative tools to help doctors and patients monitor the disease in their usual living environment and adapt treatment in a more relevant way. Nowadays, there are various body-worn sensors (BWS) proposed to monitor parkinsonian clinical features, such as motor fluctuations, dyskinesia, tremor, bradykinesia, freezing of gait (FoG) or gait disturbances. BWS have been used as add-on tool for patients’ management or research purpose. Here, we propose a practical anthology, summarizing the characteristics of the most used BWS for PD patients in Europe, focusing on their role as tools to improve treatment management. Consideration regarding the use of technology to monitor non-motor features is also included. BWS obviously offer new opportunities for improving management strategy in PD but their precise scope of use in daily routine care should be clarified.

Background Parkinson’s disease (PD) encompasses motor (e.g., bradykinesia) and non-motor (e.g., apathy) symptoms. Objective We aimed to use reflexive and voluntary saccades as a proxy for bradykinesia and apathy. Methods Seventeen PD patients and thirteen controls (matched for age and educational level) were recruited. We assessed apathy using the Dimensional Apathy Scale (DAS) and bradykinesia using MDS-UPDRS III. Subjects were asked to fixate successively two green points (cues, 40° apart) alternating at 1 Hz. After 20 s, all stimuli disappeared, and participants were required to continue fixating on the previous locations of the cues at the same frequency for another 20 s. We measured the Maximal Amplitude (MA) (saccade amplitude from side to side) and its period. Linear mixed models assessed the effect of the group (patient/control), cue, DAS, and bradykinesia score. Results Overall, the DAS was similarly correlated to the period (p = 0.0157) and the MA (p = 0.0002) in the absence of a cue. However, this correlation was significant only in the patient subgroup for the MA (p = 0.0005). In the absence of cue, bradykinesia was similarly correlated to the period (p = .0001) and the MA (p = 0.0004). However, the period was better correlated to bradykinesia than the DAS. Conclusions While the saccade period best correlates with bradykinesia, maximal amplitude in the absence of cue better reflects the severity of apathy. Our paradigm may be a promising objective biomarker for assessing bradykinesia and apathy in PD.

Few studies have considered the influence of motor sign asymmetry on motivated behaviors in de novo drug-naïve Parkinson’s disease (PD). We tested whether motor sign asymmetry could be associated with different motivated behavior patterns in de novo drug-naïve PD. We performed a cross-sectional study in 128 de novo drug-naïve PD patients and used the Ardouin Scale of Behavior in Parkinson’s disease (ASBPD) to assess a set of motivated behaviors. We assessed motor asymmetry based on (i) side of motor onset and (ii) MDS-UPDRS motor score, then we compared right hemibody Parkinson’s disease to left hemibody Parkinson’s disease. According to the MDS-UPDRS motor score, patients with de novo right hemibody PD had significantly lower frequency of approach behaviors ( p  = 0.031), including nocturnal hyperactivity ( p  = 0.040), eating behavior ( p  = 0.040), creativity ( p  = 0.040), and excess of motivation ( p  = 0.017) than patients with de novo left hemibody PD. Patients with de novo left hemibody PD did not significantly differ from those with de novo right hemibody PD regarding avoidance behaviors including apathy, anxiety and depression. Our findings suggest that motor sign asymmetry may be associated with an imbalance between motivated behaviors in de novo drug-naïve Parkinson’s disease.

Objective To assess the efficacy of dalfampridine in patients with neuromyelitis optica spectrum disorder. Methods We included 15 consecutive patients, who were started on a treatment of dalfampridine 10 mg twice daily for 2 weeks. Efficacy assessment was based on walking ability improvement using Timed-25-Foot Walk and 12-item Multiple Sclerosis Walking Scale tests. Results The mean Timed-25-Foot Walk score was reduced from 14.8 (±2.4) to 11.3 (±1.9) seconds (p = 0.01). The mean score on the 12-item Multiple Sclerosis Walking Scale was reduced from 41.2 (±3.5) to 31.4 (±3.2) (p = 0.004). Conclusion Dalfampridine seems to be useful for symptomatic treatment of walking impairment in neuromyelitis optica spectrum disorder.

Parkinson’s disease (PD) is a frequent neurodegenerative disorder that combines motor and non-motor features, including impaired balance, gait disturbances, and progressive loss of mobility. Bone involvement is well established, with low bone mass and elevated fracture risk- especially hip fractures- being common findings. Because of impaired balance, gait disturbances, cognitive dysfunction, and autonomic failure, individuals with PD experience a markedly elevated risk of falls. Osteoporosis in PD likely results from a convergence of nutritional deficiencies, vitamin D insufficiency, weight loss with sarcopenia, and progressive muscle weakness. Anti-Parkinson medications such as levodopa may also contribute through hyperhomocysteinemia. In addition, dopamine depletion and chronic inflammation may further disrupt bone remodeling. This review summarizes current evidence on bone mineral density, bone quality, falls, and fractures in PD and discusses the pathophysiological mechanisms underlying this comorbidity.

Background and objectives The impact of subthalamic deep-brain stimulation (STN-DBS) on motor asymmetry and its influence on both motor and non-motor outcomes remain unclear. The present study aims at assessing the role of STN-DBS on motor asymmetry and how its modulation translates into benefits in motor function, activities of daily living (ADLs) and quality of life (QoL). Methods Postoperative motor asymmetry has been assessed on the multicentric, prospective Predictive Factors and Subthalamic Stimulation in Parkinson’s Disease cohort. Asymmetry was evaluated at both baseline (pre-DBS) and 1 year after STN-DBS. A patient was considered asymmetric when the right-to-left MDS-UPDRS part III difference was ≥ 5. In parallel, analyses have been carried out using the absolute right-to-left difference. The proportion of asymmetric patients at baseline was compared to that in the post-surgery evaluation across different medication/stimulation conditions. Results 537 PD patients have been included. The proportion of asymmetric patients was significantly reduced after both STN-DBS and medication administration (asymmetric patients: 50% in pre-DBS MedOFF, 35% in MedOFF/StimON, 26% in MedON/StimOFF, and 12% in MedON/StimON state). Older patients at surgery and with higher baseline UPDRS II scores were significantly less likely to benefit from STN-DBS at the level of motor asymmetry. No significant correlation between motor asymmetry and ADLs (UPDRS II) or overall QoL (PDQ-39) score was observed. Asymmetric patients had significantly higher mobility, communication, and daily living PDQ-39 sub-scores. Conclusions Both STN-DBS and levodopa lead to a reduction in motor asymmetry. Motor symmetry is associated with improvements in certain QoL sub-scores.

We conducted the present study to evaluate the serum levels of adipokines (leptin, total and high molecular adiponectin, resistin), a marker of cartilage breakdown (C2C), and ghrelin together with body composition in patients with knee osteoarthritis (OA). Fifty patients and 50 sex-matched healthy subjects (HS) were evaluated. Knee OA was scored according to the Kellgren-Lawrence (KL) grade. Body composition parameters including lean mass and measurements of fat mass (total fat, adiposity, fat in the android and gynoid regions, visceral fat and trunk/legs fat ratio) were obtained using dual energy X-ray absorptiometry. Most of the recruited patients (88%) had advanced knee OA with KL grade 3 or 4. The patients had higher body mass index than HS ( p  < 0.0001). Serum leptin, high molecular adiponectin, resistin and ghrelin levels did not differ between patients and HS. Total adiponectin was higher in women with OA compared to women from the HS group ( p  = 0.004). Total fat mass, adiposity and measurements of central adiposity (fat in the android region, trunk/lower limbs fat ratio and visceral fat) were increased in patients with knee OA (all p  < 0.05). Total adiponectin was borderline associated with the severity of OA. Our results show that total adiponectin is significantly increased in women with advanced knee OA. Independently of gender, patients with severe knee OA were characterized by a significant excess of fat with a distribution toward the visceral region. This abnormal body composition may contribute to the cardiometabolic profile that is described in patients with knee OA.

Body-worn sensors (BWS) could provide valuable information in the management of Parkinson’s disease and support therapeutic decisions based on objective monitoring. To study this pivotal step and better understand how relevant information is extracted from BWS results and translated into treatment adaptation, eight neurologists examined eight virtual cases composed of basic patient profiles and their BWS monitoring results. Sixty-four interpretations of monitoring results and the subsequent therapeutic decisions were collected. Relationship between interrater agreements in the BWS reading and the severity of symptoms were analyzed via correlation studies. Logistic regression was used to identify associations between the BWS parameters and suggested treatment modifications. Interrater agreements were high and significantly associated with the BWS scores. Summarized BWS scores reflecting bradykinesia, dyskinesia, and tremor predicted the direction of treatment modifications. Our results suggest that monitoring information is robustly linked to treatment adaptation and pave the way to loop systems able to automatically propose treatment modifications from BWS recordings information.