Amantadine use in the French prospective NS-Park cohort.

OBJECTIVE: To assess amantadine use and associated factors in the patients with Parkinson's disease (PD). BACKGROUND: Immediate-release amantadine is approved for the treatment of PD and is largely used in clinical practice to treat "levodopa-induced dyskinesia (LIDs). Its use varies according to countries and PD stages. The prospective NS-Park cohort collects features of PD patients followed by 26 French PD Expert Centres. METHODS: Variables used for the analyses included demographics, motor and non-motor PD symptoms and motor complications [motor fluctuations (MFs), LIDs)], antiparkinsonian pharmacological classes and levodopa equivalent daily dose (LEDD). We evaluated: (i) prevalence of amantadine use and compared clinical features of amantadine users vs. non-users (cross-sectional analysis); (ii) factors associated with amantadine initiation (longitudinal analysis); (iii) amantadine effect on LIDs, MFs, apathy, impulse control disorders and freezing of gait (Fog) (longitudinal analysis). RESULTS: Amantadine use prevalence was 12.6% (1,585/12,542, median dose = 200 mg). Amantadine users were significantly younger, with longer and more severe PD symptoms, greater LEDD and more frequent use of device-aided/surgical treatment. Factors independently associated with amantadine initiation were younger age, longer PD duration, more frequent LIDs, MFs and FoG, higher LEDD and better cognitive function. 9 of the 658 patients on amantadine had stopped it at the following visit, after 12-18 months (1.3%). New users of amantadine presented a higher improvement in LIDs and MF compared to amantadine never users. CONCLUSIONS: About 12% of PD patients within the French NS-Park cohort used amantadine, mostly those with younger age and more severe PD. Amantadine initiation was associated with a subsequent reduction in LIDs and MFs.

Classifying Idiopathic Rapid Eye Movement Sleep Behavior Disorder, Controls, and Mild Parkinson's Disease Using Gait Parameters.

BACKGROUND: Subtle gait changes associated with idiopathic rapid eye movement sleep behavior disorder (iRBD) could allow early detection of subjects with future synucleinopathies. OBJECTIVE: The aim of this study was to create a multiclass model, using statistical learning from probability distribution of gait parameters, to distinguish between patients with iRBD, healthy control subjects (HCs), and patients with Parkinson's disease (PD). METHODS: Gait parameters were collected in 21 participants with iRBD, 21 with PD, and 21 HCs, matched for age, sex, and education level. Lasso sparse linear regression explored gait features able to classify the three groups. RESULTS: The final model classified iRBD from HCs and from patients with PD equally well, with 95% accuracy, 100% sensitivity, and 90% specificity. CONCLUSIONS: Gait parameters and a pretrained statistical model can robustly distinguish participants with iRBD from HCs and patients with PD. This could be used to screen subjects with future synucleinopathies in the general population and to identify a conversion threshold to PD. © 2022 International Parkinson and Movement Disorder Society.

Fluoxetine for the Symptomatic Treatment of Multiple System Atrophy: The MSA-FLUO Trial.

BACKGROUND: There are no effective treatments for multiple system atrophy (MSA). OBJECTIVE: The objective of this study was to assess the efficacy and safety of the serotonin reuptake inhibitor fluoxetine (40 mg/d) for the symptomatic treatment of MSA. METHODS: This was a double-blind, parallel-group, placebo-controlled, randomized trial in patients with "probable" MSA. The primary outcome was the change from baseline to week 12 in the mean total score of the Unified MSA Rating Scale (UMSARS Parts I + II). Secondary outcomes included change from baseline to week 6 in total UMSARS, and change from baseline to week 12 in the Scales for Outcomes in Parkinson Disease-Autonomic Dysfunction, Beck Depression Inventory, and different domains of the MSA-Quality of Life Questionnaire. Exploratory outcomes included change from baseline to week 12 in the UMSARS Parts I and II separately and change from baseline to week 24 in the total UMSARS score. RESULTS: A total of 81 patients were randomly assigned, with no significant difference in the primary outcome (-2.13 units [95% confidence interval, CI, -4.55 to 0.29]; P = 0.08). There was a greater reduction on fluoxetine in the change from baseline to 12-week in UMSARS Part II (exploratory outcome: -1.41 units [95% CI, -2.84; 0.03]; p = 0.05) and in MSA-QoL emotional/social dimension (secondary outcome: -6.99 units [95% CI, -13.40; -0.56]; p < 0.03). A total of 5 deaths occurred (3 on fluoxetine and 2 on placebo). CONCLUSION: The MSA-FLUO failed to demonstrate fluoxetine superiority over placebo on the total UMSARS score, whereas trends in motor and emotional secondary/exploratory outcomes deserve further investigation. © 2021 International Parkinson and Movement Disorder Society.

Diagnostic Validity of the Sleep Condition Indicator to Screen for Diagnostic and Statistical Manual-5 Insomnia Disorder in Patients with Parkinson's Disease.

BACKGROUND: Insomnia is a highly common sleep disorder in patients with Parkinson's disease (PD). Yet, no screening questionnaires following the Diagnostic and Statistical Manual-5 (DSM-5) criteria have been validated in PD patients. OBJECTIVES: We assessed the validity and reliability of the French version of the sleep condition indicator (SCI), in patients with PD. METHODS: In a sample of 65 patients (46% women, mean age 63.8 ± 7.9 years) with PD, but without dementia, insomnia was assessed with a clinical interview and the SCI. Statistical analyses were performed to determine the reliability, construct validity, and divergent validity of the SCI. In addition, an explanatory factor analysis was performed to assess the underlying structure of the SCI. RESULTS: Of the 65 patients (mean duration PD 9.7 ± 6.9 years), 51% met the criteria for insomnia disorder when measured with a clinical interview. The mean SCI score was 18.05 ± 8.3. The internal consistency (α = 0.89) of the SCI was high. Using the previously defined cutoff value of ≤16, the area under the receiver operating characteristic curve was 0.86 with a sensitivity of 86% and a specificity of 87%. Exploratory factor analysis showed a 2-factor structure with a focus on sleep and daytime effects. Additionally, good construct and divergent validity were demonstrated. CONCLUSION: The SCI can be used as a valid and reliable screener for DSM-5 insomnia disorder in PD patients. Due to its short length, it is useful in both clinical practice and scientific research.

Increased Prevalence of Neurocognitive Impairment in Aging People Living With Human Immunodeficiency Virus: The ANRS EP58 HAND 55-70 Study.

BACKGROUND: There are limited data on the comparative prevalence of neurocognitive impairment (NCI) in aging people living with human immunodeficiency virus (PLHIV) and people not living with HIV. METHODS: This was a cross-sectional study of PLHIV randomly matched by age (±4 years), gender, and education with 5 HIV-uninfected individuals from the CONSTANCES cohort. PLHIV were fluent in French and sequentially included during routine outpatient visits if aged 55-70 years, with HIV viral load <50 copies/mL, and lymphocyte T-CD4 level ≥200 cells/µL in the past 24 and 12 months, respectively. The primary outcome was NCI as defined by the Frascati criteria. Multivariate normative comparison (MNC) and -1.5 standard deviations in ≥2 neurocognitive domains were secondary outcomes of NCI. RESULTS: Two hundred PLHIV were matched with 1000 controls. Median age was 62 years, and 85% were men. In PLHIV, the median T-CD4 lymphocyte level was 650 cells/µL, and median nadir T-CD4 lymphocyte level was 176 cells/µL. NCI was found in 71 (35.5%) PLHIV and in 242 (24.2%) controls (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.25, 2.41). After adjusting for confounders, HIV remained significantly associated with NCI (OR, 1.50; 95% CI, 1.04, 2.16). Adjusted results were similar with NCI defined by MNC (ORMNC, 2.95; 95% CI, 1.13, 3.50) or -1.5 SD (OR-1.5, 2.24; 95% CI, 1.39, 3.62). CONCLUSIONS: In this matched study of aging individuals, HIV was significantly associated with an increased risk of NCI after adjusting for major confounders. Results were confirmed with more stringent NCI classifications. CLINICAL TRIALS REGISTRATION: NCT02592174.

Efficacy of cognitive behavioral therapy for insomnia comorbid to Parkinson's disease: A focus on psychological and daytime functioning with a single-case design with multiple baselines.

OBJECTIVE: To test the efficacy of cognitive behavioral therapy for insomnia (CBT-i) in Parkinson's Disease (PD) and to evaluate its impact on indices of daytime and psychological functioning. METHOD: Fifteen patients with insomnia disorder (ID) comorbid to PD were enrolled in a single-case design with multiple baselines. Total wake time, sleep efficiency, and daytime sleepiness were recorded on a sleep diary. Self-reported measures of insomnia, anxiety and depressive symptoms, health-related quality of life, and psychological variables perpetuating ID were completed. All patients also underwent a clinical interview for ID diagnosis. RESULTS: CBT-i was associated with significant changes in sleep variables and ID criteria. Significant positive treatment-related effects were also noted for all indices of daytime and psychological functioning, and for variables perpetuating ID. All of these improvements were well maintained at 3-month follow-up. CONCLUSION: CBT-i is a promising therapeutic avenue for patients with PD.

Effects of Sensitive Electrical Stimulation-Based Somatosensory Cueing in Parkinson's Disease Gait and Freezing of Gait Assessment.

This study aims to investigate the effect of a somatosensory cueing on gait disorders in subjects with Parkinson's disease (PD). After having performed stepping in place and timed up and go assessing tasks, 13 participants with PD were equipped with an electrical stimulator and an inertial measurement unit (IMU) located under the lateral malleolus on the sagittal plane. Electrodes were positioned under the arch of the foot and electrical stimulation (ES) parameters (five 500 µs/phase charge-balanced biphasic pulses delivered at 200 Hz, repeated four times at 10 Hz) adjusted to deliver a sensitive signal. Online IMU signal was processed in order to trigger ES at heel off detection. Starting from a quiet standing posture, subjects were asked to walk at their preferred speed on a path including 5 m straight line, u-turn, and walk around tasks. Three situations were considered: no stimulation baseline precondition (C0), ES condition (C1), and no stimulation baseline post-condition (C0bis), for eliminating a learning effect possibility. In ES condition (C1) the time to execute the different tasks was globally decreased in all the subjects (n = 13). Participants' results were then grouped regarding whether they experienced freezing of gait (FOG) or not during C0 no stimulation baseline precondition. In "freezer" subjects (n = 9), the time to complete the entire path was reduced by 19%. FOG episodes occurrence was decreased by 12% compared to baseline conditions. This preliminary work showed a positive global effect on gait and FOG in PD by a somatosensory cueing based on sensitive electrical stimulation.

Mini-Exome Coupled to Read-Depth Based Copy Number Variation Analysis in Patients with Inherited Ataxias.

Next-generation sequencing (NGS) has an established diagnostic value for inherited ataxia. However, the need of a rigorous process of analysis and validation remains challenging. Moreover, copy number variations (CNV) or dynamic expansions of repeated sequence are classically considered not adequately detected by exome sequencing technique. We applied a strategy of mini-exome coupled to read-depth based CNV analysis to a series of 33 patients with probable inherited ataxia and onset <50 years. The mini-exome consisted of the capture of 4,813 genes having associated clinical phenotypes. Pathogenic variants were found in 42% and variants of uncertain significance in 24% of the patients. These results are comparable to those from whole exome sequencing and better than previous targeted NGS studies. CNV and dynamic expansions of repeated CAG sequence were identified in three patients. We identified both atypical presentation of known ataxia genes (ATM, NPC1) and mutations in genes very rarely associated with ataxia (ERCC4, HSD17B4). We show that mini-exome bioinformatics data analysis allows the identification of CNV and dynamic expansions of repeated sequence. Our study confirms the diagnostic value of the proposed genetic analysis strategy. We also provide an algorithm for the multidisciplinary process of analysis, interpretation, and validation of NGS data.

A Placebo-Controlled Trial of AQW051 in Patients With Moderate to Severe Levodopa-Induced Dyskinesia.

BACKGROUND: This phase 2 randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of the nicotinic acetylcholine receptor α7 agonist AQW051 in patients with Parkinson's disease and levodopa-induced dyskinesia. METHODS: Patients with idiopathic Parkinson's disease and moderate to severe levodopa-induced dyskinesia were randomized to AQW051 10 mg (n = 24), AQW051 50 mg (n = 24), or placebo (n = 23) once daily for 28 days. Coprimary end points were change in Modified Abnormal Involuntary Movement Scale and Unified Parkinson's Disease Rating Scale part III scores. Secondary outcomes included pharmacokinetics. RESULTS: In total, 67 patients completed the study. AQW051-treated patients experienced no significant improvements in Modified Abnormal Involuntary Movement Scale or Unified Parkinson's Disease Rating Scale part III scores by day 28. AQW051 was well tolerated; the most common adverse events were dyskinesia, fatigue, nausea, and falls. CONCLUSIONS: AQW051 did not significantly reduce dyskinesia or parkinsonian severity. © 2016 International Parkinson and Movement Disorder Society.

On the use of fixed-intensity functional electrical stimulation for attenuating essential tremor.

A great proportion of essential tremor (ET) patients have not so far been able to receive functional benefits from traditional therapies. In this regard, the use of functional electrical stimulation (FES) has been proposed for reducing tremor amplitude by stimulating muscles in antiphase with respect to the trembling motion. Although some studies have reported success in terms of tremor attenuation, drawbacks still exist that prevent the method from being used in real-life applications. In this article, we explore an alternative approach: a strategy based on the hypothesis that FES-induced constant muscle contraction may provide functional benefit for tremor patients. To evaluate the proposed strategy, experiments were conducted in which stimulation was intermittently turned on and off while the subjects performed a static motor task. The results of the proposed experimental protocol indicate that tremor attenuation using this strategy is feasible, as consistent tremor attenuation levels were obtained in eight out of 10 ET patients. Nonetheless, tremor reduction was not instantaneous for all successful trials, indicating that prior training with FES may improve the overall response. Furthermore, although simpler assistive devices may potentially be designed based on this technique, some experimental difficulties still exist, which suggests that further studies are necessary.

Detection of freezing of gait in Parkinson disease: preliminary results.

Freezing of gait (FOG) is a common symptom in Parkinsonism, which affects the gait pattern and is associated to a fall risk. Automatized FOG episode detection would allow systematic assessment of patient state and objective evaluation of the clinical effects of treatments. Techniques have been proposed in the literature to identify FOG episodes based on the frequency properties of inertial sensor signals. Our objective here is to adapt and extend these FOG detectors in order to include other associated gait pattern changes, like festination. The proposed approach is based on a single wireless inertial sensor placed on the patient's lower limbs. The preliminary experimental results show that existing frequency-based freezing detectors are not sufficient to detect all FOG and festination episodes and that the observation of some gait parameters such as stride length and cadence are valuable inputs to anticipate the occurrence of upcoming FOG events.

Frailty and prefrailty phenotypes increase the odds of abnormal cognitive impairment screens in people with HIV.

OBJECTIVE: Evaluate whether prefrail and frail people with HIV (PWH) have a higher risk of cognitive impairment on screens. METHODS: Analysis of PWH aged 70 or older included in the ANRS EP66 SEPTAVIH cohort, on antiretroviral therapy for at least 12 months and with a MoCA test at enrolment. Adjusted risk of a Montreal Cognitive Assessment (MoCA) less than 26 was compared in frail/prefrail versus robust PWH. RESULTS: A total of 503 PWH were enrolled with a median age of 73 years, IQR [71-77], 81.5% were male, 73.8% were French natives, 32.9% had low socio-economic status (EPICES score >30.2), and 41.3% were college graduates; 27.3% had a history of clinical AIDS. A total of 294 (58.5%) PWH had a MoCA score less than 26; 182 (36%) a MoCA score 23 or less. Frailty, prefrailty and robustness were found in 13.1, 63.6 and 23.3% participants, respectively. PWH with a MoCA less than 26 had a significantly higher risk of being frail/prefrail, this before [odds ratio (OR) = 2.31; 95% confidence interval (CI) 1.50-3.57], and after adjustment for confounders (OR = 1.80; 95% CI 1.07-3.01). The risk of being frail/prefrail in patients with a MoCA 23 or less was higher (adjusted OR = 2.75; 95% CI 1.46-5.16). Other factors independently associated with a MoCA less than 26 were older age, birth outside of France and a lower education level and being diabetic. CONCLUSION: Abnormal MoCA screens were frequent in our cohort of PWH aged 70 or older with controlled HIV disease. Cognitive impairment should be systematically screened in frail/prefrail PWH. Frailty/prefrailty, diabetes and social factors, but not HIV-related factors, are important determinants of cognitive function in PWH with controlled disease.

Volumetric changes and clinical trajectories in Parkinson's disease: a prospective multicentric study.

BACKGROUND: Longitudinal measures of structural brain changes using MRI in relation to clinical features and progression patterns in PD have been assessed in previous studies, but few were conducted in well-defined and large cohorts, including prospective clinical assessments of both motor and non-motor symptoms. OBJECTIVE: We aimed to identify brain volumetric changes characterizing PD patients, and determine whether regional brain volumetric characteristics at baseline can predict motor, psycho-behavioral and cognitive evolution at one year in a prospective cohort of PD patients. METHODS: In this multicentric 1 year longitudinal study, PD patients and healthy controls from the MPI-R2* cohort were assessed for demographical, clinical and brain volumetric characteristics. Distinct subgroups of PD patients according to motor, cognitive and psycho-behavioral evolution were identified at the end of follow-up. RESULTS: One hundred and fifty PD patients and 73 control subjects were included in our analysis. Over one year, there was no significant difference in volume variations between PD and control subjects, regardless of the brain region considered. However, we observed a reduction in posterior cingulate cortex volume at baseline in PD patients with motor deterioration at one year (p = 0.017). We also observed a bilateral reduction of the volume of the amygdala (p = 0.015 and p = 0.041) and hippocampus (p = 0.015 and p = 0.053) at baseline in patients with psycho-behavioral deterioration, regardless of age, dopaminergic treatment and center. CONCLUSION: Brain volumetric characteristics at baseline may predict clinical trajectories at 1 year in PD as posterior cingulate cortex atrophy was associated with motor decline, while amygdala and hippocampus atrophy were associated with psycho-behavioral decline.

At-Home Training With a Rhythmic Video Game for Improving Orofacial, Manual, and Gait Abilities in Parkinson's Disease: A Pilot Study.

Rhythm disorders are consistently reported in Parkinson's disease (PD). They manifest across motor domains, such as in orofacial (oral diadochokinesis), manual (finger tapping), and gait tasks. It is still unclear, however, whether these disorders are domain- and task-specific, or result from impaired common mechanisms supporting rhythm processing (general dysrhythmia). We tested the possibility that an at-home intervention delivered via a rhythmic video game on tablet improves motor performance across motor domains in PD. Patients with PD (n = 12) played at home a rhythmic video game (Rhythm Workers) on tablet, in which they finger-tapped to the beat of music, for 6 weeks. A control group (n = 11) played an active non-rhythmic video game (Tetris). A third group (n = 10) did not receive any intervention. We measured rhythmic abilities in orofacial, manual and gait motor domains, as well as rhythm perception, before and after the intervention. Patients who performed the rhythmic training improved their orofacial and manual rhythmic performance. This beneficial effect was linked to improved rhythm perception only following the rhythmic training period. We did not observe any improvement in rhythmic abilities in the other two groups. In this pilot study, we demonstrated that at-home intervention with a rhythmic video game using finger tapping can have beneficial effects on motor performance across different motor domains (manual and orofacial). This finding provides evidence of a general dysrhythmia in PD and paves the way to technology-driven interventions aiming at alleviating rhythm-related motor deficits in PD.

Intrasubject subcortical quantitative referencing to boost MRI sensitivity to Parkinson's disease.

Several postmortem studies have shown iron accumulation in the substantia nigra of Parkinson's disease patients. Iron concentration can be estimated via MRI-R2∗ mapping. To assess the changes in R2∗ occurring in Parkinson's disease patients compared to controls, a multicentre transversal study was carried out on a large cohort of Parkinson's disease patients (n = 163) with matched controls (n = 82). In this study, 44 patients and 11 controls were removed due to motion artefacts, 21 patient and 6 controls to preserve matching. Thus, 98 patients and 65 age and sex-matched healthy subjects were selected with enough image quality. The study was conducted on patients with early to late stage Parkinson's disease. The images were acquired at 3Tesla in 12 clinical centres. R2∗ values were measured in subcortical regions of interest (substantia nigra, red nucleus, striatum, globus pallidus externus and globus pallidus internus) contralateral (dominant side) and ipsilateral (non dominant side) to the most clinically affected hemibody. As the observed inter-subject R2∗ variability was significantly higher than the disease effect, an original strategy (intrasubject subcortical quantitative referencing, ISQR) was developed using the measurement of R2∗ in the red nucleus as an intra-subject reference. R2∗ values significantly increased in Parkinson's disease patients when compared with controls; in the substantia nigra (SN) in the dominant side (D) and in the non dominant side (ND), respectively (PSN_D and PSN_ND < 0.0001). After stratification into four subgroups according to the disease duration, no significant R2∗ difference was found in all regions of interest when comparing Parkinson's disease subgroups. By applying our ISQR strategy, R2(ISQR)∗ values significantly increased in the substantia nigra (PSN_D and PSN_ND < 0.0001) when comparing all Parkinson's disease patients to controls. R2(ISQR)∗ values in the substantia nigra significantly increased with the disease duration (PSN_D = 0.01; PSN_ND = 0.03) as well as the severity of the disease (Hoehn & Yahr scale <2 and ≥ 2, PSN_D = 0.02). Additionally, correlations between R2(ISQR)∗ and clinical features, mainly related to the severity of the disease, were found. Our results support the use of ISQR to reduce variations not directly related to Parkinson's disease, supporting the concept that ISQR strategy is useful for the evaluation of Parkinson's disease.

BeatWalk: Personalized Music-Based Gait Rehabilitation in Parkinson's Disease.

Taking regular walks when living with Parkinson's disease (PD) has beneficial effects on movement and quality of life. Yet, patients usually show reduced physical activity compared to healthy older adults. Using auditory stimulation such as music can facilitate walking but patients vary significantly in their response. An individualized approach adapting musical tempo to patients' gait cadence, and capitalizing on these individual differences, is likely to provide a rewarding experience, increasing motivation for walk-in PD. We aim to evaluate the observance, safety, tolerance, usability, and enjoyment of a new smartphone application. It was coupled with wearable sensors (BeatWalk) and delivered individualized musical stimulation for gait auto-rehabilitation at home. Forty-five patients with PD underwent a 1-month, outdoor, uncontrolled gait rehabilitation program, using the BeatWalk application (30 min/day, 5 days/week). The music tempo was being aligned in real-time to patients' gait cadence in a way that could foster an increase up to +10% of their spontaneous cadence. Open-label evaluation was based on BeatWalk use measures, questionnaires, and a six-minute walk test. Patients used the application 78.8% (±28.2) of the prescribed duration and enjoyed it throughout the program. The application was considered "easy to use" by 75% of the patients. Pain, fatigue, and falls did not increase. Fear of falling decreased and quality of life improved. After the program, patients improved their gait parameters in the six-minute walk test without musical stimulation. BeatWalk is an easy to use, safe, and enjoyable musical application for individualized gait rehabilitation in PD. It increases "walk for exercise" duration thanks to high observance. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02647242.

Rhythm disturbances as a potential early marker of Parkinson's disease in idiopathic REM sleep behavior disorder.

OBJECTIVE: We aimed to identify timing distortions in production and perception of rhythmic events in patients with idiopathic REM sleep behavior disorder (iRBD) as early markers of Parkinson's disease (PD). METHODS: Rhythmic skills, clinical characteristics, dysautonomia, depression, and olfaction were compared in 97 participants, including 21 participants with iRBD, 38 patients with PD, and 38 controls, matched for age, gender, and education level. Rhythmic disturbances can be easily detected with dedicated motor tasks via a tablet application. Rhythm production was tested in two conditions: to examine the ability to generate a spontaneous endogenous rhythm, tapping rate and variability in a finger tapping task without external stimulation was measured, while the ability to synchronize to an external rhythm was tested with finger tapping to external auditory cues. Rhythm perception was measured with a task, in which the participants had to detect a deviation from a regular rhythm. Participants with iRBD had dopamine transporter imaging. RESULTS: Participants with iRBD and PD revealed impaired spontaneous rhythm production and poor rhythm perception compared to controls. Impaired rhythm production was correlated with olfaction deficits, dysautonomia, impaired non-motor aspects of daily living, and dopamine uptake measures. CONCLUSIONS: Participants with iRBD show impaired rhythm production and perception; this impairment is correlated with other early markers for PD. Testing rhythmic skills with short and inexpensive tests may be promising for screening for potential future PD in iRBD patients.

Presleep Cognitive Arousal and Insomnia Comorbid to Parkinson Disease: Evidence for a Serial Mediation Model of Sleep-Related Safety Behaviors and Dysfunctional Beliefs About Sleep.

STUDY OBJECTIVES: Insomnia disorder (ID) is highly associated with Parkinson disease (PD) with great negative effect on health-related quality of life. Nonetheless, the relevance of psychological processes involved in the maintenance of insomnia is yet to be established in the context of this neurological condition. Our aim was to examine a serial meditation model of sleep-related safety behaviors and dysfunctional beliefs about sleep in association with presleep cognitive arousal and ID in patients with PD. METHODS: A total of 68 patients with PD completed self-report measures including the Sleep-Related Behaviors Questionnaire (SRBQ-20), Dysfunctional Beliefs and Attitudes about Sleep (DBAS-16), and the cognitive subscale of the Presleep Arousal Scale (PSAS-C). ID was assessed according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Bootstrapped serial mediation analyses were conducted to test indirect effects. RESULTS: Overall, 55.6% of patients with PD met diagnostic criteria for ID. The association between presleep cognitive arousal (PSAS-C) and ID was serially mediated by sleep-related safety behaviors (SRBQ-20) and strong endorsement of dysfunctional beliefs about sleep (DBAS-16) (bias-corrected 95% confidence interval for the indirect effect = 0.013, 0.093). An alternate serial mediation model in which dysfunctional beliefs about sleep precede sleep-related safety behaviors was not statistically significant (bias-corrected 95% confidence interval for the indirect effect = -0.001, 0.046). CONCLUSIONS: ID comorbid to PD is associated with the classic psychological factors perpetuating ID in neurological disease-free individuals with insomnia. Target-oriented interventions for instance cognitive behavioral therapy for chronic insomnia should be considered as a treatment approach for ID comorbid to PD. CITATION: Lebrun C, Gély-Nargeot M-C, Maudarbocus KH, Rossignol A, Geny C, Bayard S. Presleep cognitive arousal and insomnia comorbid to parkinson disease: evidence for a serial mediation model of sleep-related safety behaviors and dysfunctional beliefs about sleep. J Clin Sleep Med. 2019;15(9):1217-1224.

Heightened orofacial, manual, and gait variability in Parkinson's disease results from a general rhythmic impairment.

Individuals with Parkinson's disease (PD) experience rhythm disorders in a number of motor tasks, such as (i) oral diadochokinesis, (ii) finger tapping, and (iii) gait. These common motor deficits may be signs of "general dysrhythmia", a central disorder spanning across effectors and tasks, and potentially sharing the same neural substrate. However, to date, little is known about the relationship between rhythm impairments across domains and effectors. To test this hypothesis, we assessed whether rhythmic disturbances in three different domains (i.e., orofacial, manual, and gait) can be related in PD. Moreover, we investigated whether rhythmic motor performance across these domains can be predicted by rhythm perception, a measure of central rhythmic processing not confounded with motor output. Twenty-two PD patients (mean age: 69.5 ± 5.44) participated in the study. They underwent neurological and neuropsychological assessments, and they performed three rhythmic motor tasks. For oral diadochokinesia, participants had to repeatedly produce a trisyllable pseudoword. For gait, they walked along a computerized walkway. For the manual task, patients had to repeatedly produce finger taps. The first two rhythmic motor tasks were unpaced, and the manual tapping task was performed both without a pacing stimulus and musically paced. Rhythm perception was also tested. We observed that rhythmic variability of motor performances (inter-syllable, inter-tap, and inter-stride time error) was related between the three functions. Moreover, rhythmic performance was predicted by rhythm perception abilities, as demonstrated with a logistic regression model. Hence, rhythm impairments in different motor domains are found to be related in PD and may be underpinned by a common impaired central rhythm mechanism, revealed by a deficit in rhythm perception. These results may provide a novel perspective on how interpret the effects of rhythm-based interventions in PD, within and across motor domains.

The role of interaction and predictability in the spontaneous entrainment of movement.

People walking side by side spontaneously synchronize their steps on some occasions but not on others, which poses a challenge to theories of perception-action based on interactive dynamic systems. How can action be spontaneously entrained by some sources of perceptual information while others are selectively ignored? The predictive processing framework suggests that saliency factors such as stimulus predictability, consistent deviation, and interactivity of the stimulus control the coupling between the motor system and perceptual information. To test this, we compared entrainment of gait cadence by two interactive auditory stimuli and two noninteractive but predictable, faster than preferred stimuli that were isochronous or statistically matched to gait. One interactive stimulus had properties that are optimal for mutual entrainment as per a mathematical model of interactive periodic processes, the Kuramoto system. In particular, the stimulus was faster than the participant but also adapted its rate to a limited degree as function of phase mismatch with the participant's steps. The second interactive stimulus fully mirrored the gait cycle hence it did not induce mutual synchronization. Furthermore, healthy participants were compared to ones with impaired gait due to Parkinson's disease, a model disorder that makes movement more dependent on external cueing. The mutually interactive condition produced the strongest entrainment, in patients and healthy participants, without differences between groups. The stimulus adapted to each participant's gait while maintaining a consistent lead in phase. Auditory-motor coupling may be enhanced by stimuli that are not only predictable but also interactive in that they align to self-generated movements. (PsycINFO Database Record (c) 2019 APA, all rights reserved).