Progression of postural control and gait deficits in Parkinson's disease and freezing of gait: A longitudinal study

Background and aimsThe relationship between impaired postural control and freezing of gait (FOG) in Parkinson's disease (PD) is still unclear. Our aim was to identify if postural control deficits and gait dysfunction progress differently in freezers compared to non-freezers and whether this relates to FOG development.Methods76 PD patients, classified as freezer (n = 17) or non-freezer (n = 59), and 24 controls underwent a gait and postural control assessments at baseline and after 12 months follow-up. Non-freezers who developed FOG during the study period were categorized as FOG converters (n = 5). Gait was analyzed during walking at self-preferred pace. Postural control was assessed using the Mini-BESTest and its sub-categories: sensory orientation, anticipatory, reactive and dynamic postural control.ResultsMini-BESTest scores were lower in PD compared to controls (p < 0.001), and in freezers compared to non-freezers (p = 0.02). PD has worse anticipatory (p = 0.01), reactive (p = 0.02) and dynamic postural control (p = 0.003) compared to controls. Freezers scored lower on dynamic postural control compared to non-freezers (p = 0.02). There were no baseline differences between converters and non-converters. Decline in postural control was worse in PD compared to controls (p = 0.02) as shown by a greater decrease in the total Mini-BESTest score. Similar patterns were found in freezers (p = 0.006), who also showed more decline in anticipatory (p < 0.001) and dynamic postural control (p = 0.02) compared to non-freezers. FOG converters had a greater decline in the total Mini-BESTest (p = 0.005) and dynamic postural control scores (p = 0.04) compared to non-converters. Gait outcomes showed no significant differences in any of the analyses.ConclusionFOG is associated with more severe decline in postural control, which can be detected by the clinical Mini-BESTest.     

Initial center of pressure position prior to anticipatory postural adjustments during gait initiation in people with Parkinson's disease with freezing of gait

IntroductionFreezing of gait (FOG) in Parkinson's disease (PD) is associated with an altered posture during quiet stance as well as an impaired preparation and execution of the gait initiation process. We aimed to investigate whether an altered initial posture impacts anticipatory postural adjustments (APAs) and first-step execution during gait initiation in people with PD with FOG (PD + FOG).MethodsTwenty-seven PD+FOG, 30 PD patients without FOG and 27 age-matched healthy controls performed self-generated gait initiation. Initial mean center of pressure (COP) position prior to APA onset, characteristics of APAs and features of first-step execution were investigated.ResultsContrarily to controls, PD patients showed a COP that was initially positioned more towards the stance leg (p = 0.007). Moreover, significantly smaller backward COP shift, longer duration of swing-foot unloading phase, and lower first-step length and velocity characterized PD+FOG compared to controls. While size and duration of backward COP shift during APA and lateral COP shift during the unloading phase were main predictors of first-step length and velocity in all groups, the medio-lateral shift of the initial COP position in PD+FOG was a main predictor of first-step execution (β = −0.191, p = 0.001 for velocity).ConclusionIn PD+FOG, the more the COP was initially positioned towards the stance foot, the slower and shorter the first step. The initial medio-lateral COP position may be a compensatory strategy to address postural instability of PD+FOG. A specific training regarding postural control prior to gait preparation and execution could improve functional mobility in PD+FOG.     

Paired inhibitory stimulation and gait training modulates supplemental motor area connectivity in freezing of gait

IntroductionFreezing of gait (FOG) is a debilitating feature of Parkinson's disease (PD). Evidence suggests patients with FOG have increased cortical control of gait. The supplementary motor area (SMA) may be a key structure due to its connectivity with locomotor and cognitive networks. The objectives of this study were to determine (1) if SMA connectivity is disrupted in patients with FOG and (2) if “inhibitory” repetitive transcranial magnetic stimulation can decrease maladaptive SMA connectivity.MethodsTwo experiments were performed. In experiment 1 resting-state (T2* BOLD imaging) was compared between 38 PD freezers and 17 PD controls. In experiment 2, twenty PD patients with FOG were randomized to either 10 sessions of real or sham rTMS to the SMA (1 Hz, 110% motor threshold, 1200 pulses/session) combined with daily gait training.Results(Experiment 1) Freezers had increased connectivity between the left SMA and the vermis of the cerebellum and decreased connectivity between the SMA and the orbitofrontal cortex (p_FDR-corr <0.05). (Experiment 2) 10 sessions of active TMS reduced SMA connectivity with the anterior cingulate, angular gyrus and the medial temporal cortex, whereas sham TMS did not reduce SMA connectivity. From a behavioral perspective, both groups showed nFOG-Q improvements (F(4, 25.7) = 3.87, p = 0.014).ConclusionsThe SMA in freezers is hyper-connected to the cerebellum, a key locomotor region which may represent maladaptive compensation. In this preliminary study, 1 Hz rTMS reduced SMA connectivity however, this was not specific to the locomotor regions. Intervention outcomes may be improved with subject specific targeting of SMA.     

Clinical patterns of gait freezing in Parkinson's disease and their response to interventions: An observer-blinded study

BackgroundFreezing of gait (FOG) in Parkinson's disease (PD) is provoked by specific situations. The sensitivity of these situations to detect FOG and the relative FOG response to l-dopa and subthalamic nucleus deep brain stimulation (STN-DBS) is unknown.MethodsTwo blinded reviewers analyzed the video recordings of a standardized patient assessment before and 10 months after DBS-implantation of 124 PD patients with positive FOG according to the Unified Parkinson Rating Scale part II item 14. Baseline evaluations were done under 2 conditions (OFF- and ON-drug states). Postoperatively, the patients were evaluated under 4 conditions (OFF-drug/OFF-stim, OFF-drug/ON-stim, ON-drug/OFF-stim, and ON-drug/ON-stim). FOG frequency and its severity was rated during different provoking situations (start, turning, reaching a destination and open space hesitations) during a standardized walking task. Cumulative link mixed models were calculated to investigate the immediate and carry-over effect of medication and stimulation.ResultsEighty-one percent of patients presented FOG at least in one provoking situation on video assessment. During turning, the FOG severity was significantly worse than for the other subtypes (p < 0.0001). Both interventions improve all FOG subtypes similarly. The effect size of l-dopa and STN-DBS on subtypes were similar (p > 0.05), but the combined intervention had a stronger effect on FOG severity (p < 0.0001) compared to each intervention separately. FOG severity was lower at follow-up OFF compared to baseline OFF condition (p < 0.02) demonstrating a carry-over effect of STN-DBS.ConclusionTurning is the most sensitive provoking situation for gait freezing. STN-DBS and l-dopa improve all FOG subtypes similarly, their effect is stronger in combination.     

Smartphone-based tactile cueing improves motor performance in Parkinson's disease

IntroductionVisual and auditory cueing improve functional performance in Parkinson's disease (PD) patients. However, audiovisual processing shares many cognitive resources used for attention-dependent tasks such as communication, spatial orientation, and balance. Conversely, tactile cues (TC) may be processed faster, with minimal attentional demand, and may be more efficient means for modulating motor-cognitive performance. In this study we aimed to investigate the efficacy and limitations of TC for modulating simple (heel tapping) and more complex (walking) motor tasks (1) over a range of cueing intervals, (2) with/without a secondary motor task (holding tray with cups of water).MethodsTen PD patients (71 ± 9 years) and 10 healthy controls (69 ± 7 years) participated in the study. TCs was delivered through a smart phone attached to subjects' dominant arm and were controlled by a custom-developed Android application.ResultsPD patients and healthy controls were able to use TC to modulate heel tapping (F(3.8,1866.1) = 1008.1, p < 0.001), and partially modulate walking (F(3.5,1448.7) = 187.5, p < 0.001) tasks. In the walking task, PD patients modulated performance over a narrower range of cueing intervals (R² = 0.56) than healthy controls (R² = 0.84; group difference F(3.5,1448.7) = 8.6, p < 0.001). TC diminished synchronization error associated with performance of secondary motor task during walking in PD patients and healthy controls (main effect of Task (F(1,494) = 0.4; p = 0.527), Task X Group interaction (F(1,494) = 0.5; p = 0.493)).ConclusionThis study expands modalities of TC usage for movement modulation and motor-cognitive integration in PD patients. The smartphone TC application was validated as a user-friendly movement modulation aid.     

Postural sensory correlates of freezing of gait in Parkinson's disease

IntroductionTo elucidate the unique patterns of postural sensory deficits contributing to freezing of gait (FOG) in patients with Parkinson's disease (PD) and to identify postural sensory modalities that correlate with FOG severity.MethodsTwenty-five PD patients with FOG, 22 PD patients without FOG, and 26 age-matched controls were evaluated using a sensory organization test and clinical measures including the Unified Parkinson's Disease Rating Scale motor score, Montreal Cognitive Assessment, Frontal Assessment Battery, Activities-specific Balance Confidence, Beck Anxiety Inventory, Beck Depression Inventory, and Berg Balance Scale. Multivariable logistic regression analysis was performed for posturographic parameters and possible confounders to determine postural sensory contributors to FOG. We also correlated FOG severity, measured using a New Freezing of Gait Questionnaire, with posturographic parameters.ResultsPD patients with FOG showed worse postural sensory processing compared with those without FOG. In particular, the inability to use the vestibular information (odds ratio [OR] 1.447; 95% confidential interval [CI]: 1.120, 1.869) and poor control over the perturbed somatosensory inputs (OR 2.904; 95% CI: 1.028, 8.202) significantly contributed to FOG. Among PD patients with FOG, FOG severity was correlated with higher reliance on visual information (ρ = −0.432, p = 0.039).ConclusionsPostural sensory deficits involving specific sensory modalities are strongly associated with FOG. Quantitative measurement of postural sensory deficits in PD patients with FOG may provide a better understanding of pathomechanisms of FOG and increase the efficacy of sensory cueing strategies for alleviating FOG, by more accurately identifying suitable patients for rehabilitative therapies.     

Interprofessional education increases knowledge,promotes team building,and changes practice in the care of Parkinson's disease

ObjectiveExamine outcomes for the National Parkinson Foundation (NPF) Allied Team Training for Parkinson (ATTP), an interprofessional education (IPE) program in Parkinson's disease (PD) and team-based care for medicine, nursing, occupational, physical and music therapies, physician assistant, social work and speech-language pathology disciplines.BackgroundHealthcare professionals need education in evidence-based PD practices and working effectively in teams. Few evidence-based models of IPE in PD exist.MethodsKnowledge about PD, team-based care, the role of other disciplines and attitudes towards healthcare teams were measured before and after a protocol-driven training program. Knowledge, attitudes and practice changes were again measured at 6-month post-training. Trainee results were compared to results of controls.ResultsTwenty-six NPF–ATTP trainings were held across the U.S. (2003–2013). Compared to control participants (n = 100), trainees (n = 1468) showed statistically significant posttest improvement in all major outcomes, including self-perceived (p < 0.001) and objective knowledge (p < 0.001), Understanding Role of Other Disciplines (p < 0.001), Attitudes Toward Health Care Teams Scale (p < 0.001), and the Attitudes Toward Value of Teams (p < 0.001) subscale. Despite some decline, significant improvements were largely sustained at six-month post-training. Qualitative analyses confirmed post-training practice changes.ConclusionsThe NPF–ATTP model IPE program showed sustained positive gains in knowledge of PD, team strategies and role of other disciplines, team attitudes, and important practice improvements. Further research should examine longer-term outcomes, objectively measure practice changes and mediators, and determine impact on patient outcomes.     

Personality and addictive behaviours in early Parkinson's disease and REM sleep behaviour disorder

IntroductionChanges in personality have been described in Parkinson's disease (PD), with suggestion that those with established disease tend to be risk averse with a disinclination for addictive behaviour. However, little is known about the earliest and prodromal stages. Personality and its relationship with addictive behaviours can help answer important questions about the mechanisms underlying PD and addiction.Methods941 population-ascertained PD subjects within 3.5 years of diagnosis, 128 patients with rapid eye movement sleep behaviour disorder (RBD) and 292 control subjects were fully characterised for motor symptoms, non-motor symptoms and across the following 5 personality domains: 1) neuroticism 2) extraversion 3) conscientiousness 4) agreeableness 5) openness using the Big Five Inventory.ResultsPatients with early PD were more neurotic (p < 0.001), less extraverted (p < 0.001) and less open than controls (p < 0.001). RBD subjects showed the same pattern of being more neurotic (p < 0.001), less extraverted (p = 0.03) and less open (p < 0.001). PD patients had smoked less (p = 0.02) and drunk less alcohol (p = 0.03) than controls, but caffeine beverage consumption was similar. Being more extraverted (p < 0.001), more open (p < 0.001), and less neurotic (p < 0.001) predicted higher alcohol use, while being more extravert (p = 0.007) and less agreeable (p < 0.001) was associated with smoking more.ConclusionsA similar pattern of personality changes is seen in PD and RBD compared to a control population. Personality characteristics were associated with addictive behaviours, suggestive of a common link, but the lower rates of addictive behaviours before and after the onset of motor symptoms in PD persisted after accounting for personality.     

Thalamic volume and related visual recognition are associated with freezing of gait in non-demented patients with Parkinson's disease

BackgroundThe pathophysiology of freezing of gait (FOG) in non-demented Parkinson's disease (PD) patients remains poorly understood. Recent studies have suggested that neurochemical alterations in the cholinergic systems play a role in the development of FOG. Here, we evaluated the association between subcortical cholinergic structures and FOG in patients with non-demented PD.MethodsWe recruited 46 non-demented patients with PD, categorized into PD with (n = 16) and without FOG (n = 30) groups. We performed neuropsychological test, region-of-interest-based volumetric analysis of the substantia innominata (SI) and automatic analysis of subcortical brain structures using a computerized segmentation procedure.ResultsThe comprehensive neuropsychological assessment showed that PD patients with FOG had lower cognitive performance in the frontal executive and visual-related functions compared with those without freezing of gait. The normalized SI volume did not differ significantly between the two groups (1.65 ± 0.18 vs. 1.68 ± 0.31). The automatic analysis of subcortical structures revealed that the thalamic volumes were significantly reduced in PD patients with FOG compared with those without FOG after adjusting for age, sex, disease duration, the Unified PD Rating Scale scores and total intracranial volume (left: 6.71 vs. 7.16 cm³, p = 0.029, right: 6.47 vs. 6.91 cm³, p = 0.026). Multiple linear regression analysis revealed that thalamic volume showed significant positive correlations with visual recognition memory (left: β = 0.441, p = 0.037, right: β = 0.498, p = 0.04).ConclusionsThese data suggest that thalamic volume and related visual recognition, rather than the cortical cholinergic system arising from the SI, may be a major contributor to the development of freezing of gait in non-demented patients with PD.     

Effects of periodic robot rehabilitation using the Hybrid Assistive Limb for a year on gait function in chronic stroke patients

Using a robot for gait training in stroke patients has attracted attention for the last several decades. Previous studies reported positive effects of robot rehabilitation on gait function in the short term. However, the long-term effects of robot rehabilitation for stroke patients are still unclear. The purpose of the present study was to investigate the long-term effects of periodic gait training using the Hybrid Assistive Limb (HAL) on gait function in chronic stroke patients. Seven chronic stroke patients performed 8 gait training sessions using the HAL 3 times every few months. The maximal 10-m walk test and the 2-minute walking distance (2MWD) were measured before the first intervention and after the first, second, and third interventions. Gait speed, stride length, and cadence were calculated from the 10-m walk test. Repeated one-way analysis of variance showed a significant main effect on evaluation time of gait speed (F = 7.69, p < 0.01), 2MWD (F = 7.52, p < 0.01), stride length (F = 5.24, p < 0.01), and cadence (F = 8.43, p < 0.01). The effect sizes after the first, second, and third interventions compared to pre-intervention in gait speed (d = 0.39, 0.52, and 0.59) and 2MWD (d = 0.35, 0.46, and 0.57) showed a gradual improvement of gait function at every intervention. The results of the present study showed that gait function of chronic stroke patients improved over a year with periodic gait training using the HAL every few months.     

Quantitative susceptibility mapping differentiates between parkinsonian disorders

IntroductionIt is often challenging to clinically distinguish between Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Quantitative susceptibility mapping (QSM) is an accurate indirect method for estimating brain iron levels in vivo. This method has yet to be applied in atypical parkinsonism. We aimed to investigate differences in brain iron accumulation parkinsonian disorders and healthy controls using QSM.Methods15 patients with PSP, 11 patients with MSA, 62 patients with PD and 14 healthy controls were included in the study and their phase and magnitude data from susceptibility-weighted magnetic resonance imaging were retrospectively analyzed with an in-house pipeline to create susceptibility maps. Two-way ANCOVA were used to assess group differences. Pairwise comparisons within the ANCOVA were corrected for multiple comparisons.ResultsRed nucleus susceptibility was higher in PSP compared with PD (p < 0.001), MSA (p < 0.001) and controls (p < 0.001), which separated PSP from these groups with areas under receiver operating characteristic curve of 0.97, 0.75 and 0.98 respectively. PSP showed higher globus pallidus susceptibility compared with PD (p < 0.001), MSA (p = 0.006) and controls (p < 0.001). Putamen susceptibility was higher in MSA than in PD (p = 0.022) and controls (p = 0.026). Substantia nigra susceptibility was increased in PD compared to controls (p = 0.030).ConclusionWe show that all studied parkinsonian disorders have increased susceptibility subcortically, reflecting distinct topographical patterns of abnormal brain iron accumulation. QSM, particularly of the red nucleus, is a promising biomarker in differentiating parkinsonian disorders, and would be interesting to study longitudinally for monitoring disease progression and treatment effects.     

The Penn Parkinson's Daily Activities Questionnaire-15: Psychometric properties of a brief assessment of cognitive instrumental activities of daily living in Parkinson's disease

IntroductionTo describe the psychometric properties of the Penn Parkinson's Daily Activities Questionnaire-15 (PDAQ-15), a 15-item measure of cognitive instrumental activities of daily living for Parkinson's disease (PD) patients derived from the original 50-item PDAQ.MethodsPDAQ-15 items were chosen by expert consensus. Knowledgeable informants of PD participants (n = 161) completed the PDAQ-15. Knowledgeable informants were defined as an individual having regular contact with the PD participant. PD participants were assigned a diagnosis of normal cognition, mild cognitive impairment, or dementia based on expert consensus.ResultsPDAQ-15 scores correlated strongly with global cognition (Dementia Rating Scale-2, r = 0.71, p < 0.001) and a performance-based functional measure (Direct Assessment of Functional Status, r = 0.83; p < 0.001). PDAQ-15 scores accurately discriminated between non-demented PD participants (normal cognition/mild cognitive impairment) and PD with dementia (ROC curve area = 0.91), participants with and without any cognitive impairment (normal cognition versus mild cognitive impairment/dementia, ROC curve area = 0.85) and between participants with mild cognitive impairment and dementia (ROC curve area = 0.84).ConclusionsThe PDAQ-15 shows good discriminant validity across cognitive stages, correlates highly with global cognitive performance, and appears suitable to assess daily cognitive functioning in PD.     

Investigation on sleep and mental health of patients with Parkinson's disease during the Coronavirus disease 2019 pandemic

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic is adversely affecting sleep quality and mental health, especially in individuals with chronic disease such as Parkinson's disease (PD).MethodsWe conducted a quantitative study, which included 119 Chinese PD patients who had been treated in an outpatient neurology clinic in Wuhan and 169 age- and sex-matched healthy controls. The questionnaire survey focused on the impact of the COVID-19 pandemic on sleep, mental status, symptoms, and daily life and medical treatment of PD patients.ResultsCompared to healthy controls, PD patients had significantly higher scores in both the Pittsburgh Sleep Quality Index (PSQI) (8.13 vs 5.36, p < 0.001) and the Hospital Anxiety and Depression Scale (HADS) -Depression (4.89 vs 3.82, p = 0.022), as well as a higher prevalence of sleep disturbances with PSQI > 5 points (68.9% vs 44.4%, p < 0.001). Sleep disturbance was identified in 68.9% of PD patients. A logistic regression analysis showed that sleep disturbance of PD patients was independently associated with exacerbation of PD symptoms (OR = 3.616, 95%CI= (1.479, 8.844), p = 0.005) and anxiety (OR = 1.379, 95%CI= (1.157, 1.642), p < 0.001). Compared to male PD patients, female ones had higher PSQI scores (9.28 ± 4.41 vs 7.03 ± 4.01, p = 0.009) and anxiety (32.8% vs 0.1%, p = 0.002) and depression prevalence (34.5% vs 11.5%, p = 0.003).ConclusionThe findings of the present study emphasize the importance of mental and sleep health interventions in PD patients during the COVID-19 pandemic. Additional attention should be paid to the difficulty encountered by PD patients in seeking medical treatment.     

White matter hyperintensities mediate the impact of amyloid ß on future freezing of gait in Parkinson's disease

BackgroundFreezing of gait (FOG) is a common symptom in Parkinson's Disease (PD) patients. Previous studies have reported relationships between FOG, substantia nigra (SN) degeneration, dopamine transporter (DAT) concentration, as well as amyloid β deposition. However, there is a paucity of research on the concurrent impact of white matter damage.ObjectivesTo assess the inter-relationships between these different co-morbidities, their impact on future FOG and whether they act independently of each other.MethodsWe used baseline MRI and longitudinal gait data from 423 de novo PD patients from the Parkinson's Progression Markers Initiative (PPMI). We used deformation based morphometry (DBM) from T1-weighted MRI to measure SN atrophy, and segmentation of white matter hyperintensities (WMH) as a measure of WM pathological load. Putamen and caudate DAT levels from SPECT as well as cerebrospinal fluid (CSF) amyloid β were obtained directly from the PPMI. Following correlation analyses, we investigated whether WMH burden mediates the impact of amyloid β on future FOG.ResultsSN DBM, WMH load, putamen and caudate DAT activity and CSF amyloid β levels were significantly different between PD patients with and without future FOG (p < 0.008). Mediation analysis demonstrated an effect of CSF amyloid β levels on future FOG via WMH load, independent of SN atrophy and striatal DAT activity levels.ConclusionsAmyloid β might impact future FOG in PD patients through an increase in WMH burden, in a pathway independent of Lewy body pathology.     

Improving gait and promoting retention in individuals with Parkinson’s disease: a pilot study

We examined intensive walking practice using two instructional strategies on gait in Parkinson’s disease (PD) before and after training and on delayed retention tests. During four training sessions (15 practice trials of walking per session), subjects (N = 6 per group) were given either verbal instruction (VI) to “take a big step” or VI plus augmented feedback (FB). For FB, videotape performance-feedback (from prior trial) supplemented by performance-cues (for subsequent trial) was given after each trial. On pre- and posttests (1 week after training), the only instructions were to “walk as well as you can.” For available subjects (N = 7), retention was tested at 3, 6, or 12 months after training. Gait parameters were derived from kinematic analysis of walking during training and testing. From pre- to posttests, stride length, walking velocity and shoulder excursion increased significantly, with no change in cadence. Improvements in stride length and gait velocity above pretest levels were maintained on retention tests. During training and testing, no effects of VI versus VI + FB were found. Although the two instructional strategies did not differ, intensive practice walking with VI improved the gait pattern of individuals with PD and these gait improvements were maintained over an extended period of time.     

The effect of medication and the role of postural instability in different components of freezing of gait (FOG)

Freezing of gait (FOG) is associated with gait asymmetry and arrhythmicity, cognitive impairment in Parkinson's disease (PD). However, the role of postural instability (PI) in and the effect of dopaminergic medication (meds) on FOG are unclear. We investigated the effect of meds on FOG using a validated metric, Stepping in Place (SIP) and the relationship between PI and FOG.MethodsWe assessed static posturography (off meds), SIP, UPDRS-III (off/on meds) and the FOG-questionnaire (FOG-Q) in 15 freezers/15 non-freezers and 14 healthy controls.ResultsUPDRS-III, rigidity, tremor (P < 0.01) and axial subscores (P < 0.05) improved with meds in freezers. Only UPDRS-III and tremor improved in non-freezers (P < 0.01). Meds improved freezing episode (FE) frequency, duration and stride duration in freezers (P < 0.01). Over 73% of freezers did not freeze on meds, although one freezer had more and longer duration FEs. Meds did not improve SIP cycle asymmetry and arrhythmicity, which remained greater in freezers compared to other groups on and off meds (P < 0.01, P < 0.05 respectively). Center of pressure (CoP) mediolateral displacement and velocity (V_CoP) in both directions were larger in freezers (P < 0.05). FOG-Q was correlated with CoP anteroposterior displacement and mediolateral V_CoP (R = 0.42; R = 0.40, P < 0.05).The improvement of FOG frequency and duration but not of gait asymmetry and arrhythmicity on meds suggests that both dopaminergic and non-dopaminergic networks contribute to FOG. The correlations between postural instability and FOG severity and SIP asymmetry on meds, suggest that as the disease progresses, postural instability interferes with gait symmetry and lead to on meds FOG and falls.     

Attentional dysfunction and the punding spectrum in Parkinson's disease

BackgroundPunding is a complication of Parkinson's disease (PD) treatment and stimulant abuse that features excessive preoccupation with repetitive and/or aimless behaviors. We hypothesized that cognitive impairment and functional limitations influence how punding behaviors manifest in PD.MethodsWe extracted data on punding, hobbyism, and cognition from the Parkinson's Progression Marker Initiative (PPMI). Punding and hobbyism were measured with the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP) scale. We determined how cognition predicted punding and hobbyism behaviors—adjusting for levodopa dose, Hoehn & Yahr stage, disease duration, and age—using generalized estimating equation (GEE) logistic regression. Activities of daily living (ADL) and motor impairment were measured with the MDS-UPDRS scale.ResultsIn GEE logistic regression models, punding was selectively associated with lower scores on the Letter Number Sequencing test (LNS), the primary attention test in PPMI (Odds ratio: 0.87 (95% CI: 0.79–0.96); p = 0.022). This was corroborated by a subscale-analysis of Montreal Cognitive Assessment (MoCA) scores, as only the attention subscale was significantly associated with punding (OR: 0.59 (0.45–0.77); p < 0.001). Baseline impairment in LNS (Hazard ratio: 2.52 (1.22–5.20); p = 0.012) and MoCA attention (HR: 2.68 (1.32–5.42); p = 0.006) predicted earlier punding in Cox regression. In turn, ADL dysfunction predicted punding (OR: 1.55 (1.20–2.00); p < 0.001), but not hobbyism.ConclusionAttentional dysfunction is a domain-specific cognitive biomarker of punding risk in PD. Further, attentional capacity and functional impairment may determine the complexity of perseverative behaviors on the continuum from rudimentary punding to semi-purposeful hobbyism.     

Dorsal rather than ventral visual pathways discriminate freezing status in Parkinson's disease

BackgroundAlthough visuospatial deficits have been linked with freezing of gait (FOG) in Parkinson's disease (PD), the specific effects of dorsal and ventral visual pathway dysfunction on FOG is not well understood.MethodWe assessed visuospatial function in FOG using an angle discrimination test (dorsal visual pathway bias) and overlapping figure test (ventral visual pathway bias), and recorded overall response time, mean fixation duration and dwell time. Covariate analysis was conducted controlling for disease duration, motor severity, contrast sensitivity and attention with Bonferroni adjustments for multiple comparisons.ResultsTwenty seven people with FOG, 27 people without FOG and 24 controls were assessed. Average fixation duration during angle discrimination distinguished freezing status: [F (1, 43) = 4.77 p < 0.05] (1-way ANCOVA).ConclusionResults indicate a preferential dysfunction of dorsal occipito-parietal pathways in FOG, independent of disease severity, attentional deficit, and contrast sensitivity.     

Relation between freezing of gait and frontal function in Parkinson's disease

IntroductionFreezing of gait (FOG) is a common symptom of Parkinson's disease (PD). Although the pathophysiological mechanism of FOG is unknown, previous studies have suggested that frontal dysfunction is associated with FOG. The Behavioral Assessment of the Dysexecutive Syndrome (BADS) battery, which is wide-ranging neurological battery composed of six subtests, evaluates frontal function and is more sensitive to executive dysfunction (ED) than other tools in PD patients. This is the first study to assess the relation between FOG in the ‘on’ state and frontal dysfunction evaluated using BADS.MethodsSubjects were 65 patients with PD. Multiple logistic regression analysis was used to compare the age-controlled standardized BADS score, age, disease duration, Hoehn and Yahr (HY) stage, levodopa-equivalent daily dose, and Mini-Mental State Examination (MMSE) score across patients with FOG (n = 43) and patients without FOG (n = 22). Score on each of the six BADS subtests were compared across patients with and without FOG using the Mann–Whitney U test.ResultsMultiple logistic regression analysis revealed that FOG was related to lower age-controlled standardized BADS score (P = 0.022) and higher HY stage (P = 0.009) but not to disease duration, levodopa equivalent daily dose, or MMSE score. Among the six BADS subtests, score on the Zoo Map Test, which evaluates problem solving and planning, was lower in patients with FOG than in patients without FOG.ConclusionThese results support a relation between on-state FOG and frontal dysfunction in PD patients.     

Reduced after-effects following podokinetic adaptation in people with Parkinson's disease and freezing of gait

IntroductionGait dysfunction is common in people with Parkinson's disease (PD). Freezing of gait (FOG) is one such gait disturbance that significantly impacts mobility and quality of life in PD. Recent evidence suggests that cerebellar connectivity may differ in people with PD and FOG (PD+FOG) relative to those without FOG (PD-FOG). Investigation of gait adaptation, or the ability to change gait patterns in response to external perturbations, is cerebellum-dependent, is a practical means of probing cerebellar integrity and may provide additional insights regarding the FOG phenomenon.MethodsIn this study, we investigated gait adaptation in PD and FOG by measuring after-effects, namely whole-body rotation, following stepping on a rotating disc in PD+FOG compared to PD-FOG and older healthy adults. We refer to the period of stepping on the rotating disc as the podokinetic (PK) stimulation and after-effects as podokinetic after-rotation (PKAR). Our primary measure of adaptation was the magnitude and rate of decay of the after-effects.ResultsWe noted that PKAR was diminished in PD+FOG compared to the other groups, indicating reduced storage of the adapted gait pattern in PD+FOG. In the PD groups, FOG explained about 20% of the variability in peak velocity. Furthermore, these differences were independent of stepping cadence or motor sign severity.ConclusionOur results show that gait adaptation is impaired in PD+FOG, suggesting the cerebellum may be differentially impacted in PD+FOG compared to PD-FOG. This supports previous neuroimaging evidence of cerebellar dysfunction in PD+FOG. Overall, these data further our understanding of gait deficits in PD+FOG.