Relationships between Freezing of Gait Severity and Cognitive Deficits in Parkinson's Disease.
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ABSTRACT:
SUBMITTER: Scholl JL
PROVIDER: S-EPMC8615553 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: Olfactory dysfunction often occurs before motor onset in Parkinson's disease (PD) and can be detected with the University of Pennsylvania Smell Identification Test (UPSIT). Based on the Braak hypothesis, the olfactory bulb is one of two sites where disease pathology may start and spread to deeper brain structures. Objective: To evaluate whether a specific pattern of odorant identification on the UPSIT discriminated Parkinson's disease patients with and without freezing of gait. Methods: One hundred and twenty four consecutive participants (33 controls, 31 non-freezers, and 60 freezers) were administered the UPSIT. Using the chi-square test, each odorant on the UPSIT was ranked based on the differential ability of freezers and non-freezers to identify them correctly. Using predictive statistics and confusion matrices, the best combination of odorants and a cut-off score was determined. Results: Freezers had a shift toward a more severe hyposmia classification based on age and sex based normative values. The correct identification of nine odors (bubblegum, chocolate, smoke, wintergreen, paint thinner, orange, strawberry, grass, and peanut) was significantly worse in freezers compared to non-freezers. Correctly identifying ≤ 2 out of 3-odorants (bubblegum, chocolate, and smoke) had a 77% sensitivity and 61% specificity for categorizing freezers. The 3-odorant score was not correlated with disease duration, motor or total UPDRS scores, MoCA scores or age at testing. The predictive statistics were similar when sexes were separately categorized. Conclusions: A 3-odorant score helped categorize freezers and non-freezers with similar sensitivity and specificity to short odorant Parkinson's disease identification batteries.
| S-EPMC8397477 | biostudies-literature
Project description:Freezing of gait (FOG) is common in people with Parkinson's disease (PD) which is extremely debilitating. One hypothesis for the cause of FOG episodes is impaired cognitive control, however, this is still in debate in the literature. We aimed to assess a comprehensive range of cognitive tests in older adults and people with Parkinson's with and without FOG and associate FOG severity with cognitive performance. A total of 227 participants took part in the study which included 80 healthy older adults, 81 people with PD who did not have FOG and 66 people with PD and FOG. A comprehensive battery of neuropsychological assessments tested cognitive domains of global cognition, executive function/attention, working memory, and visuospatial function. The severity of FOG was assessed using the new FOG questionnaire and an objective FOG severity score. Cognitive performance was compared between groups using an ANCOVA adjusting for age, gender, years of education and disease severity. Correlations between cognitive performance and FOG severity were analyzed using partial correlations. Cognitive differences were observed between older adults and PD for domains of global cognition, executive function/attention, and working memory. Between those with and without FOG, there were differences for global cognition and executive function/attention, but these differences disappeared when adjusting for covariates. There were no associations between FOG severity and cognitive performance. This study identified no significant difference in cognition between those with and without FOG when adjusting for covariates, particularly disease severity. This may demonstrate that complex rehabilitation programs may be undertaken in those with FOG.
| S-EPMC7228938 | biostudies-literature
Project description:BackgroundFreezing of gait (FOG) is a disabling gait disorder influencing patients with Parkinson's disease (PD). Accumulating evidence suggests that FOG is related to the functional alterations within brain networks. We investigated the changes in brain resting-state functional connectivity (FC) in patients with PD with FOG (FOG+) and without FOG (FOG-).MethodsResting-state functional magnetic resonance imaging (RS-fMRI) data were collected from 55 PD patients (25 FOG+ and 30 FOG-) and 26 matched healthy controls (HC). Differences in intranetwork connectivity between FOG+, FOG-, and HC individuals were explored using independent component analysis (ICA).ResultsSeven resting-state networks (RSNs) with abnormalities, including motor, executive, and cognitive-related networks, were found in PD patients compared to HC. Compared to FOG- patients, FOG+ patients had increased FC in advanced cognitive and attention-related networks. In addition, the FC values of the auditory network and default mode network were positively correlated with the Gait and Falls Questionnaire (GFQ) and Freezing of Gait Questionnaire (FOGQ) scores in FOG+ patients.ConclusionsOur findings suggest that the neural basis of PD is associated with impairments of multiple functional networks. Notably, alterations of advanced cognitive and attention-related networks rather than motor networks may be related to the mechanism of FOG.
| S-EPMC7568140 | biostudies-literature
Project description:BackgroundThe relationship between freezing of gait (FOG) and levodopa response is complex. Some patients respond, some have no response and in some patients levodopa causes FOG. We present 2 cases demonstrating a diphasic worsening of FOG after levodopa dosing.CasesTwo PD patients with FOG were examined during the practically defined off state, the transition from off to on (15 and 22 minutes postdose), and in the full on state (45 and 60 minutes postdose). FOG was measured using Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III, item 11: freezing of gait. Both patients experienced worsening of FOG during the transition followed by improvement during the on state. Case 1 had serum levodopa levels measured. Videos are provided.ConclusionsTo our knowledge, this diphasic pattern of worsening of FOG has not been previously reported. The cause of this phenomenon is unknown but may relate to an inhibitory action of subthreshold levels of levodopa.
| S-EPMC7111566 | biostudies-literature
Project description:Freezing of gait (FOG) is arguably the most severe symptom associated with Parkinson's disease (PD), and often occurs while performing dual tasks or approaching narrowed and cluttered spaces. While it is well known that visual cues alleviate FOG, it is not clear if this effect may be the result of cognitive or sensorimotor mechanisms. Nevertheless, the role of vision may be a critical link that might allow us to disentangle this question. Gaze behaviour has yet to be carefully investigated while freezers approach narrow spaces, thus the overall objective of this study was to explore the interaction between cognitive and sensory-perceptual influences on FOG. In experiment #1, if cognitive load is the underlying factor leading to FOG, then one might expect that a dual-task would elicit FOG episodes even in the presence of visual cues, since the load on attention would interfere with utilization of visual cues. Alternatively, if visual cues alleviate gait despite performance of a dual-task, then it may be more probable that sensory mechanisms are at play. In compliment to this, the aim of experiment#2 was to further challenge the sensory systems, by removing vision of the lower-limbs and thereby forcing participants to rely on other forms of sensory feedback rather than vision while walking toward the narrow space. Spatiotemporal aspects of gait, percentage of gaze fixation frequency and duration, as well as skin conductance levels were measured in freezers and non-freezers across both experiments. Results from experiment#1 indicated that although freezers and non-freezers both walked with worse gait while performing the dual-task, in freezers, gait was relieved by visual cues regardless of whether the cognitive demands of the dual-task were present. At baseline and while dual-tasking, freezers demonstrated a gaze behaviour that neglected the doorway and instead focused primarily on the pathway, a strategy that non-freezers adopted only when performing the dual-task. Interestingly, with the combination of visual cues and dual-task, freezers increased the frequency and duration of fixations toward the doorway, compared to non-freezers. These results suggest that although increasing demand on attention does significantly deteriorate gait in freezers, an increase in cognitive demand is not exclusively responsible for freezing (since visual cues were able to overcome any interference elicited by the dual-task). When vision of the lower limbs was removed in experiment#2, only the freezers' gait was affected. However, when visual cues were present, freezers' gait improved regardless of the dual-task. This gait behaviour was accompanied by greater amount of time spent looking at the visual cues irrespective of the dual-task. Since removing vision of the lower-limbs hindered gait even under low attentional demand, restricted sensory feedback may be an important factor to the mechanisms underlying FOG.
| S-EPMC4682987 | biostudies-literature
Project description:Experimental data show that perceptual cues can either exacerbate or ameliorate freezing of gait (FOG) in Parkinson's Disease (PD). For example, simple visual stimuli like stripes on the floor can alleviate freezing whereas complex stimuli like narrow doorways can trigger it. We present a computational model of the cognitive and motor cortico-basal ganglia loops that explains the effects of sensory and cognitive processes on FOG. The model simulates strong causative factors of FOG including decision conflict (a disagreement of various sensory stimuli in their association with a response) and cognitive load (complexity of coupling a stimulus with downstream mechanisms that control gait execution). Specifically, the model simulates gait of PD patients (freezers and non-freezers) as they navigate a series of doorways while simultaneously responding to several Stroop word cues in a virtual reality setup. The model is based on an actor-critic architecture of Reinforcement Learning involving Utility-based decision making, where Utility is a weighted sum of Value and Risk functions. The model accounts for the following experimental data: (a) the increased foot-step latency seen in relation to high conflict cues, (b) the high number of motor arrests seen in PD freezers when faced with a complex cue compared to the simple cue, and (c) the effect of dopamine medication on these motor arrests. The freezing behavior arises as a result of addition of task parameters (doorways and cues) and not due to inherent differences in the subject group. The model predicts a differential role of risk sensitivity in PD freezers and non-freezers in the cognitive and motor loops. Additionally this first-of-its-kind model provides a plausible framework for understanding the influence of cognition on automatic motor actions in controls and Parkinson's Disease.
| S-EPMC5220109 | biostudies-literature
Project description:BACKGROUND:The etiology of freezing of gait in Parkinson's disease (PD) is yet to be clarified. Non-motor risk factors including cognitive impairment, sleep disturbance and mood disorders have been shown in freezing of gait. RESEARCH QUESTION:We aimed to determine the predictive value of non-motor features in freezing of gait development. METHODS:Data were obtained from the Parkinson's Progression Markers Initiative. Fifty PD patients with self-reported freezing of gait, and 50 PD patients without freezing of gait at the fourth year visit were included. Groups were matched for Movement Disorders Society-Unified Parkinson's Disease Rating Scale Part III scores. Several cognitive and non-cognitive tests were used for non-motor features at baseline and over time. Executive function, visuospatial function, processing speed, learning and memory tests were used for cognition. Non-cognitive tests included sleepiness, REM sleep behavior disorder, depression and anxiety scales. RESULTS:Patients with freezing of gait had higher scores on sleepiness, REM sleep behavior disorder, depression and anxiety scales. However, predictor model analysis revealed that baseline processing speed, learning and sleepiness scores were predictive of self-reported freezing of gait development over time. SIGNIFICANCE:Our findings suggest that specific cognitive deficits and sleep disorders are predictive of future freezing of gait. These features may be helpful in identifying underlying networks in freezing of gait and should be further investigated with neuroimaging studies.
| S-EPMC6773271 | biostudies-literature
Project description:BackgroundFreezing of gait is a debilitating symptom of Parkinson's disease associated with high risks of falls and poor quality of life. While productive therapy for FoG is still underway, early prediction of FoG could help high-risk PD patients to take preventive measures. In this study, we predicted the onset of FoG in de novo PD patients using a battery of risk factors from patients enrolled in PPMI cohort.MethodsBaseline characteristics were compared between subjects who developed FoG (68 patients, 37.2%, pre-FoG group) during the five-year follow up and subjects who did not (115 patients, 62.8%, non-FoG group). A multivariate logistic regression model was built based on backward stepwise selection of factors that were associated with FoG onset in the univariate analysis. ROC curves were used to assess sensitivity and specificity of the predictive model.ResultsAt baseline, age, PIGD score, cognitive functions, autonomic functions, sleep behavior, fatigue and striatal DAT uptake were significantly different in the pre-FoG group relative to the non-FoG group. However, there was no difference in genetic characteristics between the two patient sets. Univariate analysis showed several motor and non-motor factors that correlated with FoG, including PIGD score, MDS-UPDRS part II score, SDMT score, HVLT Immediate/Total Recall, MOCA, Epworth Sleepiness Scale, fatigue, SCOPA-AUT gastrointestinal score, SCOPA-AUT urinary score and CSF biomarker Abeta42. Multivariate logistic analysis stressed that high PIGD score, fatigue, worse SDMT performance and low levels of Abeta42 were independent risk factors for FoG onset in PD patients.ConclusionsCombining motor and non-motor features including PIGD score, poor cognitive functions and CSF Abeta can identify PD patients with high risk of FoG onset.
| S-EPMC9172010 | biostudies-literature
Project description:This study investigated longitudinal clinical, structural and functional brain alterations in Parkinson's disease patients with freezing of gait (PD-FoG) and in those developing (PD-FoG-converters) and not developing FoG (PD-non-converters) over two years. Moreover, this study explored if any clinical and/or MRI metric predicts FoG development. Thirty PD-FoG, 11 PD-FoG-converters and 11 PD-non-converters were followed for two years. Thirty healthy controls were included at baseline. Participants underwent clinical and MRI visits. Cortical thickness, basal ganglia volumes and functional network graph metrics were evaluated at baseline and over time. In PD groups, correlations between baseline MRI and clinical worsening were tested. A ROC curve analysis investigated if baseline clinical and MRI measures, selected using a stepwise model procedure, could differentiate PD-FoG-converters from PD-non-converters. At baseline, PD-FoG patients had widespread cortical/subcortical atrophy, while PD-FoG-converters and non-converters showed atrophy in sensorimotor areas and basal ganglia relative to controls. Over time, PD-non-converters accumulated cortical thinning of left temporal pole and pallidum without significant clinical changes. PD-FoG-converters showed worsening of disease severity, executive functions, and mood together with an accumulation of occipital atrophy, similarly to PD-FoG. At baseline, PD-FoG-converters relative to controls and PD-FoG showed higher global and parietal clustering coefficient and global local efficiency. Over time, PD-FoG-converters showed reduced parietal clustering coefficient and sensorimotor local efficiency, PD-non-converters showed increased sensorimotor path length, while PD-FoG patients showed stable graph metrics. Stepwise prediction model including dyskinesia, postural instability and gait disorders scores and parietal clustering coefficient was the best predictor of FoG conversion. Combining clinical and MRI data, ROC curves provided the highest classification power to predict the conversion (AUC = 0.95, 95%CI: 0.86-1). Structural MRI is a useful tool to monitor PD progression, while functional MRI together with clinical features may be helpful to identify FoG conversion early.
| S-EPMC9666554 | biostudies-literature
Project description:IntroductionFreezing of gait (FoG) is one of the most disabling yet poorly understood symptoms of Parkinson's disease (PD). FoG is an episodic gait pattern characterized by the inability to step that occurs on initiation or turning while walking, particularly with perception of tight surroundings. This phenomenon impairs balance, increases falls, and reduces the quality of life.Materials and methodsClinical-anatomical correlations, electrophysiology, and functional imaging have generated several mechanistic hypotheses, ranging from the most distal (abnormal central pattern generators of the spinal cord) to the most proximal (frontal executive dysfunction). Here, we review the neuroanatomy and pathophysiology of gait initiation in the context of FoG, and we discuss targets of central nervous system neuromodulation and their outcomes so far. The PubMed database was searched using these key words: neuromodulation, freezing of gait, Parkinson's disease, and gait disorders.ConclusionDespite these investigations, the pathogenesis of this process remains poorly understood. The evidence presented in this review suggests FoG to be a heterogenous phenomenon without a single unifying pathologic target. Future studies rigorously assessing targets as well as multimodal approaches will be essential to define the next generation of therapeutic treatments.
| S-EPMC8233405 | biostudies-literature