Cognitive function in people with and without freezing of gait in Parkinson's disease.
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ABSTRACT:
SUBMITTER: Morris R
PROVIDER: S-EPMC7228938 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Freezing of gait (FOG) is one of the most debilitating motor symptoms experienced by patients with Parkinson's disease (PD), as it can lead to falls and a reduced quality of life. Evidence supports an association between FOG severity and cognitive functioning; however, results remain debatable. PD patients with (PDFOG+, n = 41) and without FOG (PDFOG-, n = 39) and control healthy subjects (n = 41) participated in this study. The NIH toolbox cognition battery, the Montreal Cognitive Assessment (MoCA), and the interval timing task were used to test cognitive domains. Measurements were compared between groups using multivariable models and adjusting for covariates. Correlation analyses, linear regression, and mediation models were applied to examine relationships among disease duration and severity, FOG severity, and cognitive functioning. Significant differences were observed between controls and PD patients for all cognitive domains. PDFOG+ and PDFOG- exhibited differences in Dimensional Change Card Sort (DCCS) test, interval timing task, and MoCA scores. After adjusting for covariates in two different models, PDFOG+ and PDFOG- differed in both MoCA and DCCS scores. In addition, significant relationships between FOG severity and cognitive function (MoCA, DCCS, and interval timing) were also found. Regression models suggest that FOG severity may be a predictor of cognitive impairment, and mediation models show the effects of cognitive impairment on the relationship between disease severity and FOG severity. Overall, this study provides insight into the relationship between cognitive and FOG severity in patients with PD, which could aid in the development of therapeutic interventions to manage both.
| S-EPMC8615553 | biostudies-literature
Project description:The study aimed to investigate the neural changes that differentiate Parkinson's disease patients with freezing of gait and age-matched controls, using ambulatory electroencephalography event-related features. Compared to controls, definite freezers exhibited significantly less alpha desynchronization at the motor cortex about 300 ms before and after the start of overground walking and decreased low-beta desynchronization about 300 ms before and about 300 and 700 ms after walking onset. The late slope of motor potentials also differed in the sensory and motor areas between groups of controls, definite, and probable freezers. This difference was found both in preparation and during the execution of normal walking. The average frontal peak of motor potential was also found to be largely reduced in the definite freezers compared with the probable freezers and controls. These findings provide valuable insights into the underlying structures that are affected in patients with freezing of gait, which could be used to tailor drug development and personalize drug care for disease subtypes. In addition, the study's findings can help in the evaluation and validation of nonpharmacological therapies for patients with Parkinson's disease.
| S-EPMC10495228 | biostudies-literature
Project description:BackgroundFreezing of gait (FOG), is associated with impairment of different cognitive functions. Previous studies hypothesized that FOG may be due to a loss of automaticity.Research questionTo explore whether FOG is associated with impairment in cognitive functions, focusing on retrograde procedural memory, the memory responsible for the automatic, implicit stored procedures that have been acquired in earlier life stages.MethodsIn this cross-sectional, case-control study, 288 people with typical Parkinson's disease (PD) from the Luxembourg Parkinson's Study were assigned to Freezers (FOG+) and non-Freezers (FOG-) based on the MDS-UPDRS 2.13 (self-reported FOG episodes) and 3.11 (FOG evaluated by clinicians during gait assessment). Both groups were matched on age, sex and disease duration. Global cognition (MoCA), retrograde procedural memory and visuo-constructive abilities (CUPRO), psychomotor speed and mental flexibility (TMT) were assessed. Furthermore, we repeated our analyses by additionally controlling for depression (BDI-I).ResultsBesides lower global cognition (MoCA; p = 0.007) and mental flexibility (TMT-B and Delta-TMT; p < 0.001), FOG+ showed a lower performance in retrograde procedural memory (CUPRO-IS1; p < 0.001) compared to FOG-. After controlling additionally for depression, our main outcome variable CUPRO-IS1 remained significantly lower in FOG+ (p = 0.010).ConclusionOur findings demonstrated that besides lower global cognition and mental flexibility scores, FOG+ showed lower performance in retrograde procedural memory compared to matched FOG-control patients, even when accounting for factors such as age, sex, disease duration or depression.SignificanceIn the context of limited treatment options, especially for non-invasive therapeutic approaches, these insights on procedural memory and FOG may lead to new hypotheses on FOG etiology and consequently the development of new treatment options.
| S-EPMC10797621 | biostudies-literature
Project description:ObjectiveFreezing of gait (FoG) in Parkinson's disease (PD) has been associated with response inhibition. However, the relationship between response inhibition, neural dysfunction, and PD remains unclear. We assessed response inhibition and microstructural integrity of brain regions involved in response inhibition [right hemisphere inferior frontal cortex (IFC), bilateral pre-supplementary motor areas (preSMA), and subthalamic nuclei (STN)] in PD subjects with and without FoG and elderly controls.MethodTwenty-one people with PD and FoG (PD-FoG), 18 without FoG (PD-noFoG), and 19 age-matched controls (HC) completed a Stop-Signal Task (SST) and MRI scan. Probabilistic fiber tractography assessed structural integrity (fractional anisotropy, FA) among IFC, preSMA, and STN regions.ResultsStop-signal performance did not differ between PD and HC, nor between PD-FoG and PD-noFoG. Differences in white matter integrity were observed across groups (.001 < p < .064), but were restricted to PD versus HC groups; no differences in FA were observed between PD-FoG and PD-noFoG (p > .096). Interestingly, worse FoG was associated with higher (better) mean FA in the r-preSMA, (β = .547, p = .015). Microstructural integrity of the r-IFC, r-preSMA, and r-STN tracts correlated with stop-signal performance in HC (p ≤ .019), but not people with PD.ConclusionThese results do not support inefficient response inhibition in PD-FoG. Those with PD exhibited white matter loss in the response inhibition network, but this was not associated with FoG, nor with response inhibition deficits, suggesting FoG-specific neural changes may occur outside the response inhibition network. As shown previously, white matter loss was associated with response inhibition in elderly controls, suggesting PD may disturb this relationship.
| S-EPMC8187475 | biostudies-literature
Project description:BackgroundFreezing of gait (FOG) is a debilitating, variably expressed motor symptom in people with Parkinson's disease (PwPD) with limited treatments.ObjectiveTo determine if the rate of progression in spatiotemporal gait parameters in people converting from a noFOG to a FOG phenotype (FOGConv) was faster than non-convertors, and determine if gait parameters can help predict this conversion.MethodsPwPD were objectively monitored longitudinally, approximately every 6 months. Non-motor assessments were performed at the initial visit. Steady-state gait in the levodopa ON-state was collected using a gait mat (Protokinetics) at each visit. The rate of progression in 8 spatiotemporal gait parameters was calculated. FOG convertors (FOGConv) were classified if they did not have FOG at initial visit and developed FOG at a subsequent visit.ResultsThirty freezers (FOG) and 30 non-freezers were monitored an average of 3.5 years, with 10 non-freezers developing FOG (FOGConv). FOGConv and FOG had faster decline in mean stride-length, swing-phase-percent, and increase in mean total-double-support percent, coefficient of variability (CV) foot-strike-length and CV swing-phase-percent than the remaining non-freezers (noFOG). On univariate modeling, progression rates of mean stride-length, stride-velocity, swing-phase-percent, total-double-support-percent and of CV swing-phase-percent had high discriminative power (AUC > 0.83) for classification of the FOGConv and noFOG groups.ConclusionFOGConv had a faster temporal decline in objectively quantified gait than noFOG, and progression rates of spatiotemporal gait parameters were more predictive of FOG phenotype conversion than initial (static) parameters Objectively monitoring gait in disease prediction models may help define FOG prone groups for testing putative treatments.
| S-EPMC10578275 | 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:In Parkinson's disease, the optimal attentional focus strategy for dual-task walking may vary with freezing of gait (FOG), due to different severities of impaired automaticity. The study aimed to investigate (i) the immediate effect of attentional focus on dual-task walking in participants with and without FOG, and (ii) the training effect of attentional focus on walking, FOG, and falls. In experiment 1, FOG and non-FOG groups (16 participants each) performed a dual-task of holding two interlocking rings apart while walking, either without attention instruction or with instructions to focus attention internally or externally. Gait parameters and ring-touching times were measured. In experiment 2, 30 participants with FOG were randomized to 6 weeks of dual-task training with internal-focus or external-focus instruction. Before and after training, we recorded timed up-and-go (TUG) and TUG dual-task (TUGdt) in on-medication and off-medication states, and the numbers of FOG episodes and falls. The non-FOG group showed less step length variability and shorter ring-touching times with external-focus. The FOG group showed less step length variability, less cadence, increased gait velocity, and longer step lengths with internal-focus compared to external-focus and no-focus instructions. Both internal-focus and external-focus training reduced FOG and falls after intervention, but only internal-focus training reduced TUG and TUGdt in both on-medication and off-medication states. Our findings suggest external-focus would enhance walking automaticity and the concurrent task accuracy for non-freezers, whereas for freezers, internal-focus could increase gait stability and lead to a more positive effect on improving locomotion control and reducing falling risk.
| S-EPMC9886752 | 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