scholarly journals Relationships between Freezing of Gait Severity and Cognitive Deficits in Parkinson’s Disease

2021 ◽  
Vol 11 (11) ◽  
pp. 1496
Author(s):  
Jamie L. Scholl ◽  
Arturo I. Espinoza ◽  
Wijdan Rai ◽  
Matt Leedom ◽  
Lee A. Baugh ◽  
...  

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.

2021 ◽  
Author(s):  
Jamie L. Scholl ◽  
Arturo I. Espinoza ◽  
Matt Leedom ◽  
Lee A. Baugh ◽  
Patti Berg-Poppe ◽  
...  

Introduction: 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 reduced quality of life. Evidence supports an association between FOG severity and cognitive functioning; however, results are varied. Methods: PD patients with (PDFOG+, n=41) and without FOG (PDFOG-, n=39) and control healthy subjects (n=41) participated in the study. The NIH toolbox cognition battery, Montreal cognitive assessment (MoCA), and 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. Results: Significant differences were observed between controls and PD patients for all cognitive domains. PDFOG+ and PDFOG- exhibited differences in the 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. Conclusions: Overall, this study provides insight into the relationship between cognitive and gait impairments in patients with PD, which could aid in the development of therapeutic interventions to manage both.


2017 ◽  
Author(s):  
Young-Cho Kim ◽  
Nandakumar S. Narayanan

AbstractConsiderable evidence has shown that prefrontal neurons expressing D1-type dopamine receptors (D1DRs) are critical for working memory, flexibility, and timing. This line of work predicts that frontal neurons expressing D1DRs mediate cognitive processing. During timing tasks, one form this cognitive processing might take is time-dependent ramping activity — monotonic changes in firing rate over time. Thus, we hypothesized the prefrontal D1DR+ neurons would strongly exhibited time-dependent ramping during interval timing. We tested this idea using an interval-timing task in which we used optogenetics to tag D1DR+ neurons in the mouse medial frontal cortex (MFC). While 23% of MFC D1DR+ neurons exhibited ramping, this was significantly less than untagged MFC D1DR+ neurons. By contrast, MFC D1DR+ neurons had strong delta-frequency (1-4 Hz) coherence with other MFC ramping neurons. This coherence was phase-locked to cue onset and was strongest early in the interval. To test the significance of these interactions, we optogenetically stimulated MFC D1DR+ neurons early vs. late in the interval. We found that 2-Hz stimulation early in the interval was particularly effective in rescuing timing-related behavioral performance deficits in dopamine-depleted animals. These findings provide insight into MFC networks and have relevance for disorders such as Parkinson’s disease and schizophrenia.Significance StatementPrefrontal D1DRs are involved in cognitive processing and cognitive dysfunction in human diseases such as Parkinson’s disease and schizophrenia. We use optogenetics to identify these neurons, as well as neurons that are putatively connected to MFC D1DR+ neurons. We study these neurons in detail during an elementary cognitive task. These data could have relevance for cognitive deficits for Parkinson’s disease, schizophrenia, and other diseases involving frontal dopamine.


2019 ◽  
Author(s):  
Nesrin Helvaci Yilmaz ◽  
Mevhibe Saricaoglu ◽  
Hale Yapici Eser ◽  
Ozge Arici Duz ◽  
Burcu Polat ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
David Gordon Lichter ◽  
Ralph Holmes Boring Benedict ◽  
Linda Ann Hershey

Background. Freezing of gait (FOG) is a debilitating and incompletely understood symptom in Parkinson’s disease (PD). Objective. To determine the principal clinical factors predisposing to FOG in PD, their interactions, and associated nonmotor symptoms. Methods. 164 PD subjects were assessed in a cross-sectional retrospective study, using the MDS-UPDRS scale, MMSE, and Clinical Dementia Rating Scale. Clinical factors associated with FOG were determined using univariate analysis and nominal logistic regression. Receiver operating characteristic curves were computed, to obtain measures of sensitivity and specificity of predictors of FOG. Subgroups of patients with FOG were compared with those without FOG, based on defining aspects of their clinical phenotype. Results. Relative to non-FOG patients, those with FOG had a longer disease duration, higher PIGD and balance-gait score, higher LED, and more motor complications ( p < 0.0001 ) and were more likely to exhibit urinary dysfunction ( p < 0.0003 ), cognitive impairment, hallucinations, and psychosis ( p = 0.003 ). The balance-gait score and motor complications, at their optimum cutoff values, together predicted FOG with 86% accuracy. Interactions were noted between cognitive dysfunction and both the Bal-Gait score and motor complication status, cognitive impairment or dementia increasing the likelihood of FOG in subjects without motor complications ( p = 0.0009 ), but not in those with motor complications. Conclusions. Both disease and treatment-related factors, notably LED, influence the risk of FOG in PD, with a selective influence of cognitive dysfunction in patients with balance-gait disorder but not in those with motor fluctuations. These findings may help to inform clinical management and highlight distinct subgroups of patients with PD-FOG, which are likely to differ in their network pathophysiology.


2021 ◽  
Vol 5 (3) ◽  
pp. 539-545
Author(s):  
Meldayeni Busra ◽  
Yuliarni Syafrita ◽  
Hendra Permana

Introduction: Cognitive impairment is a non-motor symptom of Parkinson's disease (PD) which occurs as the disease progresses and affects quality of life. Many efforts have been developed in early detection of cognitive disorders, one of which is the examination of tau protein biomarkers, where the tau protein that undergoes pathological changes to form neurofibrillary tangles (NFTs) is found in Alzheimer's disease and PD and plays a role in cognitive impairment. However, the role of tau in PD is still controversial. This study aims to assess the relationship between serum tau levels and cognitive function and the factors that affect cognitive function in PD patients. Methods: This cross-sectional design was conducted at the RSUP DR. M Djamil Padang. During the period March to August 2020, 62 research subjects were obtained. Cognitive function examination was carried out by using the MoCA-Ina test and examination of serum tau levels using the Elisa method. The relationship between categorical variables was tested by Chi square and differences in serum tau levels in the group with and without cognitive impairment were tested with the Mann Whitney test, considered statistically significant if the p value <0.05. Results: With Moca Ina examination, it was found that 67.7% of patients had impaired cognitive function. The mean serum tau level was 198.004 ± 162.69 ng / L.There was a significant relationship between education level and degree of disease with cognitive function (p <0.05) and there was no difference in mean serum tau levels between groups with and without cognitive impairment. Conclusion: There is a significant relationship between education level and degree of disease with cognitive function and there is no difference in mean serum tau protein levels between the cognitive impaired group and the cognitive normal group.


2017 ◽  
Vol 24 (1) ◽  
pp. 33-44 ◽  
Author(s):  
Anna Isabel Garcia-Diaz ◽  
Barbara Segura ◽  
Hugo Cesar Baggio ◽  
Maria Jose Marti ◽  
Francesc Valldeoriola ◽  
...  

AbstractBackground: Diagnosis of mild cognitive impairment in Parkinson’s disease (PD) is relevant because it is a marker for evolution to dementia. However, the selection of suitable tests to evaluate separate cognitive domains in mild cognitive impairment related to PD remains an open question. The current work aims to investigate the neuroanatomical correlates of several visuospatial/visuoperceptual tests using the same sample and a multimodal MRI approach. Methods: The study included 36 PD patients and 20 healthy subjects matched for age, sex, and education. The visuospatial/visuoperceptual tests selected were: Pentagon Copying Test (PCT), Judgment of Line Orientation Test (JLOT), Visual Form Discrimination Test (VFDT), Facial Recognition Test (FRT), Symbol Digit Modalities Test (SMDT), and clock copying task (CLOX2). FreeSurfer was used to assess cortical thickness, and tract-based spatial statistics was used for fractional anisotropy analysis. Results: Lower performance in the PCT, JLOT, and SDMT was associated with extensive cortical thickness reductions in lateral parietal and temporal regions. VFDT and CLOX2 did not show this common pattern and correlated with more limited medial occipito-temporal and occipito-parietal regions. Performance in all visuospatial/visuoperceptual tests correlated with fractional anisotropy in the corpus callosum. Conclusions: Our findings show that JLOT, SDMT, and PCT, in addition to differentiating patients from controls, are suitable visuospatial/visuoperceptual tests to reflect cortical thinning in lateral temporo-parietal regions in PD patients. We did not observe the dissociation between dorsal and ventral streams that was expected according to the neuropsychological classification of visuospatial and visuoperceptual tests. (JINS, 2018, 24, 33–44)


2020 ◽  
Author(s):  
Qingguang Wang ◽  
Wei He ◽  
Dinghua Liu ◽  
Bojun Han ◽  
Qitao Jiang ◽  
...  

Abstract Background: To explore the alteration of pattens of anatomical and functional connectivity (FC) of posterior cingulate cortex (PCC) in Parkinson's disease (PD) patients with cognitive dysfunction and the relationship between the connection strengths and cognitive state.Methods: We prospectively enrolled 20 PD patients with mild cognitive impairment (PD-MCI), 13 PD patients with normal cognition (PD-NC) and 13 healthy controls (HCs). All subjects underwent clinical evaluations and MRI scans. By collecting, preprocessing and FC analyzing resting-state functional magnetic resonance imaging (rs-fMRI) data, we extracted default mode network (DMN) patterns, compared the differences in DMN between the three groups and the analyzed the correlation between FC value with the commonly used neuropsychological testing.Results: There were not significant differences with regard to demographic data among the three groups. The PD-MCI showed significant worse performances in general cognition, and PD-NC and HCs showed comparable performances of cognitive function. Cognitive-related differences in DMN were detected in the bilateral precuneus (BPcu). Compared with the HCs, PD-NC and PD-MCI showed significantly decreased FC within BPcu (both P < 0.001). For PD-MCI, the rho of the the Fisher’s Z-transformed FC (zFC) value within BPcu with the TMTA, DSST and CFT-20min were − 0.50, 0.66 and 0.47, respectively. For PD-NC, the rho of the zFC value within BPcu with the MMSE was 0.58.Conclusions: Our research found that BPcu was the cognitive related region in DMN. As cognition declines, FC within BPcu weaken. For PD-MCI, the higher the FC values within BPcu were related to the better the performances of TMTA, DSST and CFT-20 min DR. For PD patients with normal cognition, the FC within BPcu were positively correlated with scores of MMSE.


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