Dysfunction In Parkinson's Disease Patients Research Articles

Corpus callosum and cerebellum participate in semantic dysfunction of Parkinson's disease: a diffusion tensor imaging-based cross-sectional study.

Language dysfunction is common in Parkinson's disease (PD) patients, among which, the decline of semantic fluency is usually observed. This study aims to explore the relationship between white matter (WM) alterations and semantic fluency changes in PD patients. 127 PD patients from the Parkinson's Progression Markers Initiative cohort who received diffusion tensor imaging scanning, clinical assessment and semantic fluency test (SFT) were included. Tract-based special statistics, automated fiber quantification, graph-theoretical and network-based analyses were performed to analyze the correlation between WM structural changes, brain network features and semantic fluency in PD patients. Fractional anisotropy of corpus callosum, anterior thalamic radiation, inferior front-occipital fasciculus, and uncinate fasciculus, were positively correlated with SFT scores, while a negative correlation was identified between radial diffusion of the corpus callosum, inferior longitudinal fasciculus, and SFT scores. Automatic fiber quantification identified similar alterations with more details in these WM tracts. Brain network analysis positively correlated SFT scores with nodal efficiency of cerebellar lobule VIII, and nodal local efficiency of cerebellar lobule X. WM integrity and myelin integrity in the corpus callosum and several other language-related WM tracts may influence the semantic function in PD patients. Damage to the cerebellum lobule VIII and lobule X may also be involved in semantic dysfunction in PD patients.

Parkinsons disease diagnosis through electroencephalographic signal processing and neural network classification

Parkinsons disease diagnosis through electroencephalographic signal processing and neural network classification

Associations of blood UCH-L1 and NfL levels with cognitive dysfunction in Parkinson’s disease patients

ObjectiveUbiquitin carboxy-terminal hydrolase L1 (UCH-L1) and Neurofilament light chain (NfL) are associated with Lewy body formation, Lewy bodies are the main pathological feature of Parkinson's disease (PD). The relationship between UCH-L1 and PD cognition remains unclear, and NfL is an important marker of cognitive impairment. The aim of this study is to investigate the relationship among serum UCH-L1 levels, plasma NfL levels and cognitive dysfunction in PD patients. ResultsThere were significant differences in UCH-L1 and NfL levels among PD patients with normal cognitive function (PD-CN), PD patients with mild cognitive impairment (PD-MCI), and PD-dementia patients (PDD) (P < 0.001; P < 0.001). The PDD group had lower levels of UCH-L1 (Z = 6.721, P < 0.001; Z = 7.577, P < 0.001) and higher levels of NfL (Z = −3.626, P = 0.001; Z = −2.616P = 0.027) than the PD-NC and PD-MCI groups. Serum UCH-L1 levels were positively correlated with MMSE scores, MoCA scores, and its subitems in PD patients (P < 0.001), and plasma NfL levels were negatively correlated with MMSE scores, MoCA scores, and its items (P < 0.01) (except for “abstract”). ConclusionDecreased UCH-L1 levels and elevated NfL levels in the blood are associated with cognitive dysfunction in PD; thus, these proteins are potential biomarkers for the diagnosis of cognitive dysfunction in PD patients.

Serum glial cell line-derived neurotrophic factor (GDNF) a potential biomarker of executive function in Parkinson's disease.

Evidence shows that the impairment of executive function (EF) is mainly attributed to the degeneration of frontal-striatal dopamine pathway. Glial cell line-derived neurotrophic factor (GDNF), as the strongest protective neurotrophic factor for dopaminergic neurons (DANs), may play a role in EF to some extent. This study mainly explored the correlation between serum GDNF concentration and EF performance in Parkinson's disease (PD). This study recruited 45 healthy volunteers (health control, HC) and 105 PD patients, including 44 with mild cognitive impairment (PD-MCI), 20 with dementia (PD-D), and 20 with normal cognitive function (PD-N). Neuropsychological tests were performed to evaluate EF (working memory, inhibitory control, and cognitive flexibility), attention, language, memory, and visuospatial function. All subjects were tested for serum GDNF and homovanillic acid (HVA) levels by ELISA and LC-ESI-MS/MS, respectively. PD-MCI patients showed impairments in the trail making test (TMT) A (TMT-A), TMT-B, clock drawing test (CDT) and semantic fluency test (SFT), whereas PD-D patients performed worse in most EF tests. With the deterioration of cognitive function, the concentration of serum GDNF and HVA in PD patients decreased. In the PD group, the serum GDNF and HVA levels were negatively correlated with TMT-A (r GDNF = -0.304, P < 0.01; r HVA = -0.334, P < 0.01) and TMT-B (r GDNF = -0.329, P < 0.01; r HVA = -0.323, P < 0.01) scores. Serum GDNF levels were positively correlated with auditory verbal learning test (AVLT-H) (r = 0.252, P < 0.05) and SFT (r = 0.275, P < 0.05) scores. Serum HVA levels showed a positively correlation with digit span test (DST) (r = 0.277, P < 0.01) scores. Stepwise linear regression analysis suggested that serum GDNF and HVA concentrations and UPDRS-III were the influence factors of TMT-A and TMT-B performances in PD patients. The decrease of serum GDNF concentration in PD patients was associated with impaired inhibitory control, cognitive flexibility, and attention performances. The changes of GDNF and HVA might synergistically participate in the occurrence and development of executive dysfunction in PD patients.

Orofacial pain and dysfunction in patients with Parkinson's disease: A scoping review.

Parkinson's disease (PD) is commonly known as a disorder that affects the smooth performance of body movements. In addition to the motor impairments, patients with PD often experience pain. Both motor impairments and pain can occur throughout the body, hence including the orofacial region. However, currently, there is a lack of knowledge on the orofacial manifestations. Since orofacial pain and dysfunction can, amongst others, reduce the quality of life of patients with PD, it is important to explore the prevalence of these symptoms in the PD population. To provide a broad overview of the relevant literature on orofacial pain and dysfunction in patients with PD. Furthermore, we aim to generate hypotheses for future research on this topic. A literature search (in PubMed, Embase.com, Web of Science [Core collection], and Cochrane Library) was performed on 20 January 2022, in collaboration with a medical librarian. In total, 7180 articles were found, of which 50 were finally included in this scoping review. In the included studies, pain (e.g. orofacial pain (N= 2) and temporomandibular disorder pain (N= 2)), orofacial motor dysfunction (e.g. limited jaw movements (N= 10), reduced maximum muscle output (N= 3), chewing difficulties (N= 9), unspecified TMD (N= 3), sensory disturbances (N= 1)), and bruxism (N= 3) were observed more often in patients with PD than in healthy controls. Patients with PD experience more pain in the orofacial area and more dysfunction of the masticatory system than their healthy peers. This scoping review can increase health care providers' awareness of the problems that can be encountered in the orofacial area of PD patients, especially pain syndromes also occur in the orofacial region and not only in the extremities. Besides, dysfunction of the orofacial area is elaborated in this scoping review, which helps to understand that this limits PD patients' quality of life. Further, the outcomes of this scoping review can assist in encouraging collaboration between medicine and dentistry. Finally, this scoping review suggests new research areas, based on the gaps identified in the current literature on this topic. Ultimately, this will improve individualized strategies for reducing orofacial pain and/or dysfunction in PD patients.

Effects of repetitive transcranial magnetic stimulation on gait disorders and cognitive dysfunction in Parkinson's disease: A systematic review with meta-analysis.

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is acknowledged to be crucial to manage freezing of gait (FOG) and cognitive impairment for patients with Parkinson's disease (PD), but its effectiveness is unclear.ObjectiveTo determine the effects of rTMS on FOG and cognitive function in people with PD and to investigate potential factors that modulate the rTMS effects.MethodsDatabases searched included PubMed, Web of Science, EMBASE, and the Cochrane Library from inception to December 31, 2021. Eligible studies include a controlled randomized clinical trial of rTMS intervention for FOG and cognitive dysfunction in PD patients. The weighted mean difference (WMD) with 95% confidence intervals (CI) were calculated with fixed‐effects models. The outcome of the study included gait and cognitive assessments.ResultsSixteen studies with a total of 419 patients were included. Fixed‐effects analysis revealed that rTMS was effective in improving freezing of gait questionnaire scores (short‐term effect: WMD = −0.925, 95% CI: −1.642 to −0.209, p = .011; long‐term effect: WMD = −2.120, 95% CI: −2.751 to −1.489, p = .000), 10‐m walking time (short‐term effect: WMD = −0.456, 95% CI: −0.793 to −0.119, p = .008; long‐term effect: WMD = −0.526, 95% CI: −0.885 to −0.167, p = .004), Timed Up‐and‐Go scores (short‐term effect: WMD = −1.064, 95% CI: −1.555 to −0.572, p = .000; long‐term effect: WMD = −1.097, 95% CI: −1.422 to −0.772, p = .000), Montreal cognitive assessment (WMD = 3.714, 95% CI: 2.567 to 4.861, p = .000), and frontal assessment battery (WMD = −0.584, 95% CI: −0.934 to −0.234, p = .001).ConclusionsRTMS showed a beneficial effect on FOG and cognitive dysfunction in parkinsonism. However, the optimal rTMS protocol has not been determined and further high‐quality studies are needed.

Interval timing and midfrontal delta oscillations are impaired in Parkinson's disease patients with freezing of gait.

Gait abnormalities and cognitive dysfunction are common in patients with Parkinson's disease (PD) and get worse with disease progression. Recent evidence has suggested a strong relationship between gait abnormalities and cognitive dysfunction in PD patients and impaired cognitive control could be one of the causes for abnormal gait patterns. However, the pathophysiological mechanisms of cognitive dysfunction in PD patients with gait problems are unclear. Here, we collected scalp electroencephalography (EEG) signals during a 7-s interval timing task to investigate the cortical mechanisms of cognitive dysfunction in PD patients with (PDFOG +, n = 34) and without (PDFOG-, n = 37) freezing of gait, as well as control subjects (n = 37). Results showed that the PDFOG + group exhibited the lowest maximum response density at around 7s compared to PDFOG- and control groups, and this response density peak correlated with gait abnormalities as measured by FOG scores. EEG data demonstrated that PDFOG + had decreased midfrontal delta-band power at the onset of the target cue, which was also correlated with maximum response density and FOG scores. In addition, our classifier performed better at discriminating PDFOG + from PDFOG- and controls with an area under the curve of 0.93 when midfrontal delta power was chosen as a feature. These findings suggest that abnormal midfrontal activity in PDFOG + is related to cognitive dysfunction and describe the mechanistic relationship between cognitive and gait functions in PDFOG + . Overall, these results could advance the development of novel biosignatures and brain stimulation approaches for PDFOG + .

Plasma total tau predicts executive dysfunction in Parkinson's disease

Cognitive impairment is an important non-motor aspect of Parkinson's disease (PD). Amyloid-β and tau pathologies are well-established in Alzheimer's disease and commonly coexist with synucleinopathy in PD. However, the levels of these biomarkers in the plasma of patients with PD and their relationship with specific cognition domains remain to be clarified. The current study compared the motor severity and neuropsychological assessment of general and specific cognition, with plasma levels of α-synuclein (α-syn), amyloid-β 42 (Aβ42), and total tau (t-tau) in PD subjects. Plasma levels of α-syn, Aβ42, and t-tau were measured in 55 participants with PD through immunomagnetic reduction assay. The evaluation of motor severity and comprehensive neuropsychological assessment was performed in all participants. The level of plasma α-syn was negatively correlated with the scores of Unified Parkinson's Disease Rating Scale part III [r=(-.352), p=.008]. The level of plasma t-tau was negatively correlated with the scores of digits recall forwards and digits recall backwards [r=(-.446), p=.001; r=(-.417), p=.002, respectively]. No correlations were found between the levels of α-syn and Aβ42 and any neuropsychological tests. This study concluded a lower level of plasma α-syn was correlated with motor dysfunction in PD patients, and a higher level of plasma t-tau was correlated with lower cognitive performance, especially for attention and executive function. These results propose the possibility of using plasma biomarkers to predict specific cognitive performance in PD subjects.

Association between plasma neurofilament light chain levels and cognitive function in patients with Parkinson's disease

This study investigated the potential association between levels of plasma neurofilament light chain (NfL) and cognitive function in patients suffering from Parkinson's disease (PD) in P.R. China.We collected a total of 168 participants (130 PD patients and 38 healthy controls),and evaluated the relationship of plasma NfL levels with cognitive dysfunction in PD patients. Our results shown that plasma NfL levels increased with an increase in cognitive impairment across the three groups of PD patients: PD with normal cognition (PD-NC), 17.9 ± 8.9 pg/ml; PD with mild cognitive impairment (PD-MCI),21.9 ± 10.3 pg/ml; and PD dementia (PDD), 35.7 ± 21.7 pg/ml. Higher MMSE scores were associated with lower plasma NfL levels (r = −0.49, 95% CI -0.61 to −0.34, p < 0.0001). Our results associating plasma NfL levels with cognitive dysfunction in PD are consistent with previous studies carried out in several countries/district, based on our meta-analysis.

Clinical correlates of white matter lesions in Parkinson's disease using automated multi-modal segmentation measures

BackgroundAge-related white matter lesions (WML) are common, impact neuronal connectivity, and affect motor function and cognition. In addition to pathological nigrostriatal losses, WML are also common co-morbidities in Parkinson's disease (PD) that affect postural stability and gait. Automated brain volume measures are increasingly incorporated into the clinical reporting workflow to facilitate precision in medicine. Recently, multi-modal segmentation algorithms have been developed to overcome challenges with WML quantification based on single-modality input. ObjectiveWe evaluated WML volumes and their distribution in a case-control cohort of PD patients to predict the domain-specific clinical severity using a fully automated multi-modal segmentation algorithm. MethodsFifty-five subjects comprising of twenty PD patients and thirty-five age- and gender-matched control subjects underwent standardized motor/gait and cognitive assessments and brain MRI. Spatially differentiated WML obtained using automated segmentation algorithms on multi-modal MPRAGE and FLAIR images were used to predict domain-specific clinical severity. Preliminary statistical analysis focused on describing the relationship between WML and clinical scores, and the distribution of WML by brain regions. Subsequent stepwise regressions were performed to predict each clinical score using WML volumes in different brain regions, while controlling for age. ResultsWML volume strongly correlates with both motor and cognitive dysfunctions in PD patients (p < 0.05), with differential impact in the frontal lobe and periventricular regions on cognitive domains (p < 0.01) and severity of motor deficits (p < 0.01), respectively. ConclusionAutomated multi-modal segmentation algorithms may facilitate precision medicine through regional WML load quantification, which show potential as imaging biomarkers for predicting domain-specific disease severity in PD.

Correlations between retinal nerve fiber layer thickness and cognitive progression in Parkinson's disease: A longitudinal study

BackgroundRetinal abnormalities measured by optical coherence tomography (OCT) have been detected in both Parkinson's disease (PD) and Alzheimer's disease (AD). Cognitive impairment is not only found in AD, but 75–90% of PD patients will also develop dementia in the late stage of disease. We assessed whether baseline retinal nerve fiber layer (RNFL) thickness predicted worsening of cognitive status over time and the correlation between RNFL thickness and the detailed impaired cognitive domains in PD. MethodsRNFL thickness was measured using high-definition OCT in 78 non-dementia PD patients. Clinical and cognitive assessments were performed at baseline and at 3.61 ± 0.65 years follow-up. Linear mixed-effects models were used to examine associations between RNFL thickness and the changes in cognitive test scores, after adjusting for age, sex, disease duration and education. ResultsAnalysis of outcomes according to baseline RNFL tertiles showed worse performance in global cognitive tests, delayed memory, and executive functions in patients with a thin RNFL. During follow-up, greater cognitive deterioration was found in thin RNFL tertile patients. Lower baseline average RNFL thickness was associated with greater annualized decline in Mini-Mental State Examination and Montreal Cognitive Assessment. ConclusionThe correlation between RNFL thickness and cognitive dysfunction suggests that OCT may be useful for predicting cognitive dysfunction in PD patients.

Biofeedback Core Exercise Using Hybrid Assistive Limb for Physical Frailty Patients With or Without Parkinson's Disease.

Introduction: Elderly people often exhibit “frailty,” and motor dysfunction occurs. Several studies have reported about the relationship between motor dysfunction and frailty in Parkinson's disease (PD). This study aimed to test whether the core exercise using the hybrid assistive limb lumbar type for care support (HAL-CB02) may improve the motor functions in frailty patients with or without PD and to explore the optimal patient selection from the frailty cohort.Materials and Methods: We recruited 16 frailty patients (PD = 8; non-PD = 8). The participants performed core exercise and squats using HAL-CB02 for five sessions a week. Outcome measures were 10-m walking test, step length, timed up-and-go test, 30-s chair stand test, and visual analog scale. Evaluation was conducted at baseline, post-exercise, and 1- and 3-month follow-ups.Results: Both PD and non-PD patients showed significant improvement in all evaluation items post-exercise. Moreover, no significant difference was found in the improvement value between the two groups.Conclusions: Our results suggest that biofeedback exercise with HAL-CB02 is a safe and promising treatment for frailty patients. Motor dysfunction in PD patients may be partly due to physical frailty, and biofeedback exercise with HAL-CB02 is proposed as a treatment option.

Substance P Saliva Reduction Predicts Pharyngeal Dysphagia in Parkinson's Disease.

Introduction: Although patients with Parkinson's disease (PD) often suffer from oropharyngeal dysphagia, knowledge about the underlying pathophysiological mechanisms is limited. Substance P (SP) is a localization-independent neurotransmitter of the entire nervous system. Reduced levels of SP were found in saliva of patients with impaired cough reflex and in advanced stages of PD. The aim of the study was to investigate SP in PD patients in order to gain further insights into the underlying pathophysiology of PD-related dysphagia and to evaluate the potential of SP as a biomarker for early dysphagia.Methods: Flexible endoscopic evaluation of swallowing (FEES) was used to objectively assess pharyngeal swallowing function. From a cohort of 105 consecutive PD patients 20 subjects were recruited: in 10 of them pharyngeal dysphagia was excluded by FEES, the other 10 subjects showed signs of early pharyngeal dysphagia defined as hypopharyngeal sensory deficit with mild to moderate vallecular residues after swallowing solid consistencies. Analysis of the Substance P level in saliva of the 20 included PD patients was performed in the clinical on state condition by ELISA-type immunoassay. Significant differences were calculated by using the Mann-Whitney test.Results: Twenty PD patients with a mean age of 69.5 ± 12.5 years (8 female) were included in the study. No significant differences were found regarding gender, age, UPDRS III, Hoehn and Yahr stage, disease duration, and Levodopa equivalent dose between the non-dysphagic and dysphagic subjects. Dysphagia was mainly characterized by unrecognized residues in the valleculae without any aspiration risk for all of the tested consistencies in FEES and was thereby scored as mild in all cases. Saliva SP concentrations were significantly lower in PD patients with pharyngeal dysphagia compared to those with a normal pharyngeal swallowing function (9,644 vs. 17,591 pg/mL; p = 0.001).Conclusion: Reduced saliva SP concentrations may predict early pharyngeal swallowing dysfunction in PD patients. This finding supports the hypothesis that an impaired SP mediated neurotransmission has a significant impact for the development of dysphagia in PD patients. Larger studies are needed to confirm SP as a clinical useful biomarker for early detection of PD-related dysphagia.

Measuring executive dysfunction in Parkinson's disease: Reliability and validity of the Spanish version of Frontal Assessment Battery (FAB-E).

BackgroundDeficits in executive functions (EFs) are frequently detected in patients with Parkinson’s disease (PD). The Frontal Assessment Battery (FAB) is a screening test for assessing EFs although it has not been so far adapted and validated in Spain. We evaluated the reliability and validity of the Spanish version of the FAB (FAB-E) in PD patients.Materials and methodsOur study included 54 healthy subjects and 67 PD patients. Cognitive assessment of participants was conducted using the FAB-E, Mini-Mental State Examination (MMSE), Trail Making Test (TMT), Revised-Barcelona Test (RBT) and Executive Interview (EXIT-25). Internal consistency, intra- and test-retest reliabilities, concurrent and discriminant validity of the FAB-E were examined. To evaluate the influence of cognitive dysfunction in PD on the performance of the FAB-E, we also classified the PD patients into groups according to their cognitive status as measured by the MMSE using published criteria to identify cognitive deficits in PD.ResultsThe FAB-E showed good internal consistency (α = 0.751). The intraclass correlation coefficients (ranging from 0.559 to 0.891) and Spearman correlations (from 0.494 to 0.864) of the FAB-E subtests indicated a good-strong reliability. The total and subtest scores generally showed a good concurrent validity, except for the prehension behaviour item of the FAB-E and the Interference and Go/no-go tasks of the EXIT-25 that presented low estimates. Excluding the prehension behaviour subtest, the performance of the FAB-E was higher in the control group than in PD patients. Cognitive dysfunction in PD patients also indicated significant poorer FAB-E scores excepting the motor and prehension behaviour subtests. Discriminant analysis determined a cut-off of 14.5 was optimal to differentiate healthy subjects from PD patients. Moreover, a cut-off <12.5 allocated satisfactorily those PD patients with cognitive impairment (MMSE<26) and scores <11.5 classified suitably those PD patients with dementia (MMSE<24).ConclusionThe FAB-E is an accurate tool for evaluating EFs in patients with PD and can provide useful information for distinguishing PD patients with and without cognitive dysfunction at a bedside assessment.

Update on the clinical application of deep brain stimulation in sleep dysfunction of Parkinson's disease.

Sleep dysfunctions, including rapid eye movement sleep behavior disorder, sleep fragmentation, excessive daytime sleepiness and various other dysfunctions, can seriously affect quality of life in patients with Parkinson's disease (PD). Emerging evidence suggests that deep brain stimulation (DBS) exerts a substantial effect when used to treat sleep dysfunctions, which are common nonmotor symptoms experienced by patients with PD. However, far less is known about the specific mechanisms underlying the effects of DBS on sleep processes and the factors that potentially influence these effects. These issues therefore need to be further clarified. Intriguingly, a number of recent studies have evaluated the effects of applying DBS to various brain targets on sleep in patients with PD. Deeper research into the efficacy of applying DBS to each brain target may help determine which region should be targeted during surgery in PD patients. Furthermore, compared with pharmacological therapy, DBS had more beneficial effects on sleep symptoms, and appropriate management involving the joint application of dopamine replacement therapy and DBS might accelerate the effects of treatment. Here, we review the potential roles DBS may play and provide clinical guidance for the use of DBS in treating sleep dysfunctions in PD patients.

Correlations between abnormal iron metabolism and non-motor symptoms in Parkinson's disease.

Despite a growing body of evidence suggests that abnormal iron metabolism plays an important role in the pathogenesis of Parkinson's disease (PD), few studies explored its role in non-motor symptoms (NMS) of PD. The present study aimed to investigate the relationship between abnormal iron metabolism and NMS of PD. Seventy PD patients and 64 healthy controls were consecutively recruited to compare serum iron, ceruloplasmin, ferritin, and transferrin levels. We evaluated five classic NMS, including depression, anxiety, pain, sleep disorder, and autonomic dysfunction in PD patients using the Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA), the short form of the McGill Pain Questionnaire, the Pittsburgh Sleep Quality Index and the Scale for Outcomes in Parkinson's disease for Autonomic Symptoms, respectively. Hierarchical multiple regression analysis was used to investigate the correlations between abnormal iron metabolism and NMS. No differences in serum ceruloplasmin and ferritin levels were examined between PD patients and healthy controls, but we observed significantly decreased serum iron levels and increased serum transferrin levels in PD patients in comparison with healthy controls. After eliminating confounding factors, HAMD scores and HAMA scores were both negatively correlated with serum iron levels and positively correlated with serum transferrin levels. In summary, abnormal iron metabolism might play a crucial role in the pathogenesis of depression and anxiety in PD. Serums levels of iron and transferrin could be peripheral markers for depression and anxiety in PD.

Role of habenula and amygdala dysfunction in Parkinson disease patients with punding.

To assess whether a functional dysregulation of the habenula and amygdala, as modulators of the reward brain circuit, contributes to Parkinson disease (PD) punding. Structural and resting-state functional MRI were obtained from 22 patients with PD punding, 30 patients with PD without any impulsive-compulsive behavior (ICB) matched for disease stage and duration, motor impairment, and cognitive status, and 30 healthy controls. Resting-state functional connectivity of the habenula and amygdala bilaterally was assessed using a seed-based approach. Habenula and amygdala volumes and cortical thickness measures were obtained. Compared to both healthy controls and PD cases without any ICB (PD-no ICB), PD-punding patients showed higher functional connectivity of habenula and amygdala with thalamus and striatum bilaterally, and lower connectivity between bilateral habenula and left frontal and precentral cortices. In PD-punding relative to PD-no ICB patients, a lower functional connectivity between right amygdala and hippocampus was also observed. Habenula and amygdala volumes were not different among groups. PD-punding patients showed a cortical thinning of the left superior frontal and precentral gyri and right middle temporal gyrus and isthmus cingulate compared to healthy controls, and of the right inferior frontal gyrus compared to both controls and PD-no ICB patients. A breakdown of the connectivity among the crucial nodes of the reward circuit (i.e., habenula, amygdala, basal ganglia, frontal cortex) might be a contributory factor to punding in PD. This study provides potential instruments to detect and monitor punding in patients with PD.

Association of IGF1 gene polymorphism with Parkinson's disease in a Han Chinese population.

Accumulating evidence suggests that insulin-like growth factor 1 (IGF1) plays an important role in Parkinson's disease (PD) pathogenesis. However, it is not clear whether IGF1 polymorphism contributes to PD risk. We performed a case-control study in a Han Chinese population that included 512 sporadic PD cases and 535 matched controls. All participants were genotyped for rs972936 using the Sequenom MassARRAY iPLEX platform. Serum IGF1 levels of 61 de novo, drug-naïve PD patients and 55 age- and sex-matched controls were also measured using an enzyme-linked immunosorbent assay. Genotype frequency of rs972936-CC was significantly associated with an increased PD risk (p=0.009), especially in males (p=0.024) and late-onset patients (p=0.013). Serum IGF1 levels were significantly increased in de novo, drug-naïve PD patients compared to controls (p=0.036), although they were not correlated with motor dysfunction in PD patients (p=0.220). The present study shows that rs972936 polymorphism may increase susceptibility to PD, especially in males and late-onset patients. Furthermore, high serum IGF1 levels may be a potential diagnostic biomarker for PD in the Han Chinese population, although they do not correlate with a more severe motor dysfunction.

Assessment of Hearing Impairment in Parkinson's Disease: Implications for Differential Diagnosis and Disease Progression

Background and objective: Non-motor symptoms (NMS) of Parkinson's disease (PD) are still underestimated and causative of disability and poor quality of life. Recently, it has been suggested that hearing impairment could be included into the spectrum of NMS, although both mechanisms and phenomenology are unclear. In this study we investigated the peripheral auditory pathway of PD, in patients with asymmetric rest tremor (ART) without dopaminergic denervation, and comparison with healthy controls (HC), aiming to detect differential alterations of cochlear functioning and medial olivocochlear system (MOC).Methods: 23 PD patients, 9 with ART and 19 HC were assessed for auditory functions with clinical examination and Transient-evoked otoacoustic emissions (TEOAEs). PD and ART groups were also evaluated with Unified Parkinson's Disease Rating Scale (UPDRS) II-III and Hoehn and Yahr scale. One-way ANOVA analysis and Pearson's test were performed to measure differences between groups and correlations.Results: TEOAE responses in PD patients were significantly lower compared to HC at 3 and 4 kHz, bilaterally. PD patients showed statistically significant lower TEOAEs at the same frequencies compared to ARTs. In addition, a MOC dysfunction in PD patients was observed. Conversely, no difference was found between ART and HC in all tests performed.Conclusion: PD patients, differently from both ART patients and HC, show abnormalities of basal TEOAEs at the highest frequencies. Auditory dysfunction correlates to motor disturbances, suggesting an underlying dopaminergic pathogenic mechanism. Early recognition of hearing impairment may represent a tool for patient assessment and help in the differential diagnosis in ART patients.

Levodopa reverse stridor and prevent subsequent endotracheal intubation in Parkinson disease patients with bilateral vocal cord palsy

Background:Respiratory abnormalities are often overlooked; however, because of their potential comorbidity, they must be analyzed to determine the most effective treatment for patients with Parkinson disease (PD). Among various theories on respiratory abnormalities in PD, “upper airway obstruction” and “restrictive respiratory disorders” are 2 of the most accepted etiologies; both appear to be related to basal ganglia dysfunction. Complex vocal cord muscle dysfunction contributes to stridor, which can be a manifestation of nigrostriatal dopaminergic dysfunction. Stridor is a lethal form of upper airway obstruction in PD patients; its most frequent causes are bilateral vocal cord palsy, laryngeal spasms, and dystonia of the supra-laryngeal muscle. Several previous studies have suggested that levodopa administration induces a significant improvement of both lung function and symptoms of parkinsonian syndrome.Case Summary:We reported a 77-year-old gentleman PD patient admitted for acute levodopa-responsive stridor resulting from bilateral vocal cord palsy. Dopaminergic therapy prevented the need for subsequent endotracheal intubation and tracheostomy treatment.Conclusion:It is vital to understand that complex vocal cord muscle dysfunction may be related to nigrostriatal dopaminergic dysfunction in PD patients. The strategy of levodopa up-titration should be considered an option because it may be beneficial in relieving both stridor and parkinsonian syndrome, and in preventing respiratory failure.