Subgroup Of Parkinson's Disease Patients Research Articles

Machine learning can predict mild cognitive impairment in Parkinson's disease.

Clinical markers of cognitive decline in Parkinson's disease (PD) encompass several mental non-motor symptoms such as hallucinations, apathy, anxiety, and depression. Furthermore, freezing of gait (FOG) and specific gait alterations have been associated with cognitive dysfunction in PD. Finally, although low cerebrospinal fluid levels of amyloid-β42 have been found to predict cognitive decline in PD, hitherto PET imaging of amyloid-β (Aβ) failed to consistently demonstrate the association between Aβ plaques deposition and mild cognitive impairment in PD (PD-MCI). Finding significant features associated with PD-MCI through a machine learning approach. Patients were assessed with an extensive clinical and neuropsychological examination. Clinical evaluation included the assessment of mental non-motor symptoms and FOG using the specific items of the MDS-UPDRS I and II. Based on the neuropsychological examination, patients were classified as subjects without and with MCI (noPD-MCI, PD-MCI). All patients were evaluated using a motion analysis system. A subgroup of PD patients also underwent amyloid PET imaging. PD-MCI and noPD-MCI subjects were compared with a univariate statistical analysis on demographic data, clinical features, gait analysis variables, and amyloid PET data. Then, machine learning analysis was performed two times: Model 1 was implemented with age, clinical variables (hallucinations/psychosis, depression, anxiety, apathy, sleep problems, FOG), and gait features, while Model 2, including only the subgroup performing PET, was implemented with PET variables combined with the top five features of the former model. Seventy-five PD patients were enrolled (33 PD-MCI and 42 noPD-MCI). PD-MCI vs. noPD-MCI resulted in older and showed worse gait patterns, mainly characterized by increased dynamic instability and reduced step length; when comparing amyloid PET data, the two groups did not differ. Regarding the machine learning analyses, evaluation metrics were satisfactory for Model 1 overcoming 80% for accuracy and specificity, whereas they were disappointing for Model 2. This study demonstrates that machine learning implemented with specific clinical features and gait variables exhibits high accuracy in predicting PD-MCI, whereas amyloid PET imaging is not able to increase prediction. Additionally, our results prompt that a data mining approach on certain gait parameters might represent a reliable surrogate biomarker of PD-MCI.

Defining Atypical Anxiety in Parkinson's Disease.

Anxiety is a major complication in Parkinson's disease (PD). Many PD patients experience clinically significant anxiety not meeting Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) anxiety disorder criteria. This atypical anxiety (anxiety disorder not otherwise specified [NOS]) is often under-recognized and its diagnosis is underdeveloped. This study aimed to identify the demographic, psychiatric, and clinical characteristics of anxiety disorder NOS in PD. A cross-sectional design studied a convenience sample of 184 PD patients without dementia recruited from neurology outpatient clinics. A semi-structured interview using DSM-IV criteria categorized PD patients into current anxiety disorder NOS (n = 28), DSM-IV anxiety disorders (n = 42) or no anxiety (n = 86) groups. Logistic regression modeling identified characteristics associated with the anxiety disorder NOS group compared to DSM-IV anxiety and no anxiety groups. The anxiety disorder NOS group was associated with motor complications of PD therapy, episodic, persistent and social anxiety symptoms, depression, non-motor experiences of daily living, poor quality of life, and female sex compared to the no anxiety group. Compared to DSM-IV anxiety, those with anxiety disorder NOS demonstrated greater global cognitive impairment, more severe motor complications of PD therapy, a greater severity and functional impact of dyskinesias, and greater complexity of motor fluctuations. Persistent, episodic, and social anxiety symptoms did not significantly differ between anxiety disorder NOS and DSM-IV anxiety groups. These findings suggest that PD-specific symptoms characterize anxiety in a subgroup of PD patients who do not fulfill DSM-IV criteria for anxiety disorders.

Suboptimal response to STN-DBS in Parkinson’s disease can be identified via reaction times in a motor cognitive paradigm

Although deep brain stimulation of the subthalamic nucleus (STN-DBS) in Parkinson's disease (PD) is generally a successful therapy, adverse events and insufficient clinical effect can complicate the treatment in some patients. We studied clinical parameters and cortical oscillations related to STN-DBS to identify patients with suboptimal responses. High-density EEG was recorded during a visual oddball three-stimuli paradigm in DBS "off" and "on" conditions in 32 PD patients with STN-DBS. Pre-processed data were reconstructed into the source space and the time-frequency analysis was evaluated. We identified a subgroup of six patients with longer reaction times (RT) during the DBS "on" state than in the DBS "off" state after target stimuli. These subjects had lower motor responsiveness to DBS and decreased memory test results compared to the other subjects. Moreover, the alpha and beta power decrease (event-related desynchronizations, ERD), known as an activation correlate linked to motor and cognitive processing, was also reduced in the DBS "on" condition in these patients. A subgroup of PD patients with a suboptimal response to STN-DBS was identified. Evaluation of RT could potentially serve as a biomarker for responsiveness to STN-DBS.

Long Term Response to Levodopa in Parkinson's Disease.

Levodopa is the most efficacious medication in controlling the motor symptoms of Parkinson's disease (PD). There continues to be a controversy as to whether levodopa remains effective after years of therapy. To assess the long-term effectiveness of levodopa in PD patients. The response to levodopa in PD patients undergoing a levodopa challenge for deep brain stimulation (DBS) surgery evaluation from June 1997 through March 2017 were evaluated. The patients were broken into four groups based on disease duration (Group I: 0- 5 years, Group II: 6- 10 years, Group III: 11- 15 years, and Group IV:≥16 years). Levodopa response was calculated based on the changes in Unified Parkinson's Disease Rating Scale (UPDRS) motor and activities of daily living (ADL) scores in the medication ON and OFF states. A total of 361 PD patients were included. The mean age in Group I was 59.4 years with a mean disease duration of 3.9 years (n = 29), Group II was 61 years with a mean disease duration of 8.1 years (n = 131), Group III was 64 years with a mean disease duration of 12.8 years (n = 143), and IV was 66.5 years with a mean disease duration of 18.5 years (n = 58). There was a significant improvement in UPDRS motor and ADL scores after the levodopa challenge for all groups. In a subgroup of PD patients who were evaluated for DBS surgery, there was a marked improvement in UPDRS motor and ADL scores which did not decrease with disease progression.

Functional Magnetic Resonance Imaging Biomarkers Predicting Cognitive Progression in Parkinson Disease: Protocol for a Prospective Longitudinal Cohort Study.

BackgroundCardinal features of Parkinson disease (PD) are motor symptoms, but nonmotor features such as mild cognitive impairment (MCI) are common early in the disease process. MCI can progress and convert to dementia in advanced stages, creating significant disability and reduced quality of life. The primary pathological substrate for cognitive decline in PD is unclear, and there are no reliable biomarkers predicting the risk of conversion to dementia. A subgroup of PD patients with visual hallucinations may display more rapid conversion to dementia, suggesting that regional markers of visuoperceptual dysfunction may be sensitive to pathologic density in posterior cortical regions.ObjectiveThe purpose of this project is to characterize PD-MCI and evaluate the utility of genetic and neuroimaging biomarkers in predicting cognitive outcomes with a prospective longitudinal study. We will evaluate whether accelerated cognitive progression may be reflected in biomarkers of early posterior cortical changes reflective of α-synuclein deposition.MethodsWe will evaluate a cohort of early-stage PD patients with the following methods to predict cognitive progression: (1) serial neuropsychological evaluations including detailed visuoperceptual functioning across 4 years; (2) genetic analysis of SNCA (α-synuclein), MAPT (microtubule-associated tau), and APOE (apolipoprotein E); (3) an event-related functional magnetic resonance imaging paradigm of object recognition memory; and (4) anatomical and regional brain activation changes (resting-state functional magnetic resonance imaging) across 4 years.ResultsThe project received funding from the National Institutes of Health in August 2017, and data collection began in February 2018. Enrollment is ongoing, and subjects will be evaluated annually for 4 years extended across a 5-year project including data analysis and image processing.ConclusionsCognitive, genetic, and structural and functional magnetic resonance imaging will characterize neural network changes predictive of cognitive progression in PD across 4 years. Identification of biomarkers with sensitivity for early prediction and estimation of risk for conversion to dementia in PD will pave the way for effective intervention with neuroprotective therapies during the critical stage when treatment can have the greatest impact.International Registered Report Identifier (IRRID)DERR1-10.2196/12870

A punch in the gut – Intestinal inflammation links environmental factors to neurodegeneration in Parkinson's disease

Parkinson's disease (PD) is an etiologically heterogeneous disorder. Experimental, clinical and epidemiological data suggest that intestinal inflammation contributes to the pathogenesis of PD. This article reviews recent literature on gut microbiota and intestinal inflammation in PD. We propose that intestinal inflammation links environmental factors (e.g. an altered gut microbiota composition) to neurodegeneration in (genetically susceptible) PD patients. In addition, there is an epidemiological and genetic overlap between PD and inflammatory bowel disease. This overlap provides an opportunity to develop new treatment strategies for at least a subgroup of PD patients.

Physical performances and reconditioning of patients suffering from mild-to-moderate Parkinson's disease

Patients with Parkinson's disease (PD) have a reduced physical activity level, although exercise is especially recommended in this population [1] . Besides, motor and non-motor symptoms may also interfere with the ability to produce strenuous efforts. Yet, their baseline performances and the response to physical reconditioning have not been thoroughly investigated. The cross-sectional part of this study investigates different aspects of physical fitness of patients suffering from mild-to-moderate PD. The second part investigates the response to physical reconditioning. Sixty PD patients and 47 healthy controls (HC) matched for demographic features were tested for aerobic performances and muscle strength. Peak work load (PWL) and peak oxygen consumption (VO 2 peak) were assessed in both groups during an incremental cycle exercise test. Isokinetic knee muscle strength (IKMS) was also tested for the extensor and flexor muscles at 60° and 180°.s −1 . Subgroups of PD patients were also allocated to 12 weeks of strength training (ST, n = 17), aerobic training (AE, n = 20) or standard care control intervention ( n = 15). In comparison to HC, PD patients showed reduced PWL and VO 2 peak (respectively −19% and −14%, P ≤ 0.003). PD patients showed reduced IKMS of flexor muscles (from −17 to −24%, P ≤ 0.001), and reduced IKMS only for the most affected side of extensor muscles (−13%, P ≤ 0.015). Eighty-eight percent and 80% of the trained patients respectively completed the ST and the AE interventions. No major complication occurred during the interventions. The AE group improved PWL (+18%, P = 0.001) and VO 2 peak (+12%, P = 0.033). The ST group improved IKMS of flexors (+22–25%, P ≤ 0.02), IKMS of extensors only for the most affected side (+10–17%, P < 0.05), and PWL (+16%, P < 0.001). Aerobic and strength performances are both affected by PD. However, physical reconditioning is feasible and improves fitness of PD patients.

The Effect of Lateralization of Motor Onset and Emotional Recognition in PD Patients Using EEG.

The objective of this research was to investigate the relationship between emotion recognition and lateralization of motor onset in Parkinson's disease (PD) patients using electroencephalogram (EEG) signals. The subject pool consisted of twenty PD patients [ten with predominantly left-sided (LPD) and ten with predominantly right-sided (RPD) motor symptoms] and 20 healthy controls (HC) that were matched for age and gender. Multimodal stimuli were used to evoke simple emotions, such as happiness, sadness, fear, anger, surprise, and disgust. Artifact-free emotion EEG signals were processed using the auto regressive spectral method and then subjected to repeated ANOVA measures. No group differences were observed across behavioral measures; however, a significant reduction in EEG spectral power was observed at alpha, beta and gamma frequency oscillations in LPD, compared to RPD and HC participants, suggesting that LPD patients (inferred right-hemisphere pathology) are impaired compared to RPD patients in emotional processing. We also found that PD-related emotional processing deficits may be selective to the perception of negative emotions. Previous findings have suggested a hemispheric effect on emotion processing that could be related to emotional response impairment in a subgroup of PD patients. This study may help in clinical practice to uncover potential neurophysiologic abnormalities of emotional changes with respect to PD patient's motor onset.

Pathological Gambling in Parkinson's disease patients: Dopaminergic medication or personality traits fault?

Impulse control disorders (ICDs) are clinically relevant in Parkinson disease (PD) patients, with an established association with PD medication. Aim of our study was to study whether the increased frequency of pathological gambling (PG), reported in subgroups of PD patients, is related to specific personality tracts additional to dopaminergic medications.Thirty-seven PD patients with a personal history of PG where enrolled. Twenty one PD patients, matched for disease and dopaminergic therapy, never experiencing PG, were enrolled as controls. All subjects were tested with the Minnesota Multiphasic Inventory Personality scales (MMPI-2).Our data showed that PD group with PG exhibited significantly higher mean values of the three validity scales in comparison to the non-PG-PD group, demonstrating an higher tendency to lie. Content scales showed a significant increase of cynicism and bizarre ideation scales score in the PG-PD group, not exhibiting pathological values at the validity scales, (p: 0.02) in comparison to non-PG PD patients.According to our results, PG seems to be associated with precise personality tracts. Personality profiles of cluster A personality disturbances - Axys 2 according with DSM-5 TR (paranoid type) at MMPI-2 might be a warning index helpful in selecting dopaminergic treatment, to avoid subsequent ICDs appearance.

Subjective Visual Vertical in PD Patients with Lateral Trunk Flexion.

Lateral trunk flexion (LTF) is a common phenomenon in patients with Parkinson's disease (PD) and has recently been associated with peripheral vestibular dysfunction. Since deviation of the subjective visual vertical (SVV) is a well-recognized feature of disorders involving vestibular processing, we analyzed SVV angles in 30 PD patients with and without LTF to assess the possible role of vestibular dysfunction in the pathogenesis of LTF in PD. Quantification of SVV was obtained using a simple bedside test. PD patients with LTF had significantly greater SVV angles as compared to PD patients without LTF (median: 4.3° [range: 0.1–17.7], n = 21, versus 0.8° [0.1–1.9], n = 9; p < 0.001). 14 of 21 patients with LTF showed pathological SVV, while all 9 patients without LTF had normal SVV. Abnormal SVV was more frequent when LTF was reversible in the supine position compared to fixed LTF. In a subgroup of PD patients with LTF, pathological SVV suggests vestibular dysbalance, which might be involved in the pathophysiological mechanisms underlying LTF.

Pathological gambling in Parkinson's disease patients: dopaminergic medication or personality traits fault?

article i nfo Impulse control disorders (ICDs) are clinically relevant in Parkinson disease (PD) patients, with an established association with PD medication. Aim of our study was to study whether the increased frequency of pathological gambling (PG), reported in subgroups of PD patients, is related to specific personality tracts additional to dopa- minergic medications. Thirty-seven PD patients with a personal history of PG where enrolled. Twenty one PD patients, matched for disease and dopaminergic therapy, never experiencing PG, were enrolled as controls. All subjects were tested with the Minnesota Multiphasic Inventory Personality scales (MMPI-2). Our data showed that PD group with PG exhibited significantly higher mean values of the three validity scales in comparison to the non-PG-PD group, demonstrating an higher tendency to lie. Content scales showed a signifi- cant increase of cynicism and bizarre ideation scalesscore in the PG-PD group, not exhibiting pathological values at the validity scales, (p: 0.02) in comparison to non-PG PD patients.

No association of FAM47E rs6812193, SCARB2 rs6825004 and STX1B rs4889603 polymorphisms with Parkinson's disease in a Chinese Han population.

Recently, a series of studies found that the single-nucleotide polymorphisms (SNPs) rs6812193 in the family with sequence similarity 47, member E (FAM47E), rs6825004 in the scavenger receptor class B member 2 (SCARB2) and rs4889603 in the Syntaxin1B (STX1B) genes increase the risk for Parkinson's disease (PD). However, the results of subsequent independent studies were inconsistent. To explore the associations between the three SNPs and PD in the Chinese population, a large cohort was analyzed in a case-control study. A total of 1994 subjects, including 1179 PD and 815 healthy controls (HCs), were investigated. All subjects were genotyped for rs6812193, rs6825004 and rs4889603 using the Sequenom iPLEX Assay. There was no significant difference in additive genetic model of rs6812193, rs6825004 and rs4889603 between PD and controls, even after being stratified by sex and age. In addition, no significant differences were found between other subgroups of PD patients with regard to clinical presentation. Our findings suggested that FAM47E rs6812193, SCARB2 rs6825004 and STX1B rs4889603 do not confer a significant risk for PD in Chinese population.

Steadiness of syllable repetition in early motor stages of Parkinson's disease

Patients with Parkinson's disease (PD) show characteristic abnormalities in the performance of simple repetitive movements which can also be observed concerning speech rate and rhythm. The aim of the current study was to survey if patients with early PD already feature impairments of steady vocal pace performance based upon a simple syllable repetition paradigm. N=50 patients with PD with mild to moderate motor impairment and n=32 age-matched healthy controls were tested. Participants had to repeat a single syllable or a pair of alternating syllables in a self chosen steady pace or in a given pace of 80/min. The coefficient of variance was taken as measure of stability of repetition. As main and novel result, vocal pace performance was observed to be irregular in all patients, even in the subgroup of PD patients with only very mild motor impairment (Hoehn&Yahr stage 1), although the capacity of rapid syllable repetition was preserved. Weak correlations were found between the maximum repetition rate (but not with steadiness of repetition) and some distinctive Parkinsonian motor features as speech impairment and gait.Assumed that subsequent studies are able to confirm these preliminary results, analysis of steadiness of syllable repetition might be a promising non-invasive tool for detection of subtle abnormalities of motor speech performance even in the early motor stages of PD.

Photoreceptor layer thinning in idiopathic Parkinson's disease.

This study was undertaken to quantify retinal and intra-retinal layer thicknesses in Parkinson's disease (PD), and to evaluate whether retinal structural changes may be related to altered discrimination of color vision and to severity and duration of PD disease. We examined 97 PD patients and 32 healthy controls (HC) with spectral-domain optical coherence tomography (OCT), including intra-retinal layer segmentation. In total, we compared 111 retinal nerve fiber layer (RNFL)-scans and 114 macula scans from 68 PD patients with 62 RNFL and 63 macula scans from 32 HC. For clinical evaluation of disease severity, we used the Unified Parkinson's Disease Rating Scale (UPDRS) motor examination. To determine color discrimination, we performed the Farnsworth Munsell 100 Hue Test (FMT) in a subgroup of PD patients. We found significant combined outer nuclear and photoreceptor layer thinning in PD versus HC (118.6 vs. 123.5 µm, P = 0.001). Differences in RNFL, total macular volume, or the other retinal layer thicknesses were not detected. The OCT measures were not associated with disease severity, duration, or color vision. By showing photoreceptor cell layer thinning, our findings support previous in vivo and autopsy studies demonstrating retinal alterations in PD. Optical coherence tomography may help to assess morphological retinal changes in PD patients; however, the utility of OCT in routine clinical practice may be limited because many PD patients have difficulties complying with OCT investigation because of disease-related symptoms such as tremor, axial rigidity, or cognitive impairment.

Neural and behavioral substrates of subtypes of Parkinson’s disease

Parkinson’s disease (PD) is a neurological disorder, associated with rigidity, bradykinesia, and resting tremor, among other motor symptoms. In addition, patients with PD also show cognitive and psychiatric dysfunction, including dementia, mild cognitive impairment (MCI), depression, hallucinations, among others. Interestingly, the occurrence of these symptoms—motor, cognitive, and psychiatric—vary among individuals, such that a subgroup of PD patients might show some of the symptoms, but another subgroup does not. This has prompted neurologists and scientists to subtype PD patients depending on the severity of symptoms they show. Neural studies have also mapped different motor, cognitive, and psychiatric symptoms in PD to different brain networks. In this review, we discuss the neural and behavioral substrates of most common subtypes of PD patients, that are related to the occurrence of: (a) resting tremor (vs. nontremor-dominant); (b) MCI; (c) dementia; (d) impulse control disorders (ICD); (e) depression; and/or (f) hallucinations. We end by discussing the relationship among subtypes of PD subgroups, and the relationship among motor, cognitive, psychiatric factors in PD.

Advances in Therapeutic Options for Gait and Balance in Parkinson’s Disease

There is a need to explore non-dopaminergic approaches to treating balance and gait problems in Parkinson's disease (PD). There is emerging evidence on the role of cholinergic denervation of the pedunculopontine nucleus (PPN) thalamus system and falls in PD. Preliminary clinical trial data suggest that the subgroup of PD patients with frequent falls may be suitable candidates for future cholinergic augmentation clinical trials. Recent controlled clinical trials using methylphenidate have been unable to confirm earlier reports of improved gait in PD. Although progressive deterioration of axial motor symptoms occur with deep brain stimulation of the subthalamic nucleus or globus pallidus interna, new preliminary research suggests that other surgical stimulation sites, such as the PPN, may have a potential benefit on gait and balance impairments in PD. Continuing vigorous exercise and physical fitness should be highly encouraged to patients with PD who are at risk of physical deconditioning and fear of falling, but effective antifall physical therapy interventions remain an unmet clinical need.

Cortical α-synuclein load is associated with amyloid-β plaque burden in a subset of Parkinson’s disease patients

Amyloid-beta (Abeta) peptide pathology in Alzheimer's disease (AD) comprises extracellular plaques and cerebral amyloid angiopathy (CAA). In Parkinson's disease (PD), alpha-synuclein forms intraneuronal Lewy bodies (LBs), and cortical LBs are thought to play a major role in cognitive decline designated as PD with dementia. As there is increasing evidence that Abeta may also promote alpha-synuclein fibrillization, we assessed the relationship between LB pathology and Abeta deposition in 40 cases of PD and 20 age-matched controls. In five cortical areas, we established the severity of Abeta plaque load using an approach similar to that recommended by CERAD in AD. LB densities were determined using a morphometric approach. CAA was graded using previously described scales. The APOE genotype was established in 38 PD and 19 control cases. We have found that the overall Abeta plaque burden and, in particular, the diffuse plaque load shows a statistically significant 'large' correlation with the overall cortical LB burden. The strength of this correlation further increases in PD cases (about 50% of the cases) with moderate to high Abeta plaque load. The APOE epsilon4 allele is over-represented in this subgroup. Our data indicate a strong association between pathologically identifiable Abeta plaque burden and alpha-synuclein load in cerebral cortex and provide indirect evidence that Abeta pathology is likely to be an important factor contributing to cognitive decline in a subgroup of PD patients.

Effects of working memory capacity on inference generation during story comprehension in adults with Parkinson's disease

A group of non-demented adults with Parkinson's disease (PD) were studied to investigate how PD affects pragmatic-language processing, and, specifically, to test the hypothesis that the ability to draw inferences from discourse in PD is critically tied to the underlying working memory (WM) capacity of individual patients [Monetta, L., & Pell, M. D. (2007). Effects of verbal working memory deficits on metaphor comprehension in patients with Parkinson's disease. Brain and Language, 101, 80–89]. Thirteen PD patients and a matched group of 16 healthy control (HC) participants performed the Discourse Comprehension Test [Brookshire, R. H., & Nicholas, L. E. (1993). Discourse comprehension test. Tucson, AZ: Communication Skill Builders], a standardized test which evaluates the ability to generate inferences based on explicit or implied information relating to main ideas or details presented in short stories. Initial analyses revealed that the PD group as a whole was significantly less accurate than the HC group when comprehension questions pertained to implied as opposed to explicit information in the stories, consistent with previous findings [Murray, L. L., & Stout, J. C. (1999). Discourse comprehension in Huntington's and Parkinson's diseases. American Journal of Speech– Language Pathology, 8, 137–148]. However, subsequent analyses showed that only a subgroup of PD patients with WM deficits, and not PD patients with WM capacity within the control group range, were significantly impaired for drawing inferences (especially predictive inferences about implied details in the stories) when compared to the control group. These results build on a growing body of literature, which demonstrates that compromise of frontal–striatal systems and subsequent reductions in processing/WM capacity in PD are a major source of pragmatic-language deficits in many PD patients.

Freezing of gait: Risk factors and clinical characteristics

Freezing of gait (FOG) is a common, unique, and remarkably disabling episodic symptom in parkinsonism, affecting over 60% of patients with Parkinson's disease (PD) and is more common in patients with progressive supra-nuclear palsy (PSP) and vascular parkinsonism. In the early stages of PD, FOG is short lasting, resulting in mild disability, however, as the disease progresses it becomes a major cause of falls and loss of independence. The development of FOG in a patient with PD has recently been associated with several clinical risk factors and specific locomotion gait disturbances: (1) as PD progresses the possibility of developing FOG is increased; (2) gait and postural disturbances as initial motor symptoms increase the risk for FOG, while tremor as the initial or predominant motor symptom decreases the risk for development of FOG; (3) the presence of depression in the early or late stages of PD increases the risk for development of FOG; (4) long term treatment with dopamine agonists (excluding levodopa) was associated with a higher frequency of FOG at the early stages of PD; and (5) mental loading or dual tasking while walking increases the risk of FOG. While walking regularly (at the inter-freezing state of locomotion) PD patients who are prone to freeze, experience increased stride-to-stride variability in time and asymmetry in swing time between the left and right legs, which, in general, is not correlated with normal asymmetry in PD motor symptoms. FOG in PD is a symptom, which in most instances, improves with levodopa treatment and results in an episode which is shorter in time and which is more dynamic. MAO-B inhibition (selegiline and rasagiline) has been shown to decrease FOG severity in the early and late stages of PD. In summary, FOG is an episode, which can occur in a sub-group of PD patients who experience specific dys-rhythmicity in stepping and bi-hemispheric coordination. Furthermore, mental, as well as motor states, can increase the risk of development of FOG. Therefore, we conclude that improved treatment of the risk factors will decrease FOG frequency and severity.

Lack of association between the interleukin-1 alpha (−889) polymorphism and early-onset Parkinson's disease

An increasing number of studies have shown that an inflammatory process is part of Parkinson's disease (PD) brain pathology. Interleukin-1 (IL-1) is a multifunctional cytokine and is considered to contribute to several inflammatory diseases. Recently, we detected an associated risk in a subgroup of PD patients with a disease onset <50 years and a C to T transition in the IL-1α promoter (−889). One-hundred-seventy-six German PD patients (42.1±6.4 years; 42.4% male) and 170 unrelated age-matched control individuals (40.4±8.7 years; 57.6% male) were investigated for the presence of the IL-1α (−889C/T) polymorphism. No significant difference in the allelic distribution of the analyzed IL-1α polymorphism has been found between PD and controls. We conclude that the C/T polymorphism in the IL-1α promoter region at −889 does not increase the risk to develop PD.