Clinical Characteristics Of Parkinson's Disease Research Articles

Air Pollution and Parkinson Disease in a Population-Based Study

The role of air pollution in risk and progression of Parkinson disease (PD) is unclear. To assess whether air pollution is associated with increased risk of PD and clinical characteristics of PD. This population-based case-control study included patients with PD and matched controls from the Rochester Epidemiology Project from 1998 to 2015. Data were analyzed from January to June 2024. Mean annual exposure to particulate matter with a diameter of 2.5 µm or less (PM2.5) from 1998 to 2015 and mean annual exposure to nitrogen dioxide (NO2) from 2000 to 2014. Outcomes of interest were PD risk, all-cause mortality, presence of tremor-predominant vs akinetic rigid PD, and development of dyskinesia. Models were adjusted for age, sex, race and ethnicity, year of index, and urban vs rural residence. A total of 346 patients with PD (median [IQR] age 72 [65-80] years; 216 [62.4%] male) were identified and matched on age and sex with 4813 controls (median [IQR] age, 72 [65-79] years, 2946 [61.2%] male). Greater PM2.5 exposure was associated with increased PD risk, and this risk was greatest after restricting to populations within metropolitan cores (odds ratio [OR], 1.23; 95% CI, 1.11-1.35) for the top quintile of PM2.5 exposure compared with the bottom quintile. Greater NO2 exposure was also associated with increased PD risk when comparing the top quintile with the bottom quintile (OR, 1.13; 95% CI, 1.07-1.19). Air pollution was associated with a 36% increased risk of akinetic rigid presentation (OR per each 1-μg/m3 increase in PM2.5, 1.36; 95% CI, 1.02-1.80). In analyses among patients with PD only, higher PM2.5 exposure was associated with greater risk for developing dyskinesia (HR per 1-μg/m3 increase in PM2.5, 1.42; 95% CI, 1.17-1.73), as was increased NO2 exposure (HR per 1 μg/m3 increase in NO2, 1.13; 95% CI, 1.06-1.19). There was no association between PM2.5 and all-cause mortality among patients with PD. In this case-control study of air pollution and PD, higher levels of PM2.5 and NO2 exposure were associated with increased risk of PD; also, higher levels of PM2.5 exposure were associated with increased risk of developing akinetic rigid PD and dyskinesia compared with patients with PD exposed to lower levels. These findings suggest that reducing air pollution may reduce risk of PD, modify the PD phenotype, and reduce risk of dyskinesia.

MicroRNA Expression Profile Changes in the Leukocytes of Parkinson's Disease Patients.

Parkinson's disease (PD) is one of the most common movement disorders. It is primarily diagnosed clinically. A correct diagnosis of PD in its early stages is important for the development of a pathogenic treatment, which necessitates a search for potential biomarkers of the disease. We evaluated the diagnostic value of several microRNAs and their relationship with the clinical characteristics of PD. The study included 70 PD patients and 40 healthy volunteers. We analyzed the expression of 15 microRNAs in blood leukocytes, which were selected based on literature data and modern concepts of molecular PD pathogenesis. All patients were evaluated using the Hoehn and Yahr scale, UPDRS, NMSQ, and PDQ-39. The data analysis revealed a statistically significant increase in the expression of miR-7-5p, miR-29c-3p, and miR-185-5p and a statistically significant decrease in the expression of miR-29a-3p and miR-30c-1-5p in leukocytes in PD. However, the altered microRNA profile was shown to have a moderate diagnostic value for PD diagnosis. MicroRNA expression changes were associated with the motor and non-motor phenotypic features of PD and administration of anti-Parkinson's drugs. Also, a relationship between some of the microRNAs studied and the duration and severity of PD was found, which may potentially be used to monitor disease progression.

Upper-extremity kinematics and interlimb movement correlation in persons with Parkinson Disease on irregular terrain, cross-slope, and under dual-task condition

BackgroundA defining clinical characteristics of Parkinson disease is reduced upper-extremity movements. Irregular terrain, the presence of a cross slope, and dual-task conditions have been found to alter the lower-limb gait characteristics of persons with Parkinson disease but there is little information how different environmental and cognitive conditions impact upper-limb kinematics as well as interlimb movement correlation. Research questionDo environmental conditions, such as irregular terrain and the presence of cross slope, as well as dual-task condition impact the upper-extremity kinematics and interlimb movement correlation of persons with Parkinson disease compared to healthy, age-matched controls? MethodsThree-dimensional whole-body gait data were collected for nine participants with mild-to-moderate Parkinson disease and nine healthy age-matched control participants. All participants ambulated on a regular terrain, irregular terrain, with and without cross slope, and under dual and single-task conditions. The primary outcomes were arm swing magnitude, arm swing asymmetry, and normalized cross-correlation between the ipsilateral arms and contralateral legs, which characterized movement correlation. ResultsFor all conditions, persons with Parkinson disease exhibited reduced arm swing magnitude and greater arm swing asymmetry compared to the healthy controls. All participants increased their arm swing magnitude on the irregular surface and under the dual-task condition. In the healthy group, the arm swing asymmetry was invariant to terrain but declined under the dual-task condition while the persons with Parkinson disease exhibited increased asymmetry on the cross slope, on the irregular terrain, and under the dual-task condition. Interlimb movement correlation decreased on the irregular terrain for the persons with Parkinson disease while the healthy group exhibited decreased interlimb movement correlation on the cross slope as well as under the dual-task condition. SignificancePersons with Parkinson disease were able to increase their arm swing magnitude when their balance was challenged and the most significant threat to their safety as defined by the greatest reduction in the interlimb movement correlation was the irregular terrain.

Risk factors of impulsive-compulsive behaviors in PD patients: a meta-analysis.

To summarize the reliable risk factors of impulsive-compulsive behaviors (ICBs) in Parkinson's disease (PD) patients through a meta-analysis on studies in which PD-ICBs were diagnosed by clinical interview. PubMed, Embase, Web of Science, CNKI and Wanfang databases were searched. We selected studies ensuring that diagnosis of ICBs in PD patients depends on semi-structured interviews according to the clinical diagnostic criteria of ICBs. The Newcastle-Ottawa Scale was used to evaluate quality of the included studies. The analyzed factors included demographic information, clinical characteristics of PD and medications. A total of 856 records were screened and 66 full texts were evaluated, and 13 studies (684 PD patients with ICBs [PD-ICBs] and 3,382 PD patients without ICBs [PD-non-ICBs]) were included. Compared with PD-non-ICBs, PD-ICBs were younger in age (-3.7 [-5.53, -1.87], P < 0.0001), with a greater proportion of males (1.64 [1.21, 2.22], P = 0.001), with a younger age of PD onset (-5.42 [-7.87, -2.97], P < 0.0001) and a longer course of PD (1.30 [0.38, 2.22], P = 0.005). PD-ICBs were also associated with higher HAM-D (1.74 [0.47, 3.01], P = 0.007), more levodopa dosage (1.74 [1.09, 2.77], P = 0.02) and dopamine receptor agonists (DA) use (3.96 [2.74, 5.71), P < 0.00001), and higher average dose (levodopa 117.53 [53.59, 181.46], P = 0.0003; DA 80.03 [46.16, 113.90], P < 0.00001), as well as more amantadine use (2.20 [1.42, 3.40], P = 0.0004). The meta-analysis of most factors showed less heterogeneity, except age, age of onset, PD duration, Hoehn and Yahr stage, MMSE and drug dosage. However, whether rapid eye movement sleep behavior disorder, dyskinesia, genetic polymorphism and other factors are risk factors for PD-ICBs remains unclear. This meta-analysis suggests that males, young, early disease onset, long disease duration, depression, dose of levodopa, dopamine receptor agonists and amantadine are risk factors of ICBs in PD patients.

Role of Microgliosis and NLRP3 Inflammasome in Parkinson's Disease Pathogenesis and Therapy.

Parkinson's disease (PD) is a neurodegenerative disorder marked primarily by motor symptoms such as rigidity, bradykinesia, postural instability and resting tremor associated with dopaminergic neuronal loss in the Substantia Nigra pars compacta (SNpc) and deficit of dopamine in the basal ganglia. These motor symptoms can be preceded by pre-motor symptoms whose recognition can be useful to apply different strategies to evaluate risk, early diagnosis and prevention of PD progression. Although clinical characteristics of PD are well defined, its pathogenesis is still not completely known, what makes discoveries of therapies capable of curing patients difficult to be reached. Several theories about the cause of idiopathic PD have been investigated and among them, the key role of inflammation, microglia and the inflammasome in the pathogenesis of PD has been considered. In this review, we describe the role and relation of both the inflammasome and microglial activation with the pathogenesis, symptoms, progression and the possibilities for new therapeutic strategies in PD.

Detection of Microbial 16S rRNA Gene in the Blood of Patients With Parkinson's Disease.

Emerging evidence suggests that the microbiota present in feces plays a role in Parkinson’s disease (PD). However, the alterations of the microbiome in the blood of PD patients remain unknown. To test this hypothesis, we conducted this case-control study to explore the microbiota compositions in the blood of Chinese PD patients. Microbiota communities in the blood of 45 patients and their healthy spouses were investigated using high-throughput Illumina HiSeq sequencing targeting the V3-V4 region of 16S ribosomal RNA (rRNA) gene. The relationships between the microbiota in the blood and PD clinical characteristics were analyzed. No difference was detected in the structure and richness between PD patients and healthy controls. The following genera were enriched in the blood of PD patients: Isoptericola, Cloacibacterium, Enhydrobacter and Microbacterium; whereas genus Limnobacter was enriched in the healthy controls after adjusting for age, gender, body mass index (BMI) and constipation. Additionally, the findings regarding these genera were validated in another independent group of 58 PD patients and 57 healthy controls using real-time PCR targeting genus-specific 16S rRNA genes. Furthermore, not only the genera Cloacibacterium and Isoptericola (which were identified as enriched in PD patients) but also the genera Paludibacter and Saccharofermentans were positively associated with disease duration. Some specific genera in the blood were related to mood disorders. We believe this is the first report to provide direct evidence to support the hypothesis that the identified microbiota in the blood are associated with PD. Additionally, some microbiota in the blood are closely associated with the clinical characteristics of PD. Elucidating these differences in blood microbiomes will provide a foundation to improve our understanding of the role of microbiota in the pathogenesis of PD.

Two polysomnographic features of REM sleep behavior disorder: Clinical variations insight for Parkinson's disease

IntroductionLoss of REM sleep muscle atonia (RWA) and dream-enactment behavior (DEB) are two associated features of REM sleep behavior disorder (RBD), which is frequently associated with Parkinson's disease (PD). Few studies have examined both DEB and RWA simultaneously in patients with PD. This study aimed to evaluate relationships between RWA, DEB and clinical characteristics of PD. MethodsWe conducted overnight polysomnography in 145 patients with PD. DEB (motor behaviors and/or vocalizations during REM) and increased RWA (IRWA; tonic and phasic chin EMG density ≥ 30% and ≥15%, respectively) were identified. Patients were categorized as clinical RBD (DEB and IRWA), sub-DEB positive (DEB only), subclinical RBD (IRWA only), or normal REM sleep. ResultsPatients with DEB had higher Hoehn and Yahr (H&Y) stage, Unified Parkinson's Disease Rating Scale (UPDRS) III score, levodopa equivalent dose(LEDs), and worse cognition. RWA was associated with H&Y stage, LEDs, cognition, and sleep structure in all patients. PD duration was associated with RWA, but not DEB. The PD patients who exhibited clinical or subclinical RBD, compared to sub-DEB positive, had higher H&Y stage, UPDRS III score and LEDs, lower cognitive score, worse sleep structure than the PD + cREM group. ConclusionBoth DEB and RWA were associated with severity of PD illness. Subclinical RBD might have different disease progression from sub-DEB positive. DEB symptoms may fluctuate or disappear whereas RWA may continue to develop as PD progresses. Differences in the course of DEB and RWA may reflect the difference in the degeneration process of neurodegenerative disorders.

Disease-Related Variables and Depression Among Iranian Patients with Parkinson Disease.

Background:The factors affecting the correlation between Parkinson disease (PD) and depression have remained unclear.Objectives:We assessed the prevalence of depression among patients with PD and the association between PD-related variables and depression severity.Patients and Methods:This is a cross-sectional study performed in Kermanshah Province of Iran. Sampling was based on recruitment of subjects according to inclusion and exclusion criteria. Patients with confirmed Parkinson disease who were referred to clinics of Kermanshah University of Medical Sciences participated in this study. Depression was evaluated with Beck Depression Inventory-II (BDI-II). Clinical characteristics of PD, including tremor, rigidity, impaired posture, loss of autonomic movement, changes in speech and handwriting, masked face, and hyposmia were indexed. Anhedonia was assessed with Farsi version of Snaith-Hamilton Pleasure Scale. Data were collected between April 2010 and March 2014.Results:A total of 350 patients (52.9% men and 47.1% women) participated in this investigation. Female gender (36.5% in women vs. 13.0% in men, P < 0.0001), impaired posture (27.2% in affected individuals vs. 18.8%, P = 0.002), masked face (39.0% vs. 5.2%, P < 0.0001), and hyposmia (48.7% vs. 21.0%, P = 0.001) were associated with higher susceptibility to profound depression. Lower scores of all domains of Farsi version of Snaith-Hamilton Pleasure Scale (including interest/pastimes, social interaction, sensory experience, and food/drink) were related to more severe depression (P < 0.0001 for all subscales). Severe and profound depression was found in 44% of the participants.Conclusions:This study estimated that the prevalence of major depression among Iranian individuals with PD living in Kermanshah as 44%. Major determinants of depression were female gender, rigidity, impaired posture, masked face, hyposmia, and anhedonia.

Characteristics and exacerbating factors of chronic low back pain in Parkinson's disease.

The aim of this study was to determine the exacerbating factors of chronic low back pain (LBP) and strategic points against LBP in patients with Parkinson's disease (PD). Forty-four consecutive PD patients complaining of LBP were included. Clinical characteristics of PD and LBP, spinal musculoskeletal condition, and clinical health status were evaluated. Patient age at PD and LBP onset was contiguous, and LBP time period was mainly described as constant or upon waking up. Exacerbating factors of LBP included modified Hoehn and Yahr stage and motor complications of PD, such as the wearing-off phenomenon and dyskinesia. Bone quality demonstrated osteopenia due to elevated bone resorption, with vitamins K and D insufficiencies. Spinal alignment demonstrated an increased sagittal vertical axis (120.2 ± 65.4 mm) with decreased lumbar lordosis (-24.0 ± 20.6°) and lumbar range of motion (28.7 ± 10.2°), which were significantly related to severity of LBP and quality of life assessments. This study demonstrated that exacerbating factors of LBP include stage of motor function, motor complications of PD and stooped posture with decreased lumbar lordosis and range of lumbar movement. Therefore, control of PD, including motor complications, active treatment for osteoporosis and therapeutic exercise, are important for treating chronic LBP in patients with PD.

Cerebrospinal fluid Aβ42 levels and APP processing pathway genes in Parkinson's disease.

Of recent interest is the finding that certain cerebrospinal fluid (CSF) biomarkers traditionally linked to Alzheimer's disease (AD), specifically amyloid beta protein (Aβ), are abnormal in PD CSF. The aim of this exploratory investigation was to determine whether genetic variation within the amyloid precursor protein (APP) processing pathway genes correlates with CSF Aβ42 levels in Parkinson's disease (PD). Parkinson's disease (n = 86) and control (n = 161) DNA were genotyped for 19 regulatory region tagging single-nucleotide polymorphisms (SNPs) within nine genes (APP, ADAM10, BACE1, BACE2, PSEN1, PSEN2, PEN2, NCSTN, and APH1B) involved in the cleavage of APP. The SNP genotypes were tested for their association with CSF biomarkers and PD risk while adjusting for age, sex, and APOE ɛ4 status. Significant correlation with CSF Aβ42 levels in PD was observed for two SNPs, (APP rs466448 and APH1B rs2068143). Conversely, significant correlation with CSF Aβ42 levels in controls was observed for three SNPs (APP rs214484, rs2040273, and PSEN1 rs362344). In addition, results of this exploratory investigation suggest that an APP SNP and an APH1B SNP are marginally associated with PD CSF Aβ42 levels in APOE ɛ4 noncarriers. Further hypotheses generated include that decreased CSF Aβ42 levels are in part driven by genetic variation in APP processing genes. Additional investigation into the relationship between these findings and clinical characteristics of PD, including cognitive impairment, compared with other neurodegenerative diseases, such as AD, are warranted. © 2015 International Parkinson and Movement Disorder Society.

Orthostatic hypotension in drug-naïve patients with Parkinson's disease.

Background and PurposeOrthostatic hypotension (OH) is known to be present even in patients with early Parkinson’s disease (PD). To affirm the presence of OH and find correlation between OH and other dysautonomic symptoms in PD, this study has done in newly-diagnosed PD patients.MethodsForty-five non-demented patients with no prior history of treatment for PD were recruited (17 men, 63.8 ± 10.1 years of age). All the patients were evaluated for OH before starting medications. Autonomic symptoms were evaluated with structured questionnaires. Clinical characteristics of PD were evaluated (median Hoehn and Yahr stage 2.0 (1–3), 1.3 ± 1.1 years of disease duration), and comorbid medical conditions that could affect blood pressure were also recorded.ResultsOH was prevalent, and eighteen patients (40%) showed orthostatic hypotension, and twenty-seven (60%) did not (normotensive group). There was no significant difference in demographic and clinical characteristics between groups. The presence or severity of symptoms of autonomic dysfunction in the OH group also not differed from those of the normotensive group.ConclusionsOH was prevalent even in the early stage of PD, and was not related to presence or severity of any other symptoms of autonomic dysfunction. Our findings suggest that clinicians should pay attention to OH from the early stage of disease.

Can Alzheimer's type pathology influence the clinical phenotype of Parkinson's disease?

Patients with clinical and pathological diagnosis of Parkinson's disease (PD) may, at death, also be found to have the pathological changes of Alzheimer's disease (AD). With this study we aim to determine the influence of AD pathology on the clinical phenotype of PD. We studied 64 patients who donated their brains to the University of Miami Brain Endowment Bank(TM) and fulfilled the clinical and pathological criteria for PD. For the evaluation of AD pathology we used the CERAD criteria. Dementia was diagnosed, in life, also using standard criteria. Case histories were abstracted and reviewed by one investigator (SP) who then made comparisons between patients. Patients with AD pathology (PD-AD) were older both at the time of diagnosis and death. The presence of AD pathology did not seem to influence disease duration in our cohort of PD patients. As expected there was a clear relation between AD pathology and dementia but not all PD-AD patients were demented. Psychosis and depression were also found to be more prevalent in the PD-AD patients. In the comparison between demented and non-demented PD-AD patients dementia was more likely to appear in patients with PD and definite criteria for AD. Apart from dementia AD pathology seems to be associated with a number of other clinical characteristics of PD.