The latest medical research on Parkinson’s Disease

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about parkinson’s disease gathered by our medical AI research bot.

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The Phenomenology of Primary Orthostatic Tremor.

"Movement Disorders Clinical Practice

The presence and prevalence of several neurological signs in patients with primary orthostatic tremor have not been systematically studied.

To assess the prevalence of clinical features of primary orthostatic tremor.

Video-based assessment by four raters of standardized neurological examination of 11 patients with primary orthostatic tremor.

On standing, bent knees (7/11), hem sign (6/10), and a broad base of support (6/11) were the three most prevalent signs. Examination of gait revealed abnormal tandem gait (9/11) and bent knees (6/11) as the most prevalent clinical signs. In the arms, none of the patients displayed bradykinesia, ataxia, or dystonia. In the legs, ataxia was absent in all patients and bradykinesia was present in only one patient.

Abnormal tandem gait, bent knees, hem sign, and broad base on standing are the most prevalent clinical signs in primary orthostatic tremor. We did not encounter clear extrapyramidal or unequivocal cerebellar signs.

Negative DAT-SPECT in Old Onset Parkinson's Disease: An Additional Pitfall?

"Movement Disorders Clinical Practice

Scans without evidence of dopaminergic deficit (SWEDDs) refer to patients clinically diagnosed with Parkinson's disease (PD), but showing normal findings on dopamine transporter single-photon emission computed tomography (DAT-SPECT). This entity remains highly debated, but recent findings suggesting that DAT-SPECT does not reflect either nigral cell bodies or striatal fibers of dopaminergic nigrostriatal neurons could improve our understanding of SWEDDs. Notably, compensatory downregulation of DAT in the early stages of PD seems to be less efficient in older-onset than in young-onset patients.

We report eight patients with old-onset clinical parkinsonism and a positive response to levodopa in which DAT-SPECT was normal both visually and semiquantitatively. Two subjects demonstrated an abnormal scan when repeated later.

We suggest that old-onset patients may truly have dopaminergic degeneration despite normal imaging results, presumably because they are diagnosed in the early stages confirming less efficient striatal compensatory strategies in old-age onset PD.

Level I PD-MCI Using Global Cognitive Tests and the Risk for Parkinson's Disease Dementia.

"Movement Disorders Clinical Practice

The criteria for PD-MCI allow the use of global cognitive tests. Their predictive value for conversion from PD-MCI to PDD, especially compared to comprehensive neuropsychological assessment, is unknown.

The MDS PD-MCI Study Group combined four datasets containing global cognitive tests as well as a comprehensive neuropsychological assessment to define PD-MCI (n = 467). Risk for developing PDD was examined using a Cox model. Global cognitive tests were compared to neuropsychological test batteries (Level I&II) in determining risk for PDD.

PD-MCI based on a global cognitive test (MMSE or MoCA) increases the hazard for developing PDD (respectively HR = 2.57, P = 0.001; HR = 4.14, P = <0.001). The C-statistics for MMSE (0.72) and MoCA (0.70) were lower than those based on neuropsychological tests (Level I = 0.82; Level II = 0.81). Sensitivity, specificity and diagnostic accuracy balance was best in Level II.

MMSE and MoCA predict conversion to PDD. However, Level II neuropsychological assessment seems the preferred assessment for PD-MCI.

Milestones in Tremor Research: 10 Years Later.

"Movement Disorders Clinical Practice

Major progress has occurred during the last decade in the field of tremor. From the clinical standpoint, a new classification has completely revise...

Antiphospholipid-Related Chorea: Two Case Reports and Role of Metabolic Imaging.

"Movement Disorders Clinical Practice

Antiphospholipid syndrome (APS) is a complex acquired autoimmune disease with a wide clinical spectrum. Chorea is a rare neurological manifestation of APS.

We report two elderly patients with APS-related chorea in whom functional imaging (18F-FDG positron emission tomography, FDG-PET) supported the diagnosis and compare our findings with existing literature.

Among 142 clinical cases of antiphospholipid-related chorea found in literature, only 10 had undergone brain metabolic imaging. Striatal hypermetabolism was evident in all cases (6) that underwent FDG-PET cerebral imaging. Cerebral perfusion single photon emission computed tomography (SPECT) was normal in two cases, while the other two presented with basal ganglia hypoperfusion.

Brain FDG-PET usually shows striatal hypometabolism in neurodegenerative types of chorea as opposed to striatal hypermetabolism observed in most cases of chorea from reversible etiologies, such as APS-related chorea. When a patient's clinical presentation is not clearly suggestive of either a neurodegenerative or autoimmune chorea, and first-line investigations are normal, FDG-PET may help in the differential diagnosis, especially in the presence of striatal hypermetabolism. SPECT data are less numerous and show either normal scans or basal ganglia hypoperfusion.

Pathologically Verified Corticobasal Degeneration Mimicking Richardson's Syndrome Coexisting with Clinically and Radiologically Shunt-Responsive Normal Pressure Hydrocephalus.

"Movement Disorders Clinical Practice

Normal pressure hydrocephalus (NPH) manifests as gait instability, cognitive impairment, and urinary incontinence. This clinical triad of NPH sometimes occurs with ventriculomegaly in patients with neurodegenerative disease. Patients with pathologically verified neurodegenerative diseases, such as progressive supranuclear palsy (PSP), have received antemortem diagnoses of NPH.

This study presents clinical and pathological features of a patient with pathologically verified corticobasal degeneration (CBD) coexisting with clinically shunt-responsive NPH.

We performed clinical, radiological, and pathological evaluations in a patient with CBD whose antemortem diagnosis was PSP Richardson's syndrome (PSP-RS) coexisting with shunt-responsive NPH.

A 59-year-old woman developed bradykinesia and gait instability and then frequent falls, urinary incontinence, and supranuclear vertical gaze palsy followed. At 63 years of age, her gait disturbance and urinary incontinence had deteriorated rapidly, and cognitive impairment was disclosed. There were typical findings of NPH with ventriculomegaly and disproportionately enlarged subarachnoid space hydrocephalus as well as a 2-layer appearance with decreased and increased cerebral blood perfusion. Shunt placement ameliorated gait instability for more than 1 year and improved radiological indicators of NPH. However, atrophy of the midbrain progressed with time after transient increases in size. Although the antemortem diagnosis was probable PSP-RS, pathological evaluation verified CBD. There were severe discontinuities of the ependymal lining of the lateral ventricles and subependymal rarefaction and gliosis with tau-positive deposition.

Shunt surgery could ameliorate NPH symptoms in patients with 4-repeat tauopathies. Careful assessments of clinical findings are necessary to predict the benefits of shunts as a therapeutic option for patients with neurodegenerative diseases coexisting with NPH.

Early Parkinson's Disease Phenotypes Tailored by Personality, Behavior, and Motor Symptoms.

Journal Parkinsons Disease

Previous studies described a parkinsonian personality characterized as rigid, introverted, and cautious; however, little is known about personality traits in de novo Parkinson's disease (PD) patients and their relationships with motor and neuropsychiatric symptoms.

To investigate personality in de novo PD and explore its relationship with PD symptoms.

Using Cloninger's biosocial model, we assessed personality in 193 de novo PD patients. Motor and non-motor symptoms were measured using several validated scales. Cluster analysis was conducted to investigate the interrelationship of personality traits, motor, and non-motor symptoms.

PD patients showed low novelty seeking, high harm avoidance, and normal reward dependence and persistence scores. Harm avoidance was positively correlated with the severity of depression, anxiety, and apathy (rs = [0.435, 0.676], p <  0.001) and negatively correlated with quality of life (rs = -0.492, p <  0.001). Novelty seeking, reward dependence, and persistence were negatively correlated with apathy (rs = [-0.274, -0.375], p <  0.001). Classification of patients according to personality and PD symptoms revealed 3 distinct clusters: i) neuropsychiatric phenotype (with high harm avoidance and low novelty seeking, hypodopaminergic neuropsychiatric symptoms and higher impulsivity), ii) motor phenotype (with low novelty seeking and higher motor severity), iii) benign phenotype (with low harm avoidance and high novelty seeking, reward dependence, and persistence traits clustered with lower symptoms severity and low impulsivity).

Personality in early PD patients allows us to recognize 3 patients' phenotypes. Identification of such subgroups may help to better understand their natural history. Their longitudinal follow-up will allow confirming whether some personality features might influence disease evolution and treatment.

Independent and Joint Associations of Tea Consumption and Smoking with Parkinson's Disease Risk in Chinese Adults.

Journal Parkinsons Disease

Existing limited evidence suggests that smoking and tea consumption may be associated with a lower risk of Parkinson's disease (PD). However, less is known about the independent and joint roles of these two habits, which are often clustered among Chinese, on PD risk.

To prospectively examine the independent and joint association of tea consumption and smoking with the risk of PD.

The China Kadoorie Biobank (CKB) study recruited 512,725 participants aged 30 to 79 years from ten areas across China since 2004. Information on smoking and tea consumption was collected at baseline, and PD cases were ascertained by linkage to the national health insurance system and death registry. Cox proportional hazards models were used to estimate the multivariable-adjusted hazard ratios (HRs) and corresponding 95%confidence intervals (CIs).

During a median of 10.8 years of follow-up, 922 PD cases were recorded. Compared with participants who never consumed tea, the HR (95%CI) for daily consumers was 0.68 (0.55, 0.84). Compared with participants who never or occasionally smoked, the HR (95%CI) for current smokers was 0.66 (0.53, 0.82). Those who had a clustering habit of smoking and tea consumption had a 38%(HR = 0.62; 95%CI: 0.49, 0.79) lower PD risk than those who consumed none. However, there were no statistically significant multiplicative or additive interaction for tea consumption and smoking on PD risk.

We found that smoking and daily tea consumption were independently inversely associated with the risk of PD.

Professionals' Treatment Preferences in the Prodromal Phase of Parkinson's Disease: A Discrete Choice Experiment.

Journal Parkinsons Disease

In Parkinson's disease (PD), several disease-modifying treatments are being tested in (pre-)clinical trials. To successfully implement such treatments, it is important to have insight into factors influencing the professionals' decision to start disease-modifying treatments in persons who are in the prodromal stage of PD.

We aim to identify factors that professionals deem important in deciding to a start disease-modifying treatment in the prodromal stage of PD.

We used a discrete choice experiment (DCE) to elicit preferences of neurologists and last-year neurology residents regarding treatment in the prodromal phase of PD. The DCE contained 16 hypothetical choice sets in which participants were asked to choose between two treatment options. The presented attributes included treatment effect, risk of severe side-effects, risk of mild side-effects, route of administration, and annual costs.

We included 64 neurologists and 18 last year neurology residents. Participants attached most importance to treatment effect and to the risk of severe side-effects. Participants indicated that they would discuss one of the presented treatments in daily practice more often in persons with a high risk of being in the prodromal phase compared to those with a moderate risk. Other important factors for deciding to start treatment included the amount of evidence supporting the putative treatment effect, the preferences of the person in the prodromal phase, and the life expectancy.

This study provides important insights in factors that influence decision making by professionals about starting treatment in the prodromal phase of PD.

Comparative Analysis of Total Alpha-Synuclein (αSYN) Immunoassays Reveals That They Do Not Capture the Diversity of Modified αSYN Proteoforms.

Journal Parkinsons Disease

The development of therapeutics for Parkinson's disease (PD) requires the establishment of biomarker assays to enable stratifying patients, monitoring disease progression, and assessing target engagement. Attempts to develop diagnostic assays based on detecting levels of the α-synuclein (αSYN) protein, a central player in the pathogenesis of PD, have yielded inconsistent results.

To determine whether the three commercial kits that have been extensively used for total αSYN quantification in human biological fluids (from Euroimmun, MSD, and Biolegend) are capable of capturing the diversity and complexity of relevant αSYN proteoforms.

We investigated and compared the ability of the different assays to detect the diversity of αSYN proteoforms using a library of αSYN proteins that comprise the majority of disease-relevant αSYN variants and post-translational modifications (PTMs).

Our findings showed that none of the three tested immunoassays accurately capture the totality of relevant αSYN species, and that these assays are unable to recognize most disease-associated C-terminally truncated variants of αSYN. Moreover, several N-terminal truncations and phosphorylation/nitration PTMs differentially modify the level of αSYN detection and recovery by different immunoassays, and a CSF matrix effect was observed for most of the αSYN proteoforms analyzed by the three immunoassays.

Our results show that the tested immunoassays do not capture the totality of the relevant αSYN species and therefore may not be appropriate tools to provide an accurate measure of total αSYN levels in samples containing modified forms of the protein. This highlights the need for next generation αSYN immunoassays that capture the diversity of αSYN proteoforms.

Parkinson's Disease Drug Therapies in the Clinical Trial Pipeline: 2022 Update.

Journal Parkinsons Disease

As the international community dealt with the ongoing COVID-19 pandemic, important progress continued to be made in the development of new drug-based therapies for the neurodegenerative condition of Parkinson's disease (PD) in 2021. This progress included both "symptomatic treatments" (ST - improves/reduces symptoms of the condition) and "disease modifying treatments" (DMT - attempts to delay/slow progression by addressing the underlying biology of PD), which can be categorised further based on their mechanisms of action and class of drug.

This report continues previous efforts to provide an overview of the pharmacological therapies - both ST and DMT - in clinical trials for PD during 2021- 2022, with the aim of creating greater awareness and involvement in the clinical trial process. We also hope to stimulate collaboration amongst all stakeholders, including industry, academia, advocacy organizations, and most importantly patient community.

We conducted a review of clinical trials of drug therapies for PD using trial data obtained from the ClinicalTrials.gov and World Health Organisation (WHO) registries, and performed a breakdown analysis of studies that were active as of January 31st 2022. We also assessed active drug development projects that had completed one clinical phase but were yet to start the next.

There was a total of 147 clinical trials registered on the ClinicalTrials.gov website as active during the period of analysis. Of these trials, 91 (62%)were investigating STs, while 56 (38%)focused on DMTs. Approximately 1/3 of the studies (34.7% ; 51 trials) were in Phase 1, while over half of the trials were in Phase 2 (50.3% ; 74 trials). Only 15% (22 trials) of the studies were in Phase 3, of which only 3 trials were evaluating DMTs. Novel therapeutics (42%)were the most common type of agents being tested across all phases of testing, followed by repurposed agents (34%)and reformulations (20% ).

Despite significant global health constraints, the development of new drug-based therapies for PD continued in 2021. Hopefully with a shift towards a post-pandemic world in which COVID-19 is better managed, we will see an increase in the number of clinical trials focused on drug development for PD. The need for more Phase 3 studies for DMTs remains acute.

Odor Identification by Parkinson's Disease Patients Tested by Using Sniffin' Sticks versus Natural Spices.

Parkinsons Disease

Hyposmia is a frequent symptom of Parkinson's disease (PD), which greatly impacts patients' flavor perception and their quality of life. However, PD patients recognize some odors better than others. Identifying which food odors are still recognized by PD patients may be useful for flavor enhancement. Our aim was to evaluate the olfactory identification of Sniffin' Sticks and spice odorants in PD patients and healthy controls (HC), to identify the impact of synthetic odorants compared with real-life food and the impact of odor familiarity and pleasantness on odorant identification in PD patients.

Sniffin' Sticks odorant identification was evaluated in 80 PD patients and 105 age-matched HC. In a subset, the spice odorant identification was evaluated.

The mean total score was higher for the Sniffin' Sticks than for the spice odor identification test in all participants (55.4% versus 22.5%). Sniffin' Sticks orange, peppermint, rose, and fish odorants were best correctly identified by PD patients, by 62.5, 53.8, 52.9, and 57.5%, respectively. Of the spice odor identification test, garlic and "no stimulus" were best correctly identified by PD patients, by, respectively, 38.2 and 67.6%. HC identified most Sniffin' Sticks odorants and spices better than PD patients. Odorant familiarity determined real-life food odorant identification.

This study demonstrates that some food odorants, both the commercial Sniffin' Sticks as natural odorants, are still recognized by PD patients. Sniffin' Sticks were better recognized compared with real-life odorants, by both HC and PD patients. Odorant familiarity determined PD patients' odorant identification; therefore, familiar food odorants may have potential for a future flavor enhancement. Implications. This is the first study, to our knowledge, to evaluate real-life food odor identification in PD patients. Our results provide a first step towards patient-appropriate flavor enhancement strategies in PD.