Clinical Markers May Identify Patients at Risk for Early Parkinson’s Disease Dementia: A Prospective Study

Background: The study aims at identifying features predictive of early onset of dementia in Parkinson’s disease (PD). Methods: 103 non-demented PD patients were evaluated on various scales at baseline and 89 patients at 3-year follow-up. Results: By the end of the study 43.8% of patients developed dementia. The development of dementia was linked to the baseline Mini Mental State Examination score (Pearson coefficient r = .404, p = 0.013), the presence of autonomic dysfunctions (r = −.621, p < 0.001) and insomnia (r = −.526, p = 0.001). A binary logistic regression analysis showed that the development of dementia was correlated strongly with the presence of autonomic dysfunctions (95% CI 2.60 to 52.83, p < 0.001), and insomnia (95% CI 0.60 to 0.95, p = 0.017). Conclusion: Patients with signs of autonomic dysfunction and insomnia are at higher risk for developing dementia and deserve closer monitoring of cognitive symptoms.

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CLOCK 3111T/C Variant Correlates with Motor Fluctuation and Sleep Disorders in Chinese Patients with Parkinson’s Disease

Parkinson s Disease ◽

10.1155/2018/4670380 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Fan Lou ◽

Ming Li ◽

Xiaoguang Luo ◽

Yan Ren

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Sleep Disorders ◽

Sleep Disorder ◽

Rating Scale ◽

Clock Genes ◽

Motor Fluctuation ◽

Binary Logistic Regression ◽

Chinese Patients ◽

Binary Logistic Regression Analysis

Background. The clock genes controlling biological rhythm play an important role in the pathophysiology of aging. The purpose of this study was to determine whether there is an association between a variant of the circadian locomotor output cycles kaput (CLOCK) gene and circadian dysfunction of Parkinson’s disease (PD). Methods. Six hundred and forty-six cases of Parkinson’s disease from consecutive outpatients and inpatients ward from our hospital were included in this study. Kompetitive allele-specific PCR was used to determine the frequency distribution of genotypes and alleles. The examinations for the PD group were assessed in person in order to evaluate motor symptoms, cognitive function, sleep, and depression, including the Unified Parkinson’s Disease Rating Scale (UPDRS), Mini-Mental State Examination (MMSE), Pittsburgh Sleep Quality Index (PSQI), and 17-item Hamilton Rating Scale for Depression (HAMD-17). Results. Motor fluctuation (P<0.001) and sleep disorders (P=0.007) were significantly different between the two groups. These correlations persisted after adjusting for confounding risk factors by further binary logistic regression analysis, suggesting that the CLOCK 3111T/C variant was associated with motor fluctuation (OR = 1.080, P<0.001) and a subjective sleep disorder (OR = 1.130, P=0.037). Conclusion. The CLOCK 3111T/C variant can be an independent risk factor for motor fluctuation and sleep disorder in Parkinson’s disease.

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Azathioprine immunosuppression and disease modification in Parkinson’s disease (AZA-PD): a randomised double-blind placebo-controlled phase II trial protocol

BMJ Open ◽

10.1136/bmjopen-2020-040527 ◽

2020 ◽

Vol 10 (11) ◽

pp. e040527

Author(s):

Julia C Greenland ◽

Emma Cutting ◽

Sonakshi Kadyan ◽

Simon Bond ◽

Anita Chhabra ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Immune System ◽

Phase Ii ◽

Rating Scale ◽

Positron Emission Tomography Imaging ◽

Clinical Markers ◽

Double Blind ◽

Positron Emission ◽

Immunosuppressant Medication

IntroductionThe immune system is implicated in the aetiology and progression of Parkinson’s disease (PD). Inflammation and immune activation occur both in the brain and in the periphery, and a proinflammatory cytokine profile is associated with more rapid clinical progression. Furthermore, the risk of developing PD is related to genetic variation in immune-related genes and reduced by the use of immunosuppressant medication. We are therefore conducting a ‘proof of concept’ trial of azathioprine, an immunosuppressant medication, to investigate whether suppressing the peripheral immune system has a disease-modifying effect in PD.Methods and analysisAZA-PD is a phase II randomised placebo-controlled double-blind trial in early PD. Sixty participants, with clinical markers indicating an elevated risk of disease progression and no inflammatory or immune comorbidity, will be treated (azathioprine:placebo, 1:1) for 12 months, with a further 6-month follow-up. The primary outcome is the change in the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale gait/axial score in the OFF state over the 12-month treatment period. Exploratory outcomes include additional measures of motor and cognitive function, non-motor symptoms and quality of life. In addition, peripheral and central immune markers will be investigated through analysis of blood, cerebrospinal fluid and PK-11195 positron emission tomography imaging.Ethics and disseminationThe study was approved by the London-Westminster research ethics committee (reference 19/LO/1705) and has been accepted by the Medicines and Healthcare products Regulatory Agency (MHRA) for a clinical trials authorisation (reference CTA 12854/0248/001–0001). In addition, approval has been granted from the Administration of Radioactive Substances Advisory Committee. The results of this trial will be disseminated through publication in scientific journals and presentation at national and international conferences, and a lay summary will be available on our website.Trial registration numbersISRCTN14616801 and EudraCT- 2018-003089-14.

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Constipation is Associated with Development of Cognitive Impairment in de novo Parkinson’s Disease: A Longitudinal Analysis of Two International Cohorts

Journal of Parkinson s Disease ◽

10.3233/jpd-212570 ◽

2021 ◽

pp. 1-11

Author(s):

Valentina Leta ◽

Daniele Urso ◽

Lucia Batzu ◽

Daniel Weintraub ◽

Nataliya Titova ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

De Novo ◽

Motor Dysfunction ◽

Group Differences ◽

Motor Symptoms ◽

Kaplan Meier ◽

Patients At Risk ◽

Non Motor Symptoms

Background: Constipation is regarded as one of the prodromal features of Parkinson’s disease (PD) and there is emerging evidence linking gastrointestinal dysfunction and cognitive impairment (CI) in PD. Objective: We explored whether constipation is associated with development of CI in two independent cohorts of de novo PD patients (n = 196 from the Non-motor International Longitudinal Study [NILS] and n = 423 from the Parkinson’s Progression Markers Initiative [PPMI] study). Methods: Constipation was clinically defined using the Non-Motor Symptoms Scale (NMSS) item-21 [NILS] and Scales for Outcomes in PD-Autonomic (SCOPA-AUT) item-5 [PPMI]. We assessed baseline group differences (PD with or without constipation) in CI, global non-motor symptoms burden, motor dysfunction, and striatal dopaminergic denervation. Kaplan-Meier method estimated group differences in cumulative proportion of patients with incident CI over three years. In PPMI, we subsequently performed univariate and multivariate Cox survival analyses to evaluate whether constipation predicts incident mild cognitive impairment or dementia over a 6-year period, including constipation and other known predictors of CI as covariates. Results: Patients with constipation had greater motor and global non-motor burden in both cohorts at baseline (p < 0.05). Kaplan-Meier plots showed faster conversion to CI in patients with constipation in both cohorts (p < 0.05). In PPMI, 37 subjects developed dementia during a mean follow-up of 4.9 years, and constipation was an independent predictor of dementia onset (hazard ratio = 2.311; p = 0.02). Conclusion: Constipation in de novo PD patients is associated with development of cognitive decline and may serve as a clinical biomarker for identification of patients at risk for cognitive impairment.

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Prognostic predictors relevant to end-of-life palliative care in Parkinson’s disease and related disorders: a systematic review

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2020-323939 ◽

2021 ◽

pp. jnnp-2020-323939

Author(s):

Umer Akbar ◽

Robert Brett McQueen ◽

Julienne Bemski ◽

Julie Carter ◽

Elizabeth R Goy ◽

...

Keyword(s):

Parkinson’S Disease ◽

Palliative Care ◽

Parkinson's Disease ◽

End Of Life ◽

Cause Of Death ◽

Quantitative Research ◽

Motor Dysfunction ◽

Clinical Markers ◽

Hospice Referral ◽

Survey Responses

Parkinson’s disease and related disorders (PDRD) are the second most common neurodegenerative disease and a leading cause of death. However, patients with PDRD receive less end-of-life palliative care (hospice) than other illnesses, including other neurologic illnesses. Identification of predictors of PDRD mortality may aid in increasing appropriate and timely referrals. To systematically review the literature for causes of death and predictors of mortality in PDRD to provide guidance regarding hospice/end-of-life palliative care referrals. We searched MEDLINE, PubMed, EMBASE and CINAHL databases (1970–2020) of original quantitative research using patient-level, provider-level or caregiver-level data from medical records, administrative data or survey responses associated with mortality, prognosis or cause of death in PDRD. Findings were reviewed by an International Working Group on PD and Palliative Care supported by the Parkinson’s Foundation. Of 1183 research articles, 42 studies met our inclusion criteria. We found four main domains of factors associated with mortality in PDRD: (1) demographic and clinical markers (age, sex, body mass index and comorbid illnesses), (2) motor dysfunction and global disability, (3) falls and infections and (4) non-motor symptoms. We provide suggestions for consideration of timing of hospice/end-of-life palliative care referrals. Several clinical features of advancing disease may be useful in triggering end-of-life palliative/hospice referral. Prognostic studies focused on identifying when people with PDRD are nearing their final months of life are limited. There is further need for research in this area as well as policies that support need-based palliative care for the duration of PDRD.

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Lower urinary tract symptoms in patients with Parkinson’s disease in a prospective study: Symptoms, urodynamics and considerations

European Urology Supplements ◽

10.1016/s1569-9056(17)30467-0 ◽

2017 ◽

Vol 16 (3) ◽

pp. e706-e709

Author(s):

J. Chunsong ◽

X. Cui ◽

H. Yan ◽

Q. Wang ◽

J. Li ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Urinary Tract ◽

Prospective Study ◽

Lower Urinary Tract Symptoms ◽

Lower Urinary Tract ◽

Urinary Tract Symptoms ◽

A Prospective Study ◽

Lower Urinary

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Analysis of dysgraphia in advanced Parkinson's disease patients following bilateral STN-DBS – A prospective study

Journal of the Neurological Sciences ◽

10.1016/j.jns.2021.119474 ◽

2021 ◽

Vol 429 ◽

pp. 119474

Author(s):

Swapnil Kolpakwar ◽

Rajesh Alugolu ◽

Mudumba Vijayasaradhi ◽

Rukmini Kandadai ◽

Rupam Borgohain

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Prospective Study ◽

Advanced Parkinson’S Disease ◽

A Prospective Study ◽

Stn Dbs

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Predictors of Pharyngeal Dysphagia in Patients with Parkinson’s Disease

Journal of Parkinson s Disease ◽

10.3233/jpd-202081 ◽

2020 ◽

Vol 10 (4) ◽

pp. 1727-1735

Author(s):

Inga Claus ◽

Paul Muhle ◽

Judith Suttrup ◽

Bendix Labeit ◽

Sonja Suntrup-Krueger ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Logistic Regression ◽

Rating Scale ◽

Equivalent Dose ◽

Binary Logistic Regression Analysis ◽

Screening Methods ◽

Clinical Predictors ◽

Pharyngeal Dysphagia ◽

Increased Risk

Background: Diagnosis of pharyngeal dysphagia in patients with Parkinson’s disease is often difficult as reliable screening methods are lacking so far and clinical examination fails to adequately assess the pharyngeal phase of swallowing. Objective: To identify clinical predictors indicating the presence of pharyngeal dysphagia in patients at risk. Methods: We examined pharyngeal dysphagia in a large cohort of patients with Parkinson’s disease (n = 200) divided in three clinical subtypes (tremor-dominant (TD), mainly bradykinetic (BK) and early postural instability and gait difficulty PIGD)) by using flexible endoscopic evaluation of swallowing. ANOVA-multivariance analysis and following t-tests as well as binary logistic regression analysis were performed to detect group differences and to identify clinical predictors for dysphagia. Results: Statistically significant differences were found in the dysphagic group: age, male gender, disease duration, stage of the disease, Levodopa equivalent dose and higher scores on the Unified Parkinson’s disease rating scale III and II, item 7. The PIGD subtype was affected more frequently than the TD and BK subtype. In a logistic regression model higher age (>63.5 years p < 0.05) and Levodopa equivalent dose (>475 mg, p < 0.01) were identified to be independent predictors for the presence of pharyngeal dysphagia. Conclusion: Particularly patients with an age > 63.5 years and a daily Levodopa equivalent dose >475 mg show an increased risk for pharyngeal dysphagia. These findings may partly be influenced by presbyphagia but are likely to represent disease progression. The PIGD subtype seems to be a risk factor due to more pronounced dyscoordination of oropharyngeal muscle movements.

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