The Trajectory of Motor Deterioration to Death in Parkinson's Disease

Background: Motor progression varies even among those with a single diagnosis such as Parkinson's disease (PD) and little is known about the trajectory of motor signs prior to death. Understanding deterioration patterns may help clinicians counsel patients and proactively plan interdisciplinary care, including palliative care. The objective of this study was to examine and describe Unified Parkinson's Disease Rating Scale motor score (UPDRS-III) trajectories at the end of life in PD.Methods: A retrospective chart review was performed for deceased PD patients who attended the Parkinson and Movement Disorders Program at the University of Alberta for at least 5 years between 1999 and 2018. UPDRS-III scores were recorded for all visits. Trajectory patterns were visualized with Loess curves stratified by sex and age at diagnosis. Piecewise linear models were used to individually model the UPDRS-III scores, and the trajectories obtained were clustered based on their features.Results: Among the 202 charts reviewed, 84 meeting inclusion criteria were analyzed. The UPDRS-III increased over time regardless of sex and age. Distinct trajectory variations present in PD (e.g., Consistent Deterioration, Stability-Deterioration, Improvement-Deterioration, Deterioration-Improvement-Deterioration) were identified. Twenty-five percent of the patients were classified as Undetermined/Irregular trajectories. In addition, regardless of trajectory type, many patients experienced a steep increase in UPDRS-III approaching death. Those with disease diagnosis after age 65 years had a shorter survival time, compared to PD patients with a younger age of onset.Conclusion: Our study identified dominant types of motor trajectory in PD that can help clinicians understand their patients' course of illness. This information can help counsel patients regarding the variability in motor deterioration and should alert physicians to recognize a terminal decline. Age of disease onset was correlated with survival time.

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Suicidal Ideation in Parkinson's Disease

CNS Spectrums ◽

10.1017/s109285290002040x ◽

2009 ◽

Vol 14 (8) ◽

pp. 431-436 ◽

Cited By ~ 21

Author(s):

Arthur Kummer ◽

Francisco Cardoso ◽

Antonio Lucio Teixeira

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Suicidal Ideation ◽

Major Depression ◽

Attempted Suicide ◽

Rating Scale ◽

Suicide Attempts ◽

Disease Onset ◽

Mini Mental Status Exam ◽

Hamilton Rating Scale

ABSTRACTObjective: To assess the frequency of suicidal ideation and suicide attempts in patients with Parkinson's disease.Methods: The Mini International Neuropsychiatric Interview (MINI), Beck Depression Inventory (BDI), and Hamilton Rating Scale for Depression (HAM-D) were administered to 90 consecutive, non-demented Parkinson's disease patients. They were also submitted to a complete neurologic examination which included brief cognitive batteries, the Mini Mental Status Exam, and Frontal Assessment Battery. We analyzed the scores of the section of the MINI related to the risk of suicide as well as the specific questions of BDI and HAM-D concerning suicidal ideation.Results: No patient had ever attempted suicide. According to MINI, suicidal ideation was present in 13 patients (14.4%) with Parkinson's disease. All instruments assessed the risk of suicide in a similar way. Suicidal ideation was associated only with lower age (P=.022), lower age of Parkinson's disease onset (P=.021), panic disorder (P=.004), social anxiety disorder (P=.007), and major depression (P<.001). Logistic regression analysis indicated that major depression was the main predictor of suicidal ideation.Conclusion: Suicide attempts seem to be uncommon in Parkinson's disease, despite the fact that the rates of suicidal ideation are possibly elevated. Depression seems to be the most important predictor of suicidal ideation in Parkinson's disease.

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Gut microbiota in Parkinson’s disease patients: hospital-based study

The Egyptian Journal of Neurology Psychiatry and Neurosurgery ◽

10.1186/s41983-021-00407-z ◽

2021 ◽

Vol 57 (1) ◽

Author(s):

Eman M. Khedr ◽

Anwar M. Ali ◽

Enas Deaf ◽

Hebatallah M. Hassan ◽

Ahmed Alaa ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Lactic Acid ◽

Gut Microbiota ◽

Rating Scale ◽

Pesticide Exposure ◽

Age Of Onset ◽

Significant Negative Correlation ◽

Control Group ◽

Dominant Type

Abstract Background Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. There is accumulating evidence that link gut microbiota to symptomatology and pathophysiology of PD. The aim of this study was to describe the pattern of gut microbiota and its association with PD and identify the effect of environmental factors on gut microbiota. This case–control study included 46 patients diagnosed as Parkinson’s disease (PD) and 31 healthy volunteers age and sex matched. Detailed history including age of onset, duration of disease, environmental risk factors, diet data, treatment, Unified Parkinson’s Disease Rating Scale (UPDRS), and gastrointestinal tract (GIT) domain of Non‐Motor Symptoms Scale (NMSS) were assessed. After extraction of bacterial DNA from the fecal samples, bacterial abundance was quantified by qPCR using 16S rRNA group-specific primers. Results Significant high abundance of Clostridium cluster IV, Akkermansia, Bifidobacterium, and lactic acid bacteria were found in the PD group compared with the control group (P < 0.001, 0.04, 0.02 and < 0.001, respectively), while Firmicutes were significantly less abundant in the PD group (P < 0.001) compared with the control group. The naive PD patients had significant abundance of Bifidobacterium, and lactic acid compared with control group. Interestingly, Akkermansia was more abundant in treated than untreated patients. There were significant associations between pesticide exposure and Bifidobacterium (P = 0.002), while no significant correlations between different gut microbiota and demographic, environment data, different rating scores or dominant type of PD. There was a significant negative correlation between the Bifidobacterium with the duration of illness (P = 0.012). Conclusion The present study highlighted a significant connection between PD and levels of certain types of gut microbiota, in support of a possible link between gut microbiota and a neurodegenerative cascade of PD.

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MIND diet associated with later onset of Parkinson's disease

10.1101/2020.07.13.20151977 ◽

2020 ◽

Author(s):

Avril Metcalfe-Roach ◽

Adam Yu ◽

Ella Golz ◽

Kristen Sundvick ◽

Mihai Cirstea ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Mediterranean Diet ◽

Dietary Habits ◽

Age Of Onset ◽

Disease Onset ◽

Cross Sectional ◽

Diet Adherence ◽

The Mind ◽

Mind Diet

Background: The MIND diet has been linked with prevention of Alzheimer's disease and cognitive decline but has not been fully assessed in the context of Parkinson's disease (PD). Objective: To determine whether MIND diet adherence is associated with the age of Parkinson's disease onset in a manner superior to that of the Mediterranean diet. Methods: Food Frequency Questionnaires from 167 participants with PD and 119 controls were scored for MIND and two versions of Mediterranean diet adherence. Scores were compared between sex and disease subgroups, and PD diet adherence was correlated with age of onset using univariate and multivariate linear models. Results: The female subgroup adhered more closely to the MIND diet than the males, and diet scores were not modified by disease status. Later age of onset correlated most strongly with MIND diet adherence in the female subgroup, corresponding to differences of up to 17.4 years (p<0.001) between low and high dietary tertiles. Greek Mediterranean adherence was also significantly associated with later PD onset across all models (p=0.05-0.03). Conversely, only Greek Mediterranean adherence remained correlated with later onset across all models in men, with differences of up to 8.4 years (p=0.002). Conclusions: This cross-sectional study finds a strong correlation of age of onset of PD with dietary habits, suggesting that nutritional strategies may be an effective tool to delay PD onset. Further studies may help to elucidate potential nutrition-related sex-specific pathophysiological mechanisms and differential prevalence rates in PD.

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Non-motor symptom burden in patients with Parkinson’s disease with impulse control disorders and compulsive behaviours: results from the COPPADIS cohort

Scientific Reports ◽

10.1038/s41598-020-73756-z ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

S. Jesús ◽

◽

M. A. Labrador-Espinosa ◽

A. D. Adarmes ◽

C. Méndel-Del Barrio ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Impulse Control ◽

Dopamine Agonists ◽

Rating Scale ◽

Disease Onset ◽

Impulse Control Disorders ◽

Nonmotor Symptoms ◽

Premorbid Personality ◽

Validated Questionnaire

Abstract The study was aimed at analysing the frequency of impulse control disorders (ICDs) and compulsive behaviours (CBs) in patients with Parkinson’s disease (PD) and in control subjects (CS) as well as the relationship between ICDs/CBs and motor, nonmotor features and dopaminergic treatment in PD patients. Data came from COPPADIS-2015, an observational, descriptive, nationwide (Spain) study. We used the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) for ICD/CB screening. The association between demographic data and ICDs/CBs was analyzed in both groups. In PD, this relationship was evaluated using clinical features and treatment-related data. As result, 613 PD patients (mean age 62.47 ± 9.09 years, 59.87% men) and 179 CS (mean age 60.84 ± 8.33 years, 47.48% men) were included. ICDs and CBs were more frequent in PD (ICDs 12.7% vs. 1.6%, p < 0.001; CBs 7.18% vs. 1.67%, p = 0.01). PD patients had more frequent previous ICDs history, premorbid impulsive personality and antidepressant treatment (p < 0.05) compared with CS. In PD, patients with ICDs/CBs presented younger age at disease onset, more frequent history of previous ICDs and premorbid personality (p < 0.05), as well as higher comorbidity with nonmotor symptoms, including depression and poor quality of life. Treatment with dopamine agonists increased the risk of ICDs/CBs, being dose dependent (p < 0.05). As conclusions, ICDs and CBs were more frequent in patients with PD than in CS. More nonmotor symptoms were present in patients with PD who had ICDs/CBs compared with those without. Dopamine agonists have a prominent effect on ICDs/CBs, which could be influenced by dose.

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Postoperative symptoms of psychosis after deep brain stimulation in patients with Parkinson’s disease

Neurosurgical FOCUS ◽

10.3171/2015.3.focus1523 ◽

2015 ◽

Vol 38 (6) ◽

pp. E5 ◽

Cited By ~ 5

Author(s):

Azam A. Qureshi ◽

Jennifer J. Cheng ◽

Abraham N. Sunshine ◽

Adela Wu ◽

Gregory M. Pontone ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Rating Scale ◽

Assessment Tool ◽

Retrospective Chart Review ◽

Clinic Visit ◽

Stimulation Parameter ◽

Deep Brain

OBJECT Cases of postoperative psychosis in Parkinson’s disease patients receiving deep brain stimulation (DBS) treatment have previously been published. However, the magnitude of symptom incidence and the clinical risk factors are currently unknown. This retrospective study sheds light on these issues by investigating psychosis in a group of 128 Parkinson’s disease patients who received DBS implants. METHODS A retrospective chart review was performed to obtain surgery dates, follow-up clinic visit dates, and associated stimulation parameter settings (contacts in use and the polarity of each along with stimulation voltage, frequency, and pulse width) for each patient. Unified Parkinson’s Disease Rating Scale II Thought Disorder scores, used as a clinical assessment tool to evaluate the presence of psychosis at each visit, were also collected. The data were compiled into a database and analyzed. RESULTS The lifetime incidence of psychosis in this cohort of patients was 28.1%. The data suggest that risk of psychosis remains fairly constant throughout the first 5 years after implantation of a DBS system and that patients older at the time of receiving the first DBS implant are not only more likely to develop psychosis, but also to develop symptoms sooner than their younger counterparts. Further analysis provides evidence that psychosis is largely independent of the clinically used electrode contact and of stimulation parameters prior to psychosis onset. CONCLUSIONS Although symptoms of psychosis are widely seen in patients with Parkinson’s disease in the years following stimulator placement, results of the present suggest that most psychoses occurring postoperatively are likely independent of implantation and stimulation settings.

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Non-motor symptoms in essential tremor, akinetic rigid and tremor-dominant subtypes of Parkinson’s disease

PLoS ONE ◽

10.1371/journal.pone.0245918 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0245918

Author(s):

Ali S. Shalash ◽

Eman Hamid ◽

Hanan Elrassas ◽

Eshak I. Bahbah ◽

Alia H. Mansour ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Essential Tremor ◽

Rating Scale ◽

Age Of Onset ◽

Urinary Symptoms ◽

Motor Symptoms ◽

Dominant Type ◽

Highly Correlated ◽

Non Motor Symptoms

Objectives To compare non-motor symptoms (NMSs) among patients with essential tremor (ET), Parkinson’s disease (PD) subtypes (akinetic-rigid type (ART) and tremor-dominant type (TDT)), and healthy controls. Patients and methods This retrospective study included 129 participants, 72 PD (33 PD-ART, 33 PD-TDT, and 6 Mixed), 29 ET patients, and 28 controls. PD patients were assessed by the unified Parkinson’s disease rating scale (UPDRS), Hoehn, and Yahr scale (H&Y), while ET patients were evaluated by the Fahn Tolosa Marin Tremor Rating Scale. All subjects were evaluated by non-motor symptoms scale (NMSS) for NMSs and Beck depression inventory (BDI) for depression. Results PD subtypes groups, ET, and controls were age and gender-matched. Compared to controls, all PD, PD subtypes, and ET showed significantly worse most of NMSs (p<0.001) and depression. Compared to ET, all PD and PD-ART had significantly worse gastrointestinal (p = 0.002), urinary symptoms (p = 0.001, p = 0.003) and depression (p = 0.002) and PD-TDT worse depression, while ET patients showed worse memory/attention than PD subtypes. Total NMSS of ET is highly correlated to depression and moderately to tremor severity and age of onset, while total of NMSS is highly correlated to depression, disease severity, and disability. Conclusion The current study demonstrated several comparable domains of NMSs of PD subtypes and ET, except worse gastrointestinal and urinary symptoms among PD-ART. Identifying different NMSs profiles is important for predicting, better assessing, and tailoring management of ET and PD subtypes.

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Genetic Variations and mRNA Expression of NRF2 in Parkinson’s Disease

Parkinson s Disease ◽

10.1155/2017/4020198 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Caroline Ran ◽

Karin Wirdefeldt ◽

Lovisa Brodin ◽

Mehrafarin Ramezani ◽

Marie Westerlund ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Mrna Expression ◽

Age Of Onset ◽

Human Lymphocytes ◽

Disease Onset ◽

Cellular Protection ◽

Expression Levels ◽

Reverse Transcription Pcr ◽

Delay Disease Onset

Nuclear factor erythroid 2-like 2 (NRF2) encodes a transcription factor regulating mechanisms of cellular protection and is activated by oxidative stress. NRF2 has therefore been hypothesized to confer protection against Parkinson’s disease and so far an NRF2 haplotype has been reported to decrease the risk of developing disease and delay disease onset. Also NRF2 adopts a nuclear localization in Parkinson’s disease, which is indicative of increased NRF2 activity. We have investigated the association between NRF2 and Parkinson’s disease in a Swedish case-control material and whether NRF2 expression levels correlate with NRF2 genetic variants, disease, or disease onset. Using pyrosequencing, we genotyped one intronic and three promoter variants in 504 patients and 509 control subjects from Stockholm. Further, we quantified NRF2 mRNA expression in EBV transfected human lymphocytes from patients and controls using quantitative real-time reverse transcription PCR. We found that one of the promoter variants, rs35652124, was associated with age of disease onset (Χ2 = 14.19, p value = 0.0067). NRF2 mRNA expression levels however did not correlate with the rs35652124 genotype, Parkinson’s disease, or age of onset in our material. More detailed studies on NRF2 are needed in order to elucidate how this gene affects pathophysiology of Parkinson’s disease.

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Plasma Extracellular Vesicle α-Synuclein Level in Patients with Parkinson’s Disease

Biomolecules ◽

10.3390/biom11050744 ◽

2021 ◽

Vol 11 (5) ◽

pp. 744

Author(s):

Chen-Chih Chung ◽

Lung Chan ◽

Jia-Hung Chen ◽

Yi-Chieh Hung ◽

Chien-Tai Hong

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scale ◽

Disease Diagnosis ◽

Extracellular Vesicle ◽

Motor Dysfunction ◽

Free Form ◽

Control Group ◽

Diagnosis And Prognosis ◽

Blood Transport

Background: The most established pathognomonic protein of Parkinson’s disease (PD), α-synuclein, is extensively investigated for disease diagnosis and prognosis; however, investigations into whether the free form of α-synuclein in the blood functions as a PD biomarker have not been fruitful. Extracellular vesicles (EVs) secreted from cells and present in blood transport molecules are novel platforms for biomarker identification. In blood EVs, α-synuclein originates predominantly from the brain without the interference of the blood–brain barrier. The present study investigated the role of plasma EV-borne α-synuclein as a biomarker of PD. Methods: Patients with mild to moderate stages of PD (n = 116) and individuals without PD (n = 46) were recruited to serve as the PD study group and the control group, respectively. Plasma EVs were isolated, and immunomagnetic reduction–based immunoassay was used to assess EV α-synuclein levels. Conventional statistical analysis was performed using SPSS 25.0, and p < 0.05 was considered significant. Results: Compared with controls, we observed significantly lower plasma EV α-synuclein levels in the patients with PD (PD: 56.0 ± 3.7 fg/mL vs. control: 74.5 ± 4.3 fg/mL, p = 0.009), and the significance remained after adjustment for age and sex. Plasma EV α-synuclein levels in the patients with PD did not correlate with age, disease duration, Part I and II scores of the Unified Parkinson’s Disease Rating Scale (UPDRS), or the Mini-Mental State Examination scores. However, such levels were significantly correlated with UPDRS Part III score, which assesses motor dysfunction. Furthermore, the severity of akinetic-rigidity symptoms, but not tremor, was inversely associated with plasma EV α-synuclein level. Conclusion: Plasma EV α-synuclein was significantly different between the control and PD group and was associated with akinetic-rigidity symptom severity in patients with PD. This study corroborates the possible diagnostic and subtyping roles of plasma EV α-synuclein in patients with PD, and it further provides a basis for this protein’s clinical relevance and feasibility as a PD biomarker.

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