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Zhurnal Nevrologii I Psikhiatrii Imeni... 2024Evaluation of nocturia and its relationship with clinical characteristics of Parkinson's disease (PD) and dopaminergic therapy.
OBJECTIVE
Evaluation of nocturia and its relationship with clinical characteristics of Parkinson's disease (PD) and dopaminergic therapy.
MATERIAL AND METHODS
One hundred and thirteen patients with PD of I-III Hoehn and Yahr stage (H&Y) were examined using the following scales: IPSS, including nocturia domain, UPDRS, Sch&En, PDQ-39, MMSE, FAB BDI, STAI-S and STAI-T, PFS-16, NMSQuest, GDSS, GSRS, and orthotest.
RESULTS
Nocturia was detected in 93 patients. It depended on the age of the patients (rS=0.345; <0.001) and was more spread among women (=0.002). We obtained positive correlations of nocturia (<0.05) with: PDQ-39 (rS=0.296), H&Y (rS=0.223), UPDRS (rS=0.265) and its items (speech, walking disorders, standing up from chair, posture and postural stability), NMSQ (rS=0.318), FAB (rS= -0.359), BDI, STAI-S and STAI-T, PFS-16, gastrointestinal parameters and blood pressure in the supine position. No significant effect of dopaminergic therapy on the severity of nocturia was found. According to regression analysis (stepwise method), predictors of nocturia are depression, higher lying blood pressure, constipation and postural instability (R2=0.474).
CONCLUSIONS
Nocturia is the most common urological symptom in patients with PD and it significantly reduces the quality of life starting from the early stages of the disease. Nocturia increases as PD progresses, it is independent of dopaminergic medications, and it is directly associated with a number of parkinsonian symptoms (postural, frontal cognitive, affective and autonomic), which are partly dopamine-resistant. This indicates the common pathogenesis of nocturia and other symptoms of PD and the significant influence of polytransmitter imbalance.
Topics: Humans; Parkinson Disease; Female; Nocturia; Male; Aged; Middle Aged; Severity of Illness Index; Quality of Life; Aged, 80 and over
PubMed: 38676677
DOI: 10.17116/jnevro202412404148 -
Seminars in Neurology Aug 2023Constipation is one of the most common gastrointestinal features of Parkinson's disease (PD), occurring in over 50% of all PD patients during the course of their...
Constipation is one of the most common gastrointestinal features of Parkinson's disease (PD), occurring in over 50% of all PD patients during the course of their disease. Furthermore, constipation is now recognized as an important, prodromal symptom and may predate the onset of the classical motor symptoms by decades. Thereafter, the prevalence and severity of constipation in PD tend to parallel the course of both motor and nonmotor phenomena such as cognitive decline and depression. Difficult defecation (obstructed defecation, dyssynergia) is the primary pathophysiology underlying constipation and likely reflects involvement by the PD process of one or more of the many skeletal muscle groups that are involved in effecting defecation. Management of constipation in PD may be complicated by several patient factors including dysphagia, cognitive impairment, depression, and weak sphincter tone. While the armamentarium available to those who treat constipation, in general, has expanded considerably in recent years, the evidence supporting any therapy in the management of this symptom in PD has remained slim.
Topics: Humans; Parkinson Disease; Constipation; Prevalence; Cognitive Dysfunction
PubMed: 37579786
DOI: 10.1055/s-0043-1771457 -
Parkinsonism & Related Disorders Aug 2023The pilot trial of deep brain stimulation (DBS) in early-stage Parkinson's disease (PD) randomized 30 patients (medication duration 0.5-4 years; without dyskinesia or... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
The pilot trial of deep brain stimulation (DBS) in early-stage Parkinson's disease (PD) randomized 30 patients (medication duration 0.5-4 years; without dyskinesia or motor fluctuations) to receive optimal drug therapy alone (early ODT) or subthalamic nucleus (STN) DBS plus ODT (early DBS + ODT). This study reports long-term neuropsychological outcomes from the early DBS pilot trial.
METHODS
This is an extension of an earlier study that examined two-year neuropsychological outcomes in the pilot trial. The primary analysis was conducted on the five-year cohort (n = 28), and a secondary analysis was conducted on the 11-year cohort (n = 12). Linear mixed effects models for each analysis compared overall trend in outcomes for randomization groups. All subjects who completed the 11-year assessment were also pooled to evaluate long-term change from baseline.
RESULTS
There were no significant differences between groups in either the five- or 11-year analyses. Across all PD patients who completed the 11-year visit, there was significant decline in Stroop Color and Color-Word and Purdue Pegboard from baseline to 11 years.
CONCLUSIONS
Previous significant differences between the groups in phonemic verbal fluency and cognitive processing speed showing more decline for early DBS + ODT subjects one year after baseline diminished as PD progressed. No cognitive domains were worse for early DBS + ODT subjects compared to standard of care subjects. There were shared declines across all subjects on cognitive processing speed and motor control, likely reflecting disease progression. More study is needed to understand the long-term neuropsychological outcomes associated with early DBS in PD.
Topics: Humans; Deep Brain Stimulation; Disease Progression; Neuropsychological Tests; Parkinson Disease; Processing Speed; Subthalamic Nucleus
PubMed: 37380539
DOI: 10.1016/j.parkreldis.2023.105479 -
The Lancet. Neurology Feb 2024
Topics: Humans; Parkinson Disease; Carbamates; Quinuclidines
PubMed: 38267177
DOI: 10.1016/S1474-4422(23)00455-6 -
Health Expectations : An International... Jun 2024Women and those with younger onset Parkinson's Disease (YOPD) are typically diagnosed later and face unique situations and challenges. This essay aims to raise awareness...
INTRODUCTION
Women and those with younger onset Parkinson's Disease (YOPD) are typically diagnosed later and face unique situations and challenges. This essay aims to raise awareness of the difficulties in diagnosing YOPD and the need for a personalised approach to care for women with YOPD.
METHODS
Two professional women with YOPD (academic physiotherapist and practicing dentist) and a female neurologist (clinician academic) came together to write a narrative essay on their personal experience and perspectives in relation to women and YOPD.
RESULTS
The essay outlines how the experience of diagnosis is likened to a complex puzzle box with many interlocking components that are hidden and difficult to solve. The concerns of the women about their identity, work, family and the future, with most supports targeting those that are older and retired are outlined.
CONCLUSION
It is concluded that YOPD is a complex puzzle to solve, but can be done by understanding all the intricate interlocking components of the puzzle and combined with greater awareness could lead to earlier diagnosis and the delivery of successful person-centred care.
PATIENT OR PUBLIC CONTRIBUTION
People with lived experience were involved in the essay conception and writing.
Topics: Humans; Parkinson Disease; Female; Middle Aged; Age of Onset
PubMed: 38896007
DOI: 10.1111/hex.14116 -
Parkinsonism & Related Disorders Jun 2024There is no consensus driven definition of "advanced" Parkinson's disease (APD) currently. APD has been described in terms of emergence of specific clinical features and... (Review)
Review
There is no consensus driven definition of "advanced" Parkinson's disease (APD) currently. APD has been described in terms of emergence of specific clinical features and clinical milestones of the disease e.g., motor fluctuations, time to increasing falls, emergence of cognitive decline, etc. The pathological burden of disease has been used to characterize various stages of the disease. Imaging markers have been associated with various motor and nonmotor symptoms of advancing disease. In this review, we present an overview of clinical, pathologic, and imaging markers of APD. We also propose a model of disease definition involving longitudinal assessments of these markers as well as quality of life metrics to better understand and predict disease progression in those with Parkinson's disease.
Topics: Parkinson Disease; Humans; Disease Progression
PubMed: 38418318
DOI: 10.1016/j.parkreldis.2024.106065 -
Movement Disorders : Official Journal... Dec 2023Parkin RBR E3 ubiquitin-protein ligase (PRKN) mutations are the most common cause of young onset and autosomal recessive Parkinson's disease (PD). PRKN is located in...
BACKGROUND
Parkin RBR E3 ubiquitin-protein ligase (PRKN) mutations are the most common cause of young onset and autosomal recessive Parkinson's disease (PD). PRKN is located in FRA6E, which is one of the common fragile sites in the human genome, making this region prone to structural variants. However, complex structural variants such as inversions of PRKN are seldom reported, suggesting that there are potentially unrevealed complex pathogenic PRKN structural variants.
OBJECTIVES
To identify complex structural variants in PRKN using long-read sequencing.
METHODS
We investigated the genetic cause of monozygotic twins presenting with a young onset dystonia-parkinsonism using targeted sequencing, whole exome sequencing, multiple ligation probe amplification, and long-read sequencing. We assessed the presence and frequency of complex inversions overlapping PRKN using whole-genome sequencing data of Accelerating Medicines Partnership Parkinson's disease (AMP-PD) and United Kingdom (UK)-Biobank datasets.
RESULTS
Multiple ligation probe amplification identified a heterozygous exon three deletion in PRKN and long-read sequencing identified a large novel inversion spanning over 7 Mb, including a large part of the coding DNA sequence of PRKN. We could diagnose the affected subjects as compound heterozygous carriers of PRKN. We analyzed whole genome sequencing data of 43,538 participants of the UK-Biobank and 4941 participants of the AMP-PD datasets. Nine inversions in the UK-Biobank and two in AMP PD were identified and were considered potentially damaging and likely to affect PRKN expression.
CONCLUSIONS
This is the first report describing a large 7 Mb inversion involving breakpoints outside of PRKN. This study highlights the importance of using long-read sequencing for structural variant analysis in unresolved young-onset PD cases. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
Topics: Humans; Heterozygote; Mutation; Parkinson Disease; Parkinsonian Disorders; Ubiquitin-Protein Ligases
PubMed: 37926948
DOI: 10.1002/mds.29610 -
Neurobiology of Disease Sep 2023The identification of biomarkers that reflect worse progression of nonmotor symptoms (NMS) in Parkinson's disease (PD) is currently an unmet need. The main aim of this...
BACKGROUND
The identification of biomarkers that reflect worse progression of nonmotor symptoms (NMS) in Parkinson's disease (PD) is currently an unmet need. The main aim of this study was to investigate whether cerebrospinal fluid (CSF) and serum neurofilament light (NfL), measured at baseline or longitudinally, can be used to predict the progression of NMS in patients with PD.
METHODS
Baseline and longitudinal NfL levels were measured in the CSF and serum in 392 PD patients and 184 healthy controls from the Parkinson's Progression Marker Initiative. NMS were assessed using several scales, including, but not restricted to, the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part I, the Geriatric Depression Scale (GDS) and the State-Trait Anxiety Inventory (STAI). The relationship between baseline and longitudinal NfL levels with changes in NMS was assessed using linear mixed effects models (LME) in PD patients. In addition, we compared CSF and serum NfL levels between groups and assessed the relationship between NfL biomarkers with baseline NMS. Finally, to assess the specificity of our findings we ran the previous LME models using other biomarkers such as CSF amyloid-β, total tau, phosphorylated tau and total α-synuclein and we also ran the models in healthy controls.
RESULTS
Baseline levels and longitudinal changes in serum and CSF NfL predicted worse longitudinal MDS-UPDRS-I and depression scores over time in PD (p < 0.01). This relationship remained significant only for CSF NfL when controlling for motor and cognitive status. Furthermore, longitudinal changes in serum and CSF NfL were associated with worse anxiety over time in PD patients (p < 0.05). In contrast to CSF NfL, serum NfL levels were slightly higher at baseline (p = 0.043) and showed significant longitudinal increases (p < 0.001) in PD patients compared to controls. There were no significant correlations between NfL levels (CSF or serum) with other NMS scales, baseline NMS variables, other biomarkers or in healthy controls.
CONCLUSIONS
Our findings indicate that both serum and CSF NfL are associated with worse longitudinal NMS burden, particularly in relation to the progression of depression and anxiety. Serum NfL showed stronger associations with NMS suggesting it could potentially be used as a non-invasive marker of NMS progression for PD.
Topics: Humans; Aged; Parkinson Disease; Intermediate Filaments; Depression; Biomarkers; Movement
PubMed: 37499883
DOI: 10.1016/j.nbd.2023.106237 -
Seminars in Neurology Aug 2023Gastrointestinal (GI) dysfunction is a common nonmotor symptom in Parkinson's disease (PD) as well as other parkinsonian syndromes and may precede the onset of motor... (Review)
Review
Gastrointestinal (GI) dysfunction is a common nonmotor symptom in Parkinson's disease (PD) as well as other parkinsonian syndromes and may precede the onset of motor symptoms by decades. Involvement of all segments of the GI tract can lead to altered responses to medications and worsened quality of life for patients. While some GI symptoms occur in isolation, others overlap. Therefore, understanding the changes in different segments of the GI tract and how they relate to altered responses to PD treatment can guide both diagnostic and pharmacological interventions. Gut microbiota plays a critical role in immune activity and modulation of the enteric and central nervous systems. Understanding this bidirectional relationship helps to elucidate the pathogenesis of neurodegeneration. This review will describe the current understanding of how GI dysfunction develops in parkinsonian syndromes, common symptoms in PD and related disorders, and available treatments.
Topics: Humans; Quality of Life; Parkinsonian Disorders; Gastrointestinal Diseases; Parkinson Disease; Central Nervous System
PubMed: 37703887
DOI: 10.1055/s-0043-1771461 -
European Journal of Neurology Oct 2023The correlates of motor parkinsonism in Alzheimer's disease (AD) remain controversial. The effects of nigrostriatal dopaminergic degeneration on parkinsonism and...
BACKGROUND AND PURPOSE
The correlates of motor parkinsonism in Alzheimer's disease (AD) remain controversial. The effects of nigrostriatal dopaminergic degeneration on parkinsonism and cognition in biomarker-validated patients with AD were evaluated.
METHODS
This study recruited 116 patients with AD who underwent dual-phase F-N-(3-fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane positron emission tomography, F-florbetaben positron emission tomography, 3 T brain magnetic resonance imaging, and Unified Parkinson's Disease Rating Scale (UPDRS) and neuropsychological tests. The mean cortical thickness in the frontal, temporal, parietal and occipital cortices, and the dopamine transporter (DAT) uptake in the caudate, anterior/posterior putamen and substantia nigra were quantified. The relationship between DAT uptake, mean lobar cortical thickness, UPDRS motor score and cognition was investigated using general linear models (GLMs) after controlling for age, sex, education, intracranial volume, and deep and periventricular white matter hyperintensities. A path analysis was performed for the UPDRS motor score with the same covariates.
RESULTS
Path analysis and multivariable GLMs for UPDRS motor score showed that lower caudate DAT uptake was directly associated with a higher UPDRS motor score, whereas caudate DAT uptake confounded the association between mean frontal/parietal thickness and UPDRS motor score. Multivariable GLMs for cognitive scores showed that lower caudate DAT uptake was associated with visuospatial/executive dysfunction independent of mean frontal or parietal thickness.
CONCLUSIONS
Nigrostriatal dopaminergic dysfunction is associated with parkinsonism and visuospatial/executive dysfunction in patients with AD.
Topics: Humans; Alzheimer Disease; Dopamine Plasma Membrane Transport Proteins; Parkinson Disease; Corpus Striatum; Parkinsonian Disorders; Cognition; Dopamine; Tomography, Emission-Computed, Single-Photon
PubMed: 37493955
DOI: 10.1111/ene.15995