Non-Motor Symptoms of Parkinson’s Disease: The Neurobiology of Early Psychiatric and Cognitive Dysfunction

2021 ◽  
pp. 107385842110119
Author(s):  
Ayan Hussein ◽  
Christopher A. Guevara ◽  
Pamela Del Valle ◽  
Swati Gupta ◽  
Deanna L. Benson ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Psychiatric Symptoms ◽  
Brain Cell ◽  
Synaptic Function ◽  
Motor Symptoms ◽  
Cognitive Symptoms ◽  
Signaling Crosstalk ◽  
Non Motor Symptoms

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that has been recognized for over 200 years by its clinically dominant motor system impairment. There are prominent non-motor symptoms as well, and among these, psychiatric symptoms of depression and anxiety and cognitive impairment are common and can appear earlier than motor symptoms. Although the neurobiology underlying these particular PD-associated non-motor symptoms is not completely understood, the identification of PARK genes that contribute to hereditary and sporadic PD has enabled genetic models in animals that, in turn, have fostered ever deepening analyses of cells, synapses, circuits, and behaviors relevant to non-motor psychiatric and cognitive symptoms of human PD. Moreover, while it has long been recognized that inflammation is a prominent component of PD, recent studies demonstrate that brain-immune signaling crosstalk has significant modulatory effects on brain cell and synaptic function in the context of psychiatric symptoms. This review provides a focused update on such progress in understanding the neurobiology of PD-related non-motor psychiatric and cognitive symptoms.

scholarly journals Evaluation of fecal microbiota transplantation in Parkinson's disease patients with constipation

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiao-yi Kuai ◽  
Xiao-han Yao ◽  
Li-juan Xu ◽  
Yu-qing Zhou ◽  
Li-ping Zhang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Neurodegenerative Disorder ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Motor Symptoms ◽  
Gastrointestinal Dysfunction ◽  
Before And After ◽  
Non Motor Symptoms

AbstractParkinson’s disease (PD) is a neurodegenerative disorder and 70–80% of PD patients suffer from gastrointestinal dysfunction such as constipation. We aimed to assess the efficacy and safety of fecal microbiota transplantation (FMT) for treating PD related to gastrointestinal dysfunction. We conducted a prospective, single- study. Eleven patients with PD received FMT. Fecal samples were collected before and after FMT and subjected to 16S ribosomal DNA (rDNA) gene sequencing. Hoehn-Yahr (H-Y) grade, Unified Parkinson's Disease Rating Scale (UPDRS) score, and the Non-Motion Symptom Questionnaire (NMSS) were used to assess improvements in motor and non-motor symptoms. PAC-QOL score and Wexner constipation score were used to assess the patient's constipation symptoms. All patients were tested by the small intestine breath hydrogen test, performed before and after FMT. Community richness (chao) and microbial structure in before-FMT PD patients were significantly different from the after-FMT. We observed an increased abundance of Blautia and Prevotella in PD patients after FMT, while the abundance of Bacteroidetes decreased dramatically. After FMT, the H-Y grade, UPDRS, and NMSS of PD patients decreased significantly. Through the lactulose H2 breath test, the intestinal bacterial overgrowth (SIBO) in PD patients returned to normal. The PAC-QOL score and Wexner constipation score in after-FMT patients decreased significantly. Our study profiles specific characteristics and microbial dysbiosis in the gut of PD patients. FMT might be a therapeutic potential for reconstructing the gut microbiota of PD patients and improving their motor and non-motor symptoms.

scholarly journals Swallowing dysfunctions in Parkinson’s disease patients: a novel challenge for the internist

2019 ◽  
Vol 13 (2) ◽  
pp. 91-94 ◽  
Author(s):  
Elena Barbagelata ◽  
Antonello Nicolini ◽  
Paola Tognetti
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Practice ◽  
Aspiration Pneumonia ◽  
Neurodegenerative Disorder ◽  
Movement Pattern ◽  
Morbidity And Mortality ◽  
Motor Symptoms ◽  
Common Causes ◽  
Non Motor Symptoms

Parkinson’s disease (PD) is a chronic neurodegenerative disorder with a typical movement pattern, as well as different, less studied non-motor symptoms such as dysphagia. Disease-related disorders in efficacy or safety in the process of swallowing usually lead to malnutrition, dehydration or pneumonia. Dysphagia and subsequent aspiration pneumonia are common causes of morbidity and mortality in those with PD. The aim of this review is to identify and evaluate the existing literature on swallowing disorders in PD and providing recommendations for clinical practice routine.

scholarly journals Non–motor Symptoms in Parkinson’s Disease: It’s Relationship with Age of Onset, Duration and Stage of Disease and the Dose and Duration of Levodopa Usage

1970 ◽  
Vol 21 (1) ◽  
pp. 12-17
Author(s):  
M Ahmed Ali ◽  
Anisul Haque ◽  
AKM Anwarulla ◽  
Quamruddin Ahmad
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Psychiatric Symptoms ◽  
Disease Onset ◽  
Motor Symptoms ◽  
Autonomic Symptoms ◽  
Prolonged Duration ◽  
Relationship Of ◽  
The Relationship ◽  
Non Motor Symptoms

Parkinson's disease is a disease of motor manifestations but non-motor symptoms are also common in Parkinson's disease. Little emphasis is put on non-motor symptoms of PD and there is little data on the relationship of non-motor symptoms to different aspects of the patient and the disease. In this study the relationship of non-motor symptoms to age at onset, duration and stage of the disease, and dose and duration of levodopa use are studied.128 patients of PD were studied for non-motor symptoms. 111 patients had different types of sensory, autonomic or psychiatric symptoms. Sensory and autonomic symptoms were significantly more common in patients with early age of disease onset and more prolonged duration of the disease, but psychiatric symptoms had no relationship with these factors. In this study it was also found that the frequencies of non-motor symptoms were related to the stage of the disease, longer the duration of the disease more and more non-motor symptoms appear so that 100% patients in stage 5 of the disease had non-motor symptoms. Also sensory and autonomic symptoms were significantly more common in patients with longer duration and higher dose of levodopa use but psychiatric symptoms were significantly commoner in patients with prolonged duration of levodopa use but not to dose of levodopa used.   doi: 10.3329/taj.v21i1.3211 TAJ 2008; 21(1): 12-17

scholarly journals A clinical-anatomical signature of Parkinson’s Disease identified with partial least squares and magnetic resonance imaging

2017 ◽  
Author(s):  
Yashar Zeighami ◽  
Seyed-Mohammad Fereshtehnejad ◽  
Mahsa Dadar ◽  
D. Louis Collins ◽  
Ronald B. Postuma ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Least Squares ◽  
Partial Least Squares ◽  
Large Scale ◽  
De Novo ◽  
Neurodegenerative Disorder ◽  
Clinical Manifestations ◽  
Motor Symptoms ◽  
Non Motor Symptoms

AbstractParkinson’s disease (PD) is a neurodegenerative disorder characterized by a wide array of motor and non-motor symptoms. It remains unclear whether neurodegeneration in discrete loci gives rise to discrete symptoms, or whether network-wide atrophy gives rise to the unique behavioural and clinical profile associated with PD. Here we apply a data-driven strategy to isolate large-scale, multivariate associations between distributed atrophy patterns and clinical phenotypes in PD. In a sample of N = 229 de novo PD patients, we estimate disease-related atrophy using deformation based morphometry (DBM) of T1 weighted MR images. Using partial least squares (PLS), we identify a network of subcortical and cortical regions whose collective atrophy is associated with a clinical phenotype encompassing motor and non-motor features. Despite the relatively early stage of the disease in the sample, the atrophy pattern encompassed lower brainstem, substantia nigra, basal ganglia and cortical areas, consistent with the Braak hypothesis. In addition, individual variation in this putative atrophy network predicted longitudinal clinical progression in both motor and non-motor symptoms. Altogether, these results demonstrate a pleiotropic mapping between neurodegeneration and the clinical manifestations of PD, and that this mapping can be detected even in de novo patients.

scholarly journals Hyposmia as a marker of (non-)motor disease severity in Parkinson’s disease

2019 ◽  
Vol 126 (11) ◽  
pp. 1471-1478 ◽  
Author(s):  
Dareia S. Roos ◽  
Jos W. R. Twisk ◽  
Pieter G. H. M. Raijmakers ◽  
Richard L. Doty ◽  
Henk W. Berendse
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Sleep Disturbances ◽  
Psychiatric Symptoms ◽  
Cell Loss ◽  
Motor Symptoms ◽  
Dopaminergic Cell ◽  
Dat Spect ◽  
Spect Scan ◽  
Non Motor Symptoms

Abstract The aim of this study was to evaluate the relationship of hyposmia in Parkinson’s disease (PD) with other motor and non-motor symptoms and with the degree of nigrostriatal dopaminergic cell loss. A total of 295 patients with a diagnosis of PD were included. Olfactory function was measured using the University of Pennsylvania Smell Identification Test (UPSIT). Motor symptoms were rated using the Unified Parkinson’s Disease Rating Scale motor subscale (UPDRS III). To evaluate other non-motor symptoms, we used the Mini-Mental State Examination (MMSE) as a measure of global cognitive function and validated questionnaires to assess sleep disturbances, psychiatric symptoms, and autonomic dysfunction. A linear regression model was used to calculate correlation coefficients between UPSIT score and motor and non-motor variables [for psychiatric symptoms a Poisson regression was performed]. In a subgroup of patients (n = 155) with a dopamine transporter (DaT) SPECT scan, a similar statistical analysis was performed, now including striatal DaT binding. In the regression models with correction for age, sex, disease duration, and multiple testing, all motor and non-motor symptoms were associated with UPSIT scores. In the subgroup of patients with a DaT-SPECT scan, there was a strong association between olfactory test scores and DaT binding in both putamen and caudate nucleus. Hyposmia in PD is associated with various motor and non-motor symptoms, like cognition, depression, anxiety, autonomic dysfunction and sleep disturbances, and with the degree of nigrostriatal dopaminergic cell loss. This finding adds further confirmation that hyposmia holds significant promise as a marker of disease progression.

scholarly journals Non-motor Symptoms in Parkinson’s Disease

2009 ◽  
Vol 4 (1) ◽  
pp. 25 ◽  
Author(s):  
Angelo Antonini ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Motor Symptoms ◽  
Significant Morbidity ◽  
Non Motor Symptoms ◽  
Common Neurodegenerative Disorder

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease and is responsible for significant morbidity and costs. Non-motor manifestations of PD can be as disabling as the classic motor symptoms. Moreover, medications used to treat PD motor symptoms may have variable effects on these non-motor domains.

scholarly journals A Stage-Based Approach to Therapy in Parkinson’s Disease

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 388 ◽  
Author(s):  
Claudia Carrarini ◽  
Mirella Russo ◽  
Fedele Dono ◽  
Martina Di Pietro ◽  
Marianna G. Rispoli ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Motor Symptoms ◽  
Pharmacological Management ◽  
Sleep Behavior ◽  
Heavy Burden ◽  
Non Motor Symptoms

Parkinson’s disease (PD) is a neurodegenerative disorder that features progressive, disabling motor symptoms, such as bradykinesia, rigidity, and resting tremor. Nevertheless, some non-motor symptoms, including depression, REM sleep behavior disorder, and olfactive impairment, are even earlier features of PD. At later stages, apathy, impulse control disorder, neuropsychiatric disturbances, and cognitive impairment can present, and they often become a heavy burden for both patients and caregivers. Indeed, PD increasingly compromises activities of daily life, even though a high variability in clinical presentation can be observed among people affected. Nowadays, symptomatic drugs and non-pharmaceutical treatments represent the best therapeutic options to improve quality of life in PD patients. The aim of the present review is to provide a practical, stage-based guide to pharmacological management of both motor and non-motor symptoms of PD. Furthermore, warning about drug side effects, contraindications, as well as dosage and methods of administration, are highlighted here, to help the physician in yielding the best therapeutic strategies for each symptom and condition in patients with PD.

Emerging Pharmacotherapies for Motor Symptoms in Parkinson’s Disease

2021 ◽  
Vol 34 (4) ◽  
pp. 263-273
Author(s):  
Mohammad Al Majali ◽  
Michael Sunnaa ◽  
Pratap Chand
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Review Article ◽  
Treatment Goals ◽  
Motor Symptoms ◽  
Adequate Treatment ◽  
Advanced Therapies ◽  
Non Motor Symptoms

Parkinson’s disease (PD) is the second commonest neurodegenerative disorder in the older adult and is characterized by progressive disabling motor symptoms of bradykinesia, tremor, rigidity, postural instability and also non motor symptoms that affect quality of life. The pharmacotherapy of PD consists of oral, transdermal, and subcutaneous medications, as well as invasive advanced therapies at later stages of the disease. PD medications are often started as monotherapy but with the progression of the illness often there is a need to add more medications and frequently comprises of a challenging polypharmacotherapy. Adverse effects of pharmacotherapy often add to the problems of adequate treatment. Patients and physicians have to prioritize treatment goals on the most disabling symptoms and the safest and most effective treatments. Almost every year newer medications and modes of delivery continue to be researched and added to the therapeutic armamentarium. This review article outlines existing and emerging pharmacotherapies for motor symptoms in PD.

Parkinson’s Disease and Parkinson-Plus Syndromes

2019 ◽  
pp. 599-630
Author(s):  
Alice Cronin-Golomb ◽  
Gretchen O. Reynolds ◽  
Robert D. Salazar ◽  
Marie-Hélène Saint-Hilaire
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Lewy Bodies ◽  
Corticobasal Degeneration ◽  
Motor Symptoms ◽  
Prodromal Phase ◽  
Full Spectrum ◽  
Brain And Behavior ◽  
Non Motor Symptoms

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder characterized by motor symptoms arising from the loss of dopamine-producing neurons in the midbrain. It is also associated with non-motor symptoms, including in cognition and mood, related to pathology elsewhere in the brain, from lower brainstem to cortex; some present well before the motor symptoms. The diagnosis of PD is based on history and clinical examination, and the cause remains unknown. The Parkinson-plus syndromes (dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration) are less common than idiopathic PD. Differential diagnosis is challenging due to substantial heterogeneity in the presentation of PD, which comprises motor subtypes, and the Parkinson-plus syndromes. Treatment is symptomatic and focuses primarily on dopamine replacement and the relief of motor symptoms, although efforts are underway to also treat the debilitating non-motor symptoms through behavioral and pharmacological interventions. Neuropsychological assessment is of value in identifying and tracking changes in cognition, with the earliest and most common problems being in attention and executive function. Research on biomarkers for PD and the Parkinson-plus syndromes is increasing in regard to genetic factors, neuroimaging, and fluid markers. Moving beyond the traditional view of PD and the Parkinson-plus syndromes as motor disorders and considering the full spectrum of symptoms will be an important step toward identifying biomarkers in the prodromal phase, as well as enhancing understanding of the course of the diseases in regard to brain and behavior, which ultimately should lead to improved care on the path to cure.

scholarly journals Neuro-Immunity and Gut Dysbiosis Drive Parkinson’s Disease-Induced Pain

2021 ◽  
Vol 12 ◽  
Author(s):  
Katiane Roversi ◽  
Natalia Callai-Silva ◽  
Karine Roversi ◽  
May Griffith ◽  
Christos Boutopoulos ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Motor Symptoms ◽  
Gut Dysbiosis ◽  
Gut Immunity ◽  
Inflammatory State ◽  
Non Motor Symptoms ◽  
Shed Light ◽  
Common Neurodegenerative Disorder

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting 1–2% of the population aged 65 and over. Additionally, non-motor symptoms such as pain and gastrointestinal dysregulation are also common in PD. These impairments might stem from a dysregulation within the gut-brain axis that alters immunity and the inflammatory state and subsequently drives neurodegeneration. There is increasing evidence linking gut dysbiosis to the severity of PD’s motor symptoms as well as to somatosensory hypersensitivities. Altogether, these interdependent features highlight the urgency of reviewing the links between the onset of PD’s non-motor symptoms and gut immunity and whether such interplays drive the progression of PD. This review will shed light on maladaptive neuro-immune crosstalk in the context of gut dysbiosis and will posit that such deleterious interplays lead to PD-induced pain hypersensitivity.

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