Interrelations between cognitive dysfunction and motor symptoms of Parkinson’s disease: behavioral and neural studies

2016 ◽  
Vol 27 (5) ◽  
pp. 535-548 ◽  
Author(s):  
Ahmed A. Moustafa ◽  
Srinivasa Chakravarthy ◽  
Joseph R. Phillips ◽  
Jacob J. Crouse ◽  
Ankur Gupta ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Dysfunction ◽  
Cognitive Deficits ◽  
Cognitive Rehabilitation ◽  
Precision Grip ◽  
Motor Deficits ◽  
Motor Symptoms ◽  
Rehabilitation Programs ◽  
Cardinal Symptoms

AbstractParkinson’s disease (PD) is characterized by a range of motor symptoms. Besides the cardinal symptoms (tremor, bradykinesia/akinesia, and rigidity), PD patients also show other motor deficits, including gait disturbance, speech deficits, and impaired handwriting. However, along with these key motor symptoms, PD patients also experience cognitive deficits in attention, executive function, working memory, and learning. Recent evidence suggests that these motor and cognitive deficits of PD are not completely dissociable, as aspects of cognitive dysfunction can impact motor performance in PD. In this article, we provide a review of behavioral and neural studies on the associations between motor symptoms and cognitive deficits in PD, specifically akinesia/bradykinesia, tremor, gait, handwriting, precision grip, and speech production. This review paves the way for providing a framework for understanding how treatment of cognitive dysfunction, for example cognitive rehabilitation programs, may in turn influence the motor symptoms of PD.

scholarly journals Cognitive Rehabilitation for Executive Dysfunction in Parkinson's Disease: Application and Current Directions

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Jessica Calleo ◽  
Cristina Burrows ◽  
Harvey Levin ◽  
Laura Marsh ◽  
Eugene Lai ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Dysfunction ◽  
Cognitive Skills ◽  
Cognitive Rehabilitation ◽  
Small Sample ◽  
Behavioral Approach ◽  
Rehabilitation Programs

Cognitive dysfunction in Parkinson's disease contributes to disability, caregiver strain, and diminished quality of life. Cognitive rehabilitation, a behavioral approach to improve cognitive skills, has potential as a treatment option to improve and maintain cognitive skills and increase quality of life for those with Parkinson's disease-related cognitive dysfunction. Four cognitive rehabilitation programs in individuals with PD are identified from the literature. Characteristics of the programs and outcomes are reviewed and critiqued. Current studies on cognitive rehabilitation in PD demonstrate feasibility and acceptability of a cognitive rehabilitation program for patients with PD, but are limited by their small sample size and data regarding generalization of effects over the long term. Because PD involves progressive heterogeneous physical, neurological, and affective difficulties, future cognitive rehabilitation programs should aim for flexibility and individualization, according to each patient's strengths and deficits.

scholarly journals Neuropsychiatric and Cognitive Deficits in Parkinson’s Disease and Their Modeling in Rodents

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 684
Author(s):  
Mélina Decourt ◽  
Haritz Jiménez-Urbieta ◽  
Marianne Benoit-Marand ◽  
Pierre-Olivier Fernagut
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Learning And Memory ◽  
Cognitive Deficits ◽  
Cognitive Disorders ◽  
Alpha Synuclein ◽  
Motor Deficits ◽  
Motor Symptoms ◽  
Rodent Models ◽  
Non Motor Symptoms

Parkinson’s disease (PD) is associated with a large burden of non-motor symptoms including olfactory and autonomic dysfunction, as well as neuropsychiatric (depression, anxiety, apathy) and cognitive disorders (executive dysfunctions, memory and learning impairments). Some of these non-motor symptoms may precede the onset of motor symptoms by several years, and they significantly worsen during the course of the disease. The lack of systematic improvement of these non-motor features by dopamine replacement therapy underlines their multifactorial origin, with an involvement of monoaminergic and cholinergic systems, as well as alpha-synuclein pathology in frontal and limbic cortical circuits. Here we describe mood and neuropsychiatric disorders in PD and review their occurrence in rodent models of PD. Altogether, toxin-based rodent models of PD indicate a significant but non-exclusive contribution of mesencephalic dopaminergic loss in anxiety, apathy, and depressive-like behaviors, as well as in learning and memory deficits. Gene-based models display significant deficits in learning and memory, as well as executive functions, highlighting the contribution of alpha-synuclein pathology to these non-motor deficits. Collectively, neuropsychiatric and cognitive deficits are recapitulated to some extent in rodent models, providing partial but nevertheless useful options to understand the pathophysiology of non-motor symptoms and develop therapeutic options for these debilitating symptoms of PD.

scholarly journals Physiotherapy versus Consecutive Physiotherapy and Cognitive Treatment in People with Parkinson’s Disease: A Pilot Randomized Cross-Over Study

2021 ◽  
Vol 11 (8) ◽  
pp. 687
Author(s):  
Valentina Varalta ◽  
Paola Poiese ◽  
Serena Recchia ◽  
Barbara Montagnana ◽  
Cristina Fonte ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Treatment Group ◽  
Cognitive Rehabilitation ◽  
Rating Scale ◽  
Verbal Learning ◽  
Functional Mobility ◽  
Cognitive Treatment ◽  
Rehabilitation Programs ◽  
Significant Difference

Background: Parkinson’s disease (PD) is characterized by motor and cognitive dysfunctions that can usually be treated by physiotherapy or cognitive training, respectively. The effects of consecutive physiotherapy and cognitive rehabilitation programs on PD deficits are less investigated. Objective: We investigated the effects of 3 months of physiotherapy (physiotherapy treatment group) or consecutive physiotherapy and cognitive (physiotherapy and cognitive treatment group) rehabilitation programs on cognitive, motor, and psychological aspects in 20 PD patients. Methods: The two groups switched programs and continued rehabilitation for another 3 months. The outcomes were score improvement on cognitive (Montreal Cognitive Assessment, Frontal Assessment Battery, Trail Making Test, Verbal Phonemic Fluency, Digit Span, and Rey Auditory Verbal Learning), motor (Unified Parkinson’s Disease Rating Scale-III, Berg Balance Scale, Two-Minute Walking Test, and Time Up and Go), and psychological (Beck Depression Inventory and State-Trait Anxiety Inventory) scales. Results: Between-group comparison revealed a significant difference in functional mobility between the two rehabilitation programs. Improvements in walking abilities were noted after both interventions, but only the patients treated with consecutive training showed better performance on functional mobility and memory tasks. Conclusion: Our findings support the hypothesis that consecutive physiotherapy plus cognitive rehabilitation may have a greater benefit than physiotherapy alone in patients with PD.

scholarly journals Validation of Cognitive Rehabilitation as a Balance Rehabilitation Strategy in Patients with Parkinson’s Disease: Study Protocol for a Randomized Controlled Trial

Medicina ◽  
2021 ◽  
Vol 57 (4) ◽  
pp. 314
Author(s):  
Aida Arroyo-Ferrer ◽  
Francisco José Sánchez-Cuesta ◽  
Yeray González-Zamorano ◽  
María Dolores del Castillo ◽  
Carolina Sastre-Barrios ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Therapy ◽  
Cognitive Processing ◽  
Processing Speed ◽  
Cognitive Rehabilitation ◽  
Neurodegenerative Disorder ◽  
Control Group ◽  
Motor Symptoms ◽  
The Impact

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. This disease is characterized by motor symptoms, such as bradykinesia, tremor, and rigidity. Although balance impairment is characteristic of advanced stages, it can be present with less intensity since the beginning of the disease. Approximately 60% of PD patients fall once a year and 40% recurrently. On the other hand, cognitive symptoms affect up to 20% of patients with PD in early stages and can even precede the onset of motor symptoms. There are cognitive requirements for balance and can be challenged when attention is diverted or reduced, linking a worse balance and a higher probability of falls with a slower cognitive processing speed and attentional problems. Cognitive rehabilitation of attention and processing speed can lead to an improvement in postural stability in patients with Parkinson’s. Methods: We present a parallel and controlled randomized clinical trial (RCT) to assess the impact on balance of a protocol based on cognitive rehabilitation focused on sustained attention through the NeuronUP platform (Neuronup SI, La Rioja, Spain) in patients with PD. For 4 weeks, patients in the experimental group will receive cognitive therapy three days a week while the control group will not receive any therapy. The protocol has been registered at trials.gov NCT04730466. Conclusions: Cognitive therapy efficacy on balance improvement may open the possibility of new rehabilitation strategies for prevention of falls in PD, reducing morbidity, and saving costs to the health care system.

scholarly journals The Add-On Effect of Lactobacillus plantarum PS128 in Patients With Parkinson's Disease: A Pilot Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Chin-Song Lu ◽  
Hsiu-Chen Chang ◽  
Yi-Hsin Weng ◽  
Chiung-Chu Chen ◽  
Yi-Shan Kuo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lactobacillus Plantarum ◽  
Outcome Measures ◽  
Rating Scale ◽  
Controlled Trial ◽  
Secondary Outcome ◽  
Motor Deficits ◽  
Motor Symptoms ◽  
Non Motor Symptoms

Background:Lactobacillus plantarum PS128 (PS128) is a specific probiotic, known as a psychobiotic, which has been demonstrated to alleviate motor deficits and inhibit neurodegenerative processes in Parkinson's disease (PD)-model mice. We hypothesize that it may also be beneficial to patients with PD based on the possible mechanism via the microbiome-gut-brain axis.Methods: This is an open-label, single-arm, baseline-controlled trial. The eligible participants were scheduled to take 60 billion colony-forming units of PS128 once per night for 12 weeks. Clinical assessments were conducted using the Unified Parkinson's Disease Rating Scale (UPDRS), modified Hoehn and Yahr scale, and change in patient “ON-OFF” diary recording as primary outcome measures. The non-motor symptoms questionnaire, Beck depression inventory-II, patient assessment of constipation symptom, 39-item Parkinson's Disease Questionnaire (PDQ-39), and Patient Global Impression of Change (PGI-C) were assessed as secondary outcome measures.Results: Twenty-five eligible patients (32% women) completed the study. The mean age was 61.84 ± 5.74 years (range, 52–72), mean disease duration was 10.12 ± 2.3 years (range, 5–14), and levodopa equivalent daily dosage was 1063.4 ± 209.5 mg/daily (range, 675–1,560). All patients remained on the same dosage of anti-parkinsonian and other drugs throughout the study. After 12 weeks of PS128 supplementation, the UPDRS motor scores improved significantly in both the OFF and ON states (p = 0.004 and p = 0.007, respectively). In addition, PS128 intervention significantly improved the duration of the ON period and OFF period as well as PDQ-39 values. However, no obvious effect of PS128 on non-motor symptoms of patients with PD was observed. Notably, the PGI-C scores improved in 17 patients (68%). PS128 intervention was also found to significantly reduce plasma myeloperoxidase and urine creatinine levels.Conclusion: The present study demonstrated that PS128 supplementation for 12 weeks with constant anti-parkinsonian medication improved the UPDRS motor score and quality of life of PD patients. We suggest that PS128 could serve as a therapeutic adjuvant for the treatment of PD. In the future, placebo-controlled studies are needed to further support the efficacy of PS128 supplementation.Clinical Trial Registration:https://clinicaltrials.gov/, identifier: NCT04389762.

Association between White Matter Lesions and Non-Motor Symptoms in Parkinson Disease

2018 ◽  
Vol 18 (2-3) ◽  
pp. 127-132 ◽  
Author(s):  
Jeong-Yoon Lee ◽  
Ji Sun Kim ◽  
Wooyoung Jang ◽  
Jinse Park ◽  
Eungseok Oh ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
White Matter ◽  
Parkinson Disease ◽  
Cognitive Dysfunction ◽  
Rating Scale ◽  
White Matter Lesions ◽  
Motor Dysfunction ◽  
Motor Symptoms ◽  
Non Motor Symptoms

Background: There are only few studies exploring the relationship between white matter lesions (WMLs) and non-motor symptoms in Parkinson disease (PD). This study aimed to investigate the association between WMLs and the severity of non-motor symptoms in PD. Methods: The severity of motor dysfunction, cognitive impairment, and non-motor symptoms was assessed by various scales in 105 PD patients. We used a visual semiquantitative rating scale and divided the subjects into four groups: no, mild, moderate, and severe WMLs. We compared the means of all scores between the four groups and analyzed the association between the severity of WMLs and the specific domain of non-motor symptoms. Results: The non-motor symptoms as assessed by the Non-Motor Symptoms Scale, Parkinson’s Disease Questionnaire (PDQ-39), Parkinson’s Disease Sleep Scale, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Neuropsychiatric Inventory (NPI), and Parkinson Fatigue Scale (PFS) were significantly worse in the patients with moderate and severe WMLs than in those without WMLs. Compared with the no WML group, the scores for motor dysfunction were significantly higher in the mild, moderate, and severe WML groups. The scores for cognitive dysfunction were significantly higher in the patients with severe WMLs than in those without WMLs. The severity of WMLs showed linear associations with PFS, BDI, BAI, NPI, and PDQ-39 scores. The severity of WMLs also correlated linearly with scores for motor and cognitive dysfunction. Conclusions: Among the non-motor symptoms, fatigue, depression, anxiety, and quality of life were significantly affected by WMLs in PD. Confirmation of the possible role of WMLs in non-motor symptoms associated with PD in a prospective manner may be crucial not only for understanding non-motor symptoms but also for the development of treatment strategies.

Development and psychometric evaluation of a scale to measure impaired self-awareness of hyper- and hypokinetic movements in Parkinson’s disease

2015 ◽  
Vol 21 (3) ◽  
pp. 221-230 ◽  
Author(s):  
Franziska Maier ◽  
Anna L. Ellereit ◽  
Carsten Eggers ◽  
Catharine J. Lewis ◽  
Esther A. Pelzer ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Psychometric Evaluation ◽  
Principal Component ◽  
Motor Deficits ◽  
Motor Symptoms ◽  
Self Awareness ◽  
Left Hand ◽  
Resting Tremor ◽  
Psychosocial Sequelae

AbstractObjective: Patients with Parkinson’s disease (PD) can show impaired self-awareness of motor deficits (ISAm). We developed a new scale that measures ISAm severity of hyper- and hypokinetic movements in PD during medication on state and defined its psychometric criteria. Method: Included were 104 right-handed, non-depressed, non-demented patients. Concerning ISAm, 38 motor symptoms were assessed using seven tasks, which were performed and self-rated concerning presence of deficit (yes/no) by all patients. The whole procedure was videotaped. Motor symptoms were then evaluated by two independent experts, blinded for patient’s ratings, concerning presence, awareness of deficit, and severity. Exploratory principal component analysis (promax rotation) was applied to reduce items. Principal axis factoring was conducted to extract factors. Reliability was examined regarding internal consistency, split-half reliability, and interrater reliability. Validity was verified by applying two additional measures of ISAm. Results: Of the initial 38 symptoms, 15 remained, assessed in five motor tasks and merged to a total severity score. Factor analysis resulted in a four factor solution (dyskinesia, resting tremor right hand, resting tremor left hand, bradykinesia). For all subscales and the total score, measures of reliability (values 0.64–0.89) and validity (effect sizes>0.3) were satisfactory. Descriptive results showed that 66% of patients had signs of ISAm (median 2, range 0–15), with ISAm being most distinct for dyskinesia. Conclusions: We provide the first validation of a test for ISAm in PD. Using this instrument, future studies can further analyze the pathophysiology of ISAm, the psychosocial sequelae, therapeutic strategies and compliance with therapy. (JINS, 2015, 21, 1–10)

scholarly journals Sexually dimorphic responses to MPTP found in microglia, inflammation and gut microbiota in a progressive monkey model of Parkinson’s disease

2020 ◽  
Author(s):  
Valerie Joers ◽  
Gunasingh Masilamoni ◽  
Doty Kempf ◽  
Alison R Weiss ◽  
Travis Rotterman ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Sex Differences ◽  
Microglial Activation ◽  
Motor Deficits ◽  
Sexually Dimorphic ◽  
Motor Symptoms ◽  
Tnf Inhibitor ◽  
Nonmotor Symptoms ◽  
Monkey Model

AbstractInflammation has been linked to the development of nonmotor symptoms in Parkinson’s disease (PD), which greatly impact patients’ quality of life and can often precede motor symptoms. Suitable animal models are critical for our understanding of the mechanisms underlying disease and the associated prodromal disturbances. The neurotoxin 1- methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkey model is commonly seen as a “gold standard” model that closely mimics the clinical motor symptoms and the nigrostriatal dopaminergic loss of PD, however MPTP toxicity extends to other nondopaminergic regions. Yet, there are limited reports monitoring the MPTP-induced progressive central and peripheral inflammation as well as other nonmotor symptoms such as gastrointestinal function and microbiota. The main objective of this study is to gain a broader understanding of central and peripheral inflammatory dysfunction triggered by exposure to a neurotoxicant known to degenerate nigral dopaminergic neurons in order to understand the potential role of inflammation in prodromal/pre-motor features of PD-like degeneration in a progressive non-human primate model of the disease. We measured inflammatory proteins in plasma and CSF and performed [18F]FEPPA PET scans to evaluate translocator proteins (TSPO) or microglial activation in a small cohort of rhesus monkeys (n=5) given weekly low doses of MPTP (0.2-0.8 mg/kg, im). Additionally, monkeys were evaluated for working memory and executive function using various behavior tasks and for gastrointestinal hyperpermeability and microbiota composition. Monkeys were also treated with novel TNF inhibitor XPro1595 (10mg/kg, n=3) or vehicle (n=2) every three days starting 11 weeks after the initiation of MPTP to determine whether nonmotor symptoms are tied to TNF signaling and whether XPro1595 would alter inflammation and microglial behavior in a progressive model of PD. Our analyses revealed sex-dependent sensitivity to MPTP that resulted in early microglial activation by PET, acute plasma IL-6 and CSF TNF, and earlier parkinsonism as measured by motor deficits in males compared to female monkeys. Sex differences were also identified in microbiota and their metabolites and targeted short chain fatty acids at both basal levels and in response to MPTP. Both sexes displayed cognitive impairment prior to a significant motor phenotype. Importantly, XPro1595 shifted peripheral and central inflammation, and significantly reduced CD68-immunoreactivity in the colon. As such, our findings revealed a sexually dimorphic inflammatory response to chronic MPTP treatment and suggest that males may have higher vulnerability than females to inflammation-induced degeneration. If these findings reflect potential differences in humans, these sex differences have significant implications for therapeutic development of inflammatory targets in the clinic.

scholarly journals Characterization of Nonmotor Symptoms in the MitoPark Mouse Model of Parkinson’s Disease

2020 ◽  
Author(s):  
Monica R. Langley ◽  
Shivani Ghaisas ◽  
Bharathi N. Palanisamy ◽  
Muhammet Ay ◽  
Huajun Jin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Antidepressant Treatment ◽  
Forced Swim Test ◽  
Cognitive Learning ◽  
Motor Deficits ◽  
Motor Symptoms ◽  
Nonmotor Symptoms ◽  
Forced Swim ◽  
Non Motor Symptoms

AbstractMitochondrial dysfunction has been implicated as a key player in the pathogenesis of Parkinson’s disease (PD). The MitoPark mouse, a transgenic mitochondrial impairment model developed by specific inactivation of TFAM in dopaminergic neurons, spontaneously exhibits progressive motor deficits and neurodegeneration, recapitulating several features of PD. Since non-motor symptoms are now recognized as important features of the prodromal stage of PD, we monitored the clinically relevant motor and nonmotor symptoms from ages 8-24 wks in MitoPark mice and their littermate controls. As expected, motor deficits in MitoPark mice began around 12-14 wks and became severe by 16-24 wks. Interestingly, male MitoPark mice showed spatial memory deficits before female mice, beginning at 8 wks and becoming most severe at 16 wks, as determined by Morris water maze. When compared to age-matched control mice, MitoPark mice exhibited olfactory deficits in novel and social scent tests as early as 10-12 wks. MitoPark mice between 16-24 wks spent more time immobile in forced swim and tail suspension tests, and made fewer entries into open arms of the elevated plus maze, indicating a depressive and anxiety-like phenotype, respectively. Importantly, depressive behavior as determined by immobility in forced swim test was reversible by antidepressant treatment with desipramine. Collectively, our results indicate that MitoPark mice progressively exhibit deficits in cognitive learning and memory, olfactory discrimination, and anxiety-and depression-like behaviors. Thus, MitoPark mice can serve as an invaluable model for studying motor and non-motor symptoms in addition to studying pathology in PD.

scholarly journals Memory deficits in Parkinson’s disease are associated with reduced beta power modulation

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Hayley J MacDonald ◽  
John-Stuart Brittain ◽  
Bernhard Spitzer ◽  
Simon Hanslmayr ◽  
Ned Jenkinson
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Duration ◽  
Memory Formation ◽  
Motor Deficits ◽  
Beta Activity ◽  
Motor Symptoms ◽  
Memory Encoding ◽  
Beta Power ◽  
Non Motor Symptoms

Abstract There is an increasing recognition of the significant non-motor symptoms that burden people with Parkinson’s disease. As such, there is a pressing need to better understand and investigate the mechanisms underpinning these non-motor deficits. The electrical activity within the brains of people with Parkinson’s disease is known to exhibit excessive power within the beta range (12–30 Hz), compared with healthy controls. The weight of evidence suggests that this abnormally high level of beta power is the cause of bradykinesia and rigidity in Parkinson’s disease. However, less is known about how the abnormal beta rhythms seen in Parkinson’s disease impact on non-motor symptoms. In healthy adults, beta power decreases are necessary for successful episodic memory formation, with greater power decreases during the encoding phase predicting which words will subsequently be remembered. Given the raised levels of beta activity in people with Parkinson’s disease, we hypothesized that the necessary decrease in power during memory encoding would be diminished and that this would interfere with episodic memory formation. Accordingly, we conducted a cross-sectional, laboratory-based experimental study to investigate whether there was a direct relationship between decreased beta modulation and memory formation in Parkinson’s disease. Electroencephalography recordings were made during an established memory-encoding paradigm to examine brain activity in a cohort of adults with Parkinson’s disease (N = 28, 20 males) and age-matched controls (N = 31, 18 males). The participants with Parkinson’s disease were aged 65 ± 6 years, with an average disease duration of 6 ± 4 years, and tested on their normal medications to avoid the confound of exacerbated motor symptoms. Parkinson’s disease participants showed impaired memory strength (P = 0.023) and reduced beta power decreases (P = 0.014) relative to controls. Longer disease duration was correlated with a larger reduction in beta modulation during encoding, and a concomitant reduction in memory performance. The inability to sufficiently decrease beta activity during semantic processing makes it a likely candidate to be the central neural mechanism underlying this type of memory deficit in Parkinson’s disease. These novel results extend the notion that pathological beta activity is causally implicated in the motor and (lesser appreciated) non-motor deficits inherent to Parkinson’s disease. These findings provide important empirical evidence that should be considered in the development of intelligent next-generation therapies.

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