Probiotics Treatment Improves Hippocampal Dependent Cognition in a Rodent Model of Parkinson’s Disease

Parkinson’s disease (PD) is a neurological disorder with motor dysfunction and a number of psychiatric symptoms. Symptoms such as anxiety and cognitive deficits emerge prior to motor symptoms and persist over time. There are limited treatments targeting PD psychiatric symptoms. Emerging studies reveal that the gut microbe is altered in PD patients. Here we assessed the effect of a probiotic treatment in a rat model of PD. We used the neurotoxin (6-hydroxydopamine, 6-OHDA) in a preclinical PD model to examine the impact of a probiotic treatment (Lacticaseibacillus rhamnosus HA-114) on anxiety and memory. Rats underwent either sham surgery or received 6-OHDA bilaterally into the striatum. Three weeks post-surgery, rats were divided into three experimental groups: a sham group that received probiotics, a 6-OHDA group that received probiotics, and the third group of 6-OHDA received the placebo formula. All rats had access to either placebo or probiotics formula for 6 weeks. All groups were assessed for anxiety-like behaviour using the elevated plus maze. Cognition was assessed for both non-hippocampal and hippocampal dependent tasks using the novel object recognition and novel place recognition. We report that the 6-OHDA lesion induced anxiety-like behaviour and deficits in hippocampal dependent cognition. Interestingly, the probiotics treatment had no impact on anxiety-like behaviour but selectively improved hippocampal dependent cognition deficits. Together, the results presented here highlight the utility of animal models in examining the neuropsychiatric symptoms of PD and the potential of probiotics as adjunctive treatment for non-motor symptoms of PD.

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The Impact of Amyloid-Beta Positivity with 18F-Florbetaben PET on Neuropsychological Aspects in Parkinson’s Disease Dementia

Metabolites ◽

10.3390/metabo10100380 ◽

2020 ◽

Vol 10 (10) ◽

pp. 380

Author(s):

Seunghee Na ◽

Hyeonseok Jeong ◽

Jong-Sik Park ◽

Yong-An Chung ◽

In-Uk Song

Keyword(s):

Alzheimer’S Disease ◽

Parkinson’S Disease ◽

Alzheimer's Disease ◽

Parkinson's Disease ◽

Amyloid Beta ◽

Neuropsychiatric Symptoms ◽

Amyloid Pet ◽

Motor Symptoms ◽

Parkinson’S Disease Dementia ◽

The Impact

The neuropathology of Parkinson’s disease dementia (PDD) is heterogenous, and the impacts of each pathophysiology and their synergistic effects are not fully understood. The aim of this study was to evaluate the frequency and impacts of co-existence with Alzheimer’s disease in patients with PDD by using 18F-florbetaben PET imaging. A total of 23 patients with PDD participated in the study. All participants underwent 18F-florbetaben PET and completed a standardized neuropsychological battery and assessment of motor symptoms. The results of cognitive tests, neuropsychiatric symptoms, and motor symptoms were analyzed between the positive and negative 18F-florbetaben PET groups. Four patients (17.4%) showed significant amyloid burden. Patients with amyloid-beta showed poorer performance in executive function and more severe neuropsychiatric symptoms than those without amyloid-beta. Motor symptoms assessed by UPDRS part III and the modified H&Y Scale were not different between the two groups. The amyloid PET scan of a patient with PDD can effectively reflect a co-existing Alzheimer’s disease pathology. Amyloid PET scans might be able to help physicians of PDD patients showing rapid progression or severe cognitive/behavioral features.

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Risk factors for neuropsychiatric symptoms in patients with Parkinson’s disease during COVID-19 pandemic in Japan

PLoS ONE ◽

10.1371/journal.pone.0245864 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0245864

Author(s):

Fukiko Kitani-Morii ◽

Takashi Kasai ◽

Go Horiguchi ◽

Satoshi Teramukai ◽

Takuma Ohmichi ◽

...

Keyword(s):

Risk Factors ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Neuropsychiatric Symptoms ◽

Multivariate Logistic Regression Analysis ◽

Clinical Depression ◽

Motor Symptoms ◽

Neuropsychiatric Complications ◽

The Impact ◽

Updrs Part

The worsening of neuropsychiatric symptoms such as depression, anxiety, and insomnia in patients with Parkinson’s disease (PD) has been a concern during the COVID-19 pandemic, because most people worked in self-isolation for fear of infection. We aimed to clarify the impact of social restrictions imposed due to the COVID-19 pandemic on neuropsychiatric symptoms in PD patients and to identify risk factors associated with these symptoms. A cross-sectional, hospital-based survey was conducted from April 22, 2020 to May 15, 2020. PD patients and their family members were asked to complete paper-based questionnaires about neuropsychiatric symptoms by mail. PD patients were evaluated for motor symptoms using MDS-UPDRS part 2 by telephone interview. A total of 71 responders (39 PD patients and 32 controls) completed the study. Although there was no difference in the age distribution, the rate of females was significantly lower in PD patients (35%) than controls (84%) (P < 0.001). Participants with clinical depression (PHQ-9 score ≥ 10) were more common in PD patients (39%) than controls (6%) (P = 0.002). Multivariate logistic regression analysis revealed that an MDS-UPDRS part 2 score was correlated with the presence of clinical depression (PHQ-9 score ≥ 10) and clinical anxiety (GAD-7 score ≥ 7) (clinical depression: OR, 1.31; 95% CI, 1.04–1.66; P = 0.025; clinical anxiety: OR, 1.36; 95% CI, 1.07–1.72; P = 0.013). In the presence of social restrictions, more attention needs to be paid to the neuropsychiatric complications of PD patients, especially those with more severe motor symptoms.

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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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The Growing Role of Cognitive Behavior Therapy in the Treatment of Parkinson’s Disease

Journal of Geriatric Psychiatry and Neurology ◽

10.1177/08919887211018274 ◽

2021 ◽

Vol 34 (4) ◽

pp. 310-320 ◽

Cited By ~ 1

Author(s):

Sneha R. Lopes ◽

Sunna Khan ◽

Suma Chand

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Behavior Therapy ◽

Cognitive Behavior Therapy ◽

Pharmacological Treatment ◽

Impulse Control ◽

Psychiatric Symptoms ◽

Neuropsychiatric Symptoms ◽

Cognitive Behavior ◽

Sufficient Power

Neuropsychiatric symptoms occur frequently in Parkinson’s disease (PD) patients. Pharmacological treatment of the psychiatric symptoms has been found to be inadequate. Cognitive behavior therapy (CBT) is an evidence based form of psychotherapy that is effective in treating a number of psychiatric disorders. In this article we examine the evidence of CBT in treating common psychiatric symptoms seen in PD patients, namely depression, anxiety, insomnia and impulse control behaviors. Most of the studies adapted CBT to address PD related concerns. Caregivers were frequently part of the CBT programs. Among the studies reviewed, randomized controlled trials showed significant effects in treating depression with CBT in PD patients. Studies have also provided preliminary data for effects of CBT on anxiety, impulse-control behaviors and insomnia. There is a need for more well designed studies with sufficient power for CBT to be established as a useful non-pharmacological treatment for psychiatric symptoms in PD.

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

Medicina ◽

10.3390/medicina57040314 ◽

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.

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Motor Symptom Asymmetry Predicts Non-motor Outcome and Quality of Life Following STN DBS in Parkinson's Disease

10.21203/rs.3.rs-871480/v1 ◽

2021 ◽

Author(s):

Julie Péron ◽

Philippe Voruz ◽

Jordan Pierce ◽

Kévin Ahrweiller ◽

Claire Haegelen ◽

...

Keyword(s):

Quality Of Life ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Motor Symptom ◽

Control Group ◽

Motor Symptoms ◽

Healthy Control ◽

The Impact ◽

Stn Dbs

Abstract Risk factors for long-term non-motor disorders and quality of life following subthalamic nucleus deep-brain stimulation (STN DBS) have not yet been fully identified. In the present study, we investigated the impact of motor symptom asymmetry in Parkinson’s disease.Data were extracted for 52 patients with Parkinson’s disease (half with left-sided motor symptoms and half with right-sided ones) who underwent bilateral STN and a matched healthy control group. Performances for cognitive tests and neuropsychiatric and quality-of-life questionnaires at 12 months post-DBS were compared with a pre-DBS baseline. Results indicated a deterioration in cognitive performance post-DBS in patients with left-sided motor symptoms. Performances of patients with right-sided motor symptoms were maintained, except for a verbal executive task. These differential effects had an impact on patients’ quality of life. The results highlight the existence of two distinct cognitive profiles of Parkinson’s disease, depending on motor symptom asymmetry. This asymmetry is a potential risk factor for non-motor adverse effects following STN DBS.

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Effects of deep brain stimulation on sleep-wake disturbances in patients with Parkinson's disease: A narrative review

Current Neuropharmacology ◽

10.2174/1570159x19666210215115718 ◽

2021 ◽

Vol 19 ◽

Author(s):

Yu Jin Jung ◽

Han-Joon Kim ◽

Sun Ha Paek ◽

Beomseok Jeon

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Early Stage ◽

Motor Symptoms ◽

Specific Effects ◽

The Impact ◽

Non Motor Symptoms ◽

Deep Brain

: Sleep-wake disturbances (SWD) are one of the most common non-motor symptoms in Parkinson's disease (PD) and can appear in the early stage even before the onset of motor symptoms. Deep brain stimulation (DBS) is an established treatment for the motor symptoms in patients with advanced PD. However, the effect of DBS on SWD and its specific mechanisms are not widely understood and remain controversial. In addition to the circuit-mediated direct effect, DBS may improve SWD by an indirect effect such as the resolution of nocturnal motor complications and a reduction of dopaminergic medication. Here, the authors review the recent literatures regarding the impact of DBS on SWD in patients with PD. Furthermore, the selection of the DBS targets and the specific effects of applying DBS to each target on SWD in PD are also discussed.

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

Neurodegenerative Diseases ◽

10.1159/000489311 ◽

2018 ◽

Vol 18 (2-3) ◽

pp. 127-132 ◽

Cited By ~ 3

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.

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