[Investigation of the Relationship Between Akkermansia Genomic Diversity in Gut Microbiota and Parkinson's Disease Dementia]. / Parkinson Hastaligi Demansi ile Bagirsak Mikrobiyotasindaki Akkermansia Genomik Çesitliligi Arasindaki Iliskinin Incelenmesi.

Although it is known that the relative abundance of Akkermansia, a bacterial genus commonly associated with health, increases in the gut microbiota of Parkinson's disease (PD) patients, the exact reason for this increase remains unclear. This study was aimed to identify potential changes in Akkermansia within the gut microbiota of PD patients in Türkiye. For this purpose, shotgun metagenomics and a novel Akkermansia genus-specific amplicon sequencing technique was used to investigate the presence of specific Akkermansia strains associated with cognitive impairment (CI) stages in PD and to examine potential genes within these strains. In this context, four gut microbiota samples from Türkiye -three PD with dementia (PDD) and one healthy control without CI (HC)- were analyzed by shotgun metagenomics and metagenome-assembled genomes assigned to Akkermansia genus were reconstructed. Then, a custom database was created by combining these genomes with the Akkermansia genomes in public databases and next generation sequencing (NGS) compatible primers specific to the genus Akkermansia were designed using this database. After optimization of amplification and library preparation steps for genus-specific next generation sequencing, gut microbiota samples from 64 PD patients [32 PDD and 32 PD with mild CI (PD-MCI)] and 26 HCs were analyzed by genus-specific amplicon sequencing. The results revealed the presence of seven strains assigned to Akkermansia muciniphila in gut microbiota samples, two of which showed significant distribution differences (p< 0.05) between demented (PDD) and non-demented groups (PD-MCI, HC). When gene contents of the detected Akkermansia genomes were examined through comparative genomic analysis, the presence of 12 genes only in Akkermansia genomes specific to non-demented groups were predicted. The annotations of these genes showed that they were not reported before with unknown functions. In this study, for the first time, gut microbiota samples from PD patients in Türkiye were analyzed using shotgun metagenomics, a novel genus-specific amplicon sequencing method was developed specifically for the analysis of Akkermansia genus, and then Akkermansia strains and genes potentially associated with CI stages in PD were identified using this method. The results underscore that investigating the species or strain level differences could help better understanding of the changes associated with PD in the human gut microbiota.

Clinical evaluation and resting state fMRI analysis of virtual reality based training in Parkinson's disease through a randomized controlled trial.

There are few studies investigating the short-term effects of Virtual Reality based Exergaming (EG) on motor and cognition simultaneously and pursue the brain functional activity changes after these interventions in patients with Parkinson's Disease (PD). The purpose of this study was to investigate the synergistic therapeutic effects of Virtual Reality based EG on motor and cognitive symptoms in PD and its possible effects on neuroplasticity. Eligible patients with the diagnosis of PD were randomly assigned to one of the two study groups: (1) an experimental EG group, (2) an active control Exercise Therapy (ET) group. All patients participated in a 4-week exercise program consisting of 12 treatment sessions. Every session lasted 60 min. Participants underwent a motor evaluation, extensive neuropsychological assessment battery and rs-fMRI before and after the interventions. Thirty patients fulfilled the inclusion criteria and were randomly assigned to the EG and ET groups. After the dropouts, 23 patients completed the assessments and interventions (11 in EG, 13 in ET). Within group analysis showed significant improvements in both groups. Between group comparisons considering the interaction of group × time effect, showed superiority of EG in terms of general cognition, delayed visual recall memory and Boston Naming Test. These results were consistent in the within-group and between-group analysis. Finally, rs-fMRI analysis showed increased activity in the precuneus region in the time × group interaction in the favor of EG group. EG can be an effective alternative in terms of motor and cognitive outcomes in patients with PD. Compared to ET, EG may affect brain functional connectivity and can have beneficial effects on patients' cognitive functions and motor symptoms. Whenever possible, using EG and ET in combination, may have the better effects on patients daily living and patients can benefit from the advantages of both interventions.

Effect of bladder dysfunction on development of depression and anxiety in Parkinson's disease.

OBJECTIVES: Parkinson's disease (PD) often presents with movement disorder. However, besides motor complaints, there are many complaints such as anxiety, depression, urinary complaints and constipation. The aim of this study was to investigate whether neurogenic lower urinary dysfunction (NLUD), which is frequently seen in PD, has an effect on the development of anxiety and depression in these patients. MATERIALS AND METHODS: The study included 32 males (66.6%) and 16 females (33.3%); in total 48 subjects were registered. For the diagnosis and severity of PD, the UK Parkinson's Disease Society Brain Bank Criteria, Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn-Yahr scale were used. Urological evaluation was performed using history, physical examination, laboratory tests and standard forms such as IPSS and OAB-V8. RESULTS: There was no difference between the genders in terms of duration, severity and NLUD (p > 0.05). The incidence of anxiety and depression in PD patients was 62.8% and 72.1%, respectively. The prevalence of NLUD was 67.4% and depression and anxiety was found to increase (1.06 and 1.28 times, respectively) in relation to NLUD. In particular, there was a relationship between storage lower urinary tract symptoms and anxiety and depression development (p < 0.05). CONCLUSIONS: As expected, it was found that the incidence of NLUD, anxiety and depression was increased in PD. In addition, NLUD was found to be a risk factor for the development of anxiety and depression. Therefore, it is concluded that NLUD, which can potentially cause important complications, as well as motor complaints, should be closely monitored and treated in PD patients.

Nocturnal blood pressure changes in Parkinson's disease: correlation with autonomic dysfunction and vitamin D levels.

Nocturnal blood pressure (BP) changes are an indicator of autonomic dysfunction. We aim to investigate the correlation between nocturnal blood pressure (BP) variability, vitamin D levels and Parkinson's disease severity (PD) in this study. Thirty-five patients with PD participated in the study. Disease severity was evaluated by United Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr Scale (HYS). Equivalent levodopa dose was calculated and 25-hydroxyvitamin D levels were measured. The Non-Motor Symptom Questionnaire (NMSQ) was applied to all patients. Ambulatory BP monitoring for 24 h was established. Patients were divided into three groups according to nocturnal BP results: dippers (normal finding-a decline in mean nighttime BP of more than 10%); non-dippers (pathological-a decline in mean nighttime BP of less than 10%); reverse dippers (pathological-an increase in mean nighttime BP) .The mean score of the NMSQ was higher in the group with HYS > 2 (p = 0.050). Four patients were dipper, 17 patients were non-dipper and 16 patients were reverse dipper. There was no significant difference between the three groups in terms of age, gender, disease duration, age of the disease onset, disease stage, disease duration, dopamine agonist usage, levodopa equivalent dose, vitamin D level and NMSQ scores. NMSQ scores are high in advanced PD. Ambulatory BP monitoring is useful in detecting autonomic dysfunction. The number of patients with non-dipping and reverse dipping is high in PD, independent from PD severity, drug dose, vitamin D and the other NMS symptoms.

Transcranial Direct Current Stimulation in the Treatment of Essential Tremor: An Open-Label Study.

INTRODUCTION: Pharmacotherapy and thalamic stimulation are the most accepted methods used for the treatment of essential tremor (ET). Transcranial direct current stimulation (tDCS) is a noninvasive method for brain stimulation, especially to treat pain, cerebrovascular disease, and depression. tDCS applied to the cerebellar region has been shown to exhibit a modulating effect on the excitability of Purkinje cells and to cause primary motor cortex inhibition through the regulation of synaptic dentato-thalamo-cortical excitability. There is only 1 trial that studied the effect of tDCS on ET with 8 patients, and the results were not satisfactory. CASE SERIES: Six ET patients were administered the Essential Tremor Rating Assessment Scale (TETRAS) and Activities of Daily Living (ADL). We applied tDCS to the dorsolateral prefrontal areas (anode) and to inion (inion at 2 mA for 20 min in 10 consecutive sessions with a 2-d break between the first and the second 5-d sessions). One month after the initial course of therapy, 5 more tDCS sessions were administered in an every-other-day manner. TETRAS and ADL scales were readministered. The Friedman test was used to assess differences in TETRAS scores and ADL over the whole time course. CONCLUSIONS: A significant improvement was observed in TETRAS and ADL scores at the end of 50 days (P=0.015, 0.024). We concluded that although our sample group is small, tDCS might be an alternative therapy for patients with ET.