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Journal of Personalized Medicine Jun 2024Chronic kidney disease (CKD) is strongly associated with dementia. However, its independent association with Alzheimer's or Parkinson's disease remains unclear. This...
Chronic kidney disease (CKD) is strongly associated with dementia. However, its independent association with Alzheimer's or Parkinson's disease remains unclear. This study investigated the prospective association of patients with CKD aged ≥55 years with an increased risk of Alzheimer's or Parkinson's disease. We conducted a retrospective cohort analysis using a national cohort sample of approximately one million patients. Primary outcome indicators measured included incidence of all-cause dementia, Alzheimer's disease, and Parkinson's disease events using person-years at risk. The hazard ratio was adjusted using the Cox proportional hazards model. We included 952 patients without CKD and 476 with CKD over 55 years using propensity score matching. The CKD group exhibited higher incidences of all-cause dementia, Parkinson's disease, and Alzheimer's disease than the non-CKD group. Furthermore, the CKD group had an elevated risk of all-cause dementia and a significantly increased risk of Parkinson's disease, especially among older women. Notably, the risk of Parkinson's disease was higher within the first 3 years of CKD diagnosis. These findings emphasize the link between CKD in mid- and late-life individuals and a higher incidence of all-cause dementia and Parkinson's disease rather than Alzheimer's disease.
PubMed: 38929818
DOI: 10.3390/jpm14060597 -
Journal of Personalized Medicine May 2024Rolando Toro's Biodanza (SRT) is a therapeutic strategy that uses movement, music, and emotions to induce integrative living experiences. The present study aims to...
Rolando Toro's Biodanza (SRT) is a therapeutic strategy that uses movement, music, and emotions to induce integrative living experiences. The present study aims to explore the efficacy of a three-month SRT intervention on motor, cognitive, and behavioral symptoms in patients with Parkinson's disease (PD). This study employed a randomized between-group design. Twenty-eight non-demented PD patients were enrolled in this study. Out of these, fourteen patients were assigned to the active treatment group using the Biodanza SRT system and fourteen to the untreated control group. The study group attended 2 h SRT classes once a week, completing twelve lessons in twelve weeks. All patients underwent: (i) a neurological examination to measure the severity of motor symptoms, balance, mobility, and risk of falls, and (ii) a neuropsychological battery to assess cognitive status, apathy, depressive symptomatology, and perceived quality of life (QoL), at study entry (T0) and at twelve weeks (T1, end of dance training). At T1, we observed a significant improvement in motor (i.e., severity of motor symptoms and balance) and cognitive parameters (i.e., working memory and delayed verbal memory) in all treated patients compared with the controls. Furthermore, a significant improvement in the social support dimension was found in all treated patients compared to the controls. A trend toward increased apathy was found in untreated patients at T1. The three-month Biodanza intervention significantly ameliorated the motor parameters of PD patients, with a parallel improvement in cognitive and QoL status. Hence, Biodanza intervention can, in the short term, represent a useful personalized medical intervention for the management of Parkinson's disease.
PubMed: 38929809
DOI: 10.3390/jpm14060588 -
Life (Basel, Switzerland) Jun 2024Parkinson's disease (PD) caused by gene triplication (3X) leads to early onset, rapid progression, and often dementia. Understanding the impact of 3X and its absence is...
Parkinson's disease (PD) caused by gene triplication (3X) leads to early onset, rapid progression, and often dementia. Understanding the impact of 3X and its absence is crucial. This study investigates the differentiation of human induced pluripotent stem cell (hiPSC)-derived floor-plate progenitors into dopaminergic neurons. Three different genotypes were evaluated in this study: patient-derived hiPSCs with 3X, a gene-edited isogenic line with a frame-shift mutation on all alleles ( 4KO), and a normal wild-type control. Our aim was to assess how the substantia nigra pars compacta (SNpc) microenvironment, damaged by 6-hydroxydopamine (6-OHDA), influences tyrosine hydroxylase-positive (Th+) neuron differentiation in these genetic variations. This study confirms successful in vitro differentiation into neuronal lineage in all cell lines. However, the 4KO line showed unusual LIM homeobox transcription factor 1 alpha (Lmx1a) extranuclear distribution. Crucially, both 3X and 4KO lines had reduced Th+ neuron expression, despite initial successful neuronal differentiation after two months post-transplantation. This indicates that while the SNpc environment supports early neuronal survival, gene alterations-either amplification or knock-out-negatively impact Th+ dopaminergic neuron maturation. These findings highlight 's critical role in PD and underscore the value of hiPSC models in studying neurodegenerative diseases.
PubMed: 38929711
DOI: 10.3390/life14060728 -
Medicina (Kaunas, Lithuania) Jun 2024Patients with movement disorders such as Parkinson's disease (PD) living in remote and underserved areas often have limited access to specialized healthcare, while the... (Review)
Review
Patients with movement disorders such as Parkinson's disease (PD) living in remote and underserved areas often have limited access to specialized healthcare, while the feasibility and reliability of the video-based examination remains unclear. The aim of this narrative review is to examine which parts of remote neurological assessment are feasible and reliable in movement disorders. Clinical studies have demonstrated that most parts of the video-based neurological examination are feasible, even in the absence of a third party, including stance and gait-if an assistive device is not required-bradykinesia, tremor, dystonia, some ocular mobility parts, coordination, and gross muscle power and sensation assessment. Technical issues (video quality, internet connection, camera placement) might affect bradykinesia and tremor evaluation, especially in mild cases, possibly due to their rhythmic nature. Rigidity, postural instability and deep tendon reflexes cannot be remotely performed unless a trained healthcare professional is present. A modified version of incomplete Unified Parkinson's Disease Rating Scale (UPDRS)-III and a related equation lacking rigidity and pull testing items can reliably predict total UPDRS-III. UPDRS-II, -IV, Timed "Up and Go", and non-motor and quality of life scales can be administered remotely, while the remote Movement Disorder Society (MDS)-UPDRS-III requires further investigation. In conclusion, most parts of neurological examination can be performed virtually in PD, except for rigidity and postural instability, while technical issues might affect the assessment of mild bradykinesia and tremor. The combined use of wearable devices may at least partially compensate for these challenges in the future.
Topics: Humans; Telemedicine; Movement Disorders; Neurologic Examination; Parkinson Disease; Tremor
PubMed: 38929575
DOI: 10.3390/medicina60060958 -
Medicina (Kaunas, Lithuania) Jun 2024: Although the growing literature is now focusing on the long-term effects of Deep Brain Stimulation (DBS) in Parkinson's disease (PD), there is still a large gap of...
: Although the growing literature is now focusing on the long-term effects of Deep Brain Stimulation (DBS) in Parkinson's disease (PD), there is still a large gap of knowledge about its long-term implications in rehabilitation. Therefore, this study aimed at investigating the effects of rehabilitation in PD patients years after DBS implantation. This retrospective case-control study analyzed records from Moriggia-Pelascini Hospital, Italy from September 2022 to January 2024. Data of PD patients ( = 47) with (DBS group, = 22) and without (control group, = 25) DBS were considered. All study participants underwent a daily rehabilitation program lasting four weeks, including warm-up, aerobic exercises, strength training, postural exercises, and proprioceptive activities. The outcomes assessed were the Unified Parkinson's Disease Rating Scale (UPDRS), Berg Balance Scale (BBS), Timed Up and Go (TUG), 6 Min Walk Test (6MWT), and Self-Assessment Parkinson Disease Scale (SPDDS). DBS group showed significant improvements in terms of all outcome measures after the rehabilitation intervention (UPDRS III: -7.0 (-11.5 to -1.0); = 0.001; UPDRS I II IV: -12.0 (-19.0 to -4.5); = 0.001; BBS: 7.0 (3.8 to 10.3); < 0.001; TUG (s): -2.8 (-5.7 to -1.1); < 0.001; SPDDS: -8 (-13.0 to -4.0); < 0.001; 6MWT (m): 81 (37.3 to 132.3); < 0.001). No differences were reported in the between-group analysis (p: NS). : This study emphasizes positive rehabilitation effects on PD patients irrespective of DBS status. Further research is essential to elucidate long-term effects of DBS on rehabilitation outcomes of PD patients.
Topics: Humans; Parkinson Disease; Deep Brain Stimulation; Female; Male; Retrospective Studies; Aged; Middle Aged; Case-Control Studies; Treatment Outcome; Italy; Postural Balance
PubMed: 38929544
DOI: 10.3390/medicina60060927 -
Medicina (Kaunas, Lithuania) May 2024: Currently, no tool exists to predict clinical outcomes in patients with advanced Parkinson's disease (PD) under levodopa-carbidopa intestinal gel (LCIG) treatment. The... (Observational Study)
Observational Study
An Artificial Neural Network Predicts Gender Differences of Motor and Non-Motor Symptoms of Patients with Advanced Parkinson's Disease under Levodopa-Carbidopa Intestinal Gel.
: Currently, no tool exists to predict clinical outcomes in patients with advanced Parkinson's disease (PD) under levodopa-carbidopa intestinal gel (LCIG) treatment. The aim of this study was to develop a novel deep neural network model to predict the clinical outcomes of patients with advanced PD after two years of LCIG therapy. : This was a longitudinal, 24-month observational study of 59 patients with advanced PD in a multicenter registry under LCIG treatment from September 2019 to September 2021, including 43 movement disorder centers. The data set includes 649 measurements of patients, which make an irregular time series, and they are turned into regular time series during the preprocessing phase. Motor status was assessed with the Unified Parkinson's Disease Rating Scale (UPDRS) Parts III (off) and IV. The NMS was assessed by the NMS Questionnaire (NMSQ) and the Geriatric Depression Scale (GDS), the quality of life by PDQ-39, and severity by Hoehn and Yahr (HY). Multivariate linear regression, ARIMA, SARIMA, and Long Short-Term Memory-Recurrent NeuralNetwork (LSTM-RNN) models were used. : LCIG significantly improved dyskinesia duration and quality of life, with men experiencing a 19% and women a 10% greater improvement, respectively. Multivariate linear regression models showed that UPDRS-III decreased by 1.5 and 4.39 units per one-unit increase in the PDQ-39 and UPDRS-IV indexes, respectively. Although the ARIMA-(2,0,2) model is the best one with AIC criterion 101.8 and validation criteria MAE = 0.25, RMSE = 0.59, and RS = 0.49, it failed to predict PD patients' features over a long period of time. Among all the time series models, the LSTM-RNN model predicts these clinical characteristics with the highest accuracy (MAE = 0.057, RMSE = 0.079, RS = 0.0053, mean square error = 0.0069). : The LSTM-RNN model predicts, with the highest accuracy, gender-dependent clinical outcomes in patients with advanced PD after two years of LCIG therapy.
Topics: Humans; Parkinson Disease; Levodopa; Carbidopa; Male; Female; Drug Combinations; Aged; Gels; Middle Aged; Neural Networks, Computer; Longitudinal Studies; Antiparkinson Agents; Sex Factors; Quality of Life; Treatment Outcome; Severity of Illness Index
PubMed: 38929490
DOI: 10.3390/medicina60060873 -
Antioxidants (Basel, Switzerland) Jun 2024Cell death involving oxidative stress and mitochondrial dysfunction is a major cause of dopaminergic neuronal loss in the substantia nigra (SN) of Parkinson's disease...
Cell death involving oxidative stress and mitochondrial dysfunction is a major cause of dopaminergic neuronal loss in the substantia nigra (SN) of Parkinson's disease patients. Ergothioneine (ET), a natural dietary compound, has been shown to have cytoprotective functions, but neuroprotective actions against PD have not been well established. 6-Hydroxydopamine (6-OHDA) is a widely used neurotoxin to simulate the degeneration of dopaminergic (DA) neurons in Parkinson's disease. In this study, we investigated the protective effect of ET on 6-OHDA treated iPSC-derived dopaminergic neurons (iDAs) and further confirmed the protective effects in 6-OHDA-treated human neuroblastoma SH-SY5Y cells. In 6-OHDA-treated cells, decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial reactive oxygen species (mROS), reduced cellular ATP levels, and increased total protein carbonylation levels were observed. 6-OHDA treatment also significantly decreased tyrosine hydroxylase levels. These effects were significantly decreased when ET was present. Verapamil hydrochloride (VHCL), a non-specific inhibitor of the ET transporter OCTN1 abrogated ET's cytoprotective effects, indicative of an intracellular action. These results suggest that ET could be a potential therapeutic for Parkinson's disease.
PubMed: 38929132
DOI: 10.3390/antiox13060693 -
Antioxidants (Basel, Switzerland) May 2024Oxidation-reduction post-translational modifications (redox-PTMs) are chemical alterations to amino acids of proteins. Redox-PTMs participate in the regulation of... (Review)
Review
Oxidation-reduction post-translational modifications (redox-PTMs) are chemical alterations to amino acids of proteins. Redox-PTMs participate in the regulation of protein conformation, localization and function, acting as signalling effectors that impact many essential biochemical processes in the cells. Crucially, the dysregulation of redox-PTMs of proteins has been implicated in the pathophysiology of numerous human diseases, including neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. This review aims to highlight the current gaps in knowledge in the field of redox-PTMs biology and to explore new methodological advances in proteomics and computational modelling that will pave the way for a better understanding of the role and therapeutic potential of redox-PTMs of proteins in neurodegenerative diseases. Here, we summarize the main types of redox-PTMs of proteins while providing examples of their occurrence in neurodegenerative diseases and an overview of the state-of-the-art methods used for their detection. We explore the potential of novel computational modelling approaches as essential tools to obtain insights into the precise role of redox-PTMs in regulating protein structure and function. We also discuss the complex crosstalk between various PTMs that occur in living cells. Finally, we argue that redox-PTMs of proteins could be used in the future as diagnosis and prognosis biomarkers for neurodegenerative diseases.
PubMed: 38929122
DOI: 10.3390/antiox13060681 -
Antioxidants (Basel, Switzerland) May 2024Parkinson's disease (PD) is a neurodegenerative disorder that affects people's health. Constipation is probably one of the most prominent gastrointestinal symptoms...
Parkinson's disease (PD) is a neurodegenerative disorder that affects people's health. Constipation is probably one of the most prominent gastrointestinal symptoms (non-motor symptoms) of PD with devastating consequences. The aim of this research work is to formulate a functional food product, supplemented with inulin, cocoa, and Moringa, which can be an adjuvant in the treatment of constipation. The product was prepared according to a muffin or "Chilean cake" recipe; this basic muffin was prepared with additions of inulin (MI), inulin + cacao (MIC), and inulin + Moringa (MIM). A physical-chemical analysis of the macronutrients and an antioxidant capacity assessment of the samples were conducted, as well as a sensory evaluation performed by a group of people suffering from Parkinson's disease. A statistically significant difference was observed in the soluble ( = 0.0023) and insoluble ( = 0.0015) fiber values between the control samples and all samples. Furthermore, inulin + cacao improved the antioxidant capacity and folate intake compared to the control. Inulin alone has been shown to have antioxidant capacity according to ABTS (262.5728 ± 34.74 μmol TE/g) and DPPH (9.092518 ± 10.43 μmol TE/g) assays. A sensory evaluation showed a preference for the product with inulin and for the product with inulin + cacao, with a 78% purchase intention being reported by the subjects who evaluated the products. The incorporation of inulin and cacao improved the nutritional value of the muffins; the dietary fiber, antioxidant capacity and folate content are some of the features that stood out. A bakery product enriched with inulin, cocoa and Moringa could serve as a nutritional strategy to enhance nutritional value, thus helping in the treatment of constipation.
PubMed: 38929120
DOI: 10.3390/antiox13060683 -
Antioxidants (Basel, Switzerland) May 2024Oxidative stress, an imbalance between reactive oxygen species (ROS) and endogenous antioxidants, plays an important role in the development of neurodegenerative... (Review)
Review
Oxidative stress, an imbalance between reactive oxygen species (ROS) and endogenous antioxidants, plays an important role in the development of neurodegenerative diseases, including Parkinson's. The human brain is vulnerable to oxidative stress because of the high rate of oxygen that it needs and the high levels of polyunsaturated fatty acids, which are substrates of lipid peroxidation. Natural antioxidants inhibit oxidation and reduce oxidative stress, preventing cancer, inflammation, and neurodegenerative disorders. Furthermore, in the literature, it is reported that antioxidants, due to their possible neuroprotective activity, may offer an interesting option for better symptom management, even Parkinson's disease (PD). Natural antioxidants are usually found in several foods, such as fruits, vegetables, meat, fish, and oil, and in food wastes, such as seeds, peels, leaves, and skin. They can help the system of endogenous antioxidants, protect or repair cellular components from oxidative stress, and even halt lipid, protein, and DNA damage to neurons. This review will examine the extent of knowledge from the last ten years, about the neuroprotective potential effect of natural antioxidants present in food and food by-products, in in vivo and in vitro PD models. Additionally, this study will demonstrate that the pool of dietary antioxidants may be an important tool in the prevention of PD and an opportunity for cost savings in the public health area.
PubMed: 38929084
DOI: 10.3390/antiox13060645