-
Cureus May 2024Alzheimer's and Parkinson's diseases are among the most prevalent neurodegenerative conditions affecting aging populations globally, presenting significant challenges in... (Review)
Review
Alzheimer's and Parkinson's diseases are among the most prevalent neurodegenerative conditions affecting aging populations globally, presenting significant challenges in early diagnosis and management. This narrative review explores the pivotal role of advanced neuroimaging techniques in detecting and managing these diseases at early stages, potentially slowing their progression through timely interventions. Recent advancements in MRI, such as ultra-high-field systems and functional MRI, have enhanced the sensitivity for detecting subtle structural and functional changes. Additionally, the development of novel amyloid-beta tracers and other emerging modalities like optical imaging and transcranial ultrasonography have improved the diagnostic accuracy and capability of existing methods. This review highlights the clinical applications of these technologies in Alzheimer's and Parkinson's diseases, where they have shown improved diagnostic performance, enabling earlier intervention and better prognostic outcomes. Moreover, the integration of artificial intelligence (AI) and longitudinal research is emerging as a promising enhancement to refine early detection strategies further. However, this review also addresses the technical, ethical, and accessibility challenges in the field, advocating for the more extensive use of advanced imaging technologies to overcome these barriers. Finally, we emphasize the need for a holistic approach that incorporates both neurological and psychiatric perspectives, which is crucial for optimizing patient care and outcomes in the management of neurodegenerative diseases.
PubMed: 38947709
DOI: 10.7759/cureus.61335 -
Frontiers in Public Health 2024There is a paucity of studies that compare older adults' attitudes toward Euthanasia in two different terminal illnesses. Moreover, these studies did not relate to...
BACKGROUND
There is a paucity of studies that compare older adults' attitudes toward Euthanasia in two different terminal illnesses. Moreover, these studies did not relate to potentially influencing psycho-social factors. The current study aimed to examine the impact of a diverse range of variables on attitudes among older adults toward Euthanasia in two medical conditions: cancer and Parkinson's disease.
METHODS
A total of 501 individuals aged 75 and above participated in the study. Attitudes toward Euthanasia were measured using vignettes which described two conditions: an 80-year-old man with metastatic cancer and another man in an advanced stage of Parkinson's disease. The questionnaire included measures of relevant experience (with a close family member or a friend dying from a terminal illness), self-efficacy, will to live, satisfaction with life, will to prolong life, fear of death and dying, social support, and psycho-social characteristics. The data were analyzed using hierarchical linear regression models.
RESULTS
A more positive attitude toward Euthanasia was found in the case of cancer compared to Parkinson's disease. Being a woman, having more years of education, lower level of religiosity, greater fear of death and dying and higher self-efficacy contributes to more favorable attitudes toward Euthanasia in both end-of life conditions.
CONCLUSIONS
The finding that attitudes toward Euthanasia are statistically significantly more positive in the case of cancer compared to Parkinson's disease can be attributed to the greater prevalence of cancer in the population, and to the public's awareness of the suffering associated with each of these medical conditions. Beyond the important role of the socio-demographic characteristics of gender, education, and religiosity, it appears that fear of death and dying and self-efficacy are important psychological factors in explaining attitudes toward Euthanasia in both illnesses among older people. These findings shed light on older adults' attitudes toward Euthanasia in debilitating illnesses.
Topics: Humans; Male; Female; Parkinson Disease; Aged, 80 and over; Aged; Attitude to Death; Neoplasms; Euthanasia; Surveys and Questionnaires; Self Efficacy; Terminal Care
PubMed: 38947343
DOI: 10.3389/fpubh.2024.1393535 -
World Journal of Orthopedics Jun 2024Dual mobility (DM) bearings have gained significant attention in the field of total hip arthroplasty (THA) as a valid treatment option in cases of revision for... (Review)
Review
Dual mobility (DM) bearings have gained significant attention in the field of total hip arthroplasty (THA) as a valid treatment option in cases of revision for instability after THA whereas its use in primary THA is still a matter of debate. This manuscript explores the pathology, incidence, diagnosis, treatment options, prognosis, ongoing studies in the literature, and future perspectives related to the use of DM bearings employed in primary THA. DM bearings are primarily designed to address one of the major concerns in THA: Instability of the prosthetic hip. Instability is both for the surgeon and the patient a devastating postoperative complication, leading to significant pain and subsequent apprehension by the patient and may require revision surgeries. The use of DM implants poses the worry of wear-related complications, such as accelerated polyethylene wear and osteolysis, which also pose challenges to long-term implant survival. This technique has seen a steady rise in recent years, with multiple studies reporting favorable outcomes. The incidence of their utilization varies among institutions and surgeons, reflecting differing preferences and patient populations. The diagnosis of instability and wear-related complications in THA often involves clinical assessment, imaging modalities such as X-rays, computed tomography scans, and sometimes advanced imaging techniques like magnetic resonance imaging. DM bearings can be considered as an option when patients present neurologic pathologies such as Parkinson's disease or recurrent dislocations after THA. DM bearings provide an additional articulation point within the implant, facilitating a greater range of motion and inherent stability. This design allows for reduced risk of dislocation and improved functional outcomes. Various implant manufacturers offer different designs and sizes of DM bearings to suit individual patient needs. Current literature suggests that the use of DM bearings in primary THA has demonstrated promising outcomes in terms of enhanced stability, reduced dislocation rates, and improved patient satisfaction. However, long-term studies with larger patient cohorts are necessary to establish the durability and longevity of these implants. Several ongoing studies are investigating the role of DM bearings in primary THA. These studies focus on evaluating long-term implant survivorship, assessing wear patterns, analyzing patient-reported outcomes, and comparing the effectiveness of DM bearings with traditional THA designs. The future of DM bearings in primary THA holds potential for further advancements. Research efforts are aimed at refining implant materials, optimizing designs, and studying the influence of surgical techniques on implant performance. Additionally, continued investigation into the long-term outcomes and cost-effectiveness of DM bearings will play a crucial role in shaping their future use. While further research is warranted, the current evidence supports their potential as a beneficial solution in improving surgical outcomes and patient satisfaction.
PubMed: 38947268
DOI: 10.5312/wjo.v15.i6.512 -
International Journal of Cardiology.... Aug 2024It is currently unknown whether 3D-mapping and micro-electrodes add meaningful benefits in catheter ablation of Wolff-Parkinson-White (WPW) syndrome and challenging,...
BACKGROUND
It is currently unknown whether 3D-mapping and micro-electrodes add meaningful benefits in catheter ablation of Wolff-Parkinson-White (WPW) syndrome and challenging, e.g. -Hisian accessory pathways (APs).
OBJECTIVES
To compare the mapping resolution, acute success and complication rates in patients with WPW syndrome undergoing a first-time catheter ablation using only a contact force-sensing ablation catheter for mapping or a multi-electrode high-resolution mapping catheter.
METHODS
Fifty consecutive 3D-mapping procedures for WPW syndrome using a 3.5-mm ablation catheter (n = 27) or a multi-electrode high-resolution catheter (n = 23) were retrospectively analyzed regarding mapping resolution defined as first 5/10 msec isochronal activation area, number of RF applications to achieve AP block, occurence of AP automaticity during RF delivery, and acute success and complication rates.
RESULTS
Catheter ablation was successful in 48/50 patients with a median of 1 (IQR 1-2) RF applications. Compared to ablation catheter mapping, high-resolution mapping showed a significantly smaller isochronal activation area in the first 5/10 msec (1.25 ± 0.29 vs 0.15 ± 0.03 cm; < 0.001 and 3.41 ± 0.58 vs 0.55 ± 0.12 cm; < 0.0001) and significantly higher incidence of AP automaticity during RF delivery (0 vs 22 %; < 0.05). In -Hisian APs, micro-electrodes recorded distinct His electrograms and AP potentials without fusion and without AP bumping permitting safe and effective -Hisian AP ablation.
CONCLUSIONS
High-resolution mapping increases the mapping accuracy of the AP and its insertion site leading to a significantly higher incidence of AP automaticity during RF delivery. Micro-electrodes provide clinically relevant advantages in -hisian AP mapping improving efficacy and safety of -Hisian AP ablation.
PubMed: 38946712
DOI: 10.1016/j.ijcha.2024.101435 -
European Journal of Neurology Jul 2024Parkinson's disease (PD) is an age-related condition characterized by substantial phenotypic variability. Consequently, pathways and proteins involved in biological...
BACKGROUND AND PURPOSE
Parkinson's disease (PD) is an age-related condition characterized by substantial phenotypic variability. Consequently, pathways and proteins involved in biological aging, such as the central aging pathway comprising insulin-like growth factor 1-α-Klotho-sirtuin 1-forkhead box O3-peroxisome proliferator-activated receptor γ, may potentially influence disease progression.
METHODS
Cerebrospinal fluid (CSF) levels of α-Klotho in 471 PD patients were examined. Of the 471 patients, 96 carried a GBA1 variant (PD GBA1), whilst the 375 non-carriers were classified as PD wild-type (PD WT). Each patient was stratified into a CSF α-Klotho tertile group based on the individual level. Kaplan-Meier survival curves and Cox regression analysis stratified by tertile groups were conducted. These longitudinal data were available for 255 patients. Follow-up times reached from 8.4 to 12.4 years. The stratification into PD WT and PD GBA1 was undertaken to evaluate potential continuum patterns, particularly in relation to CSF levels.
RESULTS
Higher CSF levels of α-Klotho were associated with a significant later onset of cognitive impairment. Elevated levels of α-Klotho in CSF were linked to higher Montreal Cognitive Assessment scores in male PD patients with GBA1 mutations.
CONCLUSIONS
Our results indicate that higher CSF levels of α-Klotho are associated with a delayed cognitive decline in PD. Notably, this correlation is more prominently observed in PD patients with GBA1 mutations, potentially reflecting the accelerated biological aging profile characteristic of individuals harboring GBA1 variants.
PubMed: 38946703
DOI: 10.1111/ene.16388 -
Experimental Dermatology Jul 2024The 16th non-collagenous domain (NC16A) of BP180 is the main antigenic target of autoantibodies in bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP)....
The 16th non-collagenous domain (NC16A) of BP180 is the main antigenic target of autoantibodies in bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP). Commercially available assays detect serum autoantibodies against NC16A in the majority of BP (80%-90%) and in approximately 50% of MMP patients. However, a standardized test system for detecting antibodies against other regions of BP180 is still lacking. Moreover, anti-BP180 autoantibodies have been found in neurological conditions such as multiple sclerosis and Parkinson disease. This study aimed at identifying primary epitopes recognized by BP autoantibodies on the BP180 ectodomain. Serum samples of 51 BP and 30 MMP patients both without anti-NC16A reactivity were included along with 44 multiple sclerosis and 75 Parkinson disease sera. Four overlapping His-tagged proteins covering the entire BP180 ectodomain (BP180(ec)1-4) were cloned, expressed, purified and tested for reactivity by immunoblot. IgG antibodies to BP180(ec)3 were detected in 98% of BP, 77% of MMP and 2% of normal human sera. Only weak reactivity was detected for neurological diseases against BP180(ec)1, BP180(ec)2 and BP180(ec)4, in 3%, 11% and 7% of tested multiple sclerosis sera, respectively. 8% of Parkinson disease sera reacted with BP180(ec)2 and 9% with BP180(ec)4. In conclusion, this study successfully identified epitopes recognized by BP autoantibodies outside the NC16A domain in pemphigoid diseases. These findings contribute to a better understanding of the immune response in BP and MMP with potential implications for a future diagnostic assay for NC16A-negative pemphigoid patients.
Topics: Humans; Parkinson Disease; Collagen Type XVII; Non-Fibrillar Collagens; Pemphigoid, Bullous; Autoantigens; Multiple Sclerosis; Autoantibodies; Pemphigoid, Benign Mucous Membrane; Immunoglobulin G; Epitopes; Protein Domains; Female; Male; Aged
PubMed: 38946225
DOI: 10.1111/exd.15125 -
Movement Disorders : Official Journal... Jun 2024Various forms of Parkinson's disease, including its common sporadic form, are characterized by prominent α-synuclein (αSyn) aggregation in affected brain regions.... (Review)
Review
Various forms of Parkinson's disease, including its common sporadic form, are characterized by prominent α-synuclein (αSyn) aggregation in affected brain regions. However, the role of αSyn in the pathogenesis and evolution of the disease remains unclear, despite vast research efforts of more than a quarter century. A better understanding of the role of αSyn, either primary or secondary, is critical for developing disease-modifying therapies. Previous attempts to hone this research have been challenged by experimental limitations, but recent technological advances may facilitate progress. The Scientific Issues Committee of the International Parkinson and Movement Disorder Society (MDS) charged a panel of experts in the field to discuss current scientific priorities and identify research strategies with potential for a breakthrough. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
PubMed: 38946200
DOI: 10.1002/mds.29897 -
Journal of Cellular Biochemistry Jun 2024The 14-3-3 family of proteins are highly conserved acidic eukaryotic proteins (25-32 kDa) abundantly present in the body. Through numerous binding partners, the 14-3-3... (Review)
Review
The 14-3-3 family of proteins are highly conserved acidic eukaryotic proteins (25-32 kDa) abundantly present in the body. Through numerous binding partners, the 14-3-3 is responsible for many essential cellular pathways, such as cell cycle regulation and gene transcription control. Hence, its dysregulation has been linked to the onset of critical illnesses such as cancers, neurodegenerative diseases and viral infections. Interestingly, explorative studies have revealed an inverse correlation of 14-3-3 protein in cancer and neurodegenerative diseases, and the direct manipulation of 14-3-3 by virus to enhance infection capacity has dramatically extended its significance. Of these, COVID-19 has been linked to the 14-3-3 proteins by the interference of the SARS-CoV-2 nucleocapsid (N) protein during virion assembly. Given its predisposition towards multiple essential host signalling pathways, it is vital to understand the holistic interactions between the 14-3-3 protein to unravel its potential therapeutic unit in the future. As such, the general structure and properties of the 14-3-3 family of proteins, as well as their known biological functions and implications in cancer, neurodegeneration, and viruses, were covered in this review. Furthermore, the potential therapeutic target of 14-3-3 proteins in the associated diseases was discussed.
PubMed: 38946063
DOI: 10.1002/jcb.30624 -
Journal of Nutritional Science and... 2024Pyridoxamine (PM) is one of the natural vitamins B6 (VB6) and functions as an endogenous inhibitor for the formation of AGEs (advanced glycation end products). The AGEs...
Pyridoxamine (PM) is one of the natural vitamins B6 (VB6) and functions as an endogenous inhibitor for the formation of AGEs (advanced glycation end products). The AGEs are implicated in aging, diabetes, and various neuropsychiatric disease, including schizophrenia, Alzheimer's disease, and Parkinson's disease. However, it is unclear whether the absence of PM per se accumulates AGEs in vivo and causes behavioral dysfunctions. To address these points, we raised PM-deficient fruit flies, Drosophila melanogaster, with the sterilized defined medium. Flies reared in a PM-deficient medium accumulated AGEs and reduced lifespan, impaired gustatory response, sleep, courtship behavior, and olfactory learning. These results suggest that PM suppresses AGE accumulation in vivo and is required for regulating innate and empirical behaviors.
Topics: Animals; Drosophila melanogaster; Glycation End Products, Advanced; Pyridoxamine; Behavior, Animal; Longevity; Male; Sleep; Female; Sexual Behavior, Animal; Learning
PubMed: 38945891
DOI: 10.3177/jnsv.70.252 -
Brain and Behavior Jul 2024Semantic fluency is the ability to name items from a given category within a limited time, which relies on semantic knowledge, working memory, and executive function....
INTRODUCTION
Semantic fluency is the ability to name items from a given category within a limited time, which relies on semantic knowledge, working memory, and executive function. Similar to patients with Parkinson's disease (PD), patients with progressive supranuclear palsy (PSP) scored lower than healthy adults in the well-established semantic fluency test. However, it is unclear how unique are the produced words. This study examined the relationship between semantic fluency and words' uniqueness in patients with PSP.
METHODS
Twenty-seven patients with PSP Richardson's syndrome (PSP-RS), 37 patients with PD, and 41 healthy controls (HC) performed a standard semantic fluency test (animals), and their verbal responses were audio-recorded. We used the uniqueness to reflect the ability to produce both original and effective work, that is, creativity.
RESULTS
The PSP-RS group produced fewer correct words and fewer unique words than the PD and HC groups. Moreover, the correlation between fluency and uniqueness was positive in the HC and PD groups but negative in the PSP-RS group. Importantly, the actual levodopa dose was positively correlated with the fluency but negatively correlated with the uniqueness in PSP-RS. The PSP-RS patients who took a greater dose of levodopa tended to produce more correct words but fewer unique words.
CONCLUSIONS
These results suggested that levodopa may modulate semantic fluency and uniqueness in the early stages of PSP-RS.
Topics: Humans; Supranuclear Palsy, Progressive; Male; Female; Aged; Semantics; Levodopa; Parkinson Disease; Middle Aged; Neuropsychological Tests; Antiparkinson Agents
PubMed: 38945805
DOI: 10.1002/brb3.3606