Cognitive Loss Research Articles

Effect of imipramine on memory, adult neurogenesis, neuroinflammation, and mitochondrial biogenesis in a rat model of alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline and memory loss. Imipramine, a tricyclic antidepressant, has potent anti-inflammatory and antioxidant properties in the central nervous system. The aim of this study was to investigate the neuroprotective effects of imipramine on streptozotocin (STZ)-induced memory impairment. Male Wistar rats received an intracerebroventricular injection of STZ (3 mg/kg, 3 μl/ventricle) using the stereotaxic apparatus. The Morris water maze and passive avoidance tests were used to evaluate cognitive functions. 24 h after the STZ injection, imipramine was administered intraperitoneally at doses of 10 or 20 mg/kg for 14 consecutive days. The mRNA and protein levels of neurotrophic factors (BDNF and GDNF) and pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) were measured in the hippocampus using real-time PCR and ELISA techniques, respectively. In addition, real-time PCR was used to evaluate the mRNA levels of markers associated with neurogenesis (Nestin, DCX, and Ki67) and mitochondrial biogenesis (PGC-1α, NRF-1, and TFAM). The results showed that imipramine, especially at a dose of 20 mg/kg, effectively improved STZ-induced memory impairment. This improvement was associated with an increase in neurogenesis and neurotrophic factors and a decrease in neuroinflammation and mitochondrial biogenesis dysfunction. Based on these results, imipramine appears to be a promising therapeutic option for improving cognitive functions in neurodegenerative diseases such as AD.

Complement C5a receptor 1 blockade reverses cognitive deficits following cranial radiation therapy for brain cancer.

Cranial radiation therapy (RT) for brain cancers leads to an irreversible decline in cognitive function without an available remedy. Radiation-induced cognitive deficits (RICD) are particularly a pressing problem for the survivors of pediatric and low grade glioma (LGG) patients who often live long post-RT. Radiation-induced elevated neuroinflammation and gliosis, triggered by the detrimental CNS complement cascade, lead to excessive synaptic and cognitive loss. Using intact and brain cancer-bearing mouse models, we now show that targeting anaphylatoxin complement C5a receptor (C5aR1) is neuroprotective against RICD. We used a genetic knockout, C5aR1 KO mouse, and a pharmacologic approach, employing the orally active, brain penetrant C5aR1 antagonist PMX205, to reverse RICD. Irradiated C5aR1 KO and WT mice receiving PMX205 showed significant neurocognitive improvements in object recognition memory and memory consolidation tasks. C5aR1 inhibition reduced microglial activation, astrogliosis, and synaptic loss in the irradiated brain. Importantly, C5aR1 inhibition in the syngeneic, orthotopic astrocytoma, and glioblastoma-bearing mice protected against RICD without interfering with the therapeutic efficacy of RT to reduce tumor volume in vivo . PMX205 is currently in clinical trials for amyotrophic lateral sclerosis (ALS). Thus, C5aR1 inhibition is a translationally feasible approach to address RICD, an unmet medical need.

Palliative care considerations in frail older adults.

Frailty is a common geriatric syndrome characterized by a decline in physical and cognitive abilities and an increased vulnerability to stressors such as illnesses and injuries. As the global population is aging, the prevalence of frailty is growing. Frail older adults are at substantial risk of developing mobility and self-care difficulties, hospitalization, and death. Frailty is also associated with a high symptom burden and psychosocial stress, including malnutrition, pain, fatigue, weakness, cognitive loss, depression, falls, and sleep disorders, among others. The role of palliative care is gaining attention in medical literature because frailty is associated with increased morbidity and mortality. While there are no specific guidelines yet for when palliative care should be consulted in older patients with frailty, it has been proposed that palliative care should be considered in frail patients with continued functional decline, increased healthcare utilization, and uncontrolled symptoms. Palliative care can aid in communication with patients and families, establishing goals of care and treatment preferences, improving pain and symptom control, addressing psychosocial and spiritual needs, advance care planning, caregiver needs, and end-of-life care. Once frailty is identified, a comprehensive evaluation of the patient's physical, psychosocial, and spiritual aspects of care is essential for establishing a patient-centered treatment plan. This paper aims to guide clinicians in providing patient-centered care for older adults with frailty in the outpatient setting. Through a comprehensive literature review, we describe the leading models of frailty, frailty screening tools used in the clinical setting, and the assessment and management of palliative care needs in frail patients. We also describe emerging models of care focusing on palliative care for older adults with frailty and discuss issues related to access to palliative care for this population.

THE OUTCOME OF COGNITIVE THERAPY IN PATIENTS WITH FIRST-EVER STROKE AND RECURRENT STROKE

Background: Vascular dementia (VaD) is the second most prevalent type of dementia that impacts elderly adults, succeeding Alzheimer's disease. In contrast to Alzheimer's disease, Vascular Dementia (VaD) presents a wide range of cognitive changes, which are greatly influenced by the specific neural regions that are impacted by vascular pathology. The incidence of dementia in adults with a prior history of stroke is 30%, demonstrating a frequency that is 3-5 times more than those without any discernible stroke-related impairments. In addition, the intensity or frequency of strokes may contribute to a decrease in cognitive reserve in persons with vascular dementia. Case Report: We presented two cases of VaD. The first case was a 62-year-old man with a history of ischemic stroke without sequelae a year before the complaints of frequent forgetfulness and cognitive impairment. Neuropsychological examination showed neurocognitive disturbances in orientation, attention, memory, and visuospatial domain with impaired daily activities function. The MRI result showed senile brain atrophy with chronic infarction on the right temporoparietooccipital lobe, left side mesencephalon, right side pons accompanied by cortical laminar necrosis on the right frontal lobe and left temporoparietal lobe. The second case was a 79-year-old man with history of recurrent ischemic stroke (three times since 2021-2022) with sequelae of left hemiparesis and complaints of frequent forgetfulness and cognitive impairment in the last 1 year. Neuropsychological examination showed neurocognitive disturbances in orientation, attention, and visuospatial domain with impaired daily activities function. The MRI result showed subacute multiple lacunar infarctions in right insular cortex, right frontotemporal lobe cortex, right corona radiata, with multiple chronic infarcts on the right frontotemporoparietal lobe, right corona radiata, right internal genu capsule, right lateral periventricular anterior horn, pons, right left cerebellum, also senile brain atrophy. Both patients were diagnosed as VaD and given donepezil 1x10mg and memantine 1x5mg to treat the cognitive impairment. Both cases showed improvements after 6 months of therapy with MMSE from 17 to 28, MoCA-INA from 12 to 22 and MMSE from 19 to 23, MoCA-INA from 14 to 21 respectively. Discussion: The probability of acquiring vascular dementia (VaD) was strongly associated with the incidence and frequency of strokes. The prevalence of newly developed dementia after the initial stroke is approximately 10%, which increases to 30% with recurrent strokes. The likelihood of experiencing cognitive impairment and dementia after a stroke is primarily determined by the specific attributes of the stroke. While pharmacological therapy largely focuses on cognitive impairment, other factors, such as the stroke's characteristics, might contribute to neuronal and molecular abnormalities that result in cognitive loss. Two instances were shown, both demonstrating enhancements, with the initial instance, involving primary strokes, exhibiting a superior outcome compared to the subsequent instance with recurring strokes. A more profound or recurring stroke has the potential to reduce cognitive reserve, hence potentially heightening vulnerability to neurodegenerative disorders, either directly or by means of modifications in social contacts or lifestyle, which can subsequently affect cognitive performance. Conclusion: Recurrent stroke plays a role in reducing cognitive reserve and increasing the risk of dementia. Patients with VaD have shorter life expectancy, thus the severity of VaD is best managed by providing optimum acute stroke care and recurrent stroke prevention.

Genetic evidence for serum amyloid Pcomponent as a drug target in neurodegenerative disorders.

The mechanisms responsible for neuronal death causing cognitive loss in Alzheimer's disease (AD) and many other dementias are not known. Serum amyloid P component (SAP) is a constitutive plasma protein, which is cytotoxic for cerebral neurones and also promotes formation and persistence of cerebral Aβ amyloid and neurofibrillary tangles. Circulating SAP, which is produced exclusively by the liver, is normally almost completely excluded from the brain. Conditions increasing brain exposure to SAP increase dementia risk, consistent with a causative role in neurodegeneration. Furthermore, neocortex content of SAP is strongly and independently associated with dementia at death. Here, seeking genomic evidence for a causal link of SAP with neurodegeneration, we meta-analysed three genome-wide association studies of 44 288 participants, then conducted cis-Mendelian randomization assessment of associations with neurodegenerative diseases. Higher genetically instrumented plasma SAP concentrations were associated with AD (odds ratio 1.07, 95% confidence interval (CI) 1.02; 1.11, p = 1.8 × 10-3), Lewy body dementia (odds ratio 1.37, 95%CI 1.19; 1.59, p = 1.5 × 10-5) and plasma tau concentration (0.06 log2(ng l-1) 95%CI 0.03; 0.08, p = 4.55 × 10-6). These genetic findings are consistent with neuropathogenicity of SAP. Depletion of SAP from the blood and the brain, by the safe, well tolerated, experimental drug miridesap may thus be neuroprotective.

Perspectives on the clinical use of anti-amyloid therapy for the treatment of Alzheimer's disease: Insights from the fields of cancer, rheumatology, and neurology.

The advent of disease-modifying therapies for Alzheimer's disease (AD) has raised many questions and debates in the field as to the clinical benefits, risks, and costs of such therapies. The controversies have resulted in the perception that many clinicians are apprehensive about prescribing these medications to their patient populations. There also remains widespread uncertainty as to the economic impact, cost benefit ratio, and safety oversight for use of these medications in standard clinical care settings. To contextualize such issues, the present study compared anti-amyloid biologic therapy (lecanemab) to four commonly used biologic agents in other fields, including trastuzumab for breast cancer, bevacizumab for lung cancer, etanercept for rheumatoid arthritis, and ocrelizumab for multiple sclerosis. The data presented demonstrate comparable costs, clinical benefits, and risks for these biologic agents in their disparate disease states. These results provide context for the costs, clinical benefits, and safety regarding the mainstream use of anti-amyloid biologic agents for the prevention of cognitive loss. While the era of disease-modifying therapies for AD is now in its infancy, there is an expectation that these discoveries will be followed by improved therapies and combination treatments leading to greater efficacy in ameliorating the clinical trajectory of AD. Anti-amyloid therapy costs are comparable to other commonly used biologics.Anti-amyloid therapy efficacy is comparable to other commonly used biologics.Anti-amyloid therapy safety is compatible with other commonly used biologics.

Searching Heterocyclic Scaffolds Used to Treat Alzheimer’s Disease: A Review

Abstract:: It is a known fact that Alzheimer's disease causes degeneration of the central nervous system, which progresses and causes memory loss as well as loss of cognition. For many years, extensive research has been undertaken to find out newer possibilities to fight this disease at a molecular level along with many long-standing and expensive clinical trials. Many scientific research programs have either been discarded or unsuccessful. However, the research has not stopped and in the process, many heterocyclic scaffolds have been tried to build up novel drug molecules to combat this disease. A literature survey reveals that many heterocycles have been explored and were found to be very useful in treating many neurodegenerative disorders, including Alzheimer’s disease, Parkinsonism and a few more. This review explains the journey and highlights the various strategies to develop new anti-Alzheimer drug candidates. It is a concise and rigorous literature excerpt involving research findings on heterocyclic scaffolds for treating this disease.

Fisetin-loaded pluronic-based nanogel: Radiation synthesis for alleviating neurocognitive impairments in a rat model of alzheimer's disease via modulation of the apoptotic cascade

Alzheimer's disease (AD) is a neurodegenerative disorder marked by cognitive impairment and memory loss. In this study, AD was experimentally induced in rats using aluminum chloride (AlCl3) and D-galactose (D-gal). Fisetin (Fis), a natural compound with antioxidant and anti-inflammatory properties, has potential for neurodegeneration management, but its low bioavailability limits clinical applications. To address this, we synthesized and characterized Pluronic-2-Acrylamido-2-methylpropane sulfonic acid (PLUR-PAMPS) nanogels using gamma radiation and successfully loaded Fis onto them (Fis-PLUR-PAMPS). The optimal formulation exhibited minimal particle size, a highly acceptable polydispersity index, and the highest zeta-potential, enhancing stability and solubilization efficiency. Our goal was to improve Fis's bioavailability and assess its efficacy against AlCl3/D-gal-induced AD. Male albino Wistar rats were pre-treated orally with Fis (40 mg/kg) or Fis-PLUR-PAMPS for seven days, followed by a seven-day intraperitoneal injection of AlCl3 and D-gal. Behavioral assessments, histopathological analysis, and biochemical evaluation of markers related to AD pathology were conducted. Results demonstrated that Fis-PLUR-PAMPS effectively mitigated cognitive impairments and neurodegenerative signs induced by AlCl3/D-gal. These findings suggest that Fis-PLUR-PAMPS nanogels enhance Fis's bioavailability and therapeutic efficacy, offering a promising approach for AD management.

AR Platform for Indoor Navigation: New Potential Approach Extensible to Older People with Cognitive Impairment

Background: Cognitive loss is one of the biggest health problems for older people. The incidence of dementia increases with age, so Alzheimer’s disease (AD), the most prevalent type of dementia, is expected to increase. Patients with dementia find it difficult to cope with their daily activities and resort to family members or caregivers. However, aging generally leads to a loss of orientation and navigation skills. This phenomenon creates great inconvenience for autonomous walking, especially in individuals with Mild Cognitive Impairment (MCI) or those suffering from Alzheimer’s disease. The loss of orientation and navigation skills is most felt when old people move from their usual environments to nursing homes or residential facilities. This necessarily involves a person’s constant presence to prevent the patient from moving without a defined destination or incurring dangerous situations. Methods: A navigation system is a support to allow older patients to move without resorting to their caregivers. This application meets the need for helping older people to move without incurring dangers. The aim of the study was to verify the possibility of applying the technology normally used for video games for the development of an indoor navigation system. There is no evidence of this in the literature. Results: We have developed an easy-to-use solution that can be extended to patients with MCI, easing the workload of caregivers and improving patient safety. The method applied was the use of the Unity Vuforia platform, with which an augmented reality APK application was produced on a smartphone. Conclusions: The model differs from traditional techniques because it does not use arrows or labels to identify the desired destination. The solution was tested in the laboratory with staff members. No animal species have been used. The destinations were successfully reached, with an error of 2%. A test was conducted against some evaluation parameters on the use of the model. The values are all close to the maximum expected value. Future developments include testing the application with a predefined protocol in a real-world environment with MCI patients.

Autoimmune/inflammatory syndrome induced by adjuvants in a patient after implantation of a polypropylene mesh for inguinal hernia repair (clinical case)

Aim. To report a clinical case of autoimmune/inflammatory syndrome, induced by adjuvants in patient after polypropylene mesh implantation for inguinal hernia repair.Materials and methods. Patient Z., male, 68 years old, was admitted to the hospital presenting muscle weakness and progressive dyspnoea. Interview and physical exam revealed signs of cognitive impairment and memory loss, proximal muscle weakness. Differential diagnosis was made to clarify genesis of symptoms, to rule out polymyositis, other systemic connective tissue diseases, oncologic diseases, hypothyroidism, infectious diseases.Results. Creatine kinase, thyroxine, thyreothropic hormone levels were normal. Clinical and immunological investigation revealed no data on polymyositis or any other systemic connective tissue disease. Yersiniosis, salmonellosis, malaria were ruled out. Chest CT scan, abdomen CT scan, gastroscopy, colonoscopy no data on the presence of malignant neoplasms. PSA level were normal. Electroneuromyography revealed signs of symmetrical axonal type damage to the motor portion of the ulnar nerves on both sides, and demyelinating type damage to the sensory portion. Prednisolone therapy was started at a dose of 40 mg per 24 hour (0.5 mg per kg), which lead to a significant clinical improvement. Based on the therapy response and positive diagnostic criteria (clinical manifestation after polypropylene mesh implantation, typical clinical manifestation – muscle weakness, chronic fatigue, cognitive impairment, neurological manifestations associated with demyelination) patient was diagnosed with autoimmune/inflammatory syndrome, induced by adjuvants (ASIA) after polypropylene mesh implantation for inguinal hernia repair.Conclusion. This clinical case report demonstrates possibility of a persistent course of the disease (symptoms were present for 15 years). Feature of this case is partial clinical improvement due to long-term uncontrolled dexamethasone use, which was prescribed empirically.

Comprehensive Overview of Alzheimer's Disease: Etiological Insights and Degradation Strategies.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and affects millions of individuals globally. AD is associated with cognitive decline and memory loss that worsens with aging. A statistical report using U.S. data on AD estimates that approximately 6.9 million individuals suffer from AD, a number projected to surge to 13.8 million by 2060. Thus, there is a critical imperative to pinpoint and address AD and its hallmark tau protein aggregation early to prevent and manage its debilitating effects. Amyloid-β and tau proteins are primarily associated with the formation of plaques and neurofibril tangles in the brain. Current research efforts focus on degrading amyloid-β and tau or inhibiting their synthesis, particularly targeting APP processing and tau hyperphosphorylation, aiming to develop effective clinical interventions. However, navigating this intricate landscape requires ongoing studies and clinical trials to develop treatments that truly make a difference. Genome-wide association studies (GWASs) across various cohorts identified 40 loci and over 300 genes associated with AD. Despite this wealth of genetic data, much remains to be understood about the functions of these genes and their role in the disease process, prompting continued investigation. By delving deeper into these genetic associations, novel targets such as kinases, proteases, cytokines, and degradation pathways, offer new directions for drug discovery and therapeutic intervention in AD. This review delves into the intricate biological pathways disrupted in AD and identifies how genetic variations within these pathways could serve as potential targets for drug discovery and treatment strategies. Through a comprehensive understanding of the molecular underpinnings of AD, researchers aim to pave the way for more effective therapies that can alleviate the burden of this devastating disease.

Black Seed Oil-Based Curcumin Nanoformulations Ameliorated Cuprizone-Induced Demyelination in the Mouse Hippocampus.

Multiple sclerosis (MS) is a neurodegenerative disease characterized by the demyelination of nerves, axonal damage, and neuroinflammation. Cognition impairment, pain, and loss of mobility are some of the usual complications of MS. It has been postulated that the overproduction of proinflammatory cytokines and reactive oxygen species (ROS) are the main factors that contribute to MS pathology. Among various animal models, the cuprizone model is the most widely used model for investigating MS-related pathology. We assessed the effects of cuprizone along with the protective effects of some black seed oil-based nanoformulations of curcumin with and without piperine, in mice hippocampus in terms of the changes in antioxidant enzymes, transcription factors, and cytokines during demyelination and remyelination processes. The results of behavioral studies point toward impairment in working memory following the feeding of cuprizone for 5weeks. However, in treatment groups, mice seemed to prevent the toxic effects of cuprizone. Nanoformulations used in this study were found to be highly effective in lowering the amount of ROS as indicated by the levels of antioxidant enzymes like catalase, superoxide dismutase, glutathione, and glutathione peroxidase. Moreover, nanoformulations CCF and CCPF were observed resisting the toxic effects of cuprizone. We observed greater expression of NFκB-p65 in the CPZ group than in the control group. CCF nanoformulation had a better inhibitory effect on NFκB-p65 than other formulations. Histological examination of the hippocampus was also conducted. Nanoformulations used here were found effective in reversing MS-related pathophysiology and hence have the potential to be applied as adjuvant therapy for MS treatment.

Glucose 6 phosphate dehydrogenase overexpression rescues the loss of cognition in the double transgenic APP/PS1 mouse model of Alzheimer’s disease

Mice models of Alzheimer's disease (APP/PS1) typically experience cognitive decline with age. G6PD overexpressing mice (G6PD-Tg) exhibit better protection from age-associated functional decline including improvements in metabolic and muscle functions as well as reduced frailty compared to their wild-type counterparts. Importantly G6PD-Tg mice show diminished accumulation of DNA oxidation in the brain at different ages in both males and females. To further explore the potential benefits of modulating the G6PD activity in neurodegenerative diseases, triple transgenic mice (3xTg G6PD) were generated, overexpressing APP, PSEN1, and G6PD genes. The cognitive decline characteristic of APP/PS1 mice was prevented in 3xTg G6PD mice, despite similar amyloid-β (Aβ) levels in the hippocampus. This challenges the dominant hypothesis in Alzheimer's disease (AD) etiology and the majority of therapeutic efforts in the field, based on the notion that Aβ is pivotal in cognitive preservation.Notably, the antioxidant properties of G6PD led to a decrease in oxidative stress parameters, such as improved GSH/GSSG and GSH/CysSSG ratios, without major changes in oxidative damage markers. Additionally, metabolic changes in 3xTg G6PD mice increased brain energy status, countering the hypometabolism observed in Alzheimer's models. Remarkably, a higher respiratory exchange ratio suggested increased carbohydrate utilization. The relative failures of Aβ-targeted clinical trials have raised significant skepticism on the amyloid cascade hypothesis and whether the development of Alzheimer's drugs has followed the correct path. Our findings highlight the significance of targeting glucose-metabolizing enzymes rather than solely focusing on Aβ in Alzheimer's research, advocating for a deeper exploration of glucose metabolism's role in cognitive preservation.

Optimization of quinolinium-carbazole theranostics for the improved photooxidation of β-amyloid aggregates with the variation of conjugation site

Alzheimer’s disease (AD), the most prevalent neurodegenerative condition, is characterized by a gradual decline in cognitive function and memory loss. Presently, it ranks as the fifth leading cause of death worldwide. Photodynamic therapy, with its operational flexibility, noninvasive approach, and high spatial and temporal resolution, has emerged as an innovative therapeutic method, enhancing therapeutic efficacy and minimizing systemic toxicity. In this work, we have designed two donor-π-acceptor (D-π-A) type photosensitizers targeting amyloid, differing in the donor and acceptor junction sites. Surprisingly we found that by altering the junction site of the donor and acceptor from the 2-position to the 3-position of carbazole, the binding affinity and singlet oxygen efficiency of compound 3-QM16 improved compared to compound 2-QM16. This modification facilitated β-amyloid imaging and photooxidative therapy. Our study might shed light on the further optimization of the photooxidation performance of photosensitizers on misfolded proteins.

A novel rat model of cerebral small vessel disease based on vascular risk factors of hypertension, aging, and cerebral hypoperfusion.

Cerebral small vessel disease (CSVD) is a major cause of vascular cognitive impairment and functional loss in elderly patients. Progressive remodeling of cerebral microvessels due to arterial hypertension or other vascular risk factors, such as aging, can cause dementia or stroke. Typical imaging characteristics of CSVD include cerebral microbleeds (CMB), brain atrophy, small subcortical infarctions, white matter hyperintensities (WMH), and enlarged perivascular spaces (EPVS). Nevertheless, no animal models that reflect all the different aspects of CSVD have been identified. Here, we generated a new CSVD animal model using D-galactose (D-gal) combined with cerebral hypoperfusion in spontaneously hypertensive rats (SHR), which showed all the hallmark pathological features of CSVD and was based on vascular risk factors. SHR were hypodermically injected with D-gal (400 mg/kg/d) and underwent modified microcoil bilateral common carotid artery stenosis surgery. Subsequently, neurological assessments and behavioral tests were performed, followed by vascular ultrasonography, electron microscopy, flow cytometry, and histological analyses. Our rat model showed multiple cerebrovascular pathologies, such as CMB, brain atrophy, subcortical small infarction, WMH, and EPVS, as well as the underlying causes of CSVD pathology, including oxidative stress injury, decreased cerebral blood flow, structural and functional damage to endothelial cells, increased blood-brain barrier permeability, and inflammation. The use of this animal model will help identify new therapeutic targets and subsequently aid the development and testing of novel therapeutic interventions. Main process of the study: Firstly, we screened for optimal conditions for mimicking aging by injecting D-gal into rats for 4 and 8 weeks. Subsequently, we performed modified microcoil BCAS intervention for 4 and 8 weeks in rats to screen for optimal hypoperfusion conditions. Finally, based on these results, we combined D-gal for 8 weeks and modified microcoil BCAS for 4 weeks to explore the changes in SHR.

Exploring the link between occupationally relevant whole body vibration and headache and neck pain: is elevated muscle tension an intermediary factor?

Whole body vibration (WBV) is linked to short- and longer-term adverse health outcomes, including cognitive impairment, stress and memory loss, loss of balance, reduced proprioception, visual and vestibular disturbances, gastrointestinal problems, and musculoskeletal disorders. Epidemiological evidence supports the link between WBV and headache and head discomfort, but few experimental studies have examined this relationship, particularly with increased muscle tension, as an intermediary. This study aimed to investigate the relationship between muscle tension and vibration intensity, between perceived neck pain and headache/head discomfort and vibration intensity, and between muscle tension and reported neck pain and headache symptoms from simulated WBV based on field measurements of all-terrain vehicle operation on farm terrain. We observed significantly higher electromyography amplitude in the High condition (equivalent to EU Directive's Exposure Limit Value) compared to both Low (equivalent to EU Directive's Exposure Action Value) and Control (quiet sitting) conditions at the left upper trapezius muscle but there were no significant time effects. Neck pain and headache/head discomfort significantly increased after both Low (91% increase from baseline) and High (154% increase from baseline) vibration conditions but there were no significant differences between conditions. Based on simple regression modeling, the relationship between muscle activity and neck pain or headache was very weak (R2 = 0-0.093). Given the possibility of multiple factors contributing to headache symptoms, future research should not only consider the role of muscle tension but also sensory conflict, excessive noise, biodynamic responses, and a combination of these factors.

Peripheral Immune Cells Contribute to the Pathogenesis of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder with progressive memory and cognitive loss. Neuroinflammation is a central mechanism involved in the progression of AD. With the disruption of the blood-brain barrier (BBB), peripheral immune cells and inflammatory molecules enter into AD brain. However, the exact relationship between peripheral immune cells and AD remains unknown due to various challenges. This study aimed to investigate the potential causal association between peripheral immune cells and AD by using a two-sample Mendelian randomization (TSMR) analysis. We conducted a TSMR to decipher the causal relationship between AD and 731 types of peripheral immune cell parameters from the TBNK, regulatory T cell (Treg), myeloid cell, monocyte, maturation stages of T cell, dendritic cell (DC), and B cell panels. Various analytical methods were employed, including inverse variance weighting (IVW), MR Egger, and weighted median methods. The Cochran's Q statistic, MR-Egger intercept, and MR-PRESSO tests were used to verify the heterogeneity and horizontal pleiotropy of the results. To further verify our results, we also conducted a replication analysis. The analysis identified CD33 on CD14 + monocyte (OR = 1.03; 95% CI, 1.01-1.04;p = 1.14E-04; adjust-p = 0.042) had an increased risk association for AD, which was verified by the replication study. CD33 on CD33dim HLA DR + CD11b- cell (OR = 1.02; 95% CI, 1.01-1.04;p = 2.87E-04; adjust-p = 0.035) had an increased risk association for AD, while secreting CD4 regulatory T cell %CD4 regulatory T cell (OR = 0.97; 95% CI, 0.96-0.99;p = 1.90E-04; adjust-p = 0.046) and CD25 on switched memory B cell (OR = 0.95; 95% CI, 0.92-0.98;p = 2.87E-04; adjust-p = 0.042) were discovered to be related to a lower risk of AD. However, the causal effect of these three immune cells on AD was insufficiently validated in the replication analysis. The MR analysis suggests a potential causal relationship between peripheral immune cells and the risk of AD. Further extensive research is needed on the specific role of peripheral immune cells in AD.

Neurodegenerative pathways and metabolic changes in the hippocampus and cortex of mice exposed to urban particulate matter: Insights from an integrated interactome analysis

Recently, urban particulate matter (UPM) exposure has been associated with the development of brain disorders. This study uses bioinformatic analyses to elucidate the molecular unexplored mechanisms underlying the effects of UPM exposure on the brain.Mice are exposed to UPM (from 3 days to 20 weeks), and their behavioral patterns measured. We measure pathology and gene expression in the hippocampus and cortical regions of the brain. An integrated interactome of genes is established, which enriches information on metabolic processes. Using this network, we isolate the core genes that are differentially expressed in the samples.We observe cognitive loss and pathological changes in the brains of mice at 16 or 20 weeks of exposure. Through network analysis of core-differential genes and measurement of pathway activity, we identify differences in the response to UPM exposure between the hippocampus and cortex. However, neurodegenerative disease pathways are implicated in both tissues following short-term exposure to UPM. There were also significant changes in metabolic function in both tissues depending on UPM exposure time. Additionally, the cortex of UPM-exposed mice shows more similarities with psychiatric disorders than with neurodegenerative diseases. The connectivity map database is used to isolate genes contributing to changes in expression due to UPM exposure.New approaches for inhibiting or preventing the brain damage caused by UPM exposure can be developed by targeting the functions and selected genes identified in this study.

Effect of Self-transcendence, Self-distancing, and Family Functionality on Self-care Agency in Older Adults.

To determine the effect of self-distancing, self-transcendence, and family functioning on self-care agency in Mexican older adults. Correlational-explanatory design, with a sample of 253 elderly, collecting data through a simple random sampling. A personal data questionnaire was applied, the scale of: self-transcendence, the self-distancing subscale, the family APGAR and the ability to self-care in Mexican population from different demographic groups. Descriptive and inferential statistics were applied (Mann-Whitney U and a structural equation model) and the study was approved by a registered ethics committee. The study had participation from 253 elderly, with a mean age of 68.02 years, with prevalence of the female sex (60.1%); the level of education was primary school or lower (51.4%). It was observed that the group of chronic diseases had lower self-distancing (U = 4.449.5, p = 0.038) and greater self-transcendence (U = 4177.0, p = 0.008), and selfcare (U = 4365.5, p = 0.024) than the group without chronic diseases. It was also found that self-transcendence, self-distancing, and family functionality produce a positive effect of 37% on selfcare. Self-distancing, self-transcendence, and family functionality explain an important proportion of selfcare in the elderly. Said knowledge permits understanding the care behavior of the elderly and, thus, propose future educational interventions by nursing to prevent or avoid functional, cognitive loss and social effects.

Emerging Nanotechnology for the Treatment of Alzheimer's Disease.

Nanotechnology is a great choice for medical research, and the green synthesis approach is a novel and better way to synthesize nanoparticles. Biological sources are cost-effective, environmentally friendly, and allow large-scale production of nanoparticles. Naturally obtained 3 β-hydroxy-urs- 12-en-28-oic acids reported for neuroprotective and dendritic structure are reported as solubility enhancers. Plants are free from toxic substances and act as natural capping agents. In this review, the pharmacological properties of ursolic acid (UA) and the structural properties of the dendritic structure are discussed. UA acid appears to have negligible toxicity and immunogenicity, as well as favorable biodistribution, according to the current study, and the dendritic structure improves drug solubility, prevents drug degradation, increases circulation time, and potentially targets by using different pathways with different routes of administration. Nanotechnology is a field in which materials are synthesized at the nanoscale. Nanotechnology could be the next frontier of humankind's technological advancement. Richard Feynman first used the term 'Nanotechnology' in his lecture, "There is Plenty of Room at the Bottom", on 29th December, 1959, and since then, interest has increased in the research on nanoparticles. Nanotechnology is capable of helping humanity by solving major challenges, particularly in neurological disorders like Alzheimer's disease (AD), the most prevalent type, which may account for 60-70% of cases. Other significant forms of dementia include vascular dementia, dementia with Lewy bodies (abnormal protein aggregates that form inside nerve cells), and a number of illnesses that exacerbate frontotemporal dementia. Dementia is an acquired loss of cognition in several cognitive domains that are severe enough to interfere with social or professional functioning. However, dementia frequently co-occurs with other neuropathologies, typically AD with cerebrovascular dysfunction. Clinical presentations show that neurodegenerative diseases are often incurable because patients permanently lose some neurons. A growing body of research suggests that they also advance our knowledge of the processes that are probably crucial for maintaining the health and functionality of the brain. Serious neurological impairment and neuronal death are the main features of neurodegenerative illnesses, which are also extremely crippling ailments. The most prevalent neurodegenerative disorders cause cognitive impairment and dementia, and as average life expectancy rises globally, their effects become more noticeable.