Dementia In Older People Research Articles

Molecular Docking and Drug Kinetics Assessment for Structure-Based Drug Design of New Piperazine-Containing Hydrazone Derivatives as Effective Alzheimer Inhibitors

The neurodegenerative condition known as Alzheimer's disease (AD) impairs cognitive function and produces dementia in older people. The disease's precise mechanism is still a mystery. Four drugs are available. However, they all have a long list of adverse effects and only help people with their warning signs. Medicinal chemists are searching for ways to treat this disease. There is discussion about creating and using a new class of multifunctional small molecule inhibitors. The hydrazone scaffold was used to create a wide range of chemicals. This is because hydrazone derivatives may disrupt the self-assembly of amyloid beta (A), one of the factors that cause fibrils and oligomers. They may also reverse the effects of harmful compounds like free radicals on effective therapeutic agents like medications that penetrate the central nervous system. Structure-based drug design methods were used in this investigation. A protein target (code ID 4EY7) was selected based on published literature research and factors like a lower resolution value (2.35), no mutation, Homo sapiens, and the X-ray diffraction technique. Fifteen Hydrazone derivatives with increased interactions, higher binding scores, and improved drug-like properties and drug kinetic parameters were designed using the protein target, engineered to interact with compounds of interest (a lead compound with a higher binding energy). Promising pharmacotherapeutic drugs for AD treatment may be developed using the results of these investigations.

Hospital mortality in patients with and without dementia by age groups, speciality departments and primary admission diagnoses

In times of demographic change, the number of patients affected by Alzheimer's disease and other related dementias will increase dramatically [1]. This increasing prevalence will also have an impact on hospitals. They will be confronted with an increased workload due to rising admissions of dementia patients and their need for complex treatment and care measures [2]. A recent study by Sampson et al [3] examined the prevalence of dementia in older people over the age of 70 admitted to hospital as emergency cases. The study found that more than 42% of admitted patients suffered from dementia. These results are consistent with a cross-sectional study of patients aged 65 years and older in randomly selected general hospitals in Germany [4]. It confirmed that 40% of patients over the age of 65 suffered from mild cognitive impairment or dementia. These patients were more frequently treated for dehydration, electrolyte disturbances, urinary tract infections, bruises and fractures, as well as symptoms and findings of unknown nature [5]. Patients with severe impairments, such as dementia, require special care. A key aspect that requires attention is the hospital mortality of this population group. An observational cohort study from 2010 linked data from three national registers in the Netherlands, which included 40,500 patients aged 60 to 100 years. It showed that in addition to male gender (adjusted hazard ratio (HR) 1.52, 95% confidence interval (95% CI) 1.43-1.63) and older age (adjusted HR 1.03, 95% CI 1.03-1.04), the presence of Alzheimer's disease (adjusted HR 1.21, 95% CI 1.13-1.29) also increased the risk of hospital mortality [6]. Later studies confirmed this increased likelihood of hospital mortality in patients with Alzheimer's disease or other related dementias with comparable results (odds and hazard ratios between 1.1 and 1.2) [7, 8]. Dementia is therefore a predictor of hospital mortality in hospitalised persons.

Loneliness and aging

Scientific evidence on loneliness shows that this feeling can act as a decisive negative factor in maintaining health. In this sense, an editorial on the subject stated that the damage to health is clear and associated loneliness with an increased risk of cardiovascular diseases, hypertension, diabetes, infectious diseases, impaired cognitive function, depression and anxiety. The editorial also highlighted that this is an issue that requires society's attention and, as a result, a committee was created to study loneliness and social isolation.(1) Due to the evidence of the harm it can cause or worsen, loneliness has become one of the major health concerns in the 21st century. As a result, initiatives have been developed and the governments of the United Kingdom and Japan created Ministries of Loneliness in 2018 and 2021, respectively.(2) Also, a health authority in the United States showed the consequences of insufficient connection for physical health and highlighted a 29% higher risk of heart disease, a 32% higher occurrence of stroke and a 50% higher chance of developing dementia in older people. In addition, it estimated that the lack of social connection increases the risk of premature death by more than 60%.(3) . . .

Utility of neuromelanin-sensitive MRI in the diagnosis of dementia with Lewy bodies.

Dementia with Lewy bodies (DLB) is recognized as the second most common cause of degenerative dementia in older people with Alzheimer's disease (AD), and distinguishing between these 2 diseases may be challenging in clinical practice. However, accurate differentiation is important because these 2 diseases have different prognoses and require different care. Recently, several studies have reported that neuromelanin-sensitive MRI can detect neurodegeneration in the substantia nigra pars compacta (SNc). DLB patients are considered to demonstrate degeneration and a reduction of dopaminergic neurons in the SNc. Therefore, neuromelanin-sensitive MRI may be useful for the diagnosis of DLB. Therefore, in this study, we aimed to investigate the usefulness of neuromelanin-sensitive MRI in the distinguishing DLB from AD. A total of 21 probable DLB and 22 probable AD patients were enrolled. All participants underwent both DaT-SPECT and neuromelanin-sensitive MRI. A combined model of neuromelanin-sensitive MRI and Dopamine transporter single-photon emission computed tomography (DaT-SPECT) was created using logistic regression analysis (forced entry method). There was no difference in the diagnostic utility of neuromelanin-sensitive MRI and DaT-SPECT in distinguishing DLB from AD. There was no significant correlation between the results of neuromelanin-sensitive MRI and DaT-SPECT in DLB patients. The combination of neuromelanin-sensitive MRI and DaT-SPECT demonstrated higher diagnostic performance in distinguishing between DLB and AD compared with neuromelanin-sensitive MRI alone. Additionally, although the combination of both modalities showed a larger AUC compared with DaT-SPECT alone, the difference was not statistically significant. Neuromelanin-sensitive MRI may be equally or even more useful than DaT-SPECT in the clinical differentiation of DLB from AD. Furthermore, the combination of neuromelanin-sensitive MRI and DaT-SPECT may be a highly sensitive imaging marker for distinguishing DLB from AD.

Indole-based heterocyclic conjugates: Design, synthesis, in silico studies and cholinesterase inhibition

Alzheimer's disease (AD), characterized by cognitive decline, behavioral changes, and amnesia, ultimately leads to dementia in older people. Despite decades of study, there is still no effective way to prevent, retard, or reduce the symptoms of AD. In this paper, we report indole-based heterocyclic conjugates as cholinesterase inhibitors. Compounds 14c (IC50s AChE = 0.30 µM; BuChE = 10.16 µM) and 14h (IC50s AChE = 0.58 µM; BuChE = 15.13 µM) display efficacy against both AChE and BuChE. These derivatives did not exhibit toxicity against the HEK-293 and SH-SY5Y cell lines. Docking analysis demonstrated better binding affinity of these compounds (docking score, 14c = –9.06 kcal/mol; 14h = –9.03 kcal/mol) with recombinant human acetylcholinesterase (PDB ID:- 4EY7) as compared to the reference drug donepezil (–8.52 kcal/mol). Molecular dynamics analysis demonstrated better MMGBSA binding free energy of these compounds (14c = –33.10 kcal/mol; 14h = –36.64 kcal/mol) with recombinant human acetylcholinesterase as compared to the reference drug donepezil (-32.20 kcal/mol). These compounds bind in the active site of acetylcholinesterase and maintain stability similar to donepezil during a 200 ns MD simulation. Moreover, these compounds exhibit recognizable ADME characteristics.

The longitudinal associations between ambient air pollution exposure and dementia in the UK: results from the cognitive function and ageing study II and Wales

BackgroundAir pollution has been recognised as a potential risk factor for dementia. Yet recent epidemiological research shows mixed evidence. The aim of this study is to investigate the longitudinal associations between ambient air pollution exposure and dementia in older people across five urban and rural areas in the UK.MethodsThis study was based on two population-based cohort studies of 11329 people aged ≥ 65 in the Cognitive Function and Ageing Study II (2008–2011) and Wales (2011–2013). An algorithmic diagnosis method was used to identify dementia cases. Annual concentrations of four air pollutants (NO2, O3, PM10, PM2.5) were modelled for the year 2012 and linked via the participants’ postcodes. Multistate modelling was used to examine the effects of exposure to air pollutants on incident dementia incorporating death and adjusting for sociodemographic factors and area deprivation. A random-effect meta-analysis was carried out to summarise results from the current and nine existing cohort studies.ResultsHigher exposure levels of NO2 (HR: 1.04; 95% CI: 0.94, 1.14), O3 (HR: 0.90; 95% CI: 0.70, 1.15), PM10 (HR: 1.17; 95% CI: 0.86, 1.58), PM2.5 (HR: 1.41; 95% CI: 0.71, 2.79) were not strongly associated with dementia in the two UK-based cohorts. Inconsistent directions and strengths of the associations were observed across the two cohorts, five areas, and nine existing studies.ConclusionsIn contrast to the literature, this study did not find clear associations between air pollution and dementia. Future research needs to investigate how methodological and contextual factors can affect evidence in this field and clarity the influence of air pollution exposure on cognitive health over the lifecourse.

Unveiling Gene Interactions in Alzheimer's Disease by Integrating Genetic and Epigenetic Data with a Network-Based Approach.

Alzheimer's Disease (AD) is a complex disease and the leading cause of dementia in older people. We aimed to uncover aspects of AD's pathogenesis that may contribute to drug repurposing efforts by integrating DNA methylation and genetic data. Implementing the network-based tool, a dense module search of genome-wide association studies (dmGWAS), we integrated a large-scale GWAS dataset with DNA methylation data to identify gene network modules associated with AD. Our analysis yielded 286 significant gene network modules. Notably, the foremost module included the BIN1 gene, showing the largest GWAS signal, and the GNAS gene, the most significantly hypermethylated. We conducted Web-based Cell-type-Specific Enrichment Analysis (WebCSEA) on genes within the top 10% of dmGWAS modules, highlighting monocyte as the most significant cell type (p < 5 × 10-12). Functional enrichment analysis revealed Gene Ontology Biological Process terms relevant to AD pathology (adjusted p < 0.05). Additionally, drug target enrichment identified five FDA-approved targets (p-value = 0.03) for further research. In summary, dmGWAS integration of genetic and epigenetic signals unveiled new gene interactions related to AD, offering promising avenues for future studies.

Impact of cataract surgery on cognitive impairment in older people.

To examine the impact of cataract surgery on mild cognitive impairment (MCI) and dementia in older people. This prospective observational study included patients aged 75 years and older who underwent cataract surgery between 2019 and 2021. Mini-mental state examination (MMSE) and MMSE for the visually impaired (MMSE-blind) were measured to evaluate cognitive function before and 3 months after cataract surgery. MMSE score at baseline was used to categorize patients into dementia (MMSE ≤ 23) and MCI groups (23 < MMSE ≤ 27). Logistic regression models were used to estimate associations between improvement in cognitive function and other factors. Of 132 patients screened for inclusion in the study, 88 met the inclusion criteria; 39 patients were assigned to the dementia group (mean age, 85.7 ± 4.2 years) and 49 to the MCI group (mean age, 84.2 ± 3.4 years). The MCI group showed significant improvement from before to after surgery in the MMSE score (25.65 ± 1.03 vs. 27.08 ± 1.99, respectively, p < 0.001) and MMSE-blind score (18.04 ± 1.14 vs. 19.41 ± 2.01, respectively, p < 0.001). Cognitive function improved significantly in the MCI group compared with the dementia group (odds ratio, 2.85; 95% confidence interval, 1.02-7.97; and p = 0.046). Cataract surgery significantly increases cognitive test scores in older patients with MCI. After cataract surgery, the likelihood of improvement in cognitive function may be highly dependent on a patient's preoperative cognitive state.

Gait Parameters can Reflect Cognitive Performance in Older Adults with Cerebral Small Vessel Disease: A Cross-sectional Research.

Cerebral small vessel disease (CSVD) is a common chronic progressive disease. It remains unclear whether high gait variability is a marker of cognitive cortical dysfunction. This study included 285 subjects (aged from 60 to 85 years, 60.3% female) including 37 controls, 179 presented as Fazekas II, and 69 presented as Fazekas III. The severity of white matter hyperintensities was assessed by the Fazekas Rating Scale. Gait parameters were assessed using a vision-based artificial intelligent gait analyzer. Cognitive function was tested by MMSE, MoCA, DST, and VFT. Three gait parameters including gait speed, gait length, and swing time were associated with cognitive performance in patients with CSVD. Gait speed was associated with cognitive performance, including MMSE (β 0.200; 95%CI 1.706-6.018; p <.001), MoCA (β 0.183; 95%CI 2.047-7.046; p <.001), DST (order) (β 0.204; 95%CI 0.563-2.093; p =.001) and VFT (β 0.162; 95%CI 0.753-4.865; p =.008). Gait length was associated with cognitive performance, including MMSE (β 0.193; 95%CI 3.475-12.845; p =.001), MoCA (β 0.213; 95%CI 6.098-16.942; p <.001), DST (order) (β 0.224; 95%CI 1.056-4.839; P <.001) and VFT (β 0.149; 95%CI 1.088- 10.114; p =.015). Swing time was associated with cognitive performance, including MMSE (β - 0.242; 95%CI -2.639 to -0.974; p<.001), MoCA (β -0.211; 95%CI -2.989 to -1.034; p <.001) and DST (reverse order) (β -0.140; 95%CI -0.568 to -0.049; p =.020). This study revealed that the relationship between gait parameters and cognitive performance in patients with CSVD and the deteriorated gait parameters can reflect cognitive impairment and even dementia in older people with CSVD.

COGNITIVE IMPAIRMENT AFTER THE DIAGNOSIS OF LATE‐ONSET EPILEPSY ‐ A SYSTEMATIC REVIEW

AbstractBackgroundThe management of late‐onset epilepsy in older people (LOE) is often suboptimal despites its high incidence. The impact of LOE is not only epileptic, it also leads to multiple consequences, such as cognitive decline, and other geriatric syndromes. Cognitive decline, as one of the major consequences of LOE, causes in turn deterioration in quality of life and loss of autonomy. However, the effect of de novo LOE on cognitive decline without dementia in older people remains poorly understood. Similarly, very few studies have analysed the risk factors associated with cognitive decline. Therefore, we conducted a systematic review to describe the long‐term effect on cognition of LOE on older people, including the incidence of cognitive decline after the diagnosis of LOE and the associated risk factors.MethodAccording to PRISMA 2020 guidelines, we searched 5 electronic databases (“EMBASE”, “Medline”, “CINAHL”, “PsycINFO”, “Web of Science”) for articles published until 27th Oct 2022. The criteria selected were patients “60 years old and older” with “late onset epilepsy” diagnosis and “cognitive decline” or “cognitive impairment”, whom do not have known brain tumor or a posttraumatic etiology. Four researchers independently screened studies based on the title and abstract, then by full text. Data extraction was done through “Covidence” platform with each study being processed by two reviewers and conflicts were solved by a third reviewer.ResultWe selected 26 out of 326 initially retrieved publications based on full text review. Most of the studies conducted so far however did not take into consideration or did not control for the baseline cognitive status of their patients before or at the onset of epilepsy and therefore could not objectively determine the real burden of late onset epilepsy on cognitive impairment in this population.ConclusionData in favour of a causal relationship between late onset epilepsy and cognitive decline in elderly with no known baseline cognitive impairment is still precarious. More studies should be conducted with more specific assessment tools that could permit us to have a better estimate of the burden of LOE on cognition such for example imaging and neuropsychological assessment before and after the incidence of epilepsy.

The Levels of Leptin, Cystatin C, Neuropilin-1 and Tau Protein in Relation to Dietary Habits in Patients with Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia in older people. Its prevalence is expected to increase, and therefore it poses a serious challenge to the healthcare system. The aim of the study was to assess the concentration of leptin, cystatin C, neuropilin-1 and tau protein, as well as the influence of dietary habits on these parameters, in a group of AD patients (n = 110) compared to 60 healthy people (n = 60). It has been shown that AD patients, compared to healthy people, are characterized by significantly higher median concentrations of leptin (9.97 vs. 3.08), cystatin c (1.53 vs. 0.56) and tau protein (8.46 vs. 4.19), but significantly lower median neuropilin-1 (69.94 vs. 167.28). Multiple regression analyses showed that leptin levels could be explained by dietary habits in 27%, cystatin C in 51%, neuropilin-1 in 41% and tau protein in 25% of cases. Modification of eating habits may contribute to improving the values of the discussed parameters.

Deep Belief Networks (DBN) with IoT-Based Alzheimer’s Disease Detection and Classification

Dementias that develop in older people test the limits of modern medicine. As far as dementia in older people goes, Alzheimer’s disease (AD) is by far the most prevalent form. For over fifty years, medical and exclusion criteria were used to diagnose AD, with an accuracy of only 85 per cent. This did not allow for a correct diagnosis, which could be validated only through postmortem examination. Diagnosis of AD can be sped up, and the course of the disease can be predicted by applying machine learning (ML) techniques to Magnetic Resonance Imaging (MRI) techniques. Dementia in specific seniors could be predicted using data from AD screenings and ML classifiers. Classifier performance for AD subjects can be enhanced by including demographic information from the MRI and the patient’s preexisting conditions. In this article, we have used the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. In addition, we proposed a framework for the AD/non-AD classification of dementia patients using longitudinal brain MRI features and Deep Belief Network (DBN) trained with the Mayfly Optimization Algorithm (MOA). An IoT-enabled portable MR imaging device is used to capture real-time patient MR images and identify anomalies in MRI scans to detect and classify AD. Our experiments validate that the predictive power of all models is greatly enhanced by including early information about comorbidities and medication characteristics. The random forest model outclasses other models in terms of precision. This research is the first to examine how AD forecasting can benefit from using multimodal time-series data. The ability to distinguish between healthy and diseased patients is demonstrated by the DBN-MOA accuracy of 97.456%, f-Score of 93.187 %, recall of 95.789 % and precision of 94.621% achieved by the proposed technique. The experimental results of this research demonstrate the efficacy, superiority, and applicability of the DBN-MOA algorithm developed for the purpose of AD diagnosis.

The therapeutic use of art as a form of nonpharmacological treatment for those living with a dementia diagnosis

The therapeutic use of art has been acknowledged as an effective nonpharmacological intervention for those living with a dementia diagnosis, with a vast array of mental health benefits. However, despite these benefits, nonpharmacological interventions are widely underused in favour of pharmacological treatments for the management of mental health and cognitive difficulties following a diagnosis of dementia in older people’s services. Case studies detailing three artistic interventions that were carried out as part of each service user’s treatment from an older people’s service in North Cumbria are discussed to demonstrate the therapeutic use of art following a dementia diagnosis, and to share the clinical observations and improvements on Geriatric Depression Scale (GDS) scores achieved within each intervention. These interventions suggest support for existing literature and aim to encourage other healthcare professionals to use person-centred, nonpharmacological interventions in the management of cognitive and mental health difficulties in later life following a dementia diagnosis.

Development and In Vivo Assessment of 4-Phenyltellanyl-7-chloroquinoline-loaded Polymeric Nanocapsules in Alzheimer's Disease Models.

Alzheimer's disease (AD) is the most common form of dementia in older people, and available treatments are palliative and produce undesirable side effects. The 4-phenyltellanyl-7-chloroquinoline (TQ) is an organochalcogen compound studied due to its pharmacological properties, particularly its antioxidant potential. However, TQ possesses some drawbacks such as low aqueous solubility and high toxicity, thus warranting the search for tools that improve the safety and effectiveness of new compounds. Here, we developed and investigated the biological effects of TQ-loaded polymeric nanocapsules (NCTQ) in an AD model in transgenic Caenorhabditis elegans expressing human Aβ1-42 in their body-wall muscles and Swiss mice injected with Aβ25-35. The NCTQ displayed good physicochemical properties, including nanometer size and maximum encapsulation capacity. The treatment showed low toxicity, reduced Aβ peptide-induced paralysis, and activated an endoplasmic reticulum chaperone in the C. elegans model. The Aβ injection in mice caused memory impairment, which NCTQ mitigated by improving working, long-term, and aversive memory. Additionally, no changes in biochemical markers were evidenced in mice, demonstrating that there was no hepatotoxicity in the tested doses. Altogether, these findings provide insights into the neuroprotective effects of TQ and indicate that NCTQ is a promising candidate for AD treatment.

DISCOVERY OF DONEPEZIL-LIKE COMPOUNDS AS POTENTIAL ACETYLCHOLINESTERASE INHIBITORS DETERMINED BY PHARMACOPHORE MAPPING-BASED VIRTUAL SCREENING AND MOLECULAR DOCKING

Objective&#x0D; Alzheimer's disease (AD) is the most common cause&#x0D; of dementia in older people due to abnormalities in&#x0D; the cholinergic system. Acetylcholinesterase has&#x0D; an important role in the regulation of the cholinergic&#x0D; system. Therefore, targeting AChE is one of the most&#x0D; promising strategies for the treatment of AD. Although&#x0D; several approved drugs to treat AD, it is still needed&#x0D; to develop potential inhibitor candidates. Therefore,&#x0D; the aim of this study is to discover newly donepezillike&#x0D; natural compounds and their synthetic derivatives&#x0D; targeting acetylcholinesterase enzyme (AChE).&#x0D; Material and Method&#x0D; A pharmacophore model of a known drug, donepezil&#x0D; was generated. Using the pharmacophore mapping&#x0D; module of the Discovery Studio 2021 program,&#x0D; the chemical library containing natural products&#x0D; and synthetic derivatives was screened. The&#x0D; pharmacokinetics and drug-likeness properties of the&#x0D; screened compounds were predicted by ADMET and&#x0D; Lipinski and Veber’s rule. Some criteria were used as a&#x0D; filter. In addition, bioactive compounds of the database&#x0D; were screened. Then, molecular docking study was&#x0D; performed by using Glide/SP of Maestro (Schrödinger,&#x0D; Inc.) to determine the potential molecules.&#x0D; Results&#x0D; The binding energies were determined for hit&#x0D; compounds after molecular modeling studies.&#x0D; Furthermore, H-bonding, pi-pi stacking, pi-cation,&#x0D; and pi-alkyl interactions between the protein-ligand&#x0D; complex have been identified by various amino acid&#x0D; residues such as Tyr, Asp, His, Trp, Arg. The results&#x0D; show that the potential compounds are a promising&#x0D; candidate with binding energy compared to donepezil.&#x0D; The molecular modeling results indicate that new&#x0D; scaffolds may contribute to the discovery of new AChE&#x0D; inhibitors compared to a reference drug.&#x0D; Conclusion&#x0D; This study may lead to further studies and contribute to&#x0D; examination with in vitro analysis. The scaffolds can be&#x0D; used to design novel and effective inhibitors.

53 Cognitive Decline, Dementia and Air Pollution: A Report by the Committee on the Medical Effects of Air Pollutants

Abstract Dementia is an umbrella term for a range of conditions that affect how the brain works and, in particular, the ability to remember, think and reason. It mainly affects older people, both men and women, and gets worse over time. In recent years, there has been growing interest in the possibility that exposure to outdoor air pollution could increase the risk of dementia. COMEAP reviewed epidemiological and experimental studies and concluded that it is likely that air pollution contributes to a decline in mental ability and dementia in older people. The most likely way this occurs is through effects on the circulatory system. It is known that air pollutants, particularly fine particles, can affect the heart and blood vessels, including those of the brain. These effects are linked to vascular dementia, which is caused by damage to the blood vessels in the brain. Experimental studies suggest that air pollution may also stimulate immune cells in the brain, which can then damage nerve cells. It is also likely that some nano-sized (ultrafine) particles can enter the brain, either by transport along the olfactory nerve or by entering the circulation and crossing the blood-brain barrier. These particles may cause direct damage. Nonetheless, based on the available evidence, it does not seem likely that this is an important mechanism for the development of dementia. Recommendations were made for further research which would help develop the evidence on this important topic.

Influence of Age on Associations of Occlusal Status and Number of Present Teeth with Dementia in Community-Dwelling Older People in Japan: Cross-Sectional Study.

While occlusal status has been reported to be related to cognitive function, little is known about the influence of age on that relationship. The present study examined the associations of tooth loss and occlusal status with dementia in the older people, as well as the effects of age on those relationships. A total of 196 older participants (median age: 84 years) were enrolled. Occlusal status was assessed using functional tooth units (FTU), calculated based on the number of paired natural or artificial teeth. Logistic regression analysis was then performed using dementia as the objective variable, and FTU or number of teeth as explanatory variables. The results showed that higher FTU was associated with lower risk of dementia. Furthermore, when stratified by median age, the association was greater for those aged less than 84 years. On the other hand, there was no significant association of number of present teeth with dementia. These results suggest that the risk of dementia is lower for individuals with better occlusion and that occlusal factor may have a greater effect on dementia onset in younger older people. It is thus recommended that both occlusal function and age be incorporated as factors in programs developed for dementia prevention.

Effects of storage conditions on the stability of blood-based markers for the diagnosis of Alzheimer's disease.

Alzheimer's disease (AD) is considered the most common cause of dementia in older people. Recently, blood-based markers (BBM) Aβ1-42, Aβ1-40, and phospho Tau181 (p-Tau181) have demonstrated the potential to transform the diagnosis and prognostic assessment of AD. Our aim was to investigate the effect of different storage conditions on the quantification of these BBM and to evaluate the interchangeability of plasma and serum samples. Forty-two individuals with some degree of cognitive impairment were studied. Thirty further patients were retrospectively selected. Aβ1-42, Aβ1-40, and p-Tau181 were quantified using the LUMIPULSE-G600II automated platform. To assess interchangeability between conditions, correction factors for magnitudes that showed strong correlations were calculated, followed by classification consistency studies. Storing samples at 4 °C for 8-9days was associated with a decrease in Aβ fractions but not when stored for 1-2days. Using the ratio partially attenuated the pre-analytical effects. For p-Tau181, samples stored at 4 °C presented lower concentrations, whereas frozen samples presented higher ones. Concerning classification consistency in comparisons that revealed strong correlations (p-Tau181), the percentage of total agreement was greater than 90 % in a large number of the tested cut-offs values. Our findings provide relevant information for the standardization of sample collection and storage in the analysis of AD BBM in an automated platform. This knowledge is crucial to ensure their introduction into clinical settings.

Identification of Natural Compounds of the Apple as Inhibitors against Cholinesterase for the Treatment of Alzheimer’s Disease: An In Silico Molecular Docking Simulation and ADMET Study

Alzheimer's disease (AD), the most common type of dementia in older people, causes neurological problems associated with memory and thinking. The key enzymes involved in Alzheimer's disease pathways are acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Because of this, there is a lot of interest in finding new AChE inhibitors. Among compounds that are not alkaloids, flavonoids have stood out as good candidates. The apple fruit, Malus domestica (Rosaceae), is second only to cranberries regarding total phenolic compound concentration. Computational tools and biological databases were used to investigate enzymes and natural compounds. Molecular docking techniques were used to analyze the interactions of natural compounds of the apple with enzymes involved in the central nervous system (CNS), acetylcholinesterase, and butyrylcholinesterase, followed by binding affinity calculations using the AutoDock tool. The molecular docking results revealed that CID: 107905 exhibited the best interactions with AChE, with a binding affinity of -12.2 kcal/mol, and CID: 163103561 showed the highest binding affinity with BuChE, i.e., -11.2 kcal/mol. Importantly, it was observed that amino acid residue Trp286 of AChE was involved in hydrogen bond formation, Van Der Walls interactions, and Pi-Sigma/Pi-Pi interactions in the studied complexes. Moreover, the results of the Molecular Dynamics Simulation (MDS) analysis indicated interaction stability. This study shows that CID: 12000657 could be used as an AChE inhibitor and CID: 135398658 as a BuChE inhibitor to treat Alzheimer's disease and other neurological disorders.

MicroRNAs as a New Target for Alzheimer's Disease Treatment.

Alzheimer's disease (AD) is the most common progressive neurodegenerative disease associated with advanced age. It is characterized by cognitive decline and memory loss and accounts for most cases of dementia in older people. AD can be rooted in genetic, epigenetic, or environmental causes. No drugs or other therapeutic agents prevent or delay AD progression. MicroRNAs (miRNAs) are short and uncoded RNAs that can bind to 200 RNAs approximately. By inhibiting or destroying specific messenger RNAs (mRNAs), they control gene expression and broadly affect cellular functions. MiRNAs play important roles in regulating neuronal growth, neuronal differentiation, dendritic spine morphology, and synaptic flexibility in the nervous system. The expression levels of miRNAs are changed in neurological diseases, including AD, suggesting that they play an essential role in the pathogenesis of the disease. Therefore, targeting disrupted miRNAs may be a novel therapeutic approach against AD and offers multiple solutions, including harnessing the beneficial effects of beta-amyloid, reducing tau protein, reducing neuronal cell death, and protecting synapses in AD.