Current Alzheimer research最新文献

Background: In recent years, Virtual Reality (VR) has emerged as a promising tool to improve the well-being and functional capabilities of older adults. Although VR applications have shown positive results, their impact on user experience and therapeutic outcomes still needs to be evaluated.

Objective: This scoping review aims to analyze existing studies on VR use in older adults with neurodegenerative disorders, focusing on the factors that influence usability, satisfaction, and immersion, as well as the effects on emotional and cognitive well-being.

Materials and methods: Empirical studies in English were included on VR applications applied to older adults with cognitive impairment without study design restrictions. The search was conducted in IEEE Xplore, PubMed, Scopus, and Web of Science, identifying a total of 650 initial results. After screening, 14 studies met the inclusion criteria.

Results: Immersive VR tends to generate a greater sense of presence, which contributes to improving emotional well-being and reducing neuropsychiatric symptoms, such as apathy and depression. However, its impact on cognitive functions, including memory and executive skills, varied depending on the level of immersion and participant characteristics. Despite these positive findings, significant heterogeneity was evident in study designs, measurement instruments, and user experience indicators.

Conclusion: Virtual environments have great potential as a therapeutic tool for older adults, but their success depends on the personalization of applications and the adaptation of technology to the specific needs of this population. Future research should focus on developing standardized protocols, incorporating adaptive technologies such as artificial intelligence, and evaluating the longterm effects of VR to maximize its benefits and minimize its risks. This review was registered in the Open Science Framework (OSF) (Registration number: 10.17605/OSF.IO/PNU36).

Background: Alzheimer's disease is a chronic, neurodegenerative condition that leads to a significant cognitive decline. One of the symptoms that greatly reduces the quality of daily functioning is the deterioration of spatial orientation abilities. A non-pharmacological treatment option for Alzheimer's disease, which is also employed to improve the cognitive functioning of individuals with mild cognitive impairment, is virtual reality training.

Objective: To the best of the authors' knowledge, there is no existing systematic review on the use of virtual reality training to enhance spatial orientation in individuals with Alzheimer's disease or mild cognitive impairment. The review was therefore conducted to fill this gap. The findings of this review may support the efficacy of virtual reality in enhancing spatial orientation.

Methods: Five databases were searched. The primary inclusion criteria were study participants aged over 60 years with a diagnosis of Alzheimer's disease or mild cognitive impairment and the use of virtual reality for improving spatial orientation. Six studies meeting these criteria were ultimately included in the review.

Results: All included studies demonstrated an improvement in the spatial orientation of individuals with Alzheimer's disease or mild cognitive impairment following virtual reality training. This indicates the effectiveness of virtual reality technology in cognitive rehabilitation.

Conclusion: As virtual reality cognitive training has proven effective, its use should be more widely adopted. Further research on the application of virtual reality for enhancing spatial orientation in individuals with dementia is recommended.

Alzheimer's disease (AD) is an age-related, progressive neurodegenerative disorder of cognition with clinical features and anatomical hallmarks of amyloid-β plaques and/or neurofibrillary tangles. New studies revealed that microglia, the native immune cells in the brain, are crucial in the development of AD. The present review aims at outlining various roles of microglia in AD especially targeting their role in neuroinflammation. These indicate that microglial dysfunction contributes to AD pathology by affecting both amyloid-β phagocytosis and tau hyperphosphorylation. Other investigative molecular perpetrators, including TREM2, also influence the microglial relevance to amyloid and tau, as well as the overall disease phase. The functional microglia can protect neurons, while the dysfunctional one has the capability of derailing neuronal potentials and aggravating neurodegeneration. We have also discussed therapeutic strategies that start with targeting microglia to reduce neuroinflammation and reinstate balance. However, certain problems, including the side effects of microglial modulation, cost constraint, and accessibility, are areas of concern. In this review, the author presents the current state of knowledge on the potential of microglia-targeted treatments, their risks, and benefits. Thus, this article emphasizes the importance of the expansion of research to decipher the exact manipulation of microglia in AD with the goal of applying these findings given therapeutic approaches.

Alzheimer's disease (AD) is one of the leading causes of cognitive decline, which leads to dementia and poses significant challenges for its therapy. The reason is primarily the ineffective available treatments targeting the underlying pathology of AD. It is a neurodegenerative disease that is mainly characterised by the various molecular pathways contributing to its complex pathology, including extracellular amyloid beta (Aβ) plaques, intracellular neurofibrillary tangles (NFTs), oxidative stress, and neuroinflammation. One of the crucial features is the hyperphosphorylation of tau proteins, which is facilitated by microtubule affinity-regulating kinase-4 (MARK-4). The kinase plays a crucial role in the disease development by modifying microtubule integrity, leading to neuronal dysfunction and death. MARK-4 is thus a druggable target and has a pivotal role in AD. Amongst MARK-4 inhibitors, 16 compounds demonstrate significant capacity in molecular docking studies, showing high binding affinity to MARK-4 and promising potential for tau inhibition. Further, in-vitro investigations provide evidence of their neuroprotective properties. The present review mainly focuses on the role of MARK-4 and its potential inhibitors used in treating AD, which have been thoroughly investigated in silico and in vitro.

Introduction: Alzheimer's disease (AD) is a progressive neurological disorder for which no effective cure currently exists. Research has identified β-Secretase (BACE1) as a promising therapeutic target for the management of AD. BACE1 is involved in the rate-limiting step and produces toxic amyloid-beta (Aβ) peptides that lead to deposits in the form of amyloid plaques extracellularly, resulting in AD.

Method: In this connection, 60 small peptides were evaluated for their in-silico studies to predict the bonding orientation with BACE1. Next, 5 peptides (12, 20, 21, 51, and 52) were selected based on high scoring of Vander Waal interactions with the catalytic site of the enzyme.

Results: The identified hit peptides were synthesized using Solid-Phase Peptide Synthesis (SPPS), and Electrospray Ionization Mass Spectrometry (ESI-MS) elucidated their structures and 1 1 HNMR spectroscopy. According to their In-vitro BACE1 inhibitory study, peptides 21 having high Vander Waal forces showed significant BACE1 inhibition with IC50 = 4.64 ± 0.1μM). Moreover, the kinetic study revealed that peptide 21 is a mixed-type inhibitor and can interact at the active site and the allosteric site of BACE1.

Conclusion: According to the cytotoxicity study, peptide 21 was found to be noncytotoxic at 4.64 μM, 10 μM and 20 μM. The forthcoming target of this study is to evaluate further the effect of peptide 21 in an in-vivo mice model.

Introduction: For over a decade, AMPA receptor allosteric potentiators (AMPAkines) have shown significant effectiveness in multiple preclinical studies related to neurodegenerative and psychiatric disorders underpinned by deficient excitatory synaptic activity. Despite promising preclinical evidence, the clinical translation of AMPAkines has been slow due to the propensity of some of these compounds to produce seizures at or around therapeutic doses. Materials and: Methods: The preclinical activity of the AMPAkine CX1837 is disclosed in the current work.

Results: CX1837 enhanced synaptic transmission in hippocampal slices in vitro and dose-dependently enhanced long-term potentiation, which is believed to control memory consolidation. CX1837 boosted performance in cognition tests, such as the novel object recognition test and the win-shift radial arm maze. CX1837 also increased attentional functioning in the 5-choice serial reaction time task involving rats. CX1837 produced positive preclinical effects at 0.01-1.0 mg/kg dose and elicited epileptic effects at 10 mg/kg dose.

Discussion: CX1837 has demonstrated to have one of the largest safety margins to date in preclinical studies. Low doses of CX1837, which produce acute increases in cognition, may potentially increase neurotrophins when given chronically. This could slow the progression of Alzheimer's disease and reverse deficits secondary to ischemic stroke.

Conclusion: Together, our findings highlight CX1837 as a potential candidate for clinical development in order to treat multiple neurodegenerative and psychiatric disorders.

Introduction: The rapid growth of mobile phone use and internet access among older adults can provide valuable opportunities for clinicians and researchers to incorporate these technologies into the memory rehabilitation of patients with Alzheimer's disease (AD). Building on this opportunity, previous research has used smartphone calendar applications to cue prospective memory in patients with AD. However, in these studies, the calendar has been programmed to send cues only about the time of prospective events.

Method: We investigated the benefits of the smartphone calendar applications sending notifications about both the time and location of the prospective events. We recruited two groups. In the first group (time-and-location-cued group), we configured smartphone-based calendars to send notifications about the time and location of prospective events, while in the second group (time-cued group), we configured smartphone-based calendars to send notifications only about the time of prospective events. In both groups, we invited patients to attend three prospective events per week during a three-week period.

Results: The results demonstrated fewer omissions in the time- and location-cued group than in the time-cued group.

Conclusion: Providing patients with AD with several contextual cues through smartphone-based calendars may result in better prospective performance than providing them with only one contextual cue.

Introduction: The potential therapeutic role of nicotine in Alzheimer's disease (AD) remains controversial, particularly regarding its age-dependent effects and underlying mechanisms.

Method: This study investigated the impact of chronic nicotine administration on cognitive function and molecular pathways in Presenilin 1/2 double knockout (DKO) mice, an amyloid-β-independent model of AD. Three-month-old and eight-month-old DKO and wild-type (WT) mice received oral nicotine treatment (100 μg/ml) for three months. Behavioral assessments revealed that while the 6-month-old cohort showed no significant differences between nicotine-treated and control groups regardless of genotype, nicotine improved contextual fear memory in 11-month-old DKO mice but impaired nest-building ability and cued fear memory in age-matched WT controls. Transcriptome analysis of the prefrontal cortex identified distinct molecular responses to nicotine between genotypes.

Result: In DKO mice, nicotine modulated neuropeptide signaling and reduced astrocyte activation, while in WT mice, it disrupted cytokine-cytokine receptor interaction and neuroactive ligand- receptor interaction pathways. Western blot analysis revealed that nicotine treatment significantly reduced tau hyperphosphorylation and GFAP expression in 11-month-old DKO mice, which was further confirmed by immunohistochemistry showing decreased astrocyte activation in multiple brain regions.

Conclusion: These findings demonstrate that nicotine's effects on cognition and molecular pathways are both age- and genotype-dependent, suggesting its therapeutic potential may be limited to specific stages of neurodegeneration while potentially having adverse effects in healthy aging brains.

Introduction: This study analyzed the current status, hotspots, and development trends of tau protein research in Alzheimer's disease (AD) and to provide a reference for future research in this field. CiteSpace software was used to scientifically measure and visualize the relevant articles in the field of tau protein in AD brain from the Web of Science Core Collection database from 1991 to 2022.

Methods: A total of 568 articles were included, with an exponential growth in the number of articles published from 1991 to 2022, with an average of 17.8 articles per year. The United States is the most productive country in this field, accounting for 46.83% of the total literature. The New York State Institute for Basic Research is the most productive organization, followed by MRC Laboratory Molecular Biology in the UK. The most influential are Kings College London, University of California, San Francisco, and others. Iqbal K is the most productive author.

Results: The most productive journal is the Journal of Biological Chemistry, and the journal with the highest impact factor is Acta Neuropathologica. The journal with the highest cumulative impact factor is Nature. The research hotspots mainly focus on the formation and degradation mechanisms of tau protein paired helical filaments and abnormal phosphorylation, AD neurofibrillary tangles and degenerative changes, and model research, mainly involving tau protein abnormal phosphorylation, phosphorylation sites, dephosphorylation, aggregate helical filaments, neurofibrillary tangles mouse models.

Conclusion: The research frontier trends mainly focus on the study of pathological changes in tau protein, intervention mechanisms, and the development and practice of clinical therapeutic drugs.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative condition with rising prevalence due to the aging global population. Existing methods for diagnosing AD are struggling to detect the condition in its earliest and most treatable stages. One early indicator of AD is a substantial decrease in the brain's glucose metabolism. Metabolomics can detect metabolic disturbances in biofluids, which may be advantageous for early detection of some ADrelated changes. The study aims to predict brain hypometabolism in Alzheimer's disease using metabolomics findings and develop a predictive model based on metabolomic data.

Methods: The data used in this study were acquired from the Alzheimer's Disease Neuroimaging Initiative (ADNI) project. We conducted a longitudinal cohort study with three assessment time points to investigate the predictive ability of baseline metabolomic data for modeling longitudinal fluorodeoxyglucose-positron emission tomography (FDG-PET) trajectory changes in AD patients. A total number of 44 participants with AD were included. The cognitive abilities of participants were evaluated using the Alzheimer's Disease Assessment Scale (ADAS) and the Mini-Mental State Examination (MMSE), while the overall severity of dementia was measured by the Clinical Dementia Rating-Sum of Boxes (CDR-SB). We employed the ADNI's FDG MetaROIs (Meta Regions of Interest) dataset to identify AD-associated hypometabolism in the brain. These MetaROIs were selected based on areas frequently mentioned in FDG-PET studies of AD and MCI subjects.

Results: Across models, we observed consistent positive relationships between specific cholesterol esters - CE (20:3) (p = 0.005) and CE (18:3) (p = 0.0039) - and FDG-PET metrics, indicating these baseline metabolites may be valuable indicators of future PET score changes. Selected triglycerides like DG-O (16:0-20:4) also showed time-specific positive associations (p = 0.017).

Conclusion: This research provides new insights into the disruptions in the metabolic network linked to AD pathology. These findings could pave the way for identifying novel biomarkers and potential treatment targets for AD.