Current Alzheimer research最新文献

Introduction/objective: Age-related cognitive decline has been linked with risk factors, including physical performance. Prior studies investigating such associations were typically conducted in clinical settings within Western populations with a frequent focus on late neurocognitive diagnostic stages (i.e., Alzheimer's disease), reducing their generalizability to the Asian population and early neurocognitive stages. To address these knowledge gaps, our study investigated longitudinal associations between physical performance measures at baseline and cognitive change in global cognition, executive functioning (EF) based and non-executive functioning (non- EF) based cognitive domains within the Singaporean population. The moderating role of early neurocognitive status, namely mild cognitive impairment (MCI) and cognitively normal (CN), was also examined.

Methods: This paper examined data from 347 participants (CN = 284; MCI = 63) who participated in the Community Health and Intergenerational (CHI) study at baseline and follow-up. Data from a neurocognitive battery and three physical performance tests, namely the timed-up and go (TUG), fast gait speed (FGS) and 30-second chair-stand test (30s-CST), were analysed using multivariate linear regression models.

Results: Only one significant association between FGS scores and cognitive change in Semantic Fluency was observed; other associations were not significant. Cognitive status also significantly moderated associations between TUG/30s-CST tasks with several neurocognitive tests.

Conclusion: The lack of significant longitudinal associations between baseline physical performance measures and cognitive change differed from findings in the literature. Nevertheless, the moderating role of cognitive status further highlighted the need to account for cognitive status when exploring such associations within a heterogeneous group of older adults without dementia.

Background: Due to the heterogeneity of Alzheimer's disease (AD), the underlying pathogenic mechanisms have not been fully elucidated. Oligodendrocyte (OL) damage and myelin degeneration are prevalent features of AD pathology. When oligodendrocytes are subjected to amyloid-beta (Aβ) toxicity, this damage compromises the structural integrity of myelin and results in a reduction of myelin-associated proteins. Consequently, the impairment of myelin integrity leads to a slowdown or cessation of nerve signal transmission, ultimately contributing to cognitive dysfunction and the progression of AD. Consequently, elucidating the relationship between oligodendrocytes and AD from the perspective of oligodendrocytes is instrumental in advancing our understanding of the pathogenesis of AD.

Objective: Here, an attempt is made in this study to identify oligodendrocyte-related biomarkers of AD.

Methods: AD datasets were obtained from the Gene Expression Omnibus database and used for consensus clustering to identify subclasses. Hub genes were identified through differentially expressed genes (DEGs) analysis and oligodendrocyte gene set enrichment. Immune infiltration analysis was conducted using the CIBERSORT method. Signature genes were identified using machine learning algorithms and logistic regression. A diagnostic nomogram for predicting AD was developed and validated using external datasets and an AD model. A small molecular compound was identified using the eXtreme Sum algorithm.

Results: 46 genes were found to be significantly correlated with AD progression by examining the overlap between DEGs and oligodendrocyte genes. Two subclasses of AD, Cluster A, and Cluster B, were identified, and 9 signature genes were identified using a machine learning algorithm to construct a nomogram. Enrichment analysis showed that 9 genes are involved in apoptosis and neuronal development. Immune infiltration analysis found differences in immune cell presence between AD patients and controls. External datasets and RT-qPCR verification showed variation in signature genes between AD patients and controls. Five small molecular compounds were predicted.

Conclusion: It was found that 9 oligodendrocyte genes can be used to create a diagnostic tool for AD, which could help in developing new treatments.

Background: Creutzfeldt-Jakob disease (CJD) is a fatal degenerative brain disease characterized by rapidly progressive dementia. Sporadic CJD (sCJD) is the best-known and most common subtype. Because the disease is uncommon and has highly diverse presenting symptoms, early diagnosis is challenging. We herein report a case of probable sCJD diagnosed at a very early stage.

Case presentation: A 61-year-old female patient had mild attention and memory problems for a few months that were noticed by her husband but did not bother her and did not affect her daily life activities. The first brain magnetic resonance imaging (MRI) at another hospital was normal, lacking diffusion-weighted imaging (DWI). Although the newly taken brain MRI without DWI was normal, the patient's husband brought his patient to our outpatient clinic because he continued to think that there was a difference in his wife's attention and memory. A neurological examination of the patient revealed almost normal findings. The neuropsychiatric evaluation of the patient was consistent with mild cognitive impairment. The patient's electroencephalography taken upon admission had no characteristic findings for CJD but showed generalized epileptiform activity. Therefore, the patient was hospitalized, and a second brain MRI, including DWI sequences, was performed. DWI displayed bilateral asymmetrical typical patterns of restricted diffusion. Cerebrospinal fluid 14-3-3 was positive, and total-tau was highly elevated. She had a diagnosis of probable sCJD at an early stage. Later, the patient developed progressive dementia, ataxia, seizures, and extrapyramidal symptoms, followed by mutism, and died.

Conclusion: Although there is no cure for CJD today, early diagnosis is essential, mainly because of its potential infectivity and for future planning. Diagnosing sCJD in its early stages is difficult. However, taking into account the observations of not only the patient's history but also their longterm partners in cognitive evaluations will be helpful in making an early and accurate diagnosis.

Background: Alzheimer's disease (AD) affects approximately 50 million people globally and is expected to triple by 2050. Arctiin is a lignan found in the Arctium lappa L. plant. Arctiin possesses anti-proliferative, antioxidative and anti-adipogenic.

Objectives: We aimed to explore the potential therapeutic effects of Arctiin on rats with AD by evaluating the expression of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.

Methods: AD was induced in rats by administering 70 mg/kg of aluminum chloride through intraperitoneal injection daily for six weeks. After inducing AD, some rats were treated with 25 mg/kg of Arctiin daily for three weeks through oral gavage. Furthermore, to examine the brain tissue structure, hippocampal sections were stained with hematoxylin/eosin and anti-TLR4 antibodies. The collected samples were analyzed for gene expression and protein levels of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.

Results: In behavioral tests, rats showed a significant improvement in their behavior when treated with Arctiin. Microimages stained with hematoxylin/eosin showed that Arctiin helped to improve the structure and cohesion of the hippocampus, which was previously impaired by AD. Furthermore, Arctiin reduced the expression of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.

Conclusion: Arctiin can enhance rats' behavior and structure of the hippocampus in AD rats. This is achieved through its ability to reduce the expression of both TLR4 and NLRP3, hence inhibiting the inflammasome pathway. Furthermore, Arctiin can improve tissue fibrosis by regulating STAT3 and TGF-β. Lastly, it can block the cell cycle proteins cyclin D1 and CDK2.

Background: Dementia encompasses a range of neurodegenerative disorders characterized by cognitive decline and functional impairment. The identification of reliable biomarkers is essential for accurate diagnosis and gaining insights into the mechanisms underlying diseases.

Objective: This study aimed to investigate the plasma biomarker profiles associated with Brain- Derived Neurotrophic Factor (BDNF), Oxytocin, Neuronal Pentraxin-1 (NPTX1), Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin- 1 (IL-1) and Prolactin in Alzheimer's disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementias (FTD) and healthy controls.

Methods: Serum levels of the aforementioned biomarkers were analyzed in 23 AD, 28 DLB, 15 FTD patients recruited from outpatient units and 22 healthy controls. Diagnostic evaluations followed established criteria and standardized clinical tests were conducted. Blood samples were collected and analyzed using ELISA and electrochemiluminescence immunoassay methods.

Results: Serum BDNF and oxytocin levels did not significantly differ across groups. NPTX1, TREM2, TNF-alpha and IL-1 levels also did not show significant differences among dementia groups. However, prolactin levels exhibited distinct patterns, with lower levels in male DLB patients and higher levels in female AD patients compared to controls.

Conclusion: The study findings suggest potential shared mechanisms in dementia pathophysiology and highlight the importance of exploring neuroendocrine responses, particularly in AD and DLB. However, further research is warranted to elucidate the role of these biomarkers in dementia diagnosis and disease progression.

Introduction/objective: Alzheimer's Disease and Related Dementias (AD/ADRD) present significant caregiving challenges, with increasing burdens on informal caregivers. This study examines the potential of AI-driven Large Language Models (LLMs) in developing digital caregiving strategies for AD/ADRD. The objectives include analyzing existing caregiving education materials (CEMs) and mobile application descriptions (MADs) and aligning key caregiving tasks with digital functions across different stages of disease progression.

Methods: We analyzed 38 CEMs from the National Library of Medicine's MedlinePlus, along with associated hyperlinked web resources, and 57 MADs focused on AD digital caregiving. Using ChatGPT 3.5, essential caregiving tasks were extracted and matched with digital functionalities suitable for each stage of AD progression, while also highlighting digital literacy requirements for caregivers.

Results: The analysis categorizes AD caregiving into 4 stages-Pre-Clinical, Mild, Moderate, and Severe-identifying key tasks, such as behavior monitoring, daily assistance, direct supervision, and ensuring a safe environment. These tasks were supported by digital aids, including memory- enhancing apps, Global Positioning System (GPS) tracking, voice-controlled devices, and advanced GPS tracking for comprehensive care. Additionally, 6 essential digital literacy skills for AD/ADRD caregiving were identified: basic digital skills, communication, information management, safety and privacy, healthcare knowledge, and caregiver coordination, highlighting the need for tailored training.

Conclusion: The findings advocate for an LLM-driven strategy in designing digital caregiving interventions, particularly emphasizing a novel paradigm in AD/ADRD support, offering adaptive assistance that evolves with caregivers' needs, thereby enhancing their shared decision-making and patient care capabilities.

Background: As individuals age, they may develop Alzheimer's disease (AD), which is characterized by difficulties in speech, memory loss, and other issues related to neural function. Cycloastragenol is an active ingredient of Astragalus trojanus and has been used to treat inflammation, aging, heart disease, and cancer.

Objectives: This study aimed to explore the potential therapeutic benefits of cycloastragenol in rats with experimentally induced AD. Moreover, the underlying molecular mechanisms were also evaluated by measuring Nrf2 and HO-1, which are involved in oxidative stress, NFκB and TNF-α, which are involved in inflammation, and BCL2, BAX, and caspase-3, which are involved in apoptosis.

Methods: Sprague-Dawley rats were given 70 mg/kg of aluminum chloride intraperitoneally daily for six weeks to induce AD. Following AD induction, the rats were given 25 mg/kg of cycloastragenol daily by oral gavage for three weeks. Hippocampal sections were stained with hematoxylin/ eosin and with anti-caspase-3 antibodies. The Nrf2, HO-1, NFκB, TNF-α, BCL2, BAX, and caspase-3 gene expressions and protein levels in the samples were analyzed.

Results: Cycloastragenol significantly improved rats' behavioral test performance. It also strengthened the organization of the hippocampus. Cycloastragenol significantly improved behavioral performance and improved hippocampal structure in rats. It caused a marked decrease in the expression of NFκB, TNF-α, BAX, and caspase-3, which was associated with an increase in the expression of BCL2, Nrf2, and HO-1.

Conclusion: Cycloastragenol improved the structure of the hippocampus in rats with AD. It enhanced the outcomes of behavioral tests, decreased the concentration of AChE in the brain, and exerted antioxidant and anti-inflammatory effects. Antiapoptotic effects were also noted, leading to significant improvements in cognitive function, memory, and behavior in treated rats.

Introduction: Alzheimer's disease has an impact on handwriting (AD). Numerous researchers reported that fact. Therefore, examining handwriting characteristics could be a useful way to screen for AD. The aim of the article is to present the reliability and effectiveness of the AD-HS tool.

Methods: Most of the existing studies examine either linguistic manifestations of writing or certain motor functions. However, handwriting is a complex of cognitive and motor activities. Since the influence of AD on handwriting is individual, it is important to analyze the complete set of handwriting features. The AD-HS instrument is based on this principle. Validation of the AD-HS instrument for revealing cognitive impairment in AD-diagnosed persons in comparison to the control group. The study is based on the evaluation of free handwritten texts. AD-HS includes 40 handwriting and 2 linguistic features of handwritten texts. It is based on the standard protocol for handwriting analysis. The cumulative evaluation of all features builds a quantitative AD-Indicator (ADI) as a marker of possible AD conditions. The analyzed experiment includes 53 AD-diagnosed persons and a control group of 192 handwriting specimens from the existing database.

Results: AD-HS shows a distinct difference in evaluated ADI for the participants (the mean value equals 0.49) and the control group (the mean value equals 0.28).

Conclusion: The handwriting marker of AD could be an effective supplement instrument for earlier screening. It is also useful when traditional biomarkers and neurological tests could not be applied. AD-HS can accompany therapy as an indication of its effect on a person.

Background: Alzheimer's Disease (AD) is the most prevalent type of dementia. The early change of gut microbiota is a potential biomarker for preclinical AD patients.

Objective: The study aimed to explore changes in gut microbiota characteristics in preclinical AD patients, including those with Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI), and detect the correlation between gut microbiota characteristics and cognitive performances.

Methods: This study included 117 participants [33 MCI, 54 SCD, and 30 Healthy Controls (HC)]. We collected fresh fecal samples and blood samples from all participants and evaluated their cognitive performance. We analyzed the diversity and structure of gut microbiota in all participants through qPCR, screened characteristic microbial species through machine learning models, and explored the correlations between these species and cognitive performances and serum indicators.

Results: Compared to the healthy controls, the structure of gut microbiota in MCI and SCD patients was significantly different. The three characteristic microorganisms, including Bacteroides ovatus, Bifidobacterium adolescentis, and Roseburia inulinivorans, were screened based on the best classification model (HC and MCI) having intergroup differences. Bifidobacterium adolescentis is associated with better performance in multiple cognitive scores and several serum indicators. Roseburia inulinivorans showed negative correlations with the scores of the Functional Activities Questionnaire (FAQ).

Conclusion: The gut microbiota in patients with preclinical AD has significantly changed in terms of composition and richness. Correlations have been discovered between changes in characteristic species and cognitive performances. Gut microbiota alterations have shown promise in affecting AD pathology and cognitive deficit.

Background: The potential relationship between Alzheimer's Disease (AD) and ferroptosis has received considerable attention, yet there is no comprehensive visualization analysis in this field. This study aimed to explore the research frontiers and hotspots through bibliometric analysis.

Methods: Literature related to AD and ferroptosis was collected from the Web of Science Core Collection. Data, including countries, authors, institutions, journals, and keywords, were analyzed by Tableau Public Desktop and Citespace software.

Results: A total of 305 articles published between January 1st, 2013, and December 31st, 2023, were included, and the number of articles on the relationship between AD and ferroptosis has increased annually, with the largest number reported from China (162 articles). The articles from Professor SJ Dixon were cited most frequently. Among the top ten most cited articles, four were published in top journals. The University of Melbourne emerged as the institution with the highest number of publications (27 articles). Among the journals, most of the articles were published in Frontiers in Aging Neuroscience (13 articles, accounting for 4.26%). The co-occurrence analysis of keywords revealed that major hotspots in this field contained oxidative stress, cell death, and lipid peroxidation. Keyword burst analysis indicated that antioxidant was the term with the longest duration of high interest, while clustering analysis showed that this research area primarily focused on amyloid precursor protein, drug development, and diagnostic models.

Conclusion: Bibliometric analyses were conducted to comprehensively present the research progress and trends on the relationship between AD and ferroptosis, providing valuable evidence for future research in related fields.