To better address the severe challenges of Alzheimer's disease (AD) prevention and control in China, the national government has published the National Action Plan for Addressing the elderly people with dementia. In order to accelerate the achievement of its core objectives, the Chinese Expert Consensus on Multidisciplinary Rehabilitation Interventions for Alzheimer's Disease has been formulated by integrating multidisciplinary expert opinions and evidence-based findings, using the Delphi method combined with GRADE evidence grading. This consensus advocates a “hospital-community-family” tripartite collaborative management model to standardize systematic and multidimensional approaches for the prevention, treatment, rehabilitation, and care of AD.This consensus deliver evidence-based guidance for tripartite stakeholders (healthcare providers, community networks, and family care systems) to operationalize healthy aging strategies through standardized AD management protocols.. For preventive strategies, AD risk factors are categorized into low-, medium-, and high-risk tiers to guide the formulation of personalized prevention and intervention strategies. For therapeutic management, treatment regimens are stratified by AD clinical stages (mild/moderate/severe), incorporating Western pharmacotherapy, traditional Chinese medicine and neuromodulation techniques. Rehabilitation requires individualized protocols based on multidimensional assessments encompassing functional disability evaluations, personal preferences, and familial support systems, with active rehabilitation prioritized during early/mid-stages and passive interventions dominating advanced AD care. Rehabilitation measures include cognitive therapies (including cognitive training, cognitive stimulation, and cognitive rehabilitation), lifestyle modifications (featuring nutritional guidance and exercise regimens that combine aerobic, strength, and mind-body training), humanistic approaches (such as reminiscence and immersive technologies), art-based therapies (applying music, dance, and visual arts), nature-assisted therapies (through horticultural and animal-assisted interaction), as well as sensory modulation techniques (utilizing light therapy and aromatherapy). For moderate-to-advanced stage AD patients presenting with behavioral and psychological symptoms of dementia or profound cognitive-functional decline, care strategies should implement person-centered care frameworks to preserve self-identity, deliver integrated palliative support, and manage comorbidities through multidisciplinary coordination.

Alzheimer's disease (AD) occurs in elderly and pre-elderly, with comorbidities being a common feature throughout its whole course. This article summarized the comorbidities of AD patients across the whole course and explored the characteristics of comorbidities in three stages of AD: the preclinical stage, the mild cognitive impairment stage, and the dementia stage.It is emphasized that a holistic assessment of AD patients' health status and comorbidities is essential, with an emphasis on whole-course and individualized interventions targeting modifiable risk factors.

Alzheimer's disease (AD) is the most common neurodegenerative disorder, characterized by the pathological hallmarks of extracellular β-amyloid plaque deposition and intracellular neurofibrillary tangles. The deposition of amyloid β-protein (Aβ) is considered the initiating and central event in the pathogenesis of AD. The study of biomarkers is important for the early diagnosis, drug development, and clinical management of AD. PET and fluid biomarkers provide unique and comprehensive information. Aβ PET can detect Aβ plaque burden and spatial distribution in the brains of AD patients, while fluid biomarkers reflect the net of rates of production/clearance of analytes at a given point in time. This review summarizes the clinical application value of Aβ PET and Aβ fluid biomarkers in the diagnosis, differential diagnosis, prognosis prediction, and therapeutic efficacy assessment of AD.

Objective: To evaluate the effect of non-pharmacological intervention in AD patients. Methods: Relevant Chinese and English databases were searched to collect randomized controlled trials of non-drug intervention effect in Alzheimer's disease patients and conduct statistical treatment using Review Manager 5.3 software. Results: In 7 articles, non-pharmacological intervention improved the Mini-Mental State Examination(MMSE) score of Alzheimer's patients (WMD=-1.91,95%CI:-3.10,-0.70,Z=3.13,P=0.002) and Activity of Daily Living Scale(ADL) score (WMD=-0.09,95%CI:-0.86,0.67,Z=0.24,P=0.81). Conclusion: Compared with drug intervention or control measures, non-drug intervention can improve the intelligence and daily living function of Alzheimer's disease patients to a certain extent, but more long-term clinical data with large sample size are still needed for further verification.

Objective: Global has dealing with Alzheimer's disease. By sorting out major countries' strategic plans and project funding, we can learn systematically about the prevention and treatment of Alzheimer's disease in different countries. Methods: Research on policies, and the global scientific research project database was used to search for projects related to Alzheimer's disease. The retrieved projects were analyzed by a combination of measurement and content analysis. Results: At present, the United States has energetically built Alzheimer's disease research centers with different functions; Europe has focused on signaling pathways/regulation and discovering drug targets; Canada values biomarkers and drug targets; China has invested a lot as well. Conclusion: Some countries have made legislation on how to deal with AD. Signaling pathways/regulation, target discovery and drug development are the main contents of AD research, and effective marker screening and popular science dissemination are the future development trends of AD research.

Objective: To investigate the effect of cognitive reserve (CR) proxy variables on cognitive function in pre dementia patients with Alzheimer's disease (AD). Methods: 25 normal controls (NC) and 45 patients with mild cognitive impairment (MCI) were selected.All enrolled patients received Cognitive Reserve Index questionnaire (CRIq) to obtain the total score, education, work activities and leisure time scores, and completed the cognitive function scale assessment.Finally, correlation analysis and linear regression analysis were carried out on the proxy variables of cognitive reserve and the scores of each cognitive domain of the cognitive function scale. Results: ①Total score, education and leisure time were positively correlated with Mini-mental State Examination (MMSE) score(r=0.506, P<0.001, r=0.398, P<0.001, r=0.448, P<0.001)and Montreal Cognitive Assessment (MoCA) score(r=0.492, P<0.001, r=0.353, P=0.002, r=0.403, P<0.001) reflecting overall cognition. ② Education and number symbol conversion test, auditory word learning test, delayed recall and Boston Naming test were positively correlated (both P<0.05);The work activity was positively correlated with the number symbol test, the auditory word learning test, the delayed memory, and the number span positive memory test (both P<0.05).Leisure time was positively correlated with the total score of auditory word learning test and delayed recall, number span test, number symbol conversion test, animal word fluency and Boston naming test (both P<0.05).The total score was positively correlated with the total score of auditory word learning test and delayed recall, number span forward memorization test, animal word fluency test, number symbol conversion test and number span backward memorization test (both P<0.05). Conclusion: ① There is a correlation between comprehensive cognitive reserve and overall cognitive function in AD patients in the pre-dementia stage. ② Education level and lifelong leisure activities are correlated with the comprehensive cognitive scale, memory and language ability, while occupational complexity was correlated only with comprehensive cognitive scale and memory.

With the continuous exacerbation of the global aging trend, the prevalence of Alzheimer's disease (AD) is increasing year by year, significantly affecting people's quality of daily life. Among the known genetic factors causing AD, APOE is one of the more significant factors that play a crucial role in the development of AD. Additionally, abnormal levels of thyroid hormones, whether too high or too low, may have a negative impact on people's cognitive function. This impact, through a series of complex developmental mechanisms, ultimately leads to the progression of AD. Exploring the relationship between the two may find new ways to prevent or delay the progression of AD, providing better protection for the elderly population's health.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a long preclinical phase and a cascade of pathological events. With recent advances in blood and imaging biomarkers, the dynamic tracking of AD progression has become increasingly feasible. However, most studies have focused on single-modality markers, with limited integration across biological systems and time scales. This review adopts a time-dynamic perspective to summarize the longitudinal evolution of key blood biomarkers (e.g., Aβ42/40 ratio, p-tau217, NfL, GFAP) and imaging markers (e.g., Aβ-PET, Tau-PET, MRI) across the AD continuum. We compare the timing of initial abnormalities, progression patterns, and correlations with cognitive decline. Furthermore, we highlight integrative modeling approaches, including event-based models, and deep learning frameworks, which enable multi-modal risk prediction and individualized disease staging. The clinical potential of such integration in early screening, disease trajectory forecasting, and therapeutic decision-making is discussed, along with current limitations and future directions. This review provides a framework for developing dynamic, biology-driven precision diagnostic strategies in AD.

Objective: This study aims to apply bibliometric methods to explore the global and domestic research status, trends, and emerging topics related to apolipoprotein E (APOE) and Alzheimer's disease (AD) from 2009 to 2023. Methods: We searched the Web of Science for literature on APOE and Alzheimer's disease from January 2009 to December 2023. The retrieved data were analyzed using CiteSpace (6.2.R6) software, with visualizations generated for authors, keywords, countries, institutions, and more. Results: From 2009 to 2023, the number of research articles on APOE and Alzheimer's disease increased steadily, with a total of 4,452 publications. The United States had the highest volume of publications. Keyword co-occurrence and clustering analyses revealed "APOE" "mild cognitive impairment" and "age" as major research topics globally. Conclusion: Future research on APOE and AD will primarily focus on the genetic phenotypes of APOE and their relationship with AD, as well as exploring clinical applications of treatments targeting APOE phenotypes or altering these phenotypes to treat AD.

Objective: To observe the clinical effect of butylphthalide soft capsule combined with donepezil tablets in the treatment of patients with post-stroke cognitive impairment (PSCI). Methods: Sixty patients with PSCI were randomly divided into treatment group and control group, 30 patients in each group. The control group was given oral donepezil tablets, one tablet after meals (10 mg) every night, and the treatment group was given oral butylphthalide soft capsules on the basis of the control group, taking 2 capsules before meals, 0.2 g each. All patients were treated for 4 weeks. The levels of mini-mental state examination (MMSE), Montreal cognitive test (MoCA), modified Barthel index (MBI) and brain-derived neurotrophic factor (BDNF) were measured before and after treatment. The data were recorded and analyzed. Results: After treatment, the MMSE, MoCA and MBI scores of the two groups were higher than those before treatment, and the scores of the treatment group were higher than those of the control group, the differences were statistically significant (P<0.05). After treatment, there was no significant difference in the BDNF level of the control group compared with that before treatment, while the BDNF level of the treatment group was significantly higher than that before treatment and that of the control group (P<0.05). Conclusion: Butylphthalide soft capsule combined with donepezil tablets is superior to donepezil tablets alone in the treatment of PSCI. The combined treatment can improve the cognitive function and daily living ability of PSCI patients faster, which is worthy of further clinical recommendation.

Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide and a leading cause of dementia. Currently, there are no highly effective treatments for this condition. The imbalance between the production and clearance of Aβ(amyloid-beta) protein is considered a primary pathogenic mechanism of AD. Enhancing the clearance of Aβ in the brain during the early stages can delay the onset and progression of AD. In recent years, with the introduction of the concept of the glymphatic system and the discovery of meningeal lymphatic vessels, the directional transport of fluids within the central nervous system has become a research hotspot. The glymphatic system plays a crucial role in clearing amyloid-beta protein and holds promise as a novel approach to combat neurodegenerative diseases. This review aims to summarize the current research progress on the role of the brain's glymphatic system in AD treatment and explore its potential applications in disease management.

Cognitive impairment is the primary symptom of Alzheimer's disease (AD), manifesting as memory loss and changes in other cognitive functions. Currently, cognitive tools such as the mini-mental state examination (MMSE) and the montreal cognitive assessment (MoCA) are widely used to evaluate overall cognitive function in patients. However, these scales are time-consuming and require experienced clinicians to conduct face-to-face testing. This review aims to introduce MemTrax, a computerized continuous recognition task, and its application in cognitive assessment. In this test, subjects are required to complete a picture recognition task within approximately 90 seconds to assess their cognitive functions, mainly episodic memory, including memory processing, storage, retrieval, and reaction time.Previous studies have confirmed that its efficacy in identifying normal individuals, mild cognitive impairment (MCI), and AD patients is superior to MoCA. Moreover, combining with other biomarkers can further enhance its diagnostic efficacy, and it is also potential for assessment of treatment efficacy. Here we also introduce the application of MemTrax in various types of cognitive disorder diseases. Finally, this article proposes that MemTrax can be used as a digital tool to establish a systematic neuroscience database in the future, combining machine learning and other biomarkers to predict early dementia, as well as for large-scale cognitive screening and continuous cognitive monitoring.

Objective: This study aims to explore the application of toys and games in non-pharmacological interventions of Alzheimer's disease, and analyze the current research status, in order to provide guidance for future studies. Methods: This paper adopts literature review and thematic analysis methods. Literature searches were conducted on CNKI, Wanfang, Google Scholar, SCOPUS, Pubmed, and Science Direct using keywords such as "Alzheimer's disease," "dementia," "non-pharmacological intervention," "toys," and "games." Relevant literature from 2020 to 2024 was collected and subjected to thematic analysis. Results: The research indicates that non-pharmacological interventions for Alzheimer's disease are continuously emerging, among which a significant form of treatment is to use toys and games to enhance patients' quality of life. These toys and games stimulate cognitive and sensory functions, improve patients' social interaction abilities, promote physical activity, and alleviate negative emotions such as depression and anxiety. Conclusion: Currently, the toys used in occupational therapy for Alzheimer's disease patients mostly come from existing children's toys on the market or are simple toys developed by researchers in psychology and medicine, lacking research on how to design more tools for occupational therapy for Alzheimer's disease patients from a design perspective. Future research can start from the field of design to explore its principles and methods, in order to provide more beneficial insights and guidance for non-pharmacological interaction of Alzheimer's disease patients.

Extracellular vesicles are collectively referred to as various vesicle structures with membrane structures released by cells. Their contents include transmembrane proteins, lipids, cytoskeletal structural proteins, enzymes, transcription factors, DeoxyriboNucleic Acid, Ribonucleic Acid, and other substances.It is widely found in blood, cerebrospinal fluid and other body fluids.EV can promote intercellular communication, affect the homeostasis and function of the brain, and promote the progression of neurodegenerative diseases such as Alzheimer’s disease.This review discusses the research of EV in AD in this field.

Alzheimer's disease(AD), as a neurodegenerative disease,has an abnormally complex pathogenesis and involves various biological processes. In recent years, the role of miRNA and NLRP3 inflammasome in AD,Which has been increasingly drawing attention,is becoming more and more significant.Based on the research background and significance,the article summarizes the current understanding of the role and mechanisms of miRNA-mediated NLRP3 inflammasome in the progression of AD.It is hoped that it may provide useful reference for deeply understanding the pathogenesis of AD and exploring new treatment methods as well as bring new breakthroughs for the therapy of AD.

Objective: To explore the relationship between apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and executive function in people with early cognitive impairment (EMCI), late mild cognitive impairment (LMCI), and early Alzheimer's disease (AD) patients, and to establish a group of Normal Control (NC) as a control group, in order to provide help for clinical intervention in the AD patients. Methods: A total of 142 people aged 50-80 years were recruited from Chengdu Fourth People's Hospital, including 35 cases of EMCI, 17 cases of LMCI, 26 cases of AD and 64 cases of NC. Each patient collected the following scales for executive function assessments using The Shape Trail Test part A (STT-A), The Shape Trail Test part B (STT-B), The Animal Fluency Test (AFT), The Symbol Digit Modalities Test (SDMT), Digit Span Test (DST) at baseline. The laboratory collected morning fasting blood to detect ApoA1 and ApoB levels. Spearman correlation test was used to analyze the correlation between ApoA1, ApoB and executive function, and linear regression analysis of the influencing factors of ApoA1 and ApoB on executive function. Results: The years of education in AD group were significantly lower than that in the NC group (P<0.05); In the NC group，the time spent on STT-A and STT-B were significantly lower than that in the EMCI group, LMCI group and AD group(P<0.05); in the EMCI group, the time spent on STT-A was significantly lower than that in the AD group(P<0.05), and the AFT and SDMT scores were significantly lower than those in the NC group(P<0.05) ; in the AD group, the AFT score was significantly lower than that in the NC group and LMCI group(P<0.05) ; the SDMT and DST score was significantly lower than that in the NC group (P<0.05) ; the ApoA1 level in the AD group was significantly lower than that in the NC group and EMCI group(P<0.05) ; there was no statistically significant difference in the ApoB levels among the four groups. ApoA1 levels were positively correlated with AFT, SDMT, and DST (P<0.05), and negatively correlated with STT-A and STT-B (P<0.05) ; ApoB levels had no correlation with executive functions; after adjusting for confounding factors, the multiple linear regression results of ApoA1 and executive function showed that ApoA1 significantly positively affected SDMT (P<0.05). After diagnosis stratification, the results of linear regression between ApoA1 and SDMT showed that ApoA1 could significantly positively affect SDMT in the NC group, LMCI group, and AD group (P<0.05). Conclusion: The connection between ApoB and executive function has not been found;. ApoA1 is mainly significantly related to information processing speed in the NC group, LMCI group, and AD group, indicating that the combination of ApoA1 and information processing speed can become an important tool for exploring cognitive impairment..

Objective: To investigate the effect of Guide Care management model on self-management of Parkinson's disease patients.Methods: A total of 90 patients with Parkinson's disease who were hospitalized in the Department of Geriatric Neurology of our hospital from November 2021 to December 2022 were selected as the research objects. According to the random principle, they were divided into an experimental group and a control group, with 45 cases in each group. The control group was given routine nursing intervention, while the experimental group was given Guided Care management model intervention. The self-management ability, quality of life, disease progression, anxiety and depression of the two groups were evaluated. The intervention lasted for 6 weeks. Results: After intervention, the scores of three dimensions of self-management (daily behavior management, management cognition and disease management) in the experimental group were higher than those in the control group. The total scores of self-management and daily behavior management in the experimental group were higher than those in the control group (P< 0.001). The scores of UPDRS in both groups decreased before treatment, and the scores of motor examination, activities of daily living, mental behavior and emotion in the experimental group were significantly lower than those in the control group (P< 0.001). After intervention, the PDQ-39 scores of the two groups were significantly decreased, and the score of the experimental group was significantly lower than that of the control group (P< 0.05). After intervention, the SAS and SDS scores of the experimental group were significantly lower than those of the control group (P< 0.05). Conclusion: The Guide Care management model can improve the self-management ability of patients with Parkinson's disease and improve the clinical prognosis..

The meningeal lymphatic vessels (mLVs) play a crucial role in the complex circulation and exchange of soluble contents between the cerebrospinal fluid (CSF) and the interstitial fluid (ISF). It has been confirmed that mLVs can drain intracranial CSF and immune cells to extracranial deep cervical lymph nodes (dCLNs), thereby establishing a direct link between the central nervous system (CNS) and the peripheral immune system. Given the limited therapeutic options for Alzheimer's disease (AD), enhancing brain lymphatic flow to improve the clearance of toxic waste has emerged as a new approach to alleviating cognitive impairment. This article briefly introduces the discovery process, structure, and location of mLVs, and thoroughly discusses their physiological functions. It focuses on the relationship between mLVs and the pathogenesis of AD, aiming to provide reference for emerging therapeutic mechanisms of AD.

There have been many different opinions on the pathogenesis of Alzheimer's disease (AD), and the β-amyloid protein (Aβ) theory has always been dominant. However, many treatments targeting on Aβ have had little effect, which has led researchers to re-examine this theory. More and more research findings have made people realize that although the accumulation of Aβ plaques in the brain is closely related to cognitive decline, it may only be a manifestation of AD, not the root cause of this disease. The body's inability to clear the accumulation of proteins including Aβ due to various reasons such as chronic inflammation with brain damage may be a deeper cause of this disease. These important cell functions include endocytosis, macropinocytosis, innate phagocytosis and autophagy, and mitochondria that provide energy to these high-energy consumption applications may be the determining factor affecting these functions. Therefore, simply removing Aβ plaques may have little effect in the treatment of Alzheimer's disease. More efforts should be placed on how to improve essential cell functions like innate phagocytosis and autophagy, as well as to improve mitochondrial function to increase energy production.

Objective: We aimed to explore the association of liver fibrosis markers with cognitive decline. Methods: In this cross-sectional study, there were 8669 participants over 60 years old from 51 Community Health Centers in the Luohu District of Shenzhen from 2017 to 2018. All participants were divided into a cognitive low-risk group (n=8202) and a cognitive high-risk group (n=467) according to their scores of mini-mental state examination and education status. Blood routine examination and liver function markers were tested from fasting blood samples. The liver fibrosis markers FIB-4 and APRI were calculated with parameters such as ALT, AST, and PLT using specific formulas. We used the t-test, Mann-Whitney test, and Chi-square test to analyze the differences in general statistical characteristics and live fibrosis markers between the two groups, and binary Logistic regression analysis was used to analyze each parameter. The association between the liver fibrosis markers and alcohol drinking habits was tested by Spearman rank correlation. Results: FIB-4 was significantly higher in the cognitive high-risk group than the cognitive low-risk group [1.40 (1.13,1.78) vs. 1.49 (1.21,1.88), Z=3.595, P<0.001] but FIB-4 was not an independent risk factor of cognitive decline [OR (95%CI): 0.718 (0.444~1.159), P=0.175]. For alcohol drinkers, FIB-4 was significantly positively correlated with the age of starting drinking (r_s=0.089, P=0.005) and frequency of drinking (r_s=0.149, P<0.001). There was a positive correlation between APRI and frequency of drinking (r_s=0.078, P=0.013) as well. For people abstaining from alcohol, FIB-4 exhibited a positive correlation with the age of abstinence (r_s=0.172, P=0.014). Conclusion: FIB-4 was elevated in people with cognitive decline, and increased frequency of drinking was correlated with raised FIB-4 and APRI, and giving up drinking as soon as possible might be beneficial to prevent the cognitive decline by liver health.

Alzheimer's disease has become a great concern in the current aging society. In order to better treat this disease, it is crucial to study and understand its pathogenic mechanisms. Equally important is how to detect Alzheimer's disease early and more accurately. Here, we summarized the pathogenic mechanisms of Alzheimer's disease and compared its different detection methods.

Objective: To explore the effect of APOEɛ4 gene carrier status on amyloid deposition in the brain of Alzheimer's disease patients in Chinese population. Methods：A retrospective collection was conducted on 932 cognitively normal individuals and patients diagnosed with mild cognitive impairment or Alzheimer's disease who visited the Memory Clinic of Huashan Hospital affiliated with Fudan University from August 2018 to March 2023. Among them, there were 532 cognitive normal individuals and 400 cognitive impaired individuals, including 211 mild cognitive impairment and 189 Alzheimer's disease patients. All participants were subjected to cognitive assessment, genotype determination, and [18F] Florbetapir PET imaging quantitative analysis of A β deposition in the brain, which is converted into centiloid value. The centiloid value of each group were compared based on cognitive status, APOEɛ4 gene carrying status, gender, and other factors. Performing partial correlation analysis on the centiloid value and cognitive scores of APOEɛ4 gene carrying or non carrying group. Results: The centiloid value of the APOEɛ4 gene carrying group is higher than that of the non carrying group, and the difference is significant (26.7 ± 38.3 vs 3.7 ± 26.6, P<0.001）. In the population with cognitive impaired, the centiloid value of both male and female APOEɛ4 gene carriers were higher than those of non carriers of the same gender (36.2 ± 40.3 vs 9.7 ± 30.7, 39.2 ± 37.5 vs 17.7 ± 38.8, respectively), P<0.001）. However, there is no significant difference in centiloid value between males and females in carriers or non carriers with cognitive impaired (36.2 ± 40.3 vs 39.2 ± 37.5, 9.7 ± 30.7 vs 17.7 ± 38.8, P>0.05）. The difference in centiloid value between the cognitive normal group and the cognitive impaired group is statistically significant (0.2 ± 21.0 vs 23.5 ± 38.6, P<0.001）. In subjects with cognitive impaired or cognitive normal, there is a significant difference in centiloid value between APOEε4 carriers and non carriers (P<0.001).The difference in centiloid value between cognitive impaired and cognitive normal populations is also significant (P<0.001) in APOEε4 gene carriers or non carriers. Under the control of age, education year, and gender, there is a moderate negative correlation between the centiloid value and cognitive scores in both the APOEɛ4 gene carrying and non carrying groups (r=-0.435 and -0.449, respectively,P<0.001）. Conclusion: The deposition of amyloid protein in the brain of APOEɛ4 gene carriers is significantly higher than that of non carriers, and there is a negative correlation between amyloid protein deposition and cognition in APOEɛ4 gene carriers and non carriers.

Objective: To analyze the associations between blood brain barrier permeability and plasma orexin-A in Dementia with Lewy bodies (DLB). Methods: A total of 69 patients with probably DLB who were hospitalized in the cognitive impairment department, and 40 healthy controls in the health management center of Beijing Tiantan Hospital from January 2021 to December 2022 were retrospectively included. Demographic and clinical information and neuropsychological assessments were collected from medical records. Cerebrospinal fluid (CSF) levels of Aβ_1-40, Aβ_1-42, t-Tau and p-Tau181 and APOE genotypes were recorded. CSF/serum albumin quotient (Q-alb) was calculated to reflect the blood-brain barrier permeability, and plasma orexin-A levels were determined. Pearson and Partial correlation analysis were used to evaluate the associations between plasma orexin-A and Qalb. Results: The scores of MMSE (P < 0.001) and MoCA (P < 0.001) in DLB group were lower than those in control group, and CDR (P < 0.001), ADL (P < 0.001), NPI (P < 0.001), and the levels of plasma orexin-A (P =0.015) and Qalb (P < 0.001) were significantly higher than those of control group.In the control group, the plasma orexin-A level was significantly different in different body mass index (BMI, P =0.034) and whether there was a history of hypertension (P=0.049). Qalb level was different from BMI level (P=0.012). In DLB group, the plasma orexin-A level of subjects with stroke history was significantly lower than those without (P=0.025). Qalb levels were significantly higher in women than in men (P=0.034). In the control group, Pearson correlation and Partial correlation analysis showed a positive correlation between plasma orexin-A level and Qalb (Pearson correlation: r=0.589, P < 0.001; Partial correlation: r=0.561, P < 0.001). In DLB, Pearson correlation and Partial correlation analysis did not find significant correlation between plasma orexin-A level and Qalb and neuropsychological assessment scores (P > 0.05). Conclusion: The plasma orexin-A and Qalb levels in patients with DLB were higher than controls. The elevated plasma orexin-A level in cognitively normal elderly people is associated to the increase of blood-brain barrier permeability, suggesting that the dysfunction of orexin-A system may be a potential mechanism of blood-brain barrier disorders..

Objective: Investigate the diagnostic value of cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) in AD and the predictive value of AD transition from mild cognitive impairment (MCI) to dementia through a cross-sectional and longitudinal observational study. Methods: 787 subjects with CSF GAP-43 data were divided into normal group (n=247), MCI group (n=413) and dementia group (n=127) based on cognitive status. Kruskal-Wallis test was used to compare the differences of CSF GAP-43 between groups. Multiple logistic model was used to test the correlation between CSF GAP-43 and different cognitive states. The diagnostic efficacy of CSF GAP-43 level for AD was evaluated by receiver-operating curves (ROC) and the area under curves (AUC). The diagnostic efficacy of AD was compared with that of CSF core markers (Aβ, t-tau, p-tau). Patients with MCI were divided into stable MCI (sMCI) and progressive MCI (pMCI) according to whether they progressed to dementia within 5 years. Mann-Whitney u test was used to compare CSF GAP-43 between groups. Cox regression model was used to test the correlation between CSF GAP-43 and the progression of MCI to dementia. The predictive value of CSF GAP-43 levels in predicting MCI progression to dementia was evaluated by ROC curve. The association of CSF GAP-43 level with the risk of progression to dementia was evaluated using Kaplan-Meier survival curves. Results: The results of cross-sectional study showed that the level of CSF GAP-43 was significantly higher in the dementia group than in the normal group and the MCI group (P<0.0001). CSF GAP-43 was an independent risk factor for the onset of AD dementia (P=0.002). The AUC of CSF GAP-43, Aβ, p-tau and t-tau for the diagnosis of AD were 0.64, 0.68, 0.64 and 0.63. Follow-up analysis showed that the level of CSF GAP-43 in pMCI patients was significantly higher than that in sMCI patients (P<0.0001), and CSF GAP-43 was an independent risk factor for the progression of MCI to dementia (P=0.012). The AUC for CSF GAP-43 predicting MCI progression to dementia was 0.75 (P<0.0001, 95%CI: 0.69~0.80). The risk of progression to dementia was 3.45 times greater in MCI patients with high CSF GAP-43 levels than in MCI patients with low CSF GAP-43 levels (P<0.0001, 95%CI: 2.17~5.43).Conclusion: CSF GAP-43 level can be used in the diagnosis of AD dementia, and its diagnostic efficacy is comparable to that of CSF core biomarkers (Aβ, t-tau, p-tau). CSF GAP-43 can predict the progression of MCI to dementia and is an independent risk factor for the progression of MCI to dementia.

Objective: To investigate the characteristic of sporadic Creutzfeldt-Jakob disease(sCJD), improve the knowledge of sCJD for clinicians. Methods: We collected the clinical data, brain neuroimages and laboratory test results of a case of sCJD and reviewed relative articles. Results: The patient showed limb rigidity, involuntary movements, myoclonic jerks, speech disorders, rapidly progressive cognitive impairment, and later autonomic dysfunction, and passed away 8 months after the onset. Conclusion: The early symptoms of sCJD are atypical, varied and heterogeneous, with a high fatality rate. The diagnosis of CJD requires attention to distinguishing it from various diseases, and dynamic examination of cerebrospinal fluid, brain MRI, electroencephalogram, and even biopsy to avoid misdiagnosis and missed diagnosis.

Alzheimer's disease (AD) and osteoporosis (OP) are both age-related degenerative diseases,which mainly occur in the elderly population over the age of 60, and are becoming an increasingly common combination in the aging population. It has been proved that a variety of factors can stimulate and accelerate the occurrence of AD and OP in clinical practice. This review mainly studies the common pathogenesis of AD and OP, and discusses the pathogenesis factors such as vitamin D and vitamin K levels, signaling pathways, apolipoprotein and neuroinflammation in AD mouse models. In addition,potential treatments for these two diseases are described.

Objective: To investigate the associations of five obesity indicators, body mass index (BMI), body round index (BRI), visceral adiposity index (VAI), lipid accumulation product (LAP), and a body shape index (ABSI), with the risk of mild cognitive impairment (MCI) in middle-aged and older adults. Methods: This cross-sectional study recruited participants from Wuhan and Shiyan cities in Hubei province during 2019 and 2022. After excluding individuals with self-reported dementia or Parkinson's disease and missing general characteristics, a total of 6,917 participants were included in this study. Multiple linear regression and logistic regression models were used to evaluate the associations of body mass index and novel obesity indicators with the cognitive function. Restricted cubic spline model was used to explore the nonlinear relationships between obesity indicators and MCI. Results: Among the 6917 participants in this study, 3338 (48.3%) were males and 3579 (51.7%) were females. A total of 670 (9.7%) participants were identified as MCI. Increased BRI and ABSI were associated with decreased MMSE score and raised MCI risk (P trend < 0.001). After adjusting for confounding, compared to the Q1 subgroup, individuals in the BRI, ABSI and LAP Q4 subgroup respectively showed increased MCI risk [OR (95% CI)=1.58 (1.23,2.03), 2.54 (1.68, 3.86), 1.38 (1.08, 1.76)]. RCS confirmed the linear dose-response relationships of BRI and ABSI with MCI risk (both P for non-linear associations were > 0.05). However, BMI and VAI were not found to be correlated with MCI risk. Conclusion: High BRI, ABSI and LAP may be risk factors for cognitive decline, and BRI and ABSI may present a potential dose-response relationship with MCI risk.

Objective: Holmes tremor (HT) is a rare movement disorder. HT may also be associated with other neurological symptoms, including cognitive dysfunction. This study aims to investigate the pathophysiological mechanisms, diagnostic approaches, and therapeutic strategies for HT, thereby providing guidance for clinical management. Methods: The diagnosis of HT primarily relies on clinical features and neuroimaging techniques, such as MRI. Treatment options include pharmacological interventions (e.g., levodopa, trihexyphenidyl) and surgical approaches (e.g., deep brain stimulation, thalamotomy). A systematic review of the literature was conducted to summarize the clinical features, pathophysiological mechanisms, and treatment outcomes of HT. Results: HT symptoms typically emerge between 4 weeks and 2 years after neurological injury, associated with abnormal synaptic reorganization and collateral axonal sprouting following neuronal damage. The efficacy of pharmacological treatments varies among individuals, with levodopa showing effectiveness in approximately 54% of patients, though overall efficacy remains limited. Other medications, such as antiepileptic drugs and dopamine agonists, are also commonly used, but their effectiveness can be highly variable, with some patients showing poor response to these drugs. Surgical interventions, including deep brain stimulation, thalamotomy, lesionectomy of the original pathological focus, and ablation of specific nuclei, have demonstrated some efficacy but exhibit individual variability. There is currently no unified treatment consensus, and large-scale multicenter studies validating the long-term outcomes of novel therapies are lacking. Conclusion: The treatment of HT remains challenging, and its pathophysiological mechanisms are not yet fully understood. Future research should further investigate the pathophysiological mechanisms of HT, particularly its relationship with cognitive dysfunction, and optimize treatment strategies. Conducting multicenter studies to validate the long-term efficacy of novel therapies holds promise for improving the quality of life and prognosis of HT patients.

Objective: The aim of the current study was to explore the specific intrinsic functional connectivity between the the retrosplenial cortex (RSC) and the hippocampal subfields in healthy adults and to characterize the alterations in functional connectivity between the RSC and the hippocampal subfields in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) patients. Methods: Demographic data, neuropsychological assessments, and resting-state functional magnetic resonance imaging (fMRI) data were collected from 60 AD participants, 60 participants with aMCI, and 60 sex-matched normal controls (NCs). The bilateral RSC, other parts of the posterior cingulate cortex (PCC), and hippocampus (HPC) subfields (including the bilateral cornu ammonis fields (CA1-CA3), the dentate gyrus (DG), and subiculum (SUB)) were selected to investigate functional connectivity alterations in aMCI and AD. Results: Resting-state functional connectivity analysis demonstrated heterogeneity in the degree of connectivity between the HPC and different parts of the total PCC, with considerably greater functional connectivity of the RSC with the HPC compared with other parts of the PCC. Furthermore, the bilateral RSC exhibited widespread intrinsic functional connectivity with all HPC subfields. Compared to the NCs, the aMCI and AD groups showed different magnitudes of decreased functional connectivity between the RSC and the contralateral DG. Additionally, diminished functional connectivity between the left RSC and right DG was correlated with clinical disease severity in aMCI subjects. Conclusion: These findings confirm and extend previous studies suggesting that the RSC is extensively and functionally connected with HPC subfields and that these functional connections are selectively affected in the AD continuum, with prominent disruptions in functional connectivity between the RSC and contralateral DG underpinning episodic memory impairment associated with the disease.

Vascular dementia (VaD) is a severe syndrome of cognitive impairment caused by ischemic stroke, hemorrhagic stroke, and cerebrovascular lesions that cause hypoperfusion of memory, cognitive, and behavioral brain regions. Among the types of dementia, VaD is the second most common cause after Alzheimer's disease, but the pathogenesis of VaD is still unclear. Astrocytes are the most abundant glial cells in the central nervous system.Astrocytes have the ability to produce and release specific neurotransmitters, and express corresponding neurotransmitter receptors,which can respond to a variety of neuroactive substances.In recent years, a large number of studies have been carried out on the role of astrocytes in the central nervous system (CNS), and this article reviews the current role and mechanism of astrocytes in the progression of VaD based on the research background and research significance.We hope to provide a useful reference for understanding the pathogenesis of VaD and exploring new treatment methods and bring new breakthroughs in the treatment of clinical VaD.

Alzheimer's disease (AD) is a complex neurodegenerative disorder caused by multiple factors, characterized primarily by the deposition of amyloid β-protein (Aβ) plaques and the formation of phosphorylated Tau protein neurofibrillary tangles in the brain, which together lead to memory loss and cognitive impairment. In recent years, microRNAs(miRNAs), as an essential class of non-coding RNA molecules, have demonstrated a pivotal role in the pathogenesis of AD. miRNAs tightly regulate the generation and clearance of Aβ by targeting key genes such as APP and BACE1. Meanwhile, specific miRNAs can significantly influence the phosphorylation state of Tau protein, exerting a profound impact on neuronal stability and survival. However, despite the enormous potential of miRNAs in AD research, numerous challenges remain. For instance, the differences in miRNA expression patterns between AD patients and healthy controls, as well as their biological significance and translational relevance, require further validation. Additionally, there is currently a lack of unified and accurate criteria for assessing the reliability of miRNAs as biomarkers, and miRNA-based therapies have not yet been approved for clinical use. Therefore, future research needs to further delve into the specific mechanisms of miRNAs in AD, systematically evaluate their potential as therapeutic targets, and actively overcome existing technical and methodological challenges, in order to provide new theoretical foundations and practical strategies for the diagnosis and treatment of AD.

Objective: To comprehensively evaluate the effectiveness of driving ability as a predictor for Alzheimer's disease (AD), explore relevant data collection and analysis methods, and identify valid early warning indicators. Methods: Computerized searches were conducted in databases including CNKI, CBM, Wanfang, VIP, PubMed, and Web of Science to identify studies using driving ability for AD prediction. Literature meeting inclusion criteria was screened, and data quality was assessed. Relevant information was extracted, and heterogeneous data were integrated. Principal component analysis (PCA) was used to evaluate the importance of indicators in the driving-based warning system. Meta-analysis was performed to assess the effect of AD on driving ability. Subgroup analysis was conducted to reduce intergroup heterogeneity, with stratification based on age, gender, and Mini-Mental State Examination (MMSE) scores to examine differences in effects across groups. A multifactorial interaction subgroup analysis was further proposed to minimize intergroup heterogeneity, analyzing the combined influence of age, gender, and MMSE scores on statistical outcomes. Results: After screening, 12 studies were included. PCA results identified the three most significant indicators: spatial control (9.13%), emotional adaptation (8.78%), and navigation execution (8.36%). Meta-analysis and subgroup analysis revealed that older female patients with low MMSE scores exhibited the most severe driving-related cognitive impairment (SMD = -0.75, P < 0.001). Additionally, among male AD patients, the high-score MMSE group showed a greater absolute effect size (ΔSMD = -0.22, P < 0.001). Multifactorial interaction subgroup analysis explained 78% of the heterogeneity (Q = 12.37, P = 0.006). Conclusion: This study provides preliminary evidence that abnormal driving behavior can serve as a novel biomarker for early AD detection, with spatial orientation, emotional stability, and navigation ability identified as core indicators. However, the warning system must account for population differences (higher sensitivity in older females) and individual baseline variations (longitudinal self-referencing).

Recent studies have shown that Kallikrein-related peptidases (KLKs) play crucial roles in the pathological progression of Alzheimer's disease (AD). This review systematically summarizes the latest research advances in AD-related KLKs (KLK1, KLK6, KLK7, KLK8, and KLK10). Studies have revealed that KLK6 affects amyloid-β (Aβ) generation by inhibiting α-secretase and enhancing γ-secretase activity; KLK7, as an Aβ-degrading enzyme secreted by astrocytes, shows accelerated Aβ deposition in AD model mice when deficient; KLK8 influences the PI3K/Akt/GSK-3β signaling pathway, leading to decreased Akt phosphorylation and increased GSK-3β expression, thereby promoting Tau protein hyperphosphorylation, with significantly higher expression levels observed in female AD patients compared to males. Furthermore, KLKs impair blood-brain barrier function through mechanisms including extracellular matrix protein cleavage and reduction of endothelial cell inflammation. Meanwhile, KLK6 and KLK8 exhibit significantly elevated expression levels in the cerebrospinal fluid and blood of AD patients, suggesting their potential value as biomarkers. A deeper understanding of KLKs' mechanisms in AD will provide new insights into the early diagnosis and treatment of the disease.

Objective: To examine the clinical manifestations, imaging features, potential pathological mechanisms, differential diagnosis, and clinical significance of atypical Alzheimer's disease (AD), with the objective of enhancing comprehension of atypical AD and elevating the standard of clinical diagnosis. Methods: The clinical manifestations, laboratory findings and imaging features, and differential diagnosis of three patients with atypical AD were reviewed, and their pathological mechanisms were analyzed accordingly. Results: There was a decrease in Aβ and an increase in Tau in all three patients' cerebrospinal fluid (CSF) tests. The patient with frontal variant of AD (FvAD) started with memory loss and mental behavior abnormalities, and the brain Magnetic Resonance Imaging (MRI) showed symmetrical atrophy of bilateral frontal lobe, temporal lobe, parietal cortex and hippocampus. The patient with logopenic variant primary progressive aphasia (LvPPA) has the onset of speech clumsiness. Brain MRI shows that the left lateral fissure is wider than the right, and bilateral hippocampal atrophy is relatively mild. The patient with posterior cortical atrophy (PCA) presented with memory loss and visuospatial impairment. Brain MRI showed bilateral partooccipital lobe atrophy, widening of the right lateral fissure, and relatively mild bilateral hippocampal atrophy. Conclusions: Atypical AD are starting with speech impairment, mental behavior abnormalities, and visuospatial disorders. Because the dysmnesia symptoms of atypical AD are not typical, it is not easy to identify them early, and it is easy to be confused with frontotemporal dementia, cortical basal ganglia degeneration and Lewy body dementia. The clinical diagnosis requires a comprehensive consideration of detailed medical history and neurological examination, combined with neuropsychiatric scales, imaging, and biomarkers.

Objective: To evaluate clinical phenotypes and nocturnal sleep structure characteristics with mild cognitive impairment due to Alzheimer's disease (AD). Methods: Based on cerebrospinal fluid or positron emission tomography imaging to detect the concentration or deposition status of β-amyloid protein (Aβ) to distinguish between MCI due to AD and control group. All patients underwent polysomnography monitoring (PSG), APOE gene testing, Montreal Cognitive Assessment (MoCA), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD) assessments. Results: ① Significant differences were found in clinical characteristics such as sleep disturbance, body mass index (BMI), education years, occupations, combined with risk factors, and APOEε4 gene mutation (P<0.05); ② There were statistically significant differences in MoCA and HAMA scores between these two groups (P<0.05); ③Significant differences in N1/total sleep time (TST)%, N2/TST%, N3/TST% and rapid eye movement sleep time (REM)/TST%, average blood oxygen concentration during night-sleep time, sleep-related apnea-hypopnea index (AHI), obstructive sleep apnea (OSA) index between these two groups (P<0.05); ④Clinical phenotypes including sleep disorders, APOEε4 mutation, multiple risk factors, cognitively demanding occupations and sleep microstructural parameters were significantly correlated with MCI due to AD (P<0.05); ⑤Gender, sleep disturbance, APOEε4 gene mutation, BMI and polysomnographic indices (N1/TST%, N2/TST%, REM/TST% and OSA index) were key factors in MCI due to AD (P<0.05); ⑥N1/TST%, N2/TST%, REM/TST% and OSA index demonstrated significant linear correlations with MoCA scores (P<0.01). Conclusion: Patients with MCI due to AD exhibited distinct clinical features, including a higher prevalence of sleep disorders, elevated APOEε4 allele carrier rates, lower prevalence of multiple risk factors, a higher proportion of cognitively demanding occupations and lower BMI. Sleep parameters, including N1/TST%, N2/TST%, REM/TST% and OSA index, demonstrated significant correlations with cognitive impairment. Characteristic changes in the proportion of N1, N2 and REM sleep among MCI patients may serve as potential biomarkers for early identification of MCI due to AD.

Objective: To conduct a meta-analysis on the incidence of frailty in patients with Alzheimer's Disease (AD), in order to provide a scientific basis for the prevention of frailty in AD patients. Methods: By systematically searching CNKI, Wanfang, VIP Chinese databases, PubMed, Web of Science, Embase and Cochrane Library English databases, the epidemiological evidence of the incidence of frailness in AD patients was comprehensively obtained. The literature search period was set from the establishment of the database to March 10, 2025, and literature screening, data extraction and bias risk assessment were carried out by two researchers respectively. Statistical software Stata14.0 was used to conduct a meta-analysis of the included studies. Results: Thirteen studies were included, covering 2806 patients with Alzheimer's disease, and the analysis suggested an overall incidence of frailty of 34% (95%CI: 27%~41%). Study area, measurement tool, study time, sample size and other factors have an impact on the incidence of frailty in patients with Alzheimer's disease. Conclusion: The incidence of frailties in patients with Alzheimer's disease is high. Attention should be paid to frailties in patients with Alzheimer's disease, and early detection and intervention measures should be taken to reduce the occurrence of frailties in this population.

Accurate early diagnosis of Alzheimer’s disease (AD) represents a major challenge against the backdrop of global aging. This paper reviews research advances combining generative Artificial Intelligence (AI) with multimodal neuroimaging (including MRI and PET) to achieve early and accurate diagnosis of AD. This review systematically analyzes the applications of generative models in AD diagnosis across key areas: brain image data augmentation, pathological feature representation learning, and brain network modeling. We provide a detailed analysis of how these technologies effectively overcome critical challenges such as neuroimaging data scarcity and class imbalance. These technologies enhance the models’ classification performance on AD datasets and its ability to predict the progression of AD. Specifically, in the analysis of functional and structural brain networks, generative AI offers a new paradigm for understanding AD pathological mechanisms and enabling early prediction by constructing high-fidelity networks. Furthermore, this paper discusses the clinical translation prospects of these technologies in personalized prognosis and treatment monitoring, as well as the technical and ethical challenges in implementation. This review provides a comprehensive framework to understand the potential and development trends of generative AI, multimodal neuroimaging, and their derived functional brain network features in the auxiliary diagnosis of early AD.

Objective: To evaluate the effectiveness of caregiver group support skills training on coaches' attitudes towards dementia care and their sense of competence. Methods: A total of 56 participants in the dementia caregiver group support skills training (referred to as "coaches"; 10 male and 46 female) completed assessments of their dementia care attitudes and sense of competence before and after the training. Paired t-tests were used to compare the differences in scores for dementia care attitudes and sense of competence before and after the training. Multivariate analysis was conducted to explore the demographic factors associated with the changes in dementia care attitudes and sense of competence. Results: After the training, coaches showed a significant increase in scores for the "hope" and "personhood validation" factors of the dementia care attitude scale, as well as the total scale score (P < 0.05). Additionally, scores for the "professionalism," "relationship building," "managing caregiving challenges," and "maintaining personhood" factors of the dementia care competence scale, as well as the total scale score, significantly increased after the training (P < 0.05). Multivariate analysis indicated that only the occupation was associated with changes in the total score and "relationship building" factor of dementia care competence before and after the training; no other sociodemographic characteristics were associated with the changes in dementia care attitudes and other factors of competence scale. Conclusion: Caregiver group support skills training can improve coaches’ attitudes towards dementia care and enhance their sense of competence in caregiving.

Objective: To obtain the clinical basis for non-drug intervention in mild cognitive impairment (MCI) by exploring the efficacy of auricular acupuncture combined working memory (WM) training in patients with MCI. Methods: A total of 40 MCI patients who were hospitalized in the Department of Geriatrics at Hangzhou Wuyunshan Hospital from January to December 2023 were included and randomly divided into an observation group of 20 patients who received 3-week WM training and a control group of 20 patients who did not receive training by drawing lots. The Montreal Cognitive Assessment (MoCA) was used to evaluate the patients' cognitive function. Results: Before training, there was no significant difference in cognitive function between the two groups(P>0.05). In the observation group, the visual-spatial and executive ability and MoCA total scores of patients followed up for 6 months after training were higher than those before training, and the difference was statistically significant (P<0.05). After training, followed up for 6 months, the visual-spatial and executive function and MoCA total scores of patients in the observation group were higher than those in the control group, and the difference was statistically significant (P<0.05). Conclusion: Auricular acupoint stimulation combined with WM training can improve some cognitive functions in MCI population.

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder. Air pollution, characterized by its complex composition, diverse pollutant types, and significant spatiotemporal variability, poses both localized and long-range threats due to atmospheric transport. Certain pollutants exhibit persistence and bioaccumulative properties, exerting profound impacts on human health and social equity. These effects are further modulated by natural geographical and meteorological conditions, rendering them uniquely complex. An increasing body of evidence identifies air pollution as a significant environmental risk factor for AD. In response to growing interest, this paper provides a comprehensive review of the epidemiological evidence, pathophysiological mechanisms, and emerging methodological approaches related to air pollution's role in AD. Furthermore, it explores how compounded social determinants interact with environmental exposure to influence AD risk.