• ISSN 2096-5516 CN 10-1536/R
  • Sponsored: China Association for Alzheimer’s Disease

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  • Lu LIN, Xin MA, Gang WANG, Hongzheng WANG, Zhiqun WANG, Zhiwen WANG, Xiaoming WANG, Huifang WANG, Feiqi ZHU, Liyan QIAO, Zhaorui LIU, Zhigang QI, Bin TANG, Kuncheng LI, Zhaohui LI, Shifu XIAO, Jintai YU, Xianbo ZHOU, Hexin ZHAO, Mangsuo ZHAO, Hongbin ZHAO, Yun GU, Hong GUO, Ling GUO, Qihao GUO, Liping FU, Min LEI, Weigang PAN, Yong XU, Jun WANG, China association for Alzheimer's disease
    PDF (1531) HTML (7266)

    Alzheimer's disease (AD) is a severe neurodegenerative disorder with complex etiology, currently lacking effective treatment options. China is among the countries with the largest and fastest-growing elderly population globally, also identified as a high-risk nation for AD. Consequently, early prevention of AD emerges as one of the most crucial endeavors in the fieldof healthcare today. Building upon domestic and international research, we have formulated a Chinese-specific AD early prevention guideline, integrating evidence-based literature, intervention studies, case analyses, experiential insights, and expert consultations, and showcasing the advantages of traditional Chinese medicine, martial arts, health preservation practices, and community organization. This guideline addresses distinctive features of preventive measures and encompasses strategies at the individual, family, and society levels, advocating for proactive lifestyles, social engagement, cognitive training, physical exercise, tobacco cessation and moderate alcohol consumption, nutritional balance, adequate sleep, management of blood pressure, glucose and lipid levels, weight, and other chronic conditions, along with incorporating traditional Chinese medicine (TCM) into primary prevention efforts against AD. This guideline serves as a reference for individuals, families and communities engaged in AD prevention initiatives.

  • Yuhui LIU, Xianle BU, Xin MA, Gang WANG, Hongzheng WANG, Guihong WANG, Feiqi ZHU, Liyan QIAO, Zhaorui LIU, Yong JI, Xiaofeng LI, Yanfeng LI, Xia LI, Weizhong XIAO, Shifu XIAO, Qingjian WU, Wei ZHANG, Jintai YU, Yuying ZHOU, Qinghua HOU, Junliang YUAN, Jianjun JIA, Yun GU, Ling GUO, Qihao GUO, Dantao PENG, Zhong PEI, Weigang PAN, Yanjiang WANG, Jun WANG, China Association for Alzheimer's Disease
    PDF (619) HTML (3968)

    Based on current literature and expert panel discussions, the recommendations for drug treatment of Alzheimer's disease (AD) have been updated in accordance with previous guidelines on the diagnosis and treatment of dementia and cognitive impairment. The update emphasizes the advancements in anti-Aβ immunotherapy, with the aim of providing a reference for early and comprehensive intervention for AD. The content covers the following key aspects: the principles of AD treatment; symptomatic medications, including cholinesterase inhibitors and NMDA receptor antagonists; management of behavioral and psychological symptoms; disease-modifying therapies such as Aducanumab, Lecanemab, and Donanemab; the use of Sodium Oligomannate; and the use of traditional Chinese medicine.

  • Qun XU, J. Wesson Ashford, PIU CHAN, Shubin CHEN, Jeffrey Cummings, J. Gu Ben, Qihao GUO, Ying HAN, Yingxue HUA, Hua JIN, Nagaendran Kandiah, Haiyan LI, Xiaolei LIU, Xin LIU, Peilin LU, Zhong PEI, Xiaogeng SHI, Kai SUN, Bin TANG, Goerge Vradenburg, Huifang WAGN, Jun WANG, Xiaoming WANG, Yanrui WANG, Yanmei WANG, Yulin WANG, Wenfeng WENG, Meizhe XIN, Yulan ZHANG, Hexin ZHAO, Xianbo ZHOU, Hongzheng WANG
    PDF (458) HTML (2015)

    Dementia/cognitive impairment in elderly persons is often caused by more than one common age-related brain diseases. Alzheimer’s disease (AD) is the most common neurodegenerative disease that leads to or contributes to dementia/cognitive impairment. It is the only one of the 10 top deadliest diseases globally that has no curative nor long lasting effective symptom treatments. AD places tremendous burdens on individuals, their families, and the economies of essentially all societies. Early and timely detection and intervention has been increasingly considered to be the best strategy to combat AD. Over the last 3 decades, numerous studies have suggested approaches to reducing the risk of dementia, and up to 40% of dementia cases could be prevented or delayed by addressing risk factors, which are outlined in the 2020 Lancet report on dementia prevention. However, the current global healthcare system is not equipped sufficiently to detect AD early or in a timely fashion. For example, a recent study found that less than 10% of mild cognitive impairment (MCI) is diagnosed in primary care setting. Recently, with the full approval of the anti-Amyloid beta (Aβ) antibody drug lecanemab and donanemab for early AD and the publications of ~20-year follow-up studies establishing that modification of risk factors could markedly reduce AD-dementia incidence and increase life span, there is rapidly growing interest in early AD recognition. The Chinese Association of Alzheimer’s Disease (CAAD) recognizes the importance of early and timely detection of AD in an at-home setting and has assembled a global panel of association professionals, clinicians and researchers who are expert in different areas of AD to reach the consensus reported here with the following goals: 1) to provide individuals, family, community, associations and organizations with expert guidance, 2) on the digital tools and available resources for the screen of cognitive impairment/dementia at home and describe a work flow for the next steps for those at risk or suspected of AD, 3) discuss current available or future resources for AD biomarker as at-home screen, and 4) to establish a framework for future improvement and worldwide application if results warrantee such a direction. The experts reviewed the current available evidence, tools, resources and considered the significance of screening for AD at home and the consensus recommendations are reported here.

  • Xuhui CHEN, Mengzhen JIA, Jun HU, Jiao CHEN, Zhijian LIN, Chen ZHANG, Fang DU, Yongan SUN
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    The non-benzodiazepine sedative-hypnotic drug (Zolpidem) is used for the short-term treatment of insomnia. However, long-term high-dose use may lead to serious adverse reactions such as dizziness, headache, and falls, and may even result in cognitive decline and abnormal behavior.Furthermore, long-term use of Zolpidem may lead to drug tolerance, dependence, rebound phenomena, and withdrawal symptoms, making discontinuation difficult. Therefore, this review aims to provide a review of the mechanism of action, adverse reactions, tolerance, and special use of Zolpidem. To elucidate the mechanism of Zolpidem's adverse effect to cognitive function,in order to help chronic insomnia patients who use zolpidem long-term to avoid cognitive decline.

  • Yanxing ZHOU, Xiaohua XIAO, Chunhua LIANG, Xueqin YAN, Huoyou HU
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    This review aims to explore the molecular mechanism and pathophysiological characteristics of neuroinflammation in AD, and summarize the latest advances in drug treatment of neuroinflammation in including glial cell inhibitors (such as non-steroidal anti-inflammatory drugs, glucocorticoids, etc.), inflammatory mediator inhibitors (such as monoclonal antibodies, TNF-α inhibitors, etc.), anti-inflammatory siRNA therapy, anti-inflammatory Chinese medicine,etc. The clinical efficacy of the above drugs in the treatment of AD is compared, and their potential mechanisms of action and adverse effects are discussed, which provides a valuable reference for future research and clinical practice.

  • Xianbo ZHOU, Zhong PEI
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    Alzheimer’s disease is a huge societal issue and places a serious economic burden on the ever-aging society. Although tremendous progresses have been made in the early detection, diagnosis and treatment which bring new options and hope for patients and their families, transformative early detection, diagnosis and treatment are still being developed. Here we report the current state of AD early detection, diagnosis and drug development where promising progress are made and hopefully revolutionary therapies will be developed soon to solve this global issues with the help of timely detection, early diagnosis and precision neurology through targeting immunoneurology/multi-mechanisms and cocktail medicine.

  • Mengxun LUO, Zhihong LU, Yelin CHEN
    PDF (138) HTML (425)

    Alzheimer's Disease (AD) is a devastating neurodegenerative condition that warrants attention from all individuals, given its widespread prevalence and profound societal burden. As the population of elderly individuals continues to rise, the incidence of AD is steadily increasing. Conventional pharmacotherapeutic interventions offer only transient amelioration of certain AD symptoms, failing to halt the inexorable progression of the disease. Over the past two decades, extensive efforts have been made to develop anti-AD drugs with disease modifying potentials but all of which have been failed. Consequently, AD has long been perceived as an incurable affliction. However, lecanemab, a monoclonal antibody that targets aggregated amyloid-beta (Aβ), has demonstrated efficacy in slowing the progression of AD in a rigorously conducted randomized, double-blind, multi-center phase 3 clinical trial. This landmark advancement signifies AD as a modifiable condition, with aberrant Aβ aggregation serving as a pivotal etiological factor. This breakthrough holds epochal significance for both theoretical understanding and therapeutic modalities, heralding a transformative epoch in humanity's pursuit to conquer AD. In this review, we endeavor to summarize the cutting-edge advancements in AD research, with the aim of augmenting societal awareness and comprehension of this disease.

  • Qi MA, Peng FENG
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    Alzheimer's disease (AD) is currently a major disease that affects human life. Exploring the causes of Alzheimer's disease and seeking treatment methods are an important work for scholars in this field. Currently, a flicker stimulation therapy, which reduces β-amyloid protein through gamma oscillations to achieve the treatment of AD, has made preliminary progress, and is expected to become a new direction of AD treatment. This study introduces the scheme and principle of flicker frequency therapy for Alzheimer's disease, expounds the effect of 40Hz flicker stimulation on cerebral cortex activity, and analyzes the current limitations of this scheme, aiming to provide ideas and references for further clinical research.

  • Nanbu WANG, Xiaowei MA, Guohui WANG, Hongzheng WANG, Yan XING, Ning ZHU, Liyan QIAO, Jin QIAO, Taojie LIU, Zhi LIU, Xiandong SUN, Xiaoxia DU, Jianping LI, Chenzhong LI, Yu YANG, Zhiquan YANG, Xia HE, Youqiang SONG, Liying ZHANG, Zhiguo ZHANG, Ruiping HU, Shan XU, Qi TANG, Chuanhai CAO, Yao CUI, Shaoyang CUI, Xiaole HAN, Jikang FAN, Chi CAO, Luping SONG, Jun WANG, Profssional Branch of the China Association for Alzheimer’s Disease Cognitive Rehabilitation
    PDF (186) HTML (419)

    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.

  • Ruolin XU, Ranting HU, Wanying HUO, Wuhua XU
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    Human olfactory is inextricably linked to cognition and emotion. The dysfunction of the three is almost simultaneously appeared and accompanied by the whole disease process of Alzheimer 's disease (AD). However, the role of olfactory dysfunction in the pathological mechanism of AD and its impact on cognitive and emotional disorders have not been clearly elucidated. Based on the anatomy and physiological mechanism of olfaction, combined with the research progress of olfaction in the field of AD in recent years, this paper expounds the role of olfaction pathology in the pathological mechanism of AD, and discusses the application prospect of accurate identification technology of olfactory disorder and olfactory therapy in the prevention and treatment of AD.

  • Zhuangzhuang LI, Zhengtang LIU
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    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.

  • Xianglong HOU, Yelin CHEN
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    Different isoforms of Apolipoprotein E (ApoE) lead to different risks of Alzheimer's disease (AD). ApoE2 reduces the risk of AD, whereas ApoE4 is the main genetic risk factor for AD. The role of glia-secreted ApoE in the pathogenesis of AD has been extensively studied, whereas the contribution of neuronal ApoE remains largely unexplored. Recent studies have found that ApoE is also expressed in neurons, where it plays important roles in the pathogenesis of AD, including regulation of amyloid plaque seeding and growth, phosphorylation of Tau, and neurodegeneration, etc. Based on these studies, a gene therapeutic strategy using adeno-associated virus (AAV) to express ApoE2 in neurons is now in that phase II clinical trials for AD treatment. This article summarizes the knowledge about the emerging role of neuronal ApoE in AD pathogenesis.

  • Rui ZHANG, Zhongyue LYU, Zhiwei XU
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    Cerebral stroke, a severe cerebrovascular disease causing acute brain dysfunction, imposes a heavy burden on families and society due to its high incidence and disability rates. Patients often develop post-stroke cognitive impairment (PSCI) after stroke, which affects multiple cognitive dimensions including memory, executive function, attention, language, and visuospatial abilities. Traditional rehabilitation therapies, although somewhat effective in promoting cognitive recovery, generally suffer from slow onset, long treatment cycles, and patient compliance issues. In recent years, repetitive transcranial magnetic stimulation (rTMS), as an emerging neuromodulation technique, has shown positive effects on the cognitive function of PSCI patients by continuously applying high-intensity, transient magnetic pulses to the brain tissue, effectively modulating the excitatory state of the cerebral cortex. This review aims to summarize the mechanisms of action and clinical research progress of rTMS in the treatment of PSCI, providing a scientific basis for clinical treatment planning and inspiring future research directions.

  • Jun WANG, Shan HUANG, Yanjiang WANG
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    The early treatment of Alzheimer's disease (AD) has made a breakthrough, making it urgent for early and accurate diagnosis of AD. Blood biomarkers are ideal tools for early diagnosis and have promising application prospects. Great research progresses have been made in recent years, but a series of challenges still exist in the translational application of blood biomarkers. Here, we dissected these challenges and proposed strategies to facilitate AD blood biomarkers to clinical practice.

  • Erli FEI, Yun GU
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    Alzheimer's disease (AD) is a degenerative disease characterized by cognitive impairment, affecting over 50 million people worldwide. In recent years, the research progress of AD biomarkers and imaging diagnosis has brought new hope for the early detection and diagnosis of AD. The discovery of new pathways such as the brain-gut axis has led to the successful launch of new drugs such as GV-971, which has brought new options for the treatment of AD. But human understanding of AD is still the tip of the iceberg. Therefore, the anti-aging advantages of TCM are particularly important in the intervention of brain aging and AD. AD belongs to the category of "dementia" in traditional medicine, and traditional doctors have been fighting against it for more than 1,000 years, so TCM has a deep understanding of the treatment of "dementia", and many TCM theories coincide with modern medicine such as the brain-gut axis, which can provide more basis for the treatment of AD.

  • Lin ZHU, Feng YAN, Yuxiong CHU, Shifu XIAO
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    The prevalence of depression in the oldest-old population is higher. The symptoms are dominated by somatic manifestations and are easily overlooked and misdiagnosed, becoming a critical mental health situation. Routine assessment of mood status can help to develop adequate interventions for these old people, and appropriate psychotherapy and antidepressants are commonly recommended for old patients with depressive disorders. This review focuses on the developments of clinical research on old-elderly depression, hoping to provide a reference for clinical management.

  • Yashang WEI, Ben J. Gu
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    The continuous growth of Chinese economy and population, as well as the changes in social structure, have made China one of the countries with the fastest growing elderly population. The prevention and prognosis of geriatric diseases are facing great challenges. Alzheimer's disease (AD) is the most common age-related neurodegenerative disease. The pathological characteristics of AD are the long-term (more than 20 years) deposition of neurofibrillary tangles and amyloid plaques, which lead to the death or loss of function of neurons. At present, clinical diagnosis is mainly based on cognitive tests, imaging and cerebrospinal fluid (CSF) tests, which limits the application of these diagnostic methods in the early detection of AD. Although biomarkers such as the ratio of amyloid-β (Aβ40/42) in blood and proteins such as phosphorylated Tau-181 and Tau-217 have received widespread attention, their application is usually limited to the assessment of disease progression, because changes in Tau protein are generally considered to be secondary reactions to Aβ deposition and are not suitable for early detection. Urine contains a variety of biomolecules, and its composition can reflect the physiological and pathological changes of the body in real time, which makes urine an ideal choice for biomarker discovery and early screening of diseases. The value of urine as a non-invasive peripheral metabolite biological fluid in the early detection of AD is gradually being promoted and applied. This article mainly summarizes and prospects the research progress in developing urine biomarkers as a means of early detection of AD.

  • Chunhua LIANG, Xueqin YAN, Xiaohua XIAO, Tianfu WANG, Yaohui HUANG
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    Objective:

    White Matter Hyperintensities (WMH) is one of the common imaging features of the elderly, it shows high signals on brain MRI T2WI and FLAIR sequences, which is closely related to dementia, stroke and increased mortality. Therefore, this study mainly discusses the risk factors affecting WMH volume, and its correlation with cognitive function.

    Methods:

    A total of 184 cases of WMH patients admitted to our hospital from January 2020 to December 2022 were collected and divided into the mild WMH group and the severe WMH group according to Fazekas scale. The differences in demographic characteristics, blood lipids, and thyroid function levels between the two groups were compared. ITK-SNAP software was used to calculate WMH volume, and multi-factor regression analysis was conducted to analyze the risk factors affecting WMH volume. The difference of WMH volume between those groups with and without cognitive impairment was compared to evaluate the diagnostic ability of WMH volume for cognitive impairment.

    Results:

    There were 142 cases in mild WMH group, and 42 cases in severe WMH group. There was high consistency between the Fazekas score and WMH volume (r=0.829, P < 0.001). Patients in the severe WMH group were older, had higher prevalence of hypertension and diabetes, and had lower serum FT3 levels. WMH volume was larger in patients with hypertension and diabetes, and age was positively correlated with WMH volume (r=0.379, P < 0.001), while serum FT3 level was not significantly correlated with WMH volume. After adjusting for confounders, multiple linear analysis results suggested that age and hypertension were independently associated with WMH volume. Among the 184 subjects, 126 patients had cognitive impairment and 58 patients had normal cognition. The WMH volume of the cognitive impairment group was significantly higher than that of the normal cognitive group. The area under the curve (AUC) of WMH for predicting cognitive impairment was 0.685, the best cutoff value of WMH was 3975.77mm3, the sensitivity was 65.10%, and the specificity was 69.00%.

    Conclusion:

    Age and hypertension were independent risk factors for WMH volume, while diabetes and low FT3 levels were also associated with WMH severity. WMH is closely related to cognitive function, larger WMH volumes correlate with poorer cognitive performance. WMH contributes to the early identification of individuals with cognitive impairment.

  • Hao WANG, Taikun LU, Feiqi ZHU
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    Alzheimer's disease (AD) is the most common type of dementia in the elderly. The main pathogenesis of AD includes brain Aβ deposition, tau protein hyperphosphorylation, neuroinflammation, neuronal oxidative stress, and cerebral microcirculation disorders. In recent years, increasing evidence suggests that the liver is closely related to the pathogenesis of AD. The liver is not only the main organ for peripheral Aβ clearance, but also can affect the pathological changes of AD in the brain through a variety of ways, including cognition, emotion, cerebral perfusion and brain metabolism. This article summarizes the research on the liver's roles in the pathogenesis and treatment of AD, hoping to find more effective treatment methods for AD from the perspective of liver intervention.

  • Zhengying LU, Yuxin BAI, Jing GAO, Chun LI, Shangcheng ZHOU, Minqian LI, Ting HUANG
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    Objective:To analyze the direct economic burden of patients with dementia comorbidities and its influencing factors, and to provides a reference basis for economic cost calculation and family care burden assessment in patients with comorbid dementia. Methods: Using a self-designed questionnaire, the sociodemographic characteristics, treatment status, and direct economic burden of dementia comorbid patients in Guangzhou were collected. The Charlson Comorbidity Index (CCI) was used to assess the comorbidity burden. The direct economic burden costs were estimated using the direct method, and after a normality test showed a skewed distribution, logarithmic transformation was applied to approximate normalization before using it in a multiple linear regression model. Results: The per capita direct economic burden of dementia patients in Guangzhou in the past year was 7180.00 (3600.00, 15 568.67) yuan, of which the per capita direct medical cost was 6150.00 (3185.00, 12 590.00 ) yuan. The per capita direct non-medical cost was 0.00 (0.00, 2082.50) yuan, and Charlson Comorbidity Index (CCI) was 5.00 (5.00, 6.00), indicating a heavy comorbidity burden as well as a significant direct economic burden. The results of the multiple linear regression analysis showed that the primary factors influencing the direct economic burden of the disease were the patient's region, place of treatment, comorbid Chronic Obstructive Pulmonary Disease (COPD) or senile chronic bronchitis, comorbid heart disease, and types of dementia medications taken. Conclusion: The direct economic burden of dementia comorbid patients in Guangzhou is heavy, and the influencing factors are multi-dimensional and complex, which requires the joint efforts and complex, which requires the joint efforts and exploration of the government, society and medical institutions.

  • Xinyue BAI, Junkai WANG, Shui LIU, Zhiqun WANG
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    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and represents the most common form of dementia. Acupuncture have shown promising potential in the treatment of AD. In recent years, functional magnetic resonance imaging (fMRI) has been increasingly employed to investigate the mechanisms underlying the effects of acupuncture on brain function in AD patients. Evidence from studies indicates that acupuncture may enhance cognitive function and memory by activating specific brain regions and modulating the functional connectivity of brain networks. This review provides an overview of fMRI-based research on the application of acupuncture in AD treatment, aiming to summarize current findings and highlight areas for future investigation.

  • Huijuan GONGYE, Xiaoxiao XU, Jiao WANG, Shasha LIU
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    Objective: To systematically evaluate the effect of computer aided cognitive rehabilitation training on the overall cognitive function of patients with cognitive impairment after stroke. Methods: Pubmed, EMbase, Wanfang and CNKI databases were searched by computer to collect randomized controlled trials on the effect of computer aided cognitive rehabilitation training on the improvement of overall cognitive function in patients with cognitive impairment after stroke. The time limit was from the establishment of the database to May 2022. Literature screening, data extraction and bias risk assessment of included studies were completed by two researchers independently. Finally, RevMan5.3 software was used for Meta-analysis. Results: Nine RCTs involving 467 patients were included. Meta-analysis results showed that the effect size of MMSE was 1.97 [0.52, 3.42]. Meta-analysis results showed that the effect size of MoCA was 3.24[2.41, 4.07].In terms of cognitive function improvement, computer aided cognitive rehabilitation training is better than artificial cognitive rehabilitation training. Conclusion: Computer aided cognitive rehabilitation training for more than 4 weeks has advantages in improving the cognitive function of stroke patients. Rehabilitation programs can be made according to the specific conditions of different patients and different hospitals, so as to improve the cognitive function effectively. Limited by the quantity and quality of the included studies, the conclusions need to be verified by more high-quality studies.

  • Yongfei REN, Yelin CHEN
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    Objective:TDP-43 pathology is featured in many neurodegenerative diseases, including Alzheimer's disease (AD). Its contribution to these diseases remains unclear. One fundamental question is whether the neurotoxic effects from TDP-43 abnormalities result from its abnormal aggregation in the cytoplasm or its deficiency in the nucleus. To address this question, we investigated the mechanisms underlying TDP-43 abnormality-induced synaptic loss by analyzing how TDP-43 mutants contribute to spine abnormalities. Methods: Truncated mutants of TDP-43 were analyzed for their aggregation, effects on endogenous TDP-43, effects on dendritic spine density in cultured rat hippocampal neurons, and whether nuclear TDP-43 replenishment could prevent spine loss induced by TDP-43 abnormalities. Results: The ∆NLS∆R2 mutation of TDP-43 could mimic pathological abnormalities of TDP-43, including the formation of ThS-positive, highly phosphorylated cytoplasmic aggregates, and induction of nuclear depletion of endogenous TDP-43 in HEK 293T cells. ∆NLS∆R2 significantly reduces dendritic spine density of CA1 neurons in rat hippocampal slice cultures. This reduction in dendritic spine density can be partially blocked by co-expression of nuclear-localized TDP-43 mutant (NLS-TDP-43). Conclusion: The ∆NLS∆R2 mutation of TDP-43 recapitulates pathological abnormalities of TDP-43 and reduces dendritic spine density of CA1 neurons. Compensation for nuclear depletion of TDP-43 partially blocks the decrease in dendritic spines caused by ∆NLS∆R2, indicating that nuclear depletion of endogenous TDP-43 is a partial cause of spine loss induced by TDP-43 pathology.

  • Zixuan LIAO, Jiayu LI, Yidan LIU, Shuchun HUANG, Liumi JIANG, Xiaofeng LI
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    Objective:

    Mild cognitive impairment (MCI) represents a crucial stage in the early diagnosis and intervention of dementia. MCI due to AD is the main type of MCI. Using a single cognitive screening scale for MCI has some shortcomings such as limited sensitivity and specificity. Meanwhile, using a comprehensive neuropsychological battery for MCI screening is time consuming and laborintensive. Therefore, this study aims to explore an efficient cognitive screening scale for Chinese population of MCI due to AD, based on previously used cognitive assessment tools.

    Methods:

    A total of 27 cognitive screening tests and the Clinical Dementia Rating (CDR) scale were administered to 242 participants: 121 in the control group (CDR=0) and 121 in the MCI group (CDR=0.5). Spearman correlation analysis was used to assess the relationship between Z scores of each test and CDR scores. Tests showing significant correlations were used to construct a new screening scale for MCI. Then conduct a preliminary analysis of the sensitivity and specificity of the new scale, and establish the scoring criteria for the new scale.

    Results:

    The results of the correlation analysis showed that among the neuropsychological tests in various cognitive domains, Visual Cognitive Assessment Test(VCAT)-Language (r=-0.447, P<0.001), VCAT-Memory (r=-0.717, P<0.001), Trail Making Test(TMT)-B (r=0.426, P<0.001), Mini-Mental State Examination(MMSE)-Orientation (r=-0.271, P=0.025), MMSE-Attention (r=-0.313, P=0.009), and Clock Drawing Test(CDT) (r=-0.407, P<0.001) had the strongest correlations with CDR scores. These six cognitive tests were used to construct a new scale. And pass/fail criteria was derived that determined "possible"(one test failed), "probable" (two tests failed), and "definite" MCI (three tests failed).

    Conclusion:

    VCAT-Language; VCAT-Memory, TMT-B, MMSE-Orientation, MMSE-Attention, and CDT tests can be integrated to form a new screening scale for MCI suitable for the Chinese population of MCI due to AD. Further clinical validation is needed in the future to assess the sensitivity and feasibility of CQ-MCI.

  • Yuke SHI, Xiajing LOU, Bingsheng WANG, Bin WANG, Haiyan JIANG, Junling KANG, Shihua CAO
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    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.

  • Hua DENG
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    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.

  • Qi WU
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    With the intensifying global aging population, the number of patients with Alzheimer's disease (AD) is expected to increase sharply. Phase 3 clinical trials of anti-Aβ antibodies, lecanemab and donanemab have shown positive results, successfully slowing the progression of AD by approximately 30%. Although this progress is encouraging, we still need to explore more innovative treatment strategies to achieve a complete cure for AD. In recent years, the characterization of tRNA modification deficiency has become one of the hotspots in the field of AD research due to the rapid development of tRNA sequencing technology. As an important participant in protein translation, the deficiency of tRNA modification leads to a decrease in tRNA structural stability, protein translation efficiency and accuracy. The deficiency of tRNA modification can participate in AD progression through abnormal accumulation of misfolded proteins and mitochondrial dysfunction. Studies have shown that overexpression of low-modification tRNAs can restore protein homeostasis and treat peripheral neuropathy, so combing out the deficiency of tRNA modifications in AD could help to discover new therapeutic treatments. Recent advances in the deficiencies of U34, m5C, and m1A modifications of tRNAs in AD are reviewed, emphasizing the importance of targeting tRNAs for the treatment of AD.

  • Jingwen YAN, Zheng LUO, Yan ZHANG, Wei ZHANG, Ruifeng LU, Jinrong GUO, Sijia JIANG, Yun GU
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    Objective: The objective of this study is to examine the nutritional status of individuals diagnosed with Alzheimer's disease by assessing protein energy and micronutrient levels, and subsequently analyze its association with cognitive function. Methods: According to the predefined inclusion and exclusion criteria, a total of 100 patients diagnosed with Alzheimer's disease and an equal number of non-AD patients were meticulously selected as the control group.Based on the CDR score, the AD group was stratified into three subgroups: mild (34 cases), moderate (32 cases), and severe (34 cases) AD groups.The protein energy, and micronutrient levels of each group were assessed, and an analysis was conducted on the relevant nutritional factors influencing the progression of AD. Results: Compared to the control group, the AD group exhibited significant reductions in BMI, MNA-SF, ALB, HGB, FA, 25-(OH)D3, TC and TG levels; meanwhile, MMA and HCY levels were significantly elevated(all P<0.05).The levels of NNA-SF, HGB, and FA exhibited a declining trend across the mild AD group, moderate AD group, and severe AD group, whereas MMA demonstrated an increasing trend (all P<0.05).The severe AD group exhibited lower levels of BMI and ALB, while the mild AD group showed lower levels of HCY and 25-(OH)D3 (all P<0.05).The logistic regression analysis revealed significant correlations betweenMNA-SF, and FA with the degree of AD development (all P<0.05). Conclusion: The nutritional status of patients with Alzheimer's disease (AD) is generally poor, and there is a progressive.

  • Chao HAN, Yang LU, Guangming XU, Tingting ZHANG, Xuezhi ZHANG, Zhaorui LIU
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    Objective: To test the feasibility of the implementation of cognitive stimulation therapy (CST) among patients with mild to moderate dementia in urban nursing homes. Methods: Totally 55 patients with mild and moderate dementia in a nursing home in Tianjin were selected and received a 7-week CST treatment, twice a week. The cognitive function and quality of life were evaluated by community screening instrument for dementia (CSID), Mini-mental State Examination (MMSE), Alzheimer’s Disease Assessment Scale-Cognitive Section (ADAS-Cog) and dementia quality of life questionnaire (DEMQOL) at the baseline and the end of the seventh week. Results: After 7 weeks of CST treatment, the scores of CSID and MMSE of the 55 dementia patients increased, while the ADAS-Cog scores decreased, with statistically significant differences (P<0.05). Conclusion: CST can be scaled up in urban nursing homes.

  • Miaomiao XIANG, Xiaoxia WANG, Lunlan LI, Shanshan CAO, Ziqiao SUN
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    Objective: Exploring cognitive function in patients with acute ischemic stroke and analyzing its influencing factors. Methods: We collected 192 patients with acute ischemic stroke (AIS) who attended the Department of Neurology of the First Affiliated Hospital of Anhui Medical University from December 2021 to November 2022, and collected the general data of the patients, and evaluated all the patients with AIS by using the Changsha version of the Montreal Cognitive Function Assessment Scale (MoCA), the Pittsburgh Sleep Quality Index (PSQI), and the ability of daily living activities to explore whether the sleep quality and the ability of daily living activities are the influencing factors of cognitive function. Results: The 192 AIS patients had a cognitive function score of (22.89±3.77) and a Pittsburgh Sleep Quality Index score of (7.20±4.21).Correlation analysis shows that; The cognitive function of acute ischemic stroke patients was negatively correlated with pittsburgh sleep quality index, sleep duration, sleep efficiency and daytime dysfunction (P<0.05), and positively correlated with activities of daily living (P<0.05).Multivariate analysis showed that educational level and ability of daily living were the influencing factors of cognitive function in patients with acute ischemic stroke (P<0.05). Conclusion: The incidence of overall cognitive function decline in AIS patients is high, and cognitive function is affected by educational level and ability of daily living activities.

  • Xiaohan ZHU, Wenchao QIU, Yi CEN, Shuyun XIAO
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    Objective:

    To investigate the correlation between heart failure indexes, Chinese medicine evidence points, and cognitive function in elderly patients with chronic heart failure (CHF) combined with cognitive impairment (CI).

    Methods:

    165 elderly CHF patients were selected, and 92 CHF patients with combined CI were included according to the diagnostic criteria. The Simple Mental State Examination (MMSE) and Montreal Cognitive Assessment Scale (MoCA) were used to assess the severity of cognitive dysfunction in the patients, to complete the Chinese medicine evidence classification and Chinese medicine symptom scores, and to determine the NYHA cardiac function classification, LVEF, BNP, and IMT. The cardiac function classification, LVEF, BNP, duration of the disease, IMT, distribution of the basic Chinese medicine evidence types, and symptom. The correlation between cardiac function classification, LVEF, BNP, disease duration, IMT, Distribution of Basic Chinese Medicine Patterns and Symptom Scores, and cognitive function was analyzed.

    Results:

    The MMSE and MoCA scores of elderly patients with CHF combined with CI were not statistically significant (P < 0.05); LVEF was positively correlated with MMSE and MoCA scores; NYHA cardiac function classification, BNP, duration of heart failure, and Chinese medicine symptom scores were negatively correlated with MMSE and MoCA scores; and there was no correlation between IMT and MMSE and MoCA scores.

    Conclusion:

    In elderly patients with CHF combined with CI, there is a close relationship between NYHA cardiac function classification, BNP, duration of heart failure, LVEF, TCM symptom score, and cognitive function, and elderly patients with CHF should undergo early cognitive function assessment and early intervention.

  • Zhi LI, Fengxiang LIU, Lin SHI, Caifeng BAO, Ruixian SHI, Qi JIA, Furu LIANG
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    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.

  • Jin GAO, Yidan WEI, Zhi ZHOU, Liping FU
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    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.

  • Xianglan ZHANG, Jing ZHANG, Xiangjian ZHANG
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    Objective: To assess the potential relationship between lipoprotein(a) levels and the risk of developing different types of dementia (Alzheimer's disease, dementia with Lewy bodies, frontotemporal lobe dementia, Parkinson's disease-associated dementia, and vascular dementia) using a two-sample Mendelian randomization study approach. Methods: Genetic loci closely associated with lipoprotein(a) levels were obtained as instrumental variables (IVs) from the genome-wide association study (GWAS) pooled dataset, and two-sample Mendelian randomization (TSMR) analysis was performed with different types of dementia, with the results of the random-effects inverse variance weighting (IVW) method main. The reliability of the data was verified by multiple validity analysis using the MR-Egger method and sensitivity analysis using the leave-one-out method. Results: Elevated lipoprotein(a) levels were positively correlated with Lewy body dementia (OR = 1.67, P= 0.0005) and negatively correlated with the development of Alzheimer's disease (OR=0.95, P=0.036), and no significant correlation was found with vascular dementia, frontotemporal lobe dementia, and Parkinson's-related dementia. Conclusion: Lipoprotein(a) levels may be positively associated with the risk of developing dementia with Lewy bodies, may be negatively associated with the risk of developing Alzheimer's disease, and are not significantly associated with other types of dementia.

  • Ling GUO, Baolian DONG, Yiyin WANG, Guan ZHENG, Jinrong YA, Heyun YANG
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    Objective: To explore the effects of human umbilical cord mesenchymal stem cells (hUC-MSCs) with or without sulforaphane (SFN) on the biomarkers of the brain from APP/PS1 transigenic mice of Alzheimer's disease (2xTg-AD mice), and to provide a basis for further study or treatment strategies to AD. Methods: 8-week-old males, 24 APP/PS1 transgenic mice were randomly divided into four groups and respectively treated with PBS, SFN, hUC-MSCs, or hUC-MSCs with SFN. The cells were injected into the ventricles of the brain while SFN was delivered by i.p. to 2xTg-AD mice. The mice were euthanized at 14 days after the treatment. Aβ, Tau as biomarkers of AD in the brains, were subjected to immunofluorescence staining and Western Blot Analysis. Results: hUC-MSCs or SFN could downregulate the levels of Aβ or Tau protein in the cerebral cortex, with a better effect when they were used at the same time to 2xTg-AD mice. Conclusion: The application of hUC-MSCs with SFN may have a good therapeutic effect on early AD, and further study be needed.

  • Duoduo REN, Chenyao XIANG, Yongkang ZHAO, Xuejun CHAI, Lulu ZHANG, Yuchan ZHANG, Xiaoyan ZHU, Shanting ZHAO
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    Objective:

    The aim of this study was to explore the preventive and curative effect and mechanisms of Acer truncatum Bunge seed oil (ASO) on Alzheimer’s disease using 5×FAD transgenic mice as an animal model.

    Methods:

    1-month-old male 5×FAD transgenic mice were randomly selected and fed a standard diet supplemented with 4% ASO for 5 months (AD+ASO group), Male wild type control group (WT group) and a 5×FAD transgenic Alzheimer’s disease model group (AD group) were also included. Before sampling, animal behavioral experiments such as Barnes maze and elevated plus maze were conducted, followed by immunofluorescence staining of the hippocampus and cerebral cortex, high-throughput 16S rRNA sequencing, and bioinformatics analysis of gut microbiota.

    Results:

    Behavioral results showed that ASO intervention could improve the spatial learning and memory and ameliorate cognitive impairment of 5×FAD transgenic mice. Immunofluorescence histological results showed that ASO reduced the deposition of neuroinflammatory plaques formed by beta-amyloid peptide (Aβ) accumulation in the hippocampus and cerebral cortex by inhibiting the formation of amyloid plaques. ASO supplementation increased level of the antioxidant enzyme-glutathione peroxidase (GSH-Px) in the hippocampal tissue of AD mice, which in turn increased the body's antioxidant capacity. Bioinformatics results showed that the ASO could improve the richness and diversity of the gut microbiota in AD mice and play a positive role in regulating the gut microbiota.

    Conclusion:

    ASO can inhibit the formation of Aβ amyloid plaques by regulating the structure and abundance of gut microbiota, improve the learning and memory of AD mice and exert its neuroprotective effect, provides new materials and possibilities for protection of AD.

  • Fei XU, Wangjun TANG, Mengying HONG
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    Alzheimer's disease is a neurodegenerative disease with insidious onset, and Electroacupuncture is one way to treat Alzheimer's disease. Therefore, this article intends to summarize the experimental research on electroacupuncture treatment of Alzheimer's disease in mice in recent years, in order to provide reference for further exploring the pathogenesis of electroacupuncture treatment of Alzheimer's disease.

  • Rongrong HAO, Lirong DING, Xianghua LI, Yanxia ZHANG, Lanmin NIU
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    Objective: To explore the effect of mindfulness-based stress reduction therapy on the burden of illness of home caregivers of AD. Methods: From May 2019 to October 2022, 78 AD home caregivers were randomly divided into observation group and control group, with 39 cases in each group.The observation group was intervened with mindfulness decompression therapy, while the control group was intervened with conventional health education.The intervention of disease burden in the two groups was compared by independent sample t test, repeated test analysis of variance and x2 test. Results: The disease burden scores of the observation group and the control group were analyzed by independent sample t test before intervention, 4 weeks after intervention and 12 weeks after intervention.The results showed that there was no significant difference between the two groups before intervention (P > 0.05).The burden of disease in the observation group was significantly lower than that in the control group after intervention for 4 weeks and 12 weeks, and the difference was statistically significant (P < 0.01).The disease burden scores of the two groups were compared at three time points: before intervention, 4 weeks after intervention and 12 weeks after intervention by using repeated measures analysis of variance.There was a significant difference in disease burden between the two groups (P < 0.05);In addition, the burden of disease of caregivers in both groups decreased significantly with the intervention time (P < 0.01);The interaction of time factor and grouping factor showed that the effect of time factor was different in different groups (P < 0.01). Conclusion: Mindfulness-Based Stress Reduction can reduce the disease burden of home caregivers of AD.

  • Zhihong HUANG, Fan ZHANG, Junqing GUO, Cong ZHANG, Guoyong ZENG
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    Objective: To report a case of frontotemporal dementia who was misdiagnosed as primary psychosis. Methods: To analyze the clinical and neuroimaging features of a patient with behavioral variant frontotemporal dementia. Results: This case included a middle-aged female with mental abnormality at first, and was diagnosed as depression and schizophrenia successively in other hospitals. After treatment with related drugs, the effect was poor. Head MRI in our hospital showed bilateral frontotemporal lobe atrophy, with the left side obvious. Cranial 18F-FDG PET showed decreased metabolism in bilateral lateral frontal and temporal lobes. Ftd-related genetic testing found that the patient had a susceptibility gene mutation. Conclusion: This is a typical case of bvFTD, which was misdiagnosed as primary psychosis at an early stage, suggesting that the possibility of bvFTD should be considered in the diagnosis of mental disorders.

  • Jin ZHOU, Chunyao DONG, Yuanyuan LIN, Xia WANG, Xu WANG, Xiaomei YANG, Di SUN, Xiaolei WANG, Lihua LIANG
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    Objective:To know the effect of continuous positive airway pressure ventilation on cognitive function and the important biomarker of Alzheimer's disease, β - amyloid protein 1-42/1-40 ratio, in patients with obstructive sleep apnea syndrome. Methods: According to Random Number Table Method, 56 patients, being with obstructive sleep apnea syndrome, were randomly divided into the two groups either in treatment group or in control group, as well as each contained 28 cases. In treatment group, continuous positive pressure noninvasive ventilator was used to patients while sleeping at night, and also doing aerobic exercises day time for 3-4 hours per day. In control, only the latter was employed. The serum homocysteine level and the β-amyloid 1-42 or 1-40 were measured. And the primary results were evaluated using the Huashan version of the Auditory Verbal Learning Test (AVLT-H) and animal fluency test (AFT), which were tested at admission and three months after treatment, respectively. Results: Compared to Control, the serum level of homocysteine and β-amyloid protein 1-42/1-40 ratio in the treatment group were significantly downregulated by using treatment of continuous positive pressure noninvasive ventilator plus excesses for 3months or 6months (P<0.05), while the AVLT-H immediate recall score and AFT score were significantly upregulated than those in Control (P<0.05). Conclusion: Continuous positive airway pressure therapy can significantly improve memory and speech function in patients with obstructive sleep apnea syndrome, and reduce the HCY and A β 42/A β 40 ratio, which may have an improving effect on cognitive impairment in obstructive sleep apnea syndrome.