阿尔茨海默病（Alzheimer's disease,AD）是一种复杂的、起病隐秘的、病因不明的、缺乏特异性诊断方式的神经退行性病变。面对与日俱增的患病率,却缺乏有效的治疗方式。中医药治疗方式具有多层次、多靶点、多通路的独特优势,中西医结合方式的互补,非药物疗法的辅助,干细胞疗法、新的分子药物、抗体及蛋白疫苗、γ感官刺激等新颖的实验阶段新疗法等方式治疗AD。本文综述近年来的不同治疗方式治疗AD研究新进展,旨在为临床上治疗AD提供新思路、新方法及参考价值。

Alzheimer disease (AD) is a heterogeneous disease with a complex pathobiology. The presence of extracellular β-amyloid deposition as neuritic plaques and intracellular accumulation of hyperphosphorylated tau as neurofibrillary tangles remains the primary neuropathologic criteria for AD diagnosis. However, a number of recent fundamental discoveries highlight important pathological roles for other critical cellular and molecular processes. Despite this, no disease-modifying treatment currently exists, and numerous phase 3 clinical trials have failed to demonstrate benefits. Here, we review recent advances in our understanding of AD pathobiology and discuss current treatment strategies, highlighting recent clinical trials and opportunities for developing future disease-modifying therapies.Copyright © 2019 Elsevier Inc. All rights reserved.

Astragali radix is a traditional medicinal herb with a long history and wide application. It is frequently used in prescriptions with other medicinal materials to replenish Qi. According to the classics of traditional Chinese medicine, Astragali radix is attributed with properties such as Qi replenishing and surface solidifying, sore healing and muscle generating, and inducing diuresis to reduce edema. Modern pharmacological studies have demonstrated that some extracts and active ingredients in Astragali radix function as antioxidants. The polysaccharides, saponins, and flavonoids in Astragali radix offer beneficial effects in preventing and controlling diseases caused by oxidative stress. However, there is still a lack of comprehensive research on the effective components and molecular mechanisms through which Astragali radix exerts antioxidant activity. In this paper, we review the active components with antioxidant effects in Astragali radix; summarize the content, bioavailability, and antioxidant mechanisms; and offer a reference for the clinical application of Astragalus and the future development of novel antioxidants.

Cognitive impairment (CI) is one of the major clinical features of many neurodegenerative diseases. It can be aging-related or even appear in non-central nerve system (CNS) diseases. CI has a wide spectrum that ranges from the cognitive complaint with normal screening tests to mild CI and, at its end, dementia. Ginsenosides, agents extracted from a key Chinese herbal medicine (ginseng), show great promise as a new therapeutic option for treating CI. This review covered both clinical trials and preclinical studies to summarize the possible mechanisms of how ginsenosides affect CI in different diseases. It shows that ginsenosides can modulate signaling pathways associated with oxidative stress, apoptosis, inflammation, synaptic plasticity, and neurogenesis. The involved signaling pathways mainly include the PI3K/Akt, CREB/BDNF, Keap1/Nrf2 signaling, and NF-κB/NLRP3 inflammasome pathways. We hope to provide a theoretical basis for the treatment of CI for related diseases by ginsenosides.

Dementia affects 10% of those 65 years or older and 35% of those 90 years or older, often with profound cognitive, behavioral, and functional consequences. As the baby boomers and subsequent generations age, effective preventive and treatment strategies will assume increasing importance.Preventive measures are aimed at modifiable risk factors, many of which have been identified. To date, no randomized clinical trial data conclusively confirm that interventions of any kind can prevent dementia. Nevertheless, addressing risk factors may have other health benefits and should be considered. Alzheimer disease can be treated with cholinesterase inhibitors, memantine, and antiamyloid immunomodulators, with the last modestly slowing cognitive and functional decline in people with mild cognitive impairment or mild dementia due to Alzheimer disease. Cholinesterase inhibitors and memantine may benefit persons with other types of dementia, including dementia with Lewy bodies, Parkinson disease dementia, vascular dementia, and dementia due to traumatic brain injury. Behavioral and psychological symptoms of dementia are best treated with nonpharmacologic management, including identifying and mitigating the underlying causes and individually tailored behavioral approaches. Psychotropic medications have minimal evidence of efficacy for treating these symptoms and are associated with increased mortality and clinically meaningful risks of falls and cognitive decline. Several emerging prevention and treatment strategies hold promise to improve dementia care in the future.Although current prevention and treatment approaches to dementia have been less than optimally successful, substantial investments in dementia research will undoubtedly provide new answers to reducing the burden of dementia worldwide.

There are limited efficacious treatments for Alzheimer disease.To assess efficacy and adverse events of donanemab, an antibody designed to clear brain amyloid plaque.Multicenter (277 medical research centers/hospitals in 8 countries), randomized, double-blind, placebo-controlled, 18-month phase 3 trial that enrolled 1736 participants with early symptomatic Alzheimer disease (mild cognitive impairment/mild dementia) with amyloid and low/medium or high tau pathology based on positron emission tomography imaging from June 2020 to November 2021 (last patient visit for primary outcome in April 2023).Participants were randomized in a 1:1 ratio to receive donanemab (n = 860) or placebo (n = 876) intravenously every 4 weeks for 72 weeks. Participants in the donanemab group were switched to receive placebo in a blinded manner if dose completion criteria were met.The primary outcome was change in integrated Alzheimer Disease Rating Scale (iADRS) score from baseline to 76 weeks (range, 0-144; lower scores indicate greater impairment). There were 24 gated outcomes (primary, secondary, and exploratory), including the secondary outcome of change in the sum of boxes of the Clinical Dementia Rating Scale (CDR-SB) score (range, 0-18; higher scores indicate greater impairment). Statistical testing allocated α of.04 to testing low/medium tau population outcomes, with the remainder (.01) for combined population outcomes.Among 1736 randomized participants (mean age, 73.0 years; 996 [57.4%] women; 1182 [68.1%] with low/medium tau pathology and 552 [31.8%] with high tau pathology), 1320 (76%) completed the trial. Of the 24 gated outcomes, 23 were statistically significant. The least-squares mean (LSM) change in iADRS score at 76 weeks was -6.02 (95% CI, -7.01 to -5.03) in the donanemab group and -9.27 (95% CI, -10.23 to -8.31) in the placebo group (difference, 3.25 [95% CI, 1.88-4.62]; P < .001) in the low/medium tau population and -10.2 (95% CI, -11.22 to -9.16) with donanemab and -13.1 (95% CI, -14.10 to -12.13) with placebo (difference, 2.92 [95% CI, 1.51-4.33]; P < .001) in the combined population. LSM change in CDR-SB score at 76 weeks was 1.20 (95% CI, 1.00-1.41) with donanemab and 1.88 (95% CI, 1.68-2.08) with placebo (difference, -0.67 [95% CI, -0.95 to -0.40]; P < .001) in the low/medium tau population and 1.72 (95% CI, 1.53-1.91) with donanemab and 2.42 (95% CI, 2.24-2.60) with placebo (difference, -0.7 [95% CI, -0.95 to -0.45]; P < .001) in the combined population. Amyloid-related imaging abnormalities of edema or effusion occurred in 205 participants (24.0%; 52 symptomatic) in the donanemab group and 18 (2.1%; 0 symptomatic during study) in the placebo group and infusion-related reactions occurred in 74 participants (8.7%) with donanemab and 4 (0.5%) with placebo. Three deaths in the donanemab group and 1 in the placebo group were considered treatment related.Among participants with early symptomatic Alzheimer disease and amyloid and tau pathology, donanemab significantly slowed clinical progression at 76 weeks in those with low/medium tau and in the combined low/medium and high tau pathology population.ClinicalTrials.gov Identifier: NCT04437511.

Repetitive transcranial magnetic stimulation (rTMS) is an advanced and noninvasive technology that uses pulse stimulation to treat cognitive impairment. However, its specific effects have always been mixed with those of cognitive training, and the optimal parameter for Alzheimer's disease (AD) intervention is still ambiguous.This study aimed to summarize the therapeutic effects of pure rTMS on AD, excluding the influence of cognitive training, and to develop a preliminary rTMS treatment plan.Between 1 January 2010 and 28 February 2023, we screened randomized controlled clinical trials from five databases (PubMed, Web of Science, Embase, Cochrane, and ClinicalTrials. gov). We conducted a meta-analysis and systematic review of treatment outcomes and rTMS treatment parameters.A total of 4,606 articles were retrieved. After applying the inclusion and exclusion criteria, 16 articles, comprising 655 participants (308 males and 337 females), were included in the final analysis. The findings revealed that rTMS significantly enhances both global cognitive ability (p = 0.0002, SMD = 0.43, 95% CI = 0.20-0.66) and memory (p = 0.009, SMD = 0.37, 95% CI = 0.09-0.65). Based on follow-up periods of at least 6 weeks, the following stimulation protocols have demonstrated efficacy for AD: stimulation sites (single or multiple targets), frequency (20 Hz), stimulation time (1-2 s), interval (20-30 s), single pulses (≤2500), total pulses (>20000), duration (≥3 weeks), and sessions (≥20).This study suggests that rTMS may be an effective treatment option for patients with AD, and its potential therapeutic capabilities should be further developed in the future.

OBJECT This report describes the stereotactic technique, hospitalization, and 90-day perioperative safety of bilateral deep brain stimulation (DBS) of the fornix in patients who underwent DBS for the treatment of mild, probable Alzheimer's disease (AD). METHODS The ADvance Trial is a multicenter, 12-month, double-blind, randomized, controlled feasibility study being conducted to evaluate the safety, efficacy, and tolerability of DBS of the fornix in patients with mild, probable AD. Intraoperative and perioperative data were collected prospectively. All patients underwent postoperative MRI. Stereotactic analyses were performed in a blinded fashion by a single surgeon. Adverse events (AEs) were reported to an independent clinical events committee and adjudicated to determine the relationship between the AE and the study procedure. RESULTS Between June 6, 2012, and April 28, 2014, a total of 42 patients with mild, probable AD were treated with bilateral fornix DBS (mean age 68.2 ± 7.8 years; range 48.0-79.7 years; 23 men and 19 women). The mean planned target coordinates were x = 5.2 ± 1.0 mm (range 3.0-7.9 mm), y = 9.6 ± 0.9 mm (range 8.0-11.6 mm), z = -7.5 ± 1.2 mm (range -5.4 to -10.0 mm), and the mean postoperative stereotactic radial error on MRI was 1.5 ± 1.0 mm (range 0.2-4.0 mm). The mean length of hospitalization was 1.4 ± 0.8 days. Twenty-six (61.9%) patients experienced 64 AEs related to the study procedure, of which 7 were serious AEs experienced by 5 patients (11.9%). Four (9.5%) patients required return to surgery: 2 patients for explantation due to infection, 1 patient for lead repositioning, and 1 patient for chronic subdural hematoma. No patients experienced neurological deficits as a result of the study, and no deaths were reported. CONCLUSIONS Accurate targeting of DBS to the fornix without direct injury to it is feasible across surgeons and treatment centers. At 90 days after surgery, bilateral fornix DBS was well tolerated by patients with mild, probable AD. Clinical trial registration no.: NCT01608061 (clinicaltrials.gov).

Dementia is a complex syndrome with various presentations depending on the underlying pathologies. Low emission of transcranial near-infrared (tNIR) light can reach human brain parenchyma and be beneficial to a number of neurological and neurodegenerative disorders. We hereby examined the safety and potential therapeutic benefits of tNIR light stimulations in the treatment of dementia. Patients of mild to moderate dementia were randomized into active and sham treatment groups at 2:1 ratio. Active treatment consisted of low power tNIR light stimulations with an active photobiomodulation for 6 min twice daily during 8 consequent weeks. Sham treatment consisted of same treatment routine with a sham device. Neuropsychological battery was obtained before and after treatment. Analysis of variance (ANOVA) was used to analyze outcomes. Sixty subjects were enrolled. Fifty-seven subjects completed the study and had not reported health or adverse side effects during or after the treatment. Three subjects dropped out from trial for health issues unrelated to use of tNIR light treatment. Treatment with active device resulted in improvements of cognitive functions and changes were: an average increase of MMSE by 4.8 points; Logical Memory Tests I and II by ~3.0 points; Trail Making Tests A and B by ~24%; Boston Naming Test by ~9%; improvement of both Auditory Verbal Learning Tests in all subtest categories and overall time of performance. Many patients reported improved sleep after ~7 days of treatment. Caregivers noted that patients had less anxiety, improved mood, energy, and positive daily routine after ~14-21 days of treatment. The tNIR light treatments demonstrated safety and positive cognitive improvements in patients with dementia. Developed treatment protocol can be conveniently used at home. This study suggests that additional dementia treatment trials are warranted with a focus on mitigating caregivers’ burden with tNIR light treatment of dementia patients.

Alzheimer disease (AD) is characterized by the decline of cognitive functions such as learning and memory. Scientific society has proposed some non-pharmacological interventions, among which photobiomodulation has gained prominence for its beneficial effects. Therefore, we investigated, through systematic review, the therapeutic potential of photobiomodulation in AD. This systematic review was registered under the number CRD42019128416 in the International Prospective Record of Systematic Reviews (PROSPERO). A systematic search was conducted on the bibliographic databases (PubMed and ScienceDirect) with the keywords based on MeSH terms: "photobiomodulation therapy" or "low-level laser therapy" or "LLLT" or "light emitting diode" and "amyloid" or "Alzheimer". The data search was conducted from 2008 to 2019. We follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The search strategy included experimental and studies in the English language and photobiomodulation as a non-pharmacological intervention. We included 10 studies, being 5 studies, 4 studies and 1 study using and. To evaluate the quality of the studies, we used the Rob tool of the Systematic Review Center for Laboratory Animal Experimentation (SYRLE). The studies showed that photobiomodulation is able to reduce inflammatory response, oxidative stress and apoptotic effects generated by amyloid beta (Aβ) and restore mitochondrial function and cognitive behavior. Taken together, these results indicate that photobiomodulation may be a useful tool for treating AD.Copyright © 2020 J Lasers Med Sci.

Diet may reduce Alzheimer's dementia risk and slow cognitive decline, but the understanding of the relevant neuropathologic mechanisms remains limited. The association of dietary patterns with Alzheimer's disease (AD) pathology has been suggested using neuroimaging biomarkers. This study examined the association of MIND and Mediterranean dietary patterns with beta-amyloid load, phosphorylated tau tangles, and global AD pathology in postmortem brain tissue of older adults.Autopsied participants of the Rush Memory and Aging Project) with complete dietary information (collected through a validated food frequency questionnaire) and AD pathology data (beta-amyloid load, phosphorylated tau tangles, and global AD pathology [summarized neurofibrillary tangles, neuritic and diffuse plaques]) were included in this study. Linear regression models controlled for age at death, sex, education, APO-ε4 status, and total calories were used to investigate the dietary patterns (MIND and Mediterranean diet) and dietary components associated with AD pathology. Further effect modification was tested for APO-ε4 status and sex.Among our study participants (N=581, age at death: 91.0 ± 6.3 years; mean age at first dietary assessment: 84.2 ±5.8; 73% female; 6.8 ± 3.9 years of follow-up) dietary patterns were associated with lower global AD pathology (MIND: β= -0.022, p=0.034, standardized β=-2.0; Mediterranean: β=-0.007, p=0.039, standardized β=-2.3) and specifically less beta-amyloid load (MIND: β=-0.068, p=0.050, standardized β=-2.0; Mediterranean: β=-0.040, p=0.004, standardized β=-2.9). The findings persisted when further adjusted for physical activity, smoking, and vascular disease burden. The associations were also retained when participants with mild cognitive impairment or dementia at the baseline dietary assessment were excluded. Those in the highest tertile of green leafy vegetables intake had less global AD pathology when compared to those in the lowest tertile (Tertile-3 vs. Tertile-1: β= -0.115, p=0.0038).The MIND and Mediterranean diets are associated with less postmortem AD pathology, primarily beta-amyloid load. Among dietary components, green leafy vegetables inversely correlate with AD pathology.© 2023 American Academy of Neurology.

Research into dementia prevention is of paramount importance if the dementia epidemic is to be halted. Observational studies have identified several potentially modifiable risk factors for dementia, including hypertension, dyslipidaemia and obesity at midlife, diabetes mellitus, smoking, physical inactivity, depression and low levels of education. Randomized clinical trials are needed that investigate whether interventions targeting these risk factors can reduce the risk of cognitive decline and dementia in elderly adults, but such trials are methodologically challenging. To date, most preventive interventions have been tested in small groups, have focused on a single lifestyle factor and have yielded negative or modest results. Given the multifactorial aetiology of dementia and late-onset Alzheimer disease, multidomain interventions that target several risk factors and mechanisms simultaneously might be necessary for an optimal preventive effect. In the past few years, three large multidomain trials (FINGER, MAPT and PreDIVA) have been completed. The FINGER trial showed that a multidomain lifestyle intervention can benefit cognition in elderly people with an elevated risk of dementia. The primary results from the other trials did not show a statistically significant benefit of preventive interventions, but additional analyses among participants at risk of dementia showed beneficial effects of intervention. Overall, results from these three trials suggest that targeting of preventive interventions to at-risk individuals is an effective strategy. This Review discusses the current knowledge of lifestyle-related risk factors and results from novel trials aiming to prevent cognitive decline and dementia. Global initiatives are presented, including the World Wide FINGERS network, which aims to harmonize studies on dementia prevention, generate high-quality scientific evidence and promote its implementation.

目的 探究小续命汤（Xiaoxuming Decoction，XD）对双环己酮草酰二腙（cuprizone，CPZ）诱导的脱髓鞘小鼠的神经炎症影响。 方法 C57BL/6雄性小鼠随机分为正常对照（Control）组、CPZ组、XD1组（低剂量）和XD2（高剂量）组。每组10只小鼠，Control组不建模，其他3组每日喂饲0.2% CPZ建模，第28日起XD1和XD2组分别给予30 g·kg^–1，bid和30 g·kg^–1，tid XD灌胃，Control组和CPZ组分别给予等量生理盐水灌胃，持续至第42日。通过高架十字迷宫检测小鼠行为学表现，LFB染色和MBP免疫荧光染色观察小鼠胼胝体髓鞘脱失情况，脑组织小胶质细胞IBA1染色，荧光定量PCR和Western blot检测CD11b，HMGB1，TLR4/NLRP3/Caspase-1炎症小体和炎症介质的mRNA和蛋白质表达水平。 结果 与CPZ模型组比较，XD治疗组小鼠进入闭臂次数减少和闭臂运动距离缩短，高剂量治疗组效果尤为显著（P<0.05，P<0.01），改善胼胝体髓鞘脱失（P<0.05），降低脑组织中小胶质细胞浸润（P<0.05）；减少HMGB1、TLR4和炎症小体NLRP3的mRNA和蛋白质表达（P<0.05），降低细胞因子Caspase-1、IL-1β和IL-18的mRNA（P<0.05），抑制Akt/NF-κB通路活化（P<0.05）。 结论 XD可能通过调控NLRP3炎症小体表达，抑制脑组织中小胶质细胞活化和浸润，进而降低CPZ模型神经炎性损伤，发挥神经保护作用。

柠檬苦素类化合物是一类高度氧化的四环三萜类次生代谢产物,主要存在于芸香科（Rutaceae）和楝科（Meliaceae）植物中,包括柠檬苦素、诺米林和黄柏酮等物质。本文对柠檬苦素类化合物的生理活性进行概述,总结其各类生物学活性及作用机制,为柠檬苦素进一步用于健康保护、食品开发和农业生产等提供参考。

Neurodegenerative and neuropsychiatric diseases are increasingly affecting individuals' quality of life, thus increasing their cost to social and health systems. These diseases have overlapping mechanisms, such as oxidative stress, protein aggregation, neuroinflammation, neurotransmission impairment, mitochondrial dysfunction, and excitotoxicity. Currently, there is no cure for neurodegenerative diseases, and the available therapies have adverse effects and low efficacy. For neuropsychiatric disorders, such as depression, the current therapies are not adequate to one-third of the patients, the so-called treatment-resistant patients. So, searching for new treatments is fundamental. Medicinal plants appear as a strong alternative and complement towards new treatment protocols, as they have been used for health purposes for thousands of years. Thus, the main goal of this review is to revisit the neuroprotective potential of some of the most predominant medicinal plants (and one fungus) used in traditional Chinese medicine (TCM), focusing on their proven mechanisms of action and their chemical compositions, to give clues on how they can be useful against neurodegeneration progression.© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

The National Institute on Aging and the Alzheimer's Association convened three separate work groups in 2011 and single work groups in 2012 and 2018 to create recommendations for the diagnosis and characterization of Alzheimer's disease (AD). The present document updates the 2018 research framework in response to several recent developments. Defining diseases biologically, rather than based on syndromic presentation, has long been standard in many areas of medicine (e.g., oncology), and is becoming a unifying concept common to all neurodegenerative diseases, not just AD. The present document is consistent with this principle. Our intent is to present objective criteria for diagnosis and staging AD, incorporating recent advances in biomarkers, to serve as a bridge between research and clinical care. These criteria are not intended to provide step-by-step clinical practice guidelines for clinical workflow or specific treatment protocols, but rather serve as general principles to inform diagnosis and staging of AD that reflect current science. HIGHLIGHTS: We define Alzheimer's disease (AD) to be a biological process that begins with the appearance of AD neuropathologic change (ADNPC) while people are asymptomatic. Progression of the neuropathologic burden leads to the later appearance and progression of clinical symptoms. Early-changing Core 1 biomarkers (amyloid positron emission tomography [PET], approved cerebrospinal fluid biomarkers, and accurate plasma biomarkers [especially phosphorylated tau 217]) map onto either the amyloid beta or AD tauopathy pathway; however, these reflect the presence of ADNPC more generally (i.e., both neuritic plaques and tangles). An abnormal Core 1 biomarker result is sufficient to establish a diagnosis of AD and to inform clinical decision making throughout the disease continuum. Later-changing Core 2 biomarkers (biofluid and tau PET) can provide prognostic information, and when abnormal, will increase confidence that AD is contributing to symptoms. An integrated biological and clinical staging scheme is described that accommodates the fact that common copathologies, cognitive reserve, and resistance may modify relationships between clinical and biological AD stages.© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Digital health technologies offer valuable advantages to dementia researchers and clinicians as screening tools, diagnostic aids, and monitoring instruments. To support the use and advancement of these resources, a comprehensive overview of the current technological landscape is essential. A multi-stakeholder working group, convened by the Digital Medicine Society (DiMe), conducted a landscape review to identify digital health technologies for Alzheimer's disease and related dementia populations. We searched studies indexed in PubMed, Embase, and APA PsycInfo to identify manuscripts published between May 2003 to May 2023 reporting analytical validation, clinical validation, or usability/feasibility results for relevant digital health technologies. Additional technologies were identified through community outreach. We collated peer-reviewed manuscripts, poster presentations, or regulatory documents for 106 different technologies for Alzheimer's disease and related dementia assessment covering diverse populations such as Lewy Body, vascular dementias, frontotemporal dementias, and all severities of Alzheimer's disease. Wearable sensors represent 32% of included technologies, non-wearables 61%, and technologies with components of both account for the remaining 7%. Neurocognition is the most prevalent concept of interest, followed by physical activity and sleep. Clinical validation is reported in 69% of evidence, analytical validation in 34%, and usability/feasibility in 20% (not mutually exclusive). These findings provide clinicians and researchers a landscape overview describing the range of technologies for assessing Alzheimer's disease and related dementias. A living library of technologies is presented for the clinical and research communities which will keep findings up-to-date as the field develops.

As digital biomarkers gain traction in Alzheimer's disease (AD) diagnosis, understanding recent advancements is crucial. This review conducts a bibliometric analysis of 431 studies from five online databases: Web of Science, PubMed, Embase, IEEE Xplore, and CINAHL, and provides a scoping review of 86 artificial intelligence (AI) models. Research in this field is supported by 224 grants across 54 disciplines and 1403 institutions in 44 countries, with 2571 contributing researchers. Key focuses include motor activity, neurocognitive tests, eye tracking, and speech analysis. Classical machine learning models dominate AI research, though many lack performance reporting. Of 21 AD-focused models, the average AUC is 0.887, while 45 models for mild cognitive impairment show an average AUC of 0.821. Notably, only 2 studies incorporated external validation, and 3 studies performed model calibration. This review highlights the progress and challenges of integrating digital biomarkers into clinical practice.© 2025. The Author(s).