Memory circuits in dementia: The engram, hippocampal neurogenesis and Alzheimer's disease.

Here, we provide an in-depth consideration of our current understanding of engrams, spanning from molecular to network levels, and hippocampal neurogenesis, in health and Alzheimer's disease (AD). This review highlights novel findings in these emerging research fields and future research directions for novel therapeutic avenues for memory failure in dementia. Engrams, memory in AD, and hippocampal neurogenesis have each been extensively studied. The integration of these topics, however, has been relatively less deliberated, and is the focus of this review. We primarily focus on the dentate gyrus (DG) of the hippocampus, which is a key area of episodic memory formation. Episodic memory is significantly impaired in AD, and is also the site of adult hippocampal neurogenesis. Advancements in technology, especially opto- and chemogenetics, have made sophisticated manipulations of engram cells possible. Furthermore, innovative methods have emerged for monitoring neurons, even specific neuronal populations, in vivo while animals engage in tasks, such as calcium imaging. In vivo calcium imaging contributes to a more comprehensive understanding of engram cells. Critically, studies of the engram in the DG using these technologies have shown the important contribution of hippocampal neurogenesis for memory in both health and AD. Together, the discussion of these topics provides a holistic perspective that motivates questions for future research.

Ginkgo biloba and Its Chemical Components in the Management of Alzheimer's Disease.

The pathogenesis of Alzheimer's disease (AD), a degenerative disease of the central nervous system, remains unclear. The main manifestations of AD include cognitive and behavioral disorders, neuropsychiatric symptoms, neuroinflammation, amyloid plaques, and neurofibrillary tangles. However, current drugs for AD once the dementia stage has been reached only treat symptoms and do not delay progression, and the research and development of targeted drugs for AD have reached a bottleneck. Thus, other treatment options are needed. Bioactive ingredients derived from plants are promising therapeutic agents. Specifically, Ginkgo biloba (Gb) extracts exert anti-oxidant, anticancer, neuroplastic, neurotransmitter-modulating, blood fluidity, and anti-inflammatory effects, offering alternative options in the treatment of cardiovascular, metabolic, and neurodegenerative diseases. The main chemical components of Gb include flavonoids, terpene lactones, proanthocyanidins, organic acids, polysaccharides, and amino acids. Gb and its extracts have shown remarkable therapeutic effects on various neurodegenerative diseases, including AD, with few adverse reactions. Thus, high-quality Gb extracts are a well-established treatment option for AD. In this review, we summarize the insights derived from traditional Chinese medicine, experimental models, and emerging clinical trials on the role of Gb and its chemical components in the treatment of the main clinical manifestations of AD.

Supplements for cognitive ability in patients with mild cognitive impairment or Alzheimer's disease: a protocol for systematic review and network meta-analysis of randomised controlled trials.

INTRODUCTION: Considering the increasing incidence of Alzheimer's disease (AD) and mild cognitive impairment (MCI) worldwide, there is an urgent need to identify efficacious, safe and convenient treatments. Numerous investigations have been conducted on the use of supplements in this domain, with oral supplementation emerging as a viable therapeutic approach for AD or MCI. Nevertheless, given the multitude of available supplements, it becomes imperative to identify the optimal treatment regimen. METHODS AND ANALYSIS: Eight academic databases and three clinical trial registries will be searched from their inception to 1 June 2023. To identify randomised controlled trials investigating the effects of supplements on patients with AD or MCI, two independent reviewers (X-YZ and Y-QL) will extract relevant information from eligible articles, while the risk of bias in the included studies will be assessed using the Rob 2.0 tool developed by the Cochrane Collaboration. The primary outcome of interest is the overall cognitive function. Pair-wise meta-analysis will be conducted using RevMan V.5.3, while network meta-analysis will be carried out using Stata 17.0 and ADDIS 1.16.8. Heterogeneity test, data synthesis and subgroup analysis will be performed if necessary. The GRADE system will be employed to assess the quality of evidence. This study is scheduled to commence on 1 June 2023 and conclude on 1 October 2023. ETHICS AND DISSEMINATION: Ethics approval is not required for systematic review and network meta-analysis. The results will be submitted to a peer-reviewed journal or at a conference. TRIAL REGISTRATION NUMBER: PROSPERO (CRD42023414700).

Advancements in research on the effects of panax notoginseng saponin constituents in ameliorating learning and memory disorders.

Learning and memory disorder is a cluster of symptoms caused by neuronal aging and other diseases of the central nervous system (CNS). Panax notoginseng saponins (PNS) are a series of saponins derived from the natural active ingredients of traditional Chinese medicine (TCM) that have neuroprotective effects on the central nervous system. In this paper, we review the ameliorative effects and mechanisms of Panax notoginseng saponin-like components on learning and memory disorders to provide valuable references and insights for the development of new drugs for the treatment of learning and memory disorders. Our summary results suggest that Panax ginseng saponins have significant effects on improving learning and memory disorders, and these effects and potential mechanisms are mediated by their anti-inflammatory, anti-apoptotic, antioxidant, ß-amyloid lowering, mitochondrial homeostasis in vivo, neuronal structure and function improving, neurogenesis promoting, neurotransmitter release regulating, and probiotic homeostasis in vivo activities. These findings suggest the potential of Panax notoginseng saponin-like constituents as drug candidates for improving learning and memory disorders.

[Role of NLRP3 inflammasome in prevention and treatment of cognitive impairment-related diseases and traditional Chinese medicine intervention: a review].

Alzheimer's disease(AD), vascular dementia(VD), and traumatic brain injury(TBI) are more common cognitive impairment diseases characterized by high disability and mortality rates, imposing a heavy burden on individuals and their families. Although AD, VD, and TBI have different specific mechanisms, their pathogenesis is closely related to the nucleotide-binding oligome-rization domain-like receptor protein 3(NLRP3). The NLRP3 inflammasome is involved in neuroinflammatory responses, mediating microglial polarization, regulating the reduction of amyloid ß-protein(Aß) deposition, neurofibrillary tangles(NFTs) formation, autophagy regulation, and maintaining brain homeostasis, and synaptic stability, thereby contributing to the development of AD, VD, and TBI. Previous studies have shown that traditional Chinese medicine(TCM) can alleviate neuroinflammation, promote microglial polarization towards the M2 phenotype, reduce Aß deposition and NFTs formation, regulate autophagy, and maintain brain homeostasis by intervening in NLRP3 inflammasome, hence exerting a role in preventing and treating cognitive impairment-related diseases, reducing psychological and economic pressure on patients, and improving their quality of life. Therefore, this article elucidated the role of NLRP3 inflammasome in AD, VS, and TBI, and provided a detailed summary of the latest research results on TCM intervention in NLRP3 inflammasome for the prevention and treatment of these diseases, aiming to inherit the essence of TCM and provide references and foundations for clinical prevention and treatment of cognitive impairment-related diseases with TCM. Meanwhile, this also offers insights and directions for further research in TCM for the prevention and treatment of cognitive impairment-related diseases.

Horticultural Therapy for Individuals Coping with Dementia: Practice Recommendations Informed by Related Non-Pharmacological Interventions.

Dementia care currently presents a challenge to healthcare providers on many levels. The rapid increase in the number of people with dementia and the costs of care certainly contribute to these challenges. However, managing the behavioral and psychological symptoms of dementia (BPSDs) has become one of the most significant tasks in providing care and can lead to poor health and well-being outcomes, not only for the people living with dementia (PLWD) but also for those providing their care. Cost-effective, easily implemented, highly adaptable, empirically based alternatives are needed. Interventions such as Horticultural Therapy (HT), which is naturally informed by Montessori-Based Methods for Dementia and sensory reminiscence therapies, meets these qualifying factors. This article, based on a review of current best practices and clinical experience, hopes to provide recommendations for such an intervention along with special considerations for PLWD and adaptations for different acuity levels. With additional safe and effective, person-centered, non-pharmacological interventions available for the complex cognitive and neuropsychiatric manifestations of this disease, a better care milieu can be provided, improving the quality of life for both patients and caregivers. This article also identifies the need for continued research into the synergistic effects of person-centered behavioral and psychosocial interventions combined with environmental approaches to provide the optimal healing environment for those coping with dementia.

Therapeutic potential of saffron in brain disorders: From bench to bedside.

Saffron is a spice derived from the flower of Crocus sativus L., which has been used for centuries as a coloring and flavoring agent, as well as a source of medicinal compounds. Saffron contains various bioactive constituents, such as crocin, crocetin, safranal, picrocrocin, and kaempferol, that have shown potential benefits for human health. Among them, crocin is the most abundant and characteristic constituent of saffron, responsible for its bright red color and antioxidant properties. One of the most promising applications of saffron and its constituents is in the prevention and treatment of neurological disorders, such as depression, anxiety, Alzheimer's disease, Parkinson's disease, and other brain disorders. Saffron and its constituents have been reported to exert neuroprotective effects through various mechanisms, such as modulating neurotransmitters, enhancing neurogenesis, reducing neuroinflammation, regulating oxidative stress, activating the Nrf2 signaling pathway, and modulating epigenetic factors. Several clinical and preclinical studies have demonstrated the efficacy and safety of saffron and its constituents in improving cognitive function, mood, and other neurological outcomes. In this review, we summarize the current evidence on the therapeutic potential of saffron and its constituents in neurological disorders, from bench to bedside. We also discuss the challenges and future directions for the development of saffron-based therapies for brain health.

Effects of Banhabaekchulcheonma-Tang on Brain Injury and Cognitive Function Impairment Caused by Bilateral Common Carotid Artery Stenosis in a Mouse Model.

Vascular dementia (VD) is the second most prevalent dementia type, with no drugs approved for its treatment. Here, the effects of Banhabaekchulcheonma-Tang (BBCT) on ischemic brain injury and cognitive function impairment were investigated in a bilateral carotid artery stenosis (BCAS) mouse model. Mice were divided into sham-operated, BCAS control, L-BBCT (40 ml/kg), and H-BBCT (80 ml/kg) groups. BBCT's effects were characterized using the Y-maze test, novel object recognition test (NORT), immunofluorescence staining, RNA sequencing, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analyses. The NORT revealed cognitive function improvement in the H-BBCT group, while the Y-maze test revealed no significant difference among the four groups. The CD68+ microglia and GFAP+ astrocyte numbers were reduced in the H-BBCT group. Furthermore, H-BBCT treatment restored the dysregulation of gene expression caused by BCAS. The major BBCT targets were predicted to be cell division cycle protein 20 (CDC20), Epidermal growth factor (EGF), and tumor necrosis factor receptor-associated factor 1 (TRAF1). BBCT regulates the neuroactive ligand-receptor interaction and neuropeptide signaling pathways, as predicted by KEGG and GO analyses, respectively. BBCT significantly improved cognitive impairment in a BCAS mouse model by inhibiting microglial and astrocyte activation and regulating the expression of CDC20, EGF, TRAF1, and key proteins in the neuroactive ligand-receptor interaction and neuropeptide signaling pathways.

Music Therapy as a Complementary Treatment in Patients with Dementia Associated to Alzheimer's Disease: A Systematic Review.

Background: Alzheimer's disease (AD) is a complex condition that affects various aspects of a patient's life. Music therapy may be considered a beneficial supplementary tool to traditional therapies, that not fully address the range of AD manifestations. Objective: The purpose of this systematic review is to investigate whether music therapy can have a positive impact on AD patients and on which symptoms. Methods: The main research databases employed have been PubMed and Cochrane, using the keywords "dementia", "music therapy", "Alzheimer", "fMRI", "music", and "EEG". Results: After removing duplicates and irrelevant studies, 23 were screened using set criteria, resulting in the final inclusion of 15 studies. The total number of participants included in these studies has been of 1,196 patients. For the fMRI analysis the search resulted in 28 studies on PubMed, two of which were included in the research; the total number of participants was of 124 individuals. The studies conducted with EEG were found using PubMed. The initial search resulted in 15 studies, but after a more accurate evaluation only 2 have been included in the analysis. Conclusions: Even though the data currently available is not sufficient to draw conclusions supported by robust statistical power, the impact of music therapy on AD neuropsychiatric symptoms deserves great interest. Further research should be ushered, possibly multicentric studies, led with neuroimaging and other recent techniques, which can eventually open views on the music role in improving the cognitive status in AD.

Methanol extract of Ligusticum chuanxiong Hort. Rhizome ameliorates bilateral common carotid artery stenosis-induced cognitive deficit in mice by altering microglia and astrocyte activation.

In traditional Asian medicine, Ligusticum chuanxiong Hort also known as Conioselinum anthriscoides "Chuanxiong", is mainly used for improving blood circulation or for analgesic and anti-inflammatory purposes, but they also have a long history of use for pain disorders in the head and face, such as headache. Despite the possibility that the plant is effective for diseases such as cerebral infarction and vascular dementia (VaD), the mechanism of action is not well understood. To determine if the dried rhizomes of L. chuanxiong (Chuanxiong Rhizoma, CR) methanol extract (CRex) has activity in a VaD mice model. Through network analysis, we confirm that CR is effective in cerebrovascular diseases. In mice, we induce cognitive impairment, similar to VaD in humans, by chronically reducing the cerebral blood flow by performing bilateral common carotid artery stenosis (BCAS) and administering CRex for 6 weeks. We measure behavioral changes due to cognitive function impairment and use immunofluorescence staining to confirm if CRex can inhibit the activation of astrocytes and microglia involved in the inflammatory response in the brain. We quantify proteins involved in the mechanism, such as mitogen-activated protein kinases (MAPK), in the hippocampus and surrounding white matter, and analyze gene expression and protein interaction networks through RNA sequencing to interpret the results of the study. CRex administration rescued cognitive impairment relating to a novel object and inhibited the activation of astrocytes and microglia. Western blotting analysis revealed that CRex regulated the changes in protein expression involved in MAPK signaling such as extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38). The administration of CRex suppressed approximately 44% of the pathological changes in gene expression caused by BCAS. CRex extract effectively inhibited cognitive impairment caused by BCAS, and the mechanism through which this occurred is inhibited activation of astrocytes and microglia.

The effects of individual music therapy in nursing home residents with dementia to improve general well-being: study protocol of a randomized controlled trial.

BACKGROUND: Dementia is often associated with Neuropsychiatric Symptoms (NPS) such as agitation, depression, hallucinations, anxiety, that can cause distress for the resident with dementia in long-term care settings and can impose emotional burden on the environment. NPS are often treated with psychotropic drugs, which, however, frequently cause side effects. Alternatively, non-pharmacological interventions can improve well-being and maintain an optimal quality of life (QoL) of those living with dementia. Other QoL related outcomes, such as pain, discomfort and sleep disruption are relevant outcomes in music trials as well. Music therapy is a non-pharmacological intervention that can reduce NPS and improve well-being, and its associated symptoms in dementia. METHODS: The research will be conducted at eight nursing home facilities of a health care organization in the Netherlands. A sample size of 30 in each group (experimental and control group) is required, totalling 60 residents increased to 80 when considering expected drop out to follow up. The participants in the intervention group receive 30 min of individual music therapy (MT) in their own room by a music therapist twice a week for 12 weeks. The participants in the control group will receive 30 min of individual attention in their own room by a volunteer twice a week for 12 weeks. Assessments will be done at baseline, 6 weeks and 12 weeks. An independent observer, blinded for the intervention or control condition, will assess directly observed well-being (primary outcome) and pain (secondary outcome) before and after the sessions. Nurses will assess other secondary outcomes unblinded, i.e., perceived quality of life and NPS, both assessed with validated scales. The sleep duration will be indirectly assessed by a wrist device called MotionWatch. Information about psychotropic drug use will be derived from electronic medical chart review. DISCUSSION: The main purpose of this study is to assess the effects of individual music therapy on directly observed well-being controlled for individual attention in nursing home residents with dementia with NPS. The outcomes refer to both short-term and long-term effects consistent with therapeutic goals of care for a longer term. We hope to overcome limitations of previous study designs such as not blinded designs and music facilitators that were not only music therapists but also occupational therapists and nurses. This study should lead to more focused recommendations for practice and further research into non-pharmacological interventions in dementia such as music therapy. TRIAL REGISTRATION: The trial is registered at the International Clinical Trials Registry Platform (ICTRP) search portal in the Netherlands Trial Registration number NL7708, registration date 04-05-2019.

Therapeutic potential of clinically proven natural products in the management of dementia.

Dementia is a common neurodegenerative disorder connected to damage to nerve cells in the brain. Although some conventional drugs are available for dementia treatments and are still sanctified for dementia patients, their short- and long-term side effects and other limitations make treating patients more challenging. The authors aimed to explain novel options for treating dementia with natural products and unravel some clinically proven natural products. This article systematically reviewed recent studies that have investigated the role of natural products and their bioactive compounds for dementia. PubMed Central, Scopus, and Google Scholar databases of articles were collected, and abstracts were reviewed for relevance to the subject matter.In this review, we provide mechanistic insights of clinically validated natural products, including like- Yokukansan, Souvenaid, BDW, Hupergene, Bacopa monnier, Omega-3, Tramiprostate and Palmitoylethanolamide with which have therapeutic efficacy against dementia in the management of dementia. As shown by studies, certain natural ingredients could be used to treat and prevent dementia. We strongly believe that the medicinal plants and phytoconstituents alone or in combination with other compounds would be effective treatments against dementia with lesser side effects as compared to currently available treatments. Moreover, these products should be studied further in order to develop novel dementia medications.

Stroke in the Time of Circadian Medicine.

Time-of-day significantly influences the severity and incidence of stroke. Evidence has emerged not only for circadian governance over stroke risk factors, but also for important determinants of clinical outcome. In this review, we provide a comprehensive overview of the interplay between chronobiology and cerebrovascular disease. We discuss circadian regulation of pathophysiological mechanisms underlying stroke onset or tolerance as well as in vascular dementia. This includes cell death mechanisms, metabolism, mitochondrial function, and inflammation/immunity. Furthermore, we present clinical evidence supporting the link between disrupted circadian rhythms and increased susceptibility to stroke and dementia. We propose that circadian regulation of biochemical and physiological pathways in the brain increase susceptibility to damage after stroke in sleep and attenuate treatment effectiveness during the active phase. This review underscores the importance of considering circadian biology for understanding the pathology and treatment choice for stroke and vascular dementia and speculates that considering a patient's chronotype may be an important factor in developing precision treatment following stroke.

Therapeutic Potential of Traditional Oriental Medicines in Targeting Tau Pathology: Insights from Cell-free and Cell-based Screening.

BACKGROUND: Traditional Oriental Medicines (TOMs) formulated using a variety of medicinal plants have a low risk of side effects. In previous studies, five TOMs, namely Dangguijakyaksan, Hwanglyeonhaedoktang, Ukgansan, Palmijihwanghwan, and Jowiseungchungtang have been commonly used to treat patients with Alzheimer's disease. However, only a few studies have investigated the effects of these five TOMs on tau pathology. OBJECTIVE: This study aimed to examine the effect of five TOMs on various tau pathologies, including post-translational modifications, aggregation and deposition, tau-induced neurotoxicity, and tau-induced neuroinflammation. METHODS: Immunocytochemistry was used to investigate the hyperphosphorylation of tau induced by okadaic acid. In addition, the thioflavin T assay was used to assess the effects of the TOMs on the inhibition of tau K18 aggregation and the dissociation of tau K18 aggregates. Moreover, a water-soluble tetrazolium-1 assay and a quantitative reverse transcription polymerase chain reaction were used to evaluate the effects of the TOMs on tau-induced neurotoxicity and inflammatory cytokines in HT22 and BV2 cells, respectively. RESULTS: The five TOMs investigated in this study significantly reduced okadaic acid-induced tau hyperphosphorylation. Hwanglyeonhaedoktang inhibited the aggregation of tau and promoted the dissociation of tau aggregates. Dangguijakyaksan and Hwanglyeonhaedoktang attenuated tau-induced neurotoxicity in HT22 cells. In addition, Dangguijakyaksan, Hwanglyeonhaedoktang, Ukgansan, and Palmijihwanghwan reduced tauinduced pro-inflammatory cytokine levels in BV2 cells. CONCLUSION: Our results suggest that five TOMs are potential therapeutic candidates for tau pathology. In particular, Hwanglyeonhaedoktang showed the greatest efficacy among the five TOMs in cell-free and cell-based screening approaches. These findings suggest that Hwanglyeonhaedoktang is suitable for treating AD patients with tau pathology.

Commentary to: "Timely dying in dementia: Use patients' judgments and broaden the concept of suffering." Timely dying, suffering in dementia, and a role for family and professional caregivers in preventing it.

Broadening the concept of suffering in dementia to five types of suffering including suffering of family caregivers as proposed by Terman et al., may help raise awareness on a need to relieve suffering when living with dementia and adopt a holistic approach. However, as objective criteria in advance care plans for severe enough suffering to stop assisted feeding or other life-sustaining treatment in people with advanced dementia, these still need interpretation in the context of, for example, available treatment, and change in coping. New is the proposal to broaden severe enough suffering to suffering of family, including "bi-directional empathic suffering." We believe this creates new dilemmas regarding responsibility and may increase feelings of guilt. Quantifying suffering by adding up moderate suffering could further complicate matters. Therefore, we argue that a health care professional should guide the process and assume responsibility over current decisions to follow a person's previous wishes.

Omega-3 Fatty Acids for Depression in the Elderly and Patients with Dementia: A Systematic Review and Meta-Analysis.

This study aimed to evaluate the efficacy of omega-3 fatty acid supplementation interventions in improving depression in patients with dementia. To achieve this objective, randomized controlled trials (RCTs) were identified from primary electronic databases, focusing on the relationship between omega-3 fatty acids and depression in patients with dementia. The primary outcome was the impact of omega-3 fatty acids on post-intervention depression in patients with dementia, with subgroup analyses conducted based on the type of intervention (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) combination), duration of intervention (3 months, 6 months, 12 months, ≥24 months), cognitive function (ranging from mild cognitive impairment (MCI) to severe dementia), and daily dosage (high, medium, low, applicable to both DHA and EPA). The study has been duly registered with PROSPERO (registration ID: CRD42023408744). A meta-analysis of five studies (n = 517) included in nine systematic reviews showed that omega-3 supplementation had a non-significant trend toward affecting depressive symptoms in patients with dementia (standardized mean difference (SMD): 0.147; 95% confidence interval (CI): -0.324 to 0.049; p = 0.141). Subgroup analyses revealed that DHA supplementation significantly reduced depressive symptoms (SMD: -0.247; p = 0.039). There was no significant effect for high (SMD: -0.169; 95% CI: -0.454 to 0.116; p = 0.246) or medium (SMD: -0.061; 95% CI: -0.228 to 0.105; p = 0.470) doses of EPA. However, low doses of EPA were significantly effective (SMD: -0.953; 95% CI: -1.534 to -0.373; p = 0.001), with notable improvements in patients with MCI (SMD: -0.934; p < 0.001). The study concludes that omega-3 fatty acids, particularly through DHA supplementation, may alleviate depressive symptoms in patients with MCI. Given the limited sample size, further long-term RCTs are recommended to better understand the efficacy and optimal management of omega-3 supplementation in this population using different dosages.

Posttraumatic stress disorder in people with dementia: study protocol.

Background: Posttraumatic stress disorder (PTSD) is considered an independent risk factor for dementia. Despite the (clinical) evidence that PTSD is associated with neuropsychiatric symptoms in people with dementia, studies on its prevalence and clinical manifestation are limited, and their quality is affected by the lack of a structured method to diagnose PTSD in this population. The primary aim of the current study is to validate the 'TRAuma and DEmentia' interview as a diagnostic tool for PTSD in people with dementia and to test feasibility of EMDR treatment for people with PTSD and dementia.Methods: This prospective multi-centre study is divided into two parts. In study A, 90 participants with dementia will be included to test the criterion validity, inter-rater reliability and feasibility of the 'TRAuma and DEmentia' interview. In study B, 29 participants with dementia and PTSD will receive eye movement desensitisation and reprocessing therapy by a trained psychologist, and 29 participants with dementia and PTSD will be placed on the waiting list control group.Conclusion: This study aims to improve the diagnostic process of PTSD and to assess the effects of eye movement desensitisation and reprocessing treatment in people with dementia living in Dutch care facilities.Trial registration: NL70479.068.20 / METC 20-063 / OSF registration: https://doi.org/10.17605/OSF.IO/AKW4F.

This study protocol describes a two-part study on posttraumatic stress disorder in people with dementia in Dutch care facilities.The primary aim of the study is to validate the 'TRAuma and DEmentia' interview as a diagnostic tool for posttraumatic stress disorder in people with dementia.This study aims to test the feasibility of an evidence-based treatment for people with dementia and posttraumatic stress disorder in the form of eye movement desensitisation and reprocessing therapy.

Impact of mindfulness-based and health self-management interventions on mindfulness, self-compassion, and physical activity in older adults with subjective cognitive decline: A secondary analysis of the SCD-Well randomized controlled trial.

INTRODUCTION: Older adults experiencing subjective cognitive decline (SCD) have a higher risk of dementia. Reducing this risk through behavioral interventions, which can increase emotional well-being (mindfulness and compassion) and physical activity, is crucial in SCD. METHODS: SCD-Well is a multicenter, observer-blind, randomized, controlled, superiority trial. Three hundred forty-seven participants (mean [standard deviation] age: 72.7 [6.9] years; 64.6% women) were recruited from memory clinics in four European sites to assess the impact of an 8-week caring mindfulness-based approach for seniors (CMBAS) and a health self-management program (HSMP) on mindfulness, self-compassion, and physical activity. RESULTS: CMBAS showed a significant within-group increase in self-compassion from baseline to post-intervention and both a within- and between-group increase to follow-up visit (24 weeks). HSMP showed a significant within- and between-group increase in physical activity from baseline to post-intervention and to follow-up visit. DISCUSSION: Non-pharmacological interventions can differentially promote modifiable factors linked to healthy aging in older adults with SCD.

A novel phthalein component ameliorates neuroinflammation and cognitive dysfunction by suppressing the CXCL12/CXCR4 axis in rats with vascular dementia.

ETHNOPHARMACOLOGICAL RELEVANCE: Chuanxiong, a plant of the Umbelliferae family, is a genuine medicinal herb from Sichuan Province. Phthalides are one of its main active components and exhibit good protective effect against cerebrovascular diseases. However, the mechanism by which phthalides exert neuroprotective effects is still largely unclear. AIM OF THE STUDY: In this study, we extracted a phthalein component (named as QBT) from Ligusticum Chuanxiong, and investigated its neuroprotective effects against vascular dementia (VaD) rats and the underlying mechanism, focusing on the chemokine 12 (CXCL12)/chemokine (C-X-C motif) receptor 4 (CXCR4) axis. METHODS: A rat model of VaD was established, and treated with QBT. Cognitive dysfunction in VaD rats was assessed using the Y-maze, new object recognition, and Morris water maze tests. Neuronal damage and inflammatory response in VaD rats were examined through Nissl staining, immunofluorescence, enzyme-linked immunospecific assay, and western blotting analysis. Furthermore, the effects of QBT on CXCL12/CXCR4 axis and its downstream signaling pathways, Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT)/nuclear factor-κB (NF-κB), were investigated in VaD rats and BV2 microglial cells exposed to oxygen glucose deprivation. RESULTS: QBT significantly alleviated cognitive dysfunction and neuronal damage in VaD rats, along with inhibition of VaD-induced over-activation of microglia and astrocytes and inflammatory response. Moreover, QBT exhibited anti-inflammatory effects by inhibiting the CXCL12/CXCR4 axis and its downstream JAK2/STAT3 and PI3K/AKT/NF-κB pathways, thereby attenuating the neuroinflammatory response both in vivo and in vitro. CONCLUSION: QBT effectively mitigated neuronal damage and cognitive dysfunction in VaD rats, exerting neuroprotective effects by suppressing neuroinflammatory response through inhibition of the CXCL12/CXCR4 axis.