INTRODUCTION: Spontaneous speech is commonly disrupted in persons with Alzheimer's disease (AD) and/or Alzheimer's clinical syndrome (ACS). Importantly, different aspects of speech (e.g. formulaic versus more novel or flexible speech) place different demands on distinct cognitive systems. Formulaic language may rely on automatized procedural processes, while more novel or diverse speech requires more flexible lexical-semantic processes associated with the subsystems of declarative memory. Given that AD/ACS are associated with impaired declarative processes and relatively spared procedural processes, we predicted that individuals with ACS may show increased reliance on formulaic language along with reduced diversity in speech. METHOD: We analyzed the spontaneous speech of 81 individuals with ACS (aged 56-88) and 61 healthy controls (aged 47-80) who completed a picture description task using computational tools for the analysis of formulaic language (operationalized as proportion of frequent trigrams produced and mutual information score of trigrams) and novel language (operationalized as root type-token ratio, measure of textual lexical diversity, and semantic diversity). RESULTS: Across all measures, individuals with ACS produced significantly more formulaic language than control participants and significantly less novel language than control participants, with small-to-medium overall model effect sizes. Machine learning classifiers trained on these patterns of formulaic and novel language distinguished between controls and individuals with ACS with reasonable accuracy, sensitivity, and specificity. CONCLUSION: The spontaneous speech of individuals with ACS contains more formulaic language and less novel language than that of healthy controls, consistent with the Dual-Process Model. These differences may have clinical relevance and warrant further investigation. Keywords: Alzheimer's Disease, Alzheimer's clinical syndrome, formulaic language, lexical diversity, spontaneous speech.

The blood-brain barrier (BBB) displays a highly organized and complex structure, which is important for maintaining brain homeostasis and protecting the brain from foreign molecules or pathogens. Receptor-mediated transcytosis (RMT) is one of the main delivery pathways across the BBB for molecules that cannot pass the barrier via, e.g. paracellular diffusion. For understanding the treatment options in neurodegenerative diseases such as Alzheimer´s disease (AD), it is important to investigate transport pathways and mechanisms at the BBB for a potential delivery of drugs, antibodies or other compounds across the BBB. This review provides an overview of the different transport variants across the BBB and how they can be targeted in order to promote internalization or secretion into or out of the brain. Therefore, we want to focus on two characterized proteins: the low-density lipoprotein receptor-related protein 1 (LRP1), which is a key mediator of amyloid β (Aβ) clearance from the brain during AD, and transferrin receptor 1 (TfR1), which is already used as a target for antibody-delivery into the brain. Additionally, this review discusses two other important proteins, which have been less frequently addressed in research regarding transport mechanisms: P-glycoprotein (P-gp) as another transporter at the BBB and proprotein convertase subtilisin/kexin type 9 (PCSK9), a well-known regulator of cholesterol homeostasis which promotes the degradation of the low-density lipoprotein receptor (LDLR) and LRP1. For these four main proteins, we aim to highlight existing approaches for targeting or inhibiting the aforementioned receptors or proteins. The approaches enable a higher penetration of the BBB, a better distribution in the brain, and ultimately fewer side effects of antibodies or nanoparticles. Here, we include lecanemab, trontinemab, dual TfR/CD98hc shuttles, evolocumab and alirocumab, immunoliposomes and other nanoparticles targeting TfR1 or LRP1. We will further highlight approaches which differ from these common ideas and demonstrate the current state of the art regarding drug delivery and waste clearance across the BBB.

AIM: Competence assessment is essential for professional growth, workforce planning, and quality improvement in long-term care (LTC). However, the wide range of instruments, their limited differentiation based on various qualification levels, and the lack of standardized frameworks hinder effective use. This scoping review aimed to map international evidence on competence assessment instruments used in residential LTC nursing, broadening the scope to include acute care, community-based, and mixed-care settings to enhance the relevance and transferability of findings. METHODS: A scoping review was conducted following the Joanna Briggs Institute guidelines. Peer-reviewed and grey literature in English and German were searched across two databases (PubMed and CINAHL) between 2014 and 2024. Inclusion criteria focused on instruments assessing nursing competence through self-assessment or external evaluation, targeting various qualification levels and care contexts. RESULTS: Twenty instruments were identified. The review addressed two key research questions: (1) A wide range of self-assessment tools with generally sound psychometric properties were found, predominantly developed for registered nurses and validated in acute settings; however, few differentiated by qualification level, and no validated instruments were identified for healthcare assistants. (2) Validated peer or external evaluation instruments were scarce, highlighting a reliance on self-perception and a lack of objective assessment. Instruments for specialized domains (e.g., dementia, palliative care) demonstrated higher contextual relevance but lacked robust testing in LTC. CONCLUSION: This review highlights significant variability and identifies a crucial gap in tools available for healthcare assistants and multi-method assessments. Future efforts should focus on creating modular, theory-informed, and context-sensitive instruments that are validated across various qualification levels and care sectors. These tools are essential to support individualized learning, ensuring equitable staffing, and fostering sustainable quality improvements in long-term care.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating neurodegenerative diseases linked by similar pathological mechanisms, which, in some familial forms, may be associated with the same genetic alterations. Among them, the most common is the C9ORF72 (C9) mutation. The C9 mutation consists in an aberrant expansion of the hexanucleotide repeat (GC) that leads to the production and accumulation of toxic dipeptide repeat proteins (DPRs). Some of these C9-DPRs contribute to neuronal dysfunction and degeneration through different mechanisms. One of these involves alterations in the protein quality control (PQC) system, specifically in the autophagy-lysosomal pathway. Valosin-containing protein (VCP) is a critical component of the PQC system, assisting the degradation of misfolded proteins and damaged organelles and the maintenance of cellular homeostasis. In this study, we investigated the role of VCP in modulating pathological features associated with C9 mutation. Using neuronal cell models, we demonstrated that VCP overexpression significantly reduced C9-DPRs levels. This reduction is mediated by mechanisms involving both the ubiquitin-proteasome system (UPS) and autophagy. Additionally, we also observed that C9-DPRs induce lysosomal damage, which is counteracted by VCP overexpression, as indicated by decreased galectin-3 puncta and restored lysosomal pH. We then pharmacologically activated VCP-mediated clearance through SMER28, increasing the clearance of the most toxic DPR, the polyPR. We also determined that in this model, SMER28 activity is mediated by the UPS and is associated with the mitigation of DPR-induced lysosome damage. Additionally, using motor neurons derived from induced pluripotent stem cells (iPSC-MNs) from C9-ALS mutation carriers, we demonstrated that SMER28 treatment significantly decreased polyGA levels, a marker for C9-DPR accumulation. Moreover, SMER28 rescued C9-MNs commitment to differentiation and the alteration in the expression of autophagy-related genes. Taken together, our findings strongly support VCP as a modulator of C9 pathology and highlight its potential as a therapeutic target.

Orthostatic hypotension (OH) and the co-existence with supine hypertension (SH) are debilitating consequences of autonomic failure in Parkinson's disease (PD) and multiple system atrophy (MSA). Head-up tilt sleeping (HUTS) has the potential to treat both simultaneously. Within the Heads-Up trial, 20 persons with PD or MSA and both SH and OH were assigned randomly to two HUTS schemes with gradually increasing angles: 1° (placebo), 6° and 12°; or 6°, 12° and 18°. The effect of increasing the head of the bed (per cm) was analyzed with linear mixed models. HUTS did not reduce nocturnal SBP but improved other indicators of blood pressure control, including early morning supine SBP, nocturnal dipping profile, diurnal SBP and SBP fall upon standing, coinciding with improved orthostatic tolerance. Adherence was 100% at 6°, 80% at 12°, and 60% at 18°. Higher angles were more effective, but at the cost of lower tolerability. The trial is registered at ClinicalTrials.gov (NCT05551377, 19-09-2022).

Memory loss is linked to failure of the engram, the physical substrate associated with a specific memory. Tau is a microtubule associated protein best known for its central role in neurodegenerative dementias, yet its physiological function in memory formation remains poorly understood. In this work, we show that tau is crucial for forming long lasting memories in mice. Site-specific tau phosphorylation at threonine-205 (T205) is induced by memory encoding and is required for remote memory formation. Tau T205 phosphorylation regulates engram cell, physical unit of memory storage, recruitment and constrains extraneous local cell activation, thereby promoting efficient memory recall. Tau selectively links sensory cue presentations to the encoding ensemble, as optogenetic retrieval of remote memory is tau-independent. Pathogenic tau within active cell ensembles induces aberrant local activation and causes anterograde or retrograde amnesia when present during an encoding or recall time window, respectively. Together, these findings identify a direct physiological role for tau in engram ensemble regulation and establish a mechanistic link between tau dysfunction and memory loss.

Effective disease-modifying therapies for Alzheimer's disease (AD) remain limited. Glucagon-like peptide-1 receptor (GLP-1R) activation has shown neuroprotective potential in AD, whereas the neuropeptide Y/pancreatic polypeptide-Y4 receptor (NPY/PP-Y4R) axis has been implicated in central homeostasis and inflammatory regulation, although its role in AD remains insufficiently defined. Here, we evaluated a rationally designed bifunctional peptide predicted to target both NPY4R and GLP-1R in 5 × FAD mice and LPS-stimulated BV2 cells. In vivo, NPY4/GLP-1 improved spatial learning and memory, working memory, and exploratory behavior, and was accompanied by reduced hippocampal Aβ burden (P < 0.05), alleviated neuronal injury (P < 0.01), improved synaptic integrity (P < 0.01), and attenuated mitochondrial abnormalities (P < 0.01). These changes were associated with lower hippocampal levels of cytosolic mitochondrial DNA (mtDNA) (P < 0.05), cGAS (P < 0.05), STING (P < 0.05), and phosphorylated IRF3 (P < 0.01), together with decreased IL-1β (P < 0.05) and increased IL-10 (P < 0.05) expression. In LPS-stimulated BV2 cells, NPY4/GLP-1 similarly reduced STING-related signaling (P < 0.05) and inflammatory responses (P < 0.05). Co-treatment with the STING inhibitor C-176 provided additional support for the involvement of STING-associated inflammatory signaling under in vitro inflammatory conditions. Molecular docking suggested that NPY4/GLP-1 may interact with both NPY4R and GLP-1R, providing a structural rationale for its bifunctional design. Collectively, these findings indicate that NPY4/GLP-1 exerts beneficial effects in AD-related models and that these effects are associated with attenuation of mtDNA-cGAS-STING-related neuroinflammatory signaling. This study provides initial evidence supporting further evaluation of this novel bifunctional peptide as a candidate therapeutic strategy for AD.

This review highlight the function of insulin in the central nervous system in addition to its role in the periphery. The cerebral distribution and mechanisms of insulin and its receptor isoforms are reviewed in detail. We emphasize the essential roles of insulin in the maintenance of cerebral glucose homeostasis, modulation of cognitive performance, regulation of appetite, promotion of cerebrovascular angiogenesis, and exertion of neuroprotective effects. We demonstrate how insulin resistance exacerbates characteristic neuropathological features in Alzheimer's disease (AD) and Parkinson's disease (PD), while insulin-based interventions ameliorate these pathologies through multiple mechanisms including increasing the activity of insulin-degrading enzyme, suppressing Aβ neurotoxicity, and reducing α-synuclein deposition. The review also systematically examines the neuroprotective effects of insulin sensitizers and their potential to reduce the risk of AD, while noting the complexity of their bidirectional regulatory role in PD, which warrants further investigation. Notably, intranasal insulin administration emerges as a promising non-invasive therapeutic approach that bypasses the blood-brain barrier via olfactory and trigeminal pathways, suggesting significant potential for cognitive enhancement and neuropathological mitigation. Nonetheless, it must be noted that the optimal dosage, long-term safety, and sustained efficacy of insulin therapy remain unclear, and the current evidence is derived primarily from preclinical studies or small-scale clinical trials. In summary, this review paper underscores the critical physiological roles of insulin in the brain and outlines novel therapeutic strategies for using insulin in the treatment of AD and PD.

BACKGROUND: The level of agreement between utility values derived from self- and proxy-reports, assessed using the preference-based health-related quality of life (HRQoL) instrument, the Alzheimer's Disease Five Dimensions (AD-5D), remains unclear. We aimed to investigate the agreement between self- and proxy-reported HRQoL, measured using the AD-5D, a dementia-specific, preference-based HRQoL instrument. METHODS: The data comprise 77 Australian dyads of people with dementia and their caregivers. The agreement between AD-5D utility values derived from self- and proxy-reports was analysed using a Bland-Altman plot. The ordinary least squares regression technique was employed to identify factors associated with the AD-5D utility value sets and to assess agreement between the resulting AD-5D utility values derived from self- and proxy-reports. RESULTS: The mean AD-5D utility value derived from self-reports (0.667) was higher than the value derived from proxy-reports (0.523). The Bland-Altman plot shows that 7.79% of the differences in AD-5D utility values fell outside the limits of agreement. The regression results indicated that the AD-5D utility value derived from self-reports for people with dementia aged 80 years or older was, on average, 0.20 points lower (β = 0.20, SE = 0.10) than that for people with dementia aged less than 70 years. CONCLUSION: Utility values derived from self-reports were higher than those derived from caregiver proxy-reports. While proxy reporting is a necessary alternative when self-reporting is not feasible, these perspectives are not interchangeable. Future economic evaluations should incorporate sensitivity analyses to account for this systematic 'proxy-gap'.

INTRODUCTION: This study aimed to evaluate the usefulness of the fox finger and reverse fox finger imitation tasks as screening tools for detecting cognitive impairment, including mild cognitive impairment (MCI) and dementia. METHODS: A total of 132 older adults visiting a memory clinic were classified into four groups: cognitively normal (CN; n=16), MCI (n=43), Alzheimer's dementia (n=60), and non-Alzheimer's dementia (n=13). Participants completed both imitation tasks, and performance was compared across groups. Sensitivity and specificity were calculated, and voxel-based morphometry (VBM) was used to identify brain atrophy associated with task performance. RESULTS: The fox finger task was successfully completed by 77.5% of participants, with significantly higher success in the CN group. The reverse fox finger task was more challenging, completed by only 21.7%. The sensitivity of the reverse fox finger task for detecting dementia and MCI was 88.5% and 79.1%, respectively, whereas the fox finger task showed lower sensitivity (36.1% and 13.9%, respectively) but higher specificity (100% vs 62.5%). Fox finger failure was associated with atrophy in the bilateral inferior frontal gyri and left frontal pole. Reverse fox finger failure was linked to more widespread atrophy, including the left angular gyrus, right hippocampus, and right posterior cingulate gyrus. Binary logistic regression confirmed that reduced gray matter volume in these regions significantly predicted task failure (p<0.05). CONCLUSION: The reverse fox finger task offers high sensitivity for detecting early cognitive decline, while the fox finger task provides high specificity, supporting their clinical use as rapid, non-invasive screening tools.

INTRODUCTION: To examine the knowledge, attitude, and practice (KAP) toward Alzheimer's disease (AD) prevention among middle-aged and elderly individuals in the community. METHODS: This cross-sectional study enrolled middle-aged and elderly individuals in the community who visited Kaifeng Central Hospital (China) between November 2023 and December 2023. Demographic characteristics and KAP scores were collected using an investigator-designed questionnaire. Higher scores indicate better KAP. The factors influencing KAP were identified using multivariable logistic regression analyses. The relationships among KAP dimensions were tested using a structural equation modeling (SEM) analysis. RESULTS: A total of 1271 questionnaires were finally collected (mean age: 54.40 ± 7.45 years old; 62.71% males). The mean knowledge, attitude, and practice scores were 13.02 ± 5.26 (possible range: 0-26), 38.70 ± 4.42 (possible range: 10-50), and 25.62 ± 3.93 (possible range: 11-55), respectively, indicating poor knowledge, favorable attitude, and poor practice. The SEM analysis showed that knowledge had a positive effect on attitude (β = 0.625, P < 0.001) and practice (β = 0.605, P < 0.001), and attitude positively influenced practice (β = 0.598, P < 0.001). CONCLUSIONS: Middle-aged and elderly individuals displayed poor knowledge, favorable attitudes, and poor practices toward AD prevention. Improving knowledge and attitude should translate into better AD prevention practices.

The brain age gap (BAG), the difference between magnetic resonance imaging-predicted brain age and chronological age, is a proposed marker of neurobiological aging, yet its transdiagnostic significance remains uncertain. This meta-analysis evaluated BAG in Alzheimer's disease (AD), mild cognitive impairment (MCI), multiple sclerosis (MS), Parkinson's disease (PD), schizophrenia (SCZ), stroke, and bipolar disorder (BD) to determine shared and disorder-specific patterns of accelerated brain aging. Sixty-five MRI-based studies were included. For each cohort, BAG was extracted or calculated, and standardized mean differences (Hedges' g) were computed between patient and healthy control groups using random-effects models. Subgroup analyses and meta-regressions were conducted to assess the influence of age and disorder characteristics. Publication bias and heterogeneity were evaluated using Egger's test, I statistics, and trim-and-fill procedures. BAG was significantly elevated across all disorders. The largest effects were observed in MS (mean adjusted BAG = 7.81 years; g = 0.89) and AD (5.57 years; g = 0.66). Meta-analyses of adequately powered disorders showed moderate elevations in SCZ (4.40 years; g = 0.42) and MCI (3.77 years; g = 0.43), while PD showed smaller but significant acceleration (3.52 years; g = 0.37). Descriptively, stroke (2 cohorts; mean adjusted BAG = 4.63 years) and BD (1 cohort; mean adjusted BAG = 4.84 years) also showed elevated BAG, though insufficient study numbers precluded formal meta-analysis for these disorders. BAG was largely independent of chronological age in neurodegenerative disorders but increased with age in SCZ. These findings support BAG as a transdiagnostic indicator of apparent accelerated brain aging in conditions where the meta-analytic evidence base is robust (AD, MCI, MS, PD, SCZ), while stroke and BD remain preliminary owing to limited cohort numbers. The magnitude of BAG varies substantially across conditions, and very high between-study heterogeneity (I > 90% in most disorders) means pooled effect sizes should be interpreted alongside prediction intervals.

INTRODUCTION: Alzheimer's disease (AD) is a progressive neurological disorder associated with high prevalence. Numerous studies have been conducted to regulate the expression of inflammatory genes, indicating that any changes may ultimately lead the nervous system toward disease pathogenesis. ANXA1, VCAM1, and CCL2 are among the genes involved in immune and inflammatory pathways. In this study, we aim to examine their expression in individuals with Alzheimer's disease and healthy individuals using bioinformatics and laboratory methods. MATERIALS AND METHODS: This study aimed to analyze the differentially expressed genes (DEGs) in the entorhinal cortex with AD and identify featured genes related to AD. Gene expression profile GSE118553 was downloaded from Gene Expression Omnibus, including 37 AD and 24 control samples. Based on the filters applied to the data, the immune genes ANXA1, VCAM1, and CCL2 were selected to investigate changes in expression in Alzheimer's disease. The expression of ANXA1, VCAM1, and CCL2 genes in the peripheral blood of 50 AD patients and 50 healthy controls was examined using Real-time polymerase chain reaction (Real-time PCR). Subsequently, statistical analyses of expression differences and biomarker analysis were conducted on the resulting data. FINDINGS: In the peripheral blood of AD patients, ANXA1 expression increased, while VCAM1 expression decreased compared to controls. No significant change was observed in CCL2. the receiver operating characteristic (ROC) analysis showed that ANXA1 is effective in distinguishing AD from healthy individuals. CONCLUSION: This study provides new insights into the role of the ANXA1 gene in the pathogenesis of Alzheimer's disease, but further research is needed to confirm this role.

BACKGROUND: We aimed to conduct an individual patient data meta-analysis on blood neurofilament light chain (NfL) in ischemic stroke (IS) to enhance its clinical applicability. METHODS: We performed a systematic literature search of studies on blood NfL measured in adult patients within 30 days after IS onset and derived age- and BMI-adjusted Z-scores based on a previously published reference population of healthy controls. We collected clinical, radiological and biochemical parameters of IS patients and tested associations of NfL at defined timepoints after IS onset (D1: < 24 h; D2: 24-48 h; D3: 48-72 h; D4-5: 72-120 h; D6-7: 120-168 h; D8-30: > 168 h) with baseline characteristics and 3-month follow-up outcomes (modified Rankin Scale, mRS; survival). RESULTS: We included 4081 blood NfL values from 2872 participants (IS n = 1985, transient ischemic attack n = 88, healthy controls n = 799) of 18 published studies and 3 unpublished cohorts. In patients with IS, NfL Z-score progressively increased from D1 [median: 2.0 (IQR: 0.9-2.9)] to D6-7 [median: 3.5 (IQR: 3.0-3.8)], with discriminative ability being high for IS vs. controls (AUC: 0.79-0.97) and fair for IS vs. TIA (AUC: 0.64-0.80). Higher NfL Z-score at D1 was associated with greater risk of symptomatic intracranial hemorrhage (aOR = 1.33, p = 0.014) and, from D2 onwards, with larger infarct lesion volume (highest Spearman's rho: 0.795 at D6-7). NfL independently predicted a mRS > 2 (aOR = 1.31, p < 0.001) and mortality (aOR = 1.67, p < 0.001) at 3 months. CONCLUSIONS: Blood NfL level was progressively elevated after IS, could discriminate IS from healthy controls with high accuracy and had prognostic value for intra-hospital complications and 3-month clinical outcomes in IS.

This mixed-methods systematic review aims to synthesise current research to identify the risk and protective factors of wellbeing in the dementia social care workforce. Seven databases were searched in April 2024 for evidence published between January 2003 and April 2024, focusing on the risk and protective factors for wellbeing in the dementia social care workforce. Titles, abstracts and full text articles were screened by two reviewers. A deductive thematic analysis and narrative synthesis was performed on extracted data to reveal four themes. 5,237 qualitative and quantitative records regarding the dementia social care workforce in the UK were screened. 13 studies were included. Taking an ecological systems approach, risk and protective factors of wellbeing in the dementia social care were narratively synthesised into key themes including structural factors, interpersonal factors, personal attributes and factors generating a systemic sense of value. Our findings indicate that dementia social care workers experience many risk and protective factors to their wellbeing at multiple levels. Whilst these factors for wellbeing were categorised into themes, these often overlapped and should be considered together when addressing wellbeing in the dementia social care workforce. Therefore, a multisystem approach is required to fully address the wellbeing of the dementia social care workforce.

BACKGROUND: Models trained on accelerometer data have been proposed for detecting prodromal Parkinson's disease (PD). However, uncertainties in diagnosis timing in the UK Biobank (UKBB) may affect generalizability to other cohorts. OBJECTIVES: The aim of the study was to evaluate the performance of previously published models for prodromal PD detection in other international cohorts. METHODS: We applied the models to data from German and British cohorts of individuals with isolated or idiopathic rapid eye movement sleep behavior disorder and healthy controls. We compared hourly acceleration patterns and classification performance across cohorts. RESULTS: The British cohort exhibited visually similar activity patterns to UK Biobank but weaker statistical differences and reduced model performance. The German cohort showed no significant group differences and lower performance. No pair of cohorts demonstrated statistical equivalence. CONCLUSIONS: Models trained on UK Biobank data may capture early clinical disease rather than universal prodromal markers. Prospective validation in well-characterized cohorts is essential before clinical translation. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

AIM: This study aimed to analyse the mediating role of digital dementia in the relationship between digital fugue and digital amnesia. METHOD: The study sample consisted of students aged 18 and older who were enrolled at a state university in Turkey (n = 394). Data were collected through face-to-face interviews using the following forms: 'Personal Information Form', 'OPIZA Digital Fugue Scale', 'Digital Dementia Scale-Adult Form' and 'Digital Amnesia Scale-Adult Form'. RESULTS: The mean age of the participants was 21.17 ± 1.72 (min: 18, max: 30), 59.4% were female, and the daily internet usage time was 6.24 ± 2.43 h (min: 1, max: 18). The study findings revealed that digital fugue was a significant predictor of both digital dementia and digital amnesia, and digital dementia had a positive and substantial effect on digital amnesia (p < .001). The findings also indicated a significant total effect of digital fugue on digital amnesia; however, the inclusion of digital dementia in the model reduced the direct effect but remained significant. According to the bootstrap analysis results, the study identified the indirect effect as statistically significant, and the confidence interval did not contain a 'zero' value. CONCLUSION: The study concluded that digital dementia partly mediates the relationship between digital fugue and digital amnesia. These results indicate that digital escapism behaviours should be considered in conjunction with cognitive functions and memory processes.

BACKGROUND: As the number of people with a migration background in Germany continues to rise, it is becoming increasingly critical to provide dementia care that addresses their needs. This study investigates the specific needs and barriers faced by people with a Turkish migration background in accessing dementia-related services, as well as the challenges experienced by healthcare professionals. By directly comparing family caregivers with and without a Turkish migration background, and by including healthcare professionals with and without a migration background, this study addresses an important research gap and explores how cultural narratives shape perceptions of good dementia care. METHODS: We conducted semi-structured, in-depth interviews with 11 professionals and 15 family caregivers of Turkish and German descent in Germany from November 2023 to June 2024. Data were analyzed using qualitative content analysis to identify key themes related to care experiences, service accessibility, and cultural perceptions of good dementia care. RESULTS: Family caregivers with a Turkish migration background often had limited knowledge of dementia, experienced cultural stigma, and preferred to care for their relatives at home due to strong familial and cultural expectations as well as financial barriers. They made little use of formal support services, often due to language barriers, fear of social judgment, and lack of culturally appropriate care options. In contrast, caregivers without migration background were generally better informed, more open to external help, and more likely to access professional care services. These differences were also influenced by the educational level of the interviewees, with higher levels of education linked to better knowledge and greater use of support structures. Interviews with professionals supported these findings. The need for diagnosis tools for foreign-born people and the need for culturally sensitive care based on biographical information was emphasized. CONCLUSIONS: This study highlights the urgent need for culturally sensitive dementia care in Germany with the aim of addressing the knowledge gaps, language barriers, and ethical conflicts encountered by people with a migration background. Incorporating individuals' cultural needs into healthcare can improve access, alleviate the burden on families, and ensure that care is addressed to their needs.

BACKGROUND: Caregivers of individuals with vascular dementia (VaD) face various physical and psychological burdens in their daily caregiving responsibilities. This role is challenging, demanding, and often stressful due to the symptoms characteristic of this condition. The aim of this study was to assess the level of burden experienced by caregivers of individuals diagnosed with vascular dementia. METHODS: The study included a total of 351 participants. The research was conducted anonymously and voluntarily among informal caregivers of individuals with dementia. A survey questionnaire and the Caregiver Burden Scale (CB Scale) were employed. Statistical analysis was conducted using the χ² independence test, t-test for independent samples, Mann-Whitney test, Kruskal-Wallis test, Spearman's rank correlation coefficient, Wilcoxon signed-rank test, and Kolmogorov-Smirnov test. RESULTS: High caregiving burden was most commonly observed in the domains of General Burden (63.2%), Disappointment (59.8%), and Social Isolation (58.1%). A significantly lower percentage of caregivers reported high burden levels in the domains of Environmental Factors (36.8%) and Emotional Engagement (34.2%). CONCLUSIONS: Our study demonstrates that caregivers of individuals with VaD experience particularly high levels of overall burden, social isolation, and a sense of disappointment. The findings highlight the need for early interventions focused on psychosocial support, as well as preventive programs aimed at reducing caregiver strain. In the broader perspective, these results may serve as a starting point for developing comprehensive models of home care and public health targeted at caregivers of individuals with VaD.

The inflammasome, a supramolecular complex, plays important role in the gut-brain axis (GBA), acting as a sensor of cellular stress and danger signals. It activates inflammatory responses, and its dysregulation has been implicated in neurological diseases. Various inflammasomes, such as NLRP3, NLRC4, and AIM2, contribute to disease progression by promoting inflammation, tissue damage, and oxidative stress. These inflammasomes recognize and get activated by different stimuli, such as ATP, fluctuations in ion fluxes, nucleic acids, and molecular signatures associated with pathogens, eventually releasing inflammatory cytokines, and triggering inflammatory responses. Although the inflammatory response is orchestrated, sometimes it might happen that its dysregulation causes excessive and sustained inflammation leading to cellular damage and tissue injuries. Inhibiting or modulating these inflammasomes can therefore, provide therapeutic benefits. Targeting NLRP3, like MCC950, has shown promise in reducing inflammation. Some natural compounds have also been found to inhibit NLRP3 and other inflammasomes. Interestingly, regulating the gut microbiome can impact inflammasome activation, and reduce unsolicited inflammation. This review explores the bidirectional communication network between the gut and brain, and emphasizes the importance of understanding the role of inflammasomes in the GBA which can lead to novel therapeutic strategies for neurological diseases like Multiple Sclerosis, Parkinson's, and Alzheimer's.

Extracellular deposition of amyloid-β (Aβ) peptides in the form of plaques is the most prominent pathological hallmark of Alzheimer's disease (AD). The postulated central pathophysiological role of fibrillary Aβ plaques has, however, been questioned, and small, soluble, pre-fibrillar Aβ aggregates (oligomers) have been implicated as the crucial neurotoxic species in AD etiology. While the relationship between insoluble amyloid plaques and soluble Aβ oligomers remains unclear, it has been hypothesized that plaques may serve as reservoirs, sequestering toxic Aβ oligomers in the initial stages of the disease. Next to the canonical "full-length" Aβ1-40 and Aβ1-42 peptides, a variety of N-terminally truncated Aβ variants are present in AD brain tissue, with Aβ4-42 peptides showing high abundance. The detrimental effects of these N-terminally truncated peptides have been previously studied using the Tg4-42 mouse line, which displays neuron loss and cognitive deficits and accumulates Aβ4-42 peptides in the CA1 region of the hippocampus albeit without amyloid plaque formation. This study aimed to investigate the relationship between soluble Aβ4-42 peptides and insoluble extracellular Aβ deposits by crossing the Tg4-42 line with the plaque-bearing 5XFAD mouse model. We found that extracellular amyloid deposits in the hippocampus did not aggravate spatial memory deficits in Tg4-42 mice but rescued recognition memory deficits. Moreover, while proximal CA1 pyramidal neuron loss in the hippocampus of Tg4-42 mice was not affected by crossing with the 5XFAD line, a reduced loss of distal pyramidal neurons was observed in the filial line. Biochemically, 5XFAD/Tg4-42 mice showed a trend towards increased levels of insoluble Aβ4-x peptides in the hippocampus. Taken together, these findings support the importance of soluble Aβ oligomers in the pathogenesis of AD and provide evidence for the hypothesis that amyloid plaques provide buffering capacity.

OBJECTIVE: Investigate associations between brain pathology (pTDP-43 inclusions and microglial activation) and cognitive and behavioural impairment in patients with amyotrophic lateral sclerosis (ALS). METHODS: Based on comprehensive neuropsychological examination and behavioural assessment, 21 ALS patients of whom post mortem brain tissue was obtained, were classified as having 1) no cognitive and/or behavioural impairment (pure motor ALS), 2) mild cognitive and/or behavioural impairment (ALSci/bi), and 3) ALS with behavioural variant frontotemporal dementia (ALS-bvFTD). Immunohistochemical staining of pTDP-43 and HLA-DR-defined microglial activation was semi-quantitatively assessed in grey and/or white matter of the prefrontal cortex, thalamus, hippocampus, and motor cortex. RESULTS: Fourteen patients had pure motor ALS, four patients had ALSci/bi, and three patients had ALS-bvFTD. pTDP-43 pathology in the grey matter of the prefrontal cortex and gyrus dentatus differed between groups, especially between pure motor ALS and ALS-bvFTD. For each extra-motor brain region, pTDP-43 severity was highest in patients with ALS-bvFTD and lowest in patients with pure motor ALS, with ALSci/bi in between. This pattern was not observed for microglial activation. Associations between white matter pTDP-43 severity and cognitive/behavioural impairment were less robust than those in grey matter. CONCLUSION: Severity of cognitive and/or behavioural impairment in ALS is related to severity of pTDP-43 pathology, in particular in the grey matter of extra-motor brain regions; we did not detect a clear association with microglial activation.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and neuronal death. Approved therapies, including acetylcholinesterase inhibitors and NMDA receptor antagonists, provide only symptomatic relief without halting progression. AD involves multifaceted pathologies: amyloid-β (Aβ) accumulation, tau hyperphosphorylation, oxidative stress, neuroinflammation, mitochondrial dysfunction, and apoptosis. Multi-target natural compounds like ginsenosides from Panax ginseng show promise in preclinical models by modulating these pathways. Key ginsenosides (Rg1, Rb1, Rc, Rd, Re, Rg3) inhibit Aβ production (via BACE1 suppression and α-secretase enhancement), promote Aβ clearance (via IDE/NEP upregulation), reduce tau phosphorylation (via GSK-3β/CDK5 modulation), and exert antioxidant, anti-inflammatory, and anti-apoptotic effects. Limited clinical evidence from small open-label trials of Korean Red Ginseng suggests cognitive improvements (e.g., in ADAS-cog and MMSE scores), with good tolerability. However, poor oral bioavailability and limited blood-brain barrier (BBB) penetration remain challenges, addressable via intranasal or nanoparticle delivery. While preclinical data are robust, clinical translation is limited by study heterogeneity and small samples. Ginsenosides warrant further investigation as adjunctive multi-target agents for AD.