Neuroinflammation assumes a pivotal role in Alzheimer's disease (AD) pathogenesis. Long noncoding RNAs (lncRNAs) regulate neuroinflammation through a competitive endogenous RNA (ceRNA) mechanism. This study aimed to explore the mechanism of SNHG3/miR-128-3p/UBR5 axis in AD associated neuroinflammation. SNHG3, miR-128-3p, and UBR5 levels were recognized by reverse transcription - quantitative polymerase chain reaction (RT-qPCR). In vitro AD model was established by Aβ1-42 stimulation in human microglial cells HMC3 and neuronal cells SK‑N‑SH. Cell apoptosis was detected by flow cytometry. Enzyme - linked immunosorbent assay (ELISA) and oxidative stress indicators were used to evaluate the neuroinflammatory phenotype. Morris water maze (MWM) test assesses the spatial learning and memory abilities of amyloid precursor protein/presenilin 1 (APP/PS1) mice with AAV-si-SNHG3. Serum SNHG3 was clearly upregulated in AD patients, and negatively related to MMSE score (r = -0.691, P<0.001). SNHG3 had diagnostic potential for AD (AUC=0.847, 95% CI = 0.806-0.888, sensitivity=75.63%, specificity=76.88%). SNHG3 regulates UBR5 expression by sponges miR-128-3p. Silence of SNHG3 inhibited M1 polarization (reducing TNF-α, IL-6, and iNOS), promotes M2 polarization (increasing Arg1, IL-10, and TGF-β), inhibits IL-1β release, suppresses neuronal apoptosis, and mitigates oxidative stress damage (reducing MDA and increasing SOD) via miR-128-3p/UBR5 axis in Aβ-stimulated HMC3 cells. SNHG3 also contributes to Aβ‑induced neuronal apoptosis, inflammation, and oxidative stress in SK‑N‑SH cells. AAV-si-SNHG3 significantly enhances spatial learning and memory abilities of APP/PS1 mice, and inhibits neuroinflammation and oxidative stress in the hippocampus. This study is the first to elucidate that SNHG3 could regulate microglial polarization and neuroinflammation through the SNHG3/miR-128-3p/UBR5 axis.

INTRODUCTION: We assessed whole hippocampal and subfield volumes, in association with memory ability, in a sample including cognitively unimpaired (CU) older adults and those in early syndromic stages of pathological aging, here subjective cognitive decline (SCD) and mild cognitive impairment (MCI). METHODS: Participants completed a battery of neuropsychological tests and a 3T magnetic resonance imaging brain study that included high-resolution T2-weighted images of hippocampus and its subfields: subiculum; cornu ammonis 1, 2, and 3 (CA1, CA2, CA3); and dentate gyrus (DG). RESULTS: Significant differences were found in the left whole hippocampus, left subiculum, CA1, and DG volumes in the MCI group compared to the CU or SCD groups. Least absolute shrinkage and selection operator regression techniques revealed that left subiculum and left CA1 volume significantly predicted memory ability above and beyond whole hippocampal and other subfield volumes. DISCUSSION: We found clinical differences in memory ability in older adults were associated with focal differences in specific hippocampal subfield volumes.

INTRODUCTION: We investigated the association between cochlear implantation and the risk of cognitive decline in adults with hearing loss using a national population cohort. METHODS: Our cohort comprised 4106 participants who underwent cochlear implantation and matched controls with untreated hearing loss, followed over a median of 7.3 years. Propensity score matching was applied to control for confounders, and Kaplan-Meier analysis was used to assess time-to-event outcomes. RESULTS: Participants with cochlear implants had a significantly reduced risk of all-cause dementia (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.50-0.74), mild cognitive impairment (HR 0.53, 95% CI 0.40-0.70), and memory loss (HR 0.54, 95% CI 0.45-0.65) compared with controls. These associations remained significant in sex-stratified analyses for both male and female participants. DISCUSSION: These results support early auditory intervention as a dementia prevention strategy and warrant further research with longer follow-up periods across diverse populations.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited disease-modifying therapies. Aluminium chloride (AlCl)-induced neurotoxicity mimics key pathological features of AD, including oxidative stress, neuroinflammation, and cholinergic dysfunction. OBJECTIVE: This study aimed to evaluate the neuroprotective effect of cnicin in an AlCl-induced rat model of Alzheimer-like neurodegeneration. METHODS: Rats were divided into five groups: normal control, AlCl control (75 mg/kg/day, p.o.), AlCl with cnicin (20 and 40 mg/kg/day, p.o.), and AlCl with donepezil (5 mg/kg/day, p.o.) for 30 days. Behavioral performance was assessed using hanging wire and beam walking tests. Biochemical parameters, including acetylcholinesterase (AChE), antioxidant enzymes (SOD, CAT, GSH), malondialdehyde (MDA), and inflammatory cytokines (TNF-α, IL-1β) were analyzed, along with histopathology. RESULTS: AlCl administration induced significant behavioral deficits, increased AChE activity, oxidative stress, neuroinflammation, and neuronal damage. Cnicin treatment dose-dependently improved motor function, reduced AChE activity, restored antioxidant levels, decreased lipid peroxidation, and suppressed inflammatory markers. Histological analysis confirmed preservation of neuronal architecture, comparable to that of donepezil. CONCLUSION: Cnicin exhibits significant neuroprotective effects against AlCl-induced neurodegeneration by modulating cholinergic activity, oxidative stress, and inflammation, suggesting its potential as a therapeutic agent for AD.

OBJECTIVE: To identify factors associated with mild cognitive impairment (MCI) in older adults with multimorbidity and to develop and validate a predictive model for early screening. METHODS: This cross-sectional study consecutively enrolled 238 older adult inpatients with multimorbidity at the Affiliated Kangning Hospital of Wenzhou Medical University, China, between April 2022 and February 2025. Participants were assessed using a self-designed general information questionnaire and the Montreal Cognitive Assessment Basic Scale (MoCA-B). MCI was diagnosed according to the Chinese Expert Consensus. Associated factors were identified using logistic regression analysis. A nomogram prediction model was constructed based on these factors. The model's performance was evaluated using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). An external validation cohort (n=68) was used to further test the model. RESULTS: MCI prevalence was 26.81%. Risk factors: age ≥80 years (OR=3.23), hearing impairment (OR=4.04), and emotional disorders (OR=3.25). Protective factors: higher education (OR=0.23), more frequent physical exercise (OR=0.15), and more frequent social activities (OR=0.26) (all P<0.05). The AUC was 0.862 (training) and 0.832 (external validation). Calibration curves showed good agreement, and DCA indicated net clinical benefit across threshold probabilities of (10-65%). CONCLUSION: Age, hearing impairment, emotional disorders, education, physical exercise, and social activities are significantly associated with MCI in older adults with multimorbidity. The nomogram demonstrates good predictive accuracy and clinical utility, aiding early identification and targeted prevention.

BACKGROUND: Early detection of cognitive impairment remains a critical public health challenge. While biomarkers such as neuroimaging and cerebrospinal fluid analyses offer high sensitivity, their limited accessibility hampers widespread screening, especially in underserved settings. Speech-based markers have emerged as promising, noninvasive indicators of cognitive decline. OBJECTIVE: To develop and validate SpeechDETECT, an end-to-end speech-processing pipeline that captures fine-grained acoustic and temporal markers of cognitive impairment and provides interpretable outputs suitable for large-scale screening. METHODS: SpeechDETECT comprises six modules: (1) noise reduction / amplitude normalization; (2) an eight-domain voice-analysis framework (e.g., frequency parameters, speech fluency); (3) 50 ms segment-level feature extraction; (4) feature visualization; (5) dimensionality reduction / selection (Joint Mutual Information Maximization, LassoNet, PCA); and (6) classifier training with SHapley Additive exPlanations (SHAP). Performance was benchmarked against six acoustic toolkits (e.g., GeMAPS) on two English datasets: the DementiaBank Pitt corpus (train = 166, test = 71) with single cookie-theft picture description task and NIA PREPARE Phase 2 corpus (train = 1 064, test = 267) with multiple speech tasks. RESULTS: A Multi-Layer Perceptron trained on PCA-derived SpeechDETECT features achieved an F1-score = 0.81% and AUC-ROC = 0.80 on the Pitt test set, outperforming the best competing toolkit (AUC = 0.76). On the PREPARE test set-comprising ≤ 30 s recordings from four speech tasks-the same model attained F1 ≈ 0.67% and AUC-ROC = 0.70 demonstrating good generalizability. Cumulative-gains analysis showed that screening the top 40% of ranked participants captured ~ 70% of cognitively-impaired (CI) cases in Pitt and ~ 63% in PREPARE. SHAP revealed speech-fluency metrics (hesitation rate, pause ratio) and high-frequency formant dynamics as the most discriminative features. CONCLUSION: SpeechDETECT delivers accurate (AUC up to 0.80) and interpretable detection of early cognitive impairment across both structured and multi-task speech settings. Its fully automated, domain-informed approach enables scalable, speech-based screening and provides a foundation for multimodal systems that combine acoustic markers with clinical or biomarker data to further improve diagnostic precision The SpeechDETECT toolkit is openly available on GitHub at https://github.com/SpeechCARE/SpeechDETECT-Toolkit for researchers and clinicians. A demo tutorial video showing pipeline usage is available at https://github.com/SpeechCARE/SpeechDETECT-Toolkit/blob/main/SpeechDETECT.mp4.

The oral microbiome is implicated in a wide diversity of fundamental biological functions, with the oral cavity serving as a connection between the host and the external environment. Dental calculus, a mineralized form of dental plaque, preserves the diversity of biomolecules found in the oral cavity through time, serving as a rich source of historical microbiota. Despite its potential, dental calculus has rarely been explored outside of humans and non-human primates. Hence, it remains unclear how ubiquitous it is across mammals. Using natural history museum collections, we surveyed > 1600 specimens belonging to 142 species, representative of almost all mammalian orders, to investigate the taxonomic distribution of dental calculus, and to identify factors that most strongly contribute to its formation. We found dental calculus to be abundant across mammalian taxa, with 104 surveyed species showing calculus. High-fiber diets were most strongly associated with calculus abundance, whereas species with high protein and fat diets showed little to no calculus deposits. We found evidence of phylogenetic signal in calculus formation, pointing to the effects of oral/dental morphology. In addition, captivity strongly affected dental calculus formation in almost all dietary categories. Using this information, we made predictions about the likelihood of finding dental calculus in unsurveyed mammalian species, opening doors for its utilization for the study of oral microbiota, past and present. Our study found that dental calculus is well-preserved and readily available in natural history museum collections, making it an easily accessible source of oral microbiota from wild animals. We highlight the taxonomic diversity of species presenting dental calculus and provide information and suggestions for its use to researchers and curators alike.

Current dementia diagnostic methods can be costly, invasive, or limited in their ability to distinguish between disorders with overlapping clinical symptoms. Dysregulated microRNAs (miRNAs) have emerged as promising noninvasive biomarkers for neurodegenerative disease, but individual miRNA changes alone may not capture the complex molecular patterns needed for accurate disease classification. Machine learning provides a way to integrate multiple layers of miRNA-derived information and identify disease-specific biomarker signatures. In this study, we developed machine learning models to classify dysregulated miRNAs associated with Alzheimer's disease dementia (AD), Lewy body dementia (LBD), and frontotemporal dementia (FTD). Each miRNA was represented using sequence-derived descriptors, predicted gene targets, and KEGG pathway features. The highest-performing models trained on AD, LBD, and FTD achieved 10-fold cross-validation accuracies of 90.6%, 92.9%, and 100%, respectively. When evaluated on independent datasets, the AD, LBD, and FTD models achieved accuracies of 88.9%, 77.8%, and 90.9%, respectively. Cross-disease testing showed reduced performance when models were applied across dementia types, suggesting partially disease-specific miRNA patterns while also indicating overlap among the molecular signatures of AD, LBD, and FTD. These results suggest that machine learning-based integration of miRNA sequence, target-gene, and pathway information can improve the identification of dementia-associated biomarker signatures and may support the future development of noninvasive diagnostic tools for dementia.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder lacking effective disease-modifying therapies. A promising regenerative approach involves enhancing endogenous neurogenic capacity within the injured brain. Reactive astrocytes-stellate-like cells in the AD brain-may contribute to a pro-neurogenic environment through transcription factors (TFs) such as neurogenin 2 (NGN2) and SOX-11. This process is tightly regulated by epigenetic mechanisms, particularly SIRT-1, a neuroprotective histone deacetylase that modulates TF activity and neuronal fate. Vitamin A (V), a key regulator of differentiation and epigenetic remodeling via its active metabolite retinoic acid, is stored in astrocytes and hepatic stellate cells (HSCs). We hypothesized that AD-related astrocyte activation depletes cerebral V, mobilizes hepatic stores, contributes to liver fibrosis, and that V supplementation may restore astrocytic function, activate endogenous TFs via SIRT-1, and drive cholinergic neuron regeneration. In a scopolamine (SCO)-induced AD rat model, V biodistribution was traced using confocal microscopy. Brain and liver V deficiency were confirmed via retinol-binding protein (RBP) and ALDH1A1 expressions. Rats received V (1500, 3000, or 4500 IU/kg/day) or donepezil. Outcomes included neurogenesis (DCX), NGN2/SOX-11 expression, SIRT-1 activation, cholinergic regeneration, amyloid-β deposition, and serum tau. Liver fibrosis was assessed via TGF-β, hydroxyproline and histopathologically. AD induced systemic V depletion and liver fibrosis. Medium-dose V (VAMD) significantly enhanced neurogenesis, TF expression, SIRT-1 activation, cholinergic regeneration, and reversed liver fibrosis. VAMD demonstrated neuroregenerative and antifibrotic effects, indicating a possible therapeutic role in AD.

Alzheimer's disease (AD) is the leading cause of dementia, yet current therapies provide limited clinical benefit. Neuroinflammation, as an early and sustained driver of AD, places the NLRP3 inflammasome at the center of pathological and therapeutic focus. In this review, we synthesize recent advances in the structure, assembly, and activation of the NLRP3 inflammasome, and evaluate its contribution to AD using evidence from human brain tissues, cerebrospinal fluid, and diverse AD animal models. Available data consistently support aberrant NLRP3 activation in AD brain, where it is closely associated with amyloid-β (Aβ) deposition, tau pathology, glial reactivity, and cognitive decline. We further discuss the cell-type-specific roles of microglia and astrocytes, highlighting microglia as the principal effector cells in inflammasome-associated pathology. Mechanistically, Aβ and tau converge on NLRP3 activation through interconnected pathways involving K efflux, lysosomal rupture, mitochondrial dysfunction, and impaired autophagy. Downstream IL-1β, IL-18, and gasdermin D amplify neuroinflammation and neuronal injury. We summarize emerging therapeutic strategies directly targeting its core components or downstream effectors, as well as anti-AD agents with indirect NLRP3 modulation including endogenous molecules, repurposed drugs, and natural products. Collectively, this review regards NLRP3 inflammasome as a critical inflammatory hub and a promising target for disease-modifying therapy in AD, and provide useful perspectives on AD pathogenesis and inform the development of more rational therapeutic strategies.

Presenilins are best known as the catalytic core of γ-secretase, where familial Alzheimer's disease (FAD) mutations shift amyloid-β (Aβ) trimming toward aggregation-prone species. Yet conditional and cell-type-specific genetic analyses in mice now place presenilin (PS) biology far beyond amyloidogenesis. In PS1/PS2 conditional double-knockout (PS cDKO) models, where presenilins are inactivated postnatally in forebrain excitatory neurons, the earliest phenotype is a synaptopathy: presynaptic release probability and short-term plasticity collapse, N-methyl-D-aspartate receptor (NMDAR) function wanes, and cAMP response element-binding protein (CREB)/CREB-binding protein (CBP)-dependent transcriptional programs falter. Compensatory glial responses rapidly consolidate into a neuroinflammatory state, with inflammasome activation and cytokine surges that further erode synaptic signaling and promote tau hyperphosphorylation. Progressive cortical and callosal atrophy and ventriculomegaly follow, culminating in neuron loss, even as cortical Aβ is reduced, severing the mechanistic necessity of plaques for degeneration. Across interventions, anti-inflammatory, cholinergic, and metabolic manipulations rescue cognition and plasticity in PS cDKO mice without engaging amyloid, underscoring a disease axis that is Aβ-independent yet clinically salient. Here we synthesize lessons from PS cDKO studies, integrate them with contemporary presenilins/γ-secretase biology, and outline a translational agenda focused on presynaptic Ca microdomains, RyR-coupled release, activity-dependent gene programs, and innate immune checkpoints. We conclude that PS integrate vesicular release machinery with trophic and inflammatory homeostasis; their loss initiates a multi-scale failure cascade that redefines early AD-related neurodegeneration beyond Aβ.

Ceruloplasmin (Cp) is a multifunctional multicopper oxidase principally produced in the liver and, to a lesser extent, in the central nervous system. It regulates iron homeostasis and oxidative balance, Cp oxidizes ferrous iron (Fe²⁺) to ferric iron (Fe³⁺), thereby enabling its safe integration into transferrin and averting reactive oxygen species formation. Beyond its ferroxidase activity, Cp also serves as a major copper carrier in plasma and contributes to antioxidant defense mechanisms. Although, the imbalance of ceruloplasmin has been gradually recognized as a key marker in the pathogenesis of neurodegenerative disorders. It is associated with neurofibrillary tangles, amyloid plaques, tau hyperphosphorylation, oxidative stress, and mitochondrial dysfunction. In the past, Cp and neuropathology were first established when a decreased level of serum ceruloplasmin was reported as a diagnostic biomarker of Wilson's disease, a disorder characterized by copper build-up triggered by mutations in the ATP7B gene. Furthermore, some studies suggest the absence of Cp was known in aceruloplasminemia, a different neurodegenerative condition characterized by extensive deposition of iron in the brain and progressive neuronal loss. However, several studies have reported that Cp's function and expression undergo important modifications in Alzheimer's, Parkinson's, Wilson's disease, and other neurological conditions. These alterations in Cp are directly linked to disrupted metal homeostasis, alleviating oxidative stress and neuroinflammation. Thus, besides understanding the structural, metabolic, and biological roles of Cp, this review aims at explaining its possible effects on common neurological disorders. The review also focusses on the therapeutic opportunities targeting Cp-mediated pathways, primarily, focusing on how Cp dysfunction interrelates with copper metabolism, iron dysregulation, and neuroinflammatory signalling, as reported in various clinical and experimental studies. Understanding Cp mechanism may highlight novel strategies for overcoming these neurodegenerative diseases.

INTRODUCTION: The purpose of this study was to use a Hoffman brain phantom with an insert simulating posterior cingulate cortex (PCC) hypoperfusion to assess how Z-score-based statistical outputs change when a filtered back projection (FBP)-based normal database (NDB) is applied to ordered subset expectation maximization (OSEM) brain perfusion single-photon emission computed tomography (SPECT) images reconstructed with resolution recovery. METHODS: SPECT/computed tomography was performed with an Infinia 8 Hawkeye 4 system equipped with an extended low-energy general-purpose collimator. A custom PCC insert was fabricated using three-dimensional printing and mounted in the Hoffman phantom. Data were acquired with and without the insert, filled with iodine-123 solution. Images were reconstructed by FBP without attenuation correction, OSEM without attenuation correction, and OSEM with resolution recovery. Z-scores and Z-summation values were computed with a FBP NDB without attenuation correction and a FBP NDB with Chang attenuation correction. RESULTS: Resolution recovery produced a sharper cortical outline with higher apparent cortical contrast. With the NDB without attenuation correction, Z-scores were higher across most regions with OSEM than FBP and were highest with resolution recovery, with several regions shifting from around the Z = 2 cutoff to above it. With the Chang-corrected NDB, Z-scores were higher overall and differences among reconstruction conditions widened. Z-summation in the precuneus was highest with resolution recovery, whereas the PCC peaked with OSEM without resolution recovery. CONCLUSION: When resolution recovery-processed images are analyzed using a conventional FBP NDB, Z-score-based indices shift in a region-dependent manner, and their level varies with NDB settings, including attenuation correction. IMPLICATIONS FOR PRACTICE: The reconstruction protocol and NDB should be matched whenever possible, because mismatches may alter Z-score maps and affect cutoff-based interpretation of dementia-related hypoperfusion patterns.

Driving cessation in older adults with dementia is associated with reduced independence, social isolation, and accelerated cognitive decline, yet determining fitness to drive remains challenging. This qualitative study explored older adults' attitudes toward driving safety decisions and their preferred responses if informed that they may no longer be safe to drive. Twenty-two older adults, including individuals with mild cognitive impairment (MCI) at risk for dementia and cognitively healthy controls, participated in walking-talking interviews following cognitive and hazard perception screening assessments. Interviews explored participants' views on what should happen next if test results suggested they were unsafe to continue driving. Audio-recorded interviews were transcribed verbatim and analysed using thematic analysis. Six themes and sixteen codes were identified. Participants with MCI demonstrated greater acceptance of driving cessation, and sought confirmatory assessments, whereas healthy control participants prioritised transparency about test results, openness to remediation through lessons or vehicle adaptations, and preservation of independence. These findings highlight the importance of personalised interventions and the potential for non-invasive in-car technologies to support safe driving in individuals with early-stage dementia. This study highlights the value of qualitative methods in understanding the nuanced perspectives of older drivers and informs future strategies for managing driving cessation in cognitively impaired individuals at risk for dementia.

AIM(S): To develop a care-bundle of non-pharmacological strategies with the potential to prevent constipation in people with dementia in Residential Aged Care (RAC). DESIGN: Mixed-methods intervention development study using Modified Delphi and co-design, informed by evidence, current constipation prevention practices and stakeholder collaboration to define best practice. METHODS: The draft bundle was developed using evidence from a scoping review, consultations with aged care professionals and staff at two RAC homes and field observations. It was then refined through expert and lived-experience panels via an online Modified Delphi survey (rating relevance, acceptability and feasibility) and a face-to-face workshop to finalise items for the constipation prevention care-bundle. DATA SOURCES: Health data, interviews, observations, surveys and workshops. RESULTS: The draft care-bundle comprised 24 items; 13 reached ≥ 78% agreement in the Modified Delphi, including dietitian consultation, adequate fibre, individualised hydration and toileting plans, beverage cart, constipation risk assessment, privacy during toileting, dementia-friendly signage, toileting positioning, contrasting toilet seat, electronic alerts, staff education and resident/family information. CONCLUSION: An evidence-informed and co-designed care-bundle was co-developed with potential to prevent constipation in residents with dementia. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: This research has implications for nursing practice by offering an alternative to reliance on pharmacological strategies for preventing constipation in people with dementia. IMPACT: This co-designed and evidence-informed care-bundle has potential to reduce the incidence of constipation among the growing population with dementia. To ensure sustained use, it was co-designed with stakeholders to be fit-for-purpose. REPORTING METHOD: There were no reporting guidelines for this co-design study identified. PATIENT OR PUBLIC CONTRIBUTION: End-users, including frontline staff and older people receiving care, as well as carers of people with dementia, were engaged in the co-design as equal partners in the constipation prevention care-bundle development process.

There is considerable evidence that iron accumulation in the affected brain regions plays a role in the pathology of neurodegenerative diseases, probably because of the ability of iron ions to promote oxidative damage to important biomolecules, such as DNA, RNA, proteins and lipids (leading to lipid peroxidation). Yet recent clinical trials of iron ion-chelating agents in human neurodegenerative diseases have given unimpressive results, in several cases making the diseases worse. In using iron chelators, it is important to remember the basics of their redox chemistry, which could explain their lack of therapeutic effects. This issue is explored here, and the potential of iron ion chelation in the treatment of neurodegeneration is critically evaluated.

The microbiota-gut-brain axis (MGBA) is a bidirectional signaling pathway regulated by the gut microbiome and the central nervous system (CNS). Moreover, MGBA is crucial for normal growth, development, and physiology of the brain and gut of the host; dysfunction in MGBA has been closely linked with the development of neurological disorders. Gut dysbiosis and its metabolites modulate barrier permeability and cause gastrointestinal tract (GIT) inflammation, which is followed by an increase in pro-inflammatory cytokines, immune cell infiltration into the brain, and vagus nerve dysfunction, resulting in neuroinflammation and neuronal defects in the brain, as well as some other behavioral defects. In this review, we will discuss the molecular and neurobehavioral properties of Zebrafish as a research model to study MGBA, as well as current discoveries in humans, highlighting the vital role of MGBA in neuropathological conditions. Using Zebrafish as a genetic model in combination with in vivo imaging technology may suggest some novel mechanisms for the interaction between gut microbiota and CNS, particularly in the case of neurological disorders including Alzheimer's disease (AD), Parkinson's disease (PD) and autism spectrum disorder (ASD). A comprehensive literature search was conducted using electronic databases including PubMed, Scopus, Web of Science, and Google Scholar.

OBJECTIVES: Identifying modifiable factors that shape cognitive aging trajectories is a central goal in aging research. This study examined whether bilingualism is associated with dementia status and longitudinal cognitive decline, and whether associations vary by ethnicity or gender. METHODS: We analyzed Wave 7 data from the Health and Aging Brain Study-Health Disparities (HABS-HD), a longitudinal U.S. cohort of adults aged ≥50 years. Bilingualism was defined by self-reported use of a second language. Cross-sectional analyses included 4,140 participants (1,013 bilinguals); longitudinal analyses included 1,760 participants (522 bilinguals) followed for up to four visits at approximately 2-year intervals. Outcomes were baseline dementia status and latent factor scores for executive function and episodic memory derived from 11 neuropsychological tests. Regression and linear mixed-effects models assessed associations, adjusting for age, education, gender, ethnicity, and practice effects. RESULTS: Bilingualism was not associated with baseline dementia status or conversion to probable dementia. Cross-sectionally, associations varied by ethnicity: Hispanic bilinguals showed higher executive function and episodic memory scores. No advantage was observed in White participants; conversely, Black bilinguals had lower episodic memory scores. Longitudinally, bilingualism was associated with slower episodic memory decline independent of sociodemographic factors; no longitudinal association was observed for executive function. DISCUSSION: These findings suggest that bilingualism may confer domain-specific benefits for memory trajectories in later life, while cross-sectional differences appear shaped by sociocultural context. The results underscore the importance of considering ethnic diversity and language history when evaluating experiential influences on cognitive aging.

BACKGROUND: SGLT2 (sodium-glucose cotransporter-2) inhibitors (SGLT2is) improve outcomes in heart failure (HF), but evidence in patients with frailty and acute HF (AHF) is limited. This study investigated the association between SGLT2i use at discharge and outcomes in patients with AHF, with a focus on frailty. METHODS: We analyzed 5579 patients hospitalized for AHF enrolled between 2018 and 2024 in the prospective WET-HF2 (West Tokyo Heart Failure 2) registry in Japan (age 79 years, 43% women, body mass index 23.1, 23% ischemic cause, left ventricular ejection fraction 45%, 24% SGLT2is at discharge). Frailty was assessed using the Clinical Frailty Scale (≥4; 63%), and complementary analyses were performed using frailty-related factors (low body mass index, reduced activities of daily living, malnutrition, and dementia). The primary outcome was a composite of cardiac death or HF rehospitalization within 1 year, which occurred in 766 patients (18%). A propensity score was calculated using variables associated with SGLT2i prescription. RESULTS: After propensity score-based inverse probability of treatment weighting adjustment, SGLT2i use was associated with a lower risk of the primary outcome (hazard ratio [HR], 0.76, =0.045). This association was more pronounced in patients with frailty (HR, 0.59, =0.005), but not in patients without frailty (HR, 1.18; =0.010). Analyses using frailty-related factors yielded similar patterns. At 1 year, SGLT2i use at discharge was not associated with deterioration in body mass index or nutritional status. CONCLUSIONS: In this observational registry, SGLT2i use at discharge was associated with improved outcomes in patients with AHF, particularly those with frailty, without evidence of nutritional harm. These findings support the potential safety of SGLT2is in patients with frailty and AHF.

Cognitive impairment and Alzheimer disease and related dementias are increasingly prevalent and carry significant morbidity. Growing evidence has highlighted the complex interactions between cardiovascular and brain health, implicating vascular dysfunction in the pathogenesis of many forms of cognitive impairment. The American Heart Association (AHA) and the American Stroke Association have outlined a comprehensive framework, known as Life's Essential 8, that includes 4 behavioral health factors (healthy dietary pattern, physical activity, avoidance of nicotine, and healthy sleep) and 4 health factors (cholesterol, blood glucose, blood pressure, body mass index) that collectively define optimum cardiovascular health. Modifiable risk factors account for an estimated 40% of worldwide dementia. Adherence to Life's Essential 8 principles may also help individuals mitigate the risk of cognitive impairment via improved cardiovascular health. However, a comprehensive understanding of the causal relationships between vascular and behavioral risk factors and Alzheimer disease and related dementias remains unclear and requires further study. This narrative review summarizes well-established data and highlights new data for how health and behavioral factors included in Life's Essential 8 also promote optimal brain and cognitive health.

INTRODUCTION: Over 55 million people worldwide live with dementia, placing significant demands on family and friend caregivers. These demands lead to stress, depression, and social isolation. Caregivers report unmet needs such as access to resources, education, and emotional support. A Virtual Community of Practice (VCoP) offers a promising solution by fostering shared learning, emotional support, and practical caregiving strategies. OBJECTIVES: This study explored the (a) perceptions of caregivers and a person living with dementia of the VCoP (b) recommendations of caregivers and a person living with dementia to improve the VCoP and (c) experiences of caregivers and a person living with dementia in co-designing the VCoP. METHODS: Using a mixed-method sequential explanatory approach, ten research partners (nine caregivers and one person with dementia) participated in two virtual workshops and follow-up interviews. Survey data were collected via the System Usability Scale (SUS) and Patient and Public Engagement Evaluation Tool (PPEET). Survey data were analyzed using descriptive statistics. Thematic analysis of workshop and interview data was conducted. RESULTS: The VCoP achieved an SUS score of 94.5, indicating excellent usability. PPEET results showed high satisfaction with engagement in development. A total of eight themes were developed. Thematic analysis highlighted strengths such as ease of locating information on the website, practical content, and opportunities for sharing and learning through discussion forums. Recommendations included improving accessibility, tailoring activities to life stories, and ensuring activities maintain normalcy. Research partners felt included and supported during the workshops, enjoyed the small group atmosphere, and appreciated seeing their ideas reflected in the final product. CONCLUSIONS: The VCoP was perceived as practical for supporting caregivers. Involving people with lived experience ensured the intervention met caregiver needs. Findings underscore the importance of VCoPs and the value of co-design in creating effective caregiver support tools.

Thioflavin T (ThT) is a commonly used dye that probes amyloid fibrils associated with Alzheimer's and Parkinson's diseases. Binding to amyloid fibrils significantly enhances ThT fluorescence, while hindering the formation of the twisted intramolecular charge transfer (ICT) state in the dimethylaniline group. On the other hand, ThT fluorescence is strongly quenched in aqueous and aliphatic alcohol solutions with efficient ICT in the excited states. No direct experimental evidence for the structural changes of ThT with ICT has been reported yet. In this work, we report the structural changes of ThT during ICT by time-resolved Raman spectroscopic methods, which include the bend of the benzothiazole and the twist of the dimethylaniline group. Both femtosecond stimulated Raman spectroscopy and impulsive stimulated Raman spectroscopy suggest that the ICT coordinate of ThT can be strongly coupled with the low-frequency deformation modes. Time-dependent density functional theory calculations and the evaluated vibrational reorganization energies between the ground and excited states strongly support our experimental results based on time-resolved vibrational spectroscopy.

Jujube ( Mill.) has been consumed as a nutraceutical and medicinal food in China for millennia. Recent studies have highlighted the nutritional and bioactive properties of jujube fruit extracts, with potential to mitigate Alzheimer's disease (AD) progression through longevity-enhancing effects. Our previous study explored the lifespan-extending mechanisms of Jujube Fructus extract (JE) in (). Here, we evaluated the efficacy of zizybeoside II (ZB), separated from JE through HPLC, in extending lifespan and ameliorating AD pathology in . The results showed that ZB treatment significantly prolonged lifespan while maintaining reproductive capacity, with concurrent enhancements in normal activity and stress resistance during aging. Additionally, we found that ZB effectively alleviated various β-Amyloid (Aβ)-induced neurotoxic phenotypes in AD worms, including paralysis and behavioral deficits. Mechanistic investigations in N2a/APP695 cells demonstrated that ZB reduced the accumulation of Aβ and phosphorylated tau (p-Tau) proteins, diminished oxidative stress levels through the HSF-1/HSP16.2 pathway, and thereby slowed the progression of AD. This study provides a theoretical basis for the subsequent clinical trials of ZB in delaying AD.