Predicting the outcome of comatose patients in the intensive care unit (ICU) can inform decision making but remains challenging. Recent studies suggest that task-state electroencephalography (EEG) can detect covert cognition and facilitate patient prognosis. This study aimed to predict the outcome of comatose patients, by assessing covert processing of familiar names using a state-of-the-art EEG frequency tagging approach. Eighty-nine comatose patients following acute brain injury were recruited from five ICUs. Patients were presented with a rapid stream of familiar names and acoustically matched but unintelligible control sounds. EEG responses tracking the familiar names and control sounds were extracted in the frequency domain and utilised to predict the outcome of each patient, which was assessed at 1, 3, and 6 months post-injury using the Glasgow Outcome Scale-Extended (GOSE). Name-tracking EEG responses positively correlated with GOSE scores. A machine learning model integrating EEG responses and clinical characteristics achieved AUCs of 0.86, 0.88, and 0.86 in the test set, and 0.91, 0.90, and 0.85 in the external validation set, for predicting outcomes at 1, 3, and 6 months, respectively. These findings underscore that EEG assessment of residual processing of familiar names relates to patient outcomes and has the potential to predict outcome of comatose ICU patients.

ABSTRACT Background Emerging evidence suggests that low‐frequency neural oscillations are dynamically regulated by consciousness levels, with the recovery of low cortical activity potentially serving as a neurophysiological substrate for conscious emergence. Targeted enhancement of these low‐frequency rhythms in patients with disorders of consciousness (DoC) may constitute a promising neuromodulation strategy to facilitate consciousness recovery in severe brain injury. Objective This study systematically examined the neurophysiological effects of intermittent theta‐burst stimulation (iTBS), specifically its potential to enhance low‐frequency cortical activity and promote consciousness recovery in patients with DoC. Through multimodal neural assessments, we aimed to elucidate the mechanistic relationship between iTBS‐induced neural oscillation modulation and behavioral manifestations of consciousness improvement. Results This prospective cohort study enrolled 30 patients with DoC, of whom 18 completed the full intervention protocol. Two‐way repeated‐measures analysis of variance revealed significant group × time interaction effects on the Coma Recovery Scale‐Revised (CRS‐R) scores, F (1, 16) = 6.543, p = 0.021. Post hoc simple effects analysis demonstrated significant temporal improvement in the active transcranial magnetic stimulation (TMS) group, F (1, 16) = 36.463, p < 0.001, with mean CRS‐R scores increased from 9.300 ± 1.320 at baseline to 11.700 ± 1.409 post‐intervention ( p < 0.001). Conversely, sham stimulation revealed statistically nonsignificant changes (9.845 ± 1.476 versus 10.750 ± 1.575, p = 0.067). Neurophysiological assessments revealed emerging neurophysiological changes in the iTBS group, including enhanced resting‐state low‐frequency oscillations (delta: 21.642% increase, p = 0.449; theta: 6.800% increase, p = 0.789) and augmented auditory‐evoked responses (phrase‐level 22.917% increase, p = 0.280; syllable‐level: 22.963% increase, p = 0.504), suggesting potential neural plasticity mechanisms that require further validation. Conclusion Collectively, this study established iTBS targeting the left dorsolateral prefrontal cortex as a clinically effective and well‐tolerated neuromodulation approach for consciousness rehabilitation in patients with DoC, with therapeutic effects mediated by iTBS‐induced enhancement of thalamocortical low‐frequency oscillations. Trial Registration https://www.clinicaltrials.gov . Unique identifier: NCT03385278. Registered on October 24, 2017

Early disruption of gamma oscillations is increasingly recognized as a contributor to neurodegeneration and cognitive decline in Alzheimer's disease (AD), positioning 40-Hz stimulation as a promising neuromodulatory strategy. However, its neurophysiological and cognitive effects remain highly variable across studies, underscoring the need for a more integrated mechanistic framework. This review synthesizes current evidence on the neurobiological mechanisms engaged by 40-Hz stimulation in AD, including circuit-, cellular-, and system-level processes underlying network dynamics, glial responses, and multi-target biological effects. We further highlight the conceptual distinction between "physiological resonance" and "artificial superimposition" as a potential determinant of deep-brain engagement and therapeutic outcomes. By integrating both supportive and conflicting findings, we highlight disease stage, biological sex, and behavioral state as important contributors to the heterogeneity of 40-Hz stimulation outcomes. Building on these observations, we propose that future research should move toward mechanistic stratification and precision neuromodulation to facilitate clinical translation.

BACKGROUND:Peripheral neuropathic pain (pNP) is a prevalent and complex clinical condition that presents significant therapeutic challenges, with pharmacological options demonstrating variable efficacy and safety. OBJECTIVE:To establish expert consensus recommendations on the clinical use of pregabalin in the management of diverse pNP conditions. METHODS:A multidisciplinary panel of Chinese experts from orthopedics, pain management, neurology, oncology, dermatology, and pharmacy conducted a comprehensive literature review and synthesized clinical evidence to formulate consensus-based recommendations. RESULTS:Pregabalin, a second-generation calcium channel regulator, demonstrated broad efficacy across multiple pNP conditions, including postherpetic neuralgia (PHN), diabetic peripheral neuropathy (DPN), neuropathic cancer pain (NCP), postoperative and post-traumatic neuralgia, and trigeminal neuralgia (TN). In PHN, pregabalin significantly reduced pain intensity and improved sleep quality. In DPN, it provided consistent analgesia with improved pain scores and good tolerability. In NCP, pregabalin effectively alleviated pain, showed no significant drug-drug interactions, and was safely co-administered with chemotherapy. It was also effective in postoperative and post-traumatic neuralgia, although caution is warranted in cases of traumatic neuroma. In TN, pregabalin exhibited favorable low-dose efficacy, particularly in elderly patients, with minimal adverse effects. However, cautious use is advised in patients with nerve compression syndromes, such as carpal tunnel syndrome, and in individuals with a history of substance abuse. CONCLUSIONS:This consensus highlights pregabalin as an effective and generally well-tolerated therapeutic option for a broad range of pNP conditions. These recommendations provide clinically relevant guidance for optimizing pregabalin use, particularly within the Chinese healthcare context.

Accurate assessment of patients with disorders of consciousness (DoC) remains a major clinical challenge due to the limitations of behavior-based evaluations and task-dependent neurophysiological paradigms. Whole-night polysomnography (PSG), a passive and noninvasive monitoring tool, offers unique potential for revealing residual brain function during sleep. In this study, we propose a temporal-dynamic feature extraction and aggregation framework for PSG analysis to enable machine learning-based diagnosis and prognosis in DoC patients. Whole-night EEG/EOG signals were segmented into non-overlapping 30-second epochs, from which time-domain, spectral, and nonlinear complexity features were extracted. To obtain a unified and compact representation of variable-length feature sequences, two aggregation strategies were applied: stage- wise averaging based on sleep staging and clustering-based grouping via unsupervised learning. A two-stage feature selection pipeline further reduced dimensionality while preserving discriminative power and interpretability. Classifiers trained on the aggregated features achieved strong performance in distinguishing minimally conscious state (MCS) from vegetative state (VS), with AUC values exceeding 0.84, and demonstrated robust predictive ability for long-term recovery outcomes (AUC=0.79). These findings highlight the diagnostic and prognostic value of whole-night PSG and support the development of fully automated, task-free assessment tools for DoC.

Dementia is a growing global health challenge with limited pharmacological treatments. Emerging evidence from randomized controlled trials and prospective cohort studies suggests that healthy dietary patterns may contribute to the prevention or delay of cognitive decline. This review summarizes current evidence on the relations of overall dietary patterns and specific foods and nutrients to cognitive aging, with a particular focus on the potential role of gut microbiota, which is largely shaped by diet. Certain healthy dietary patterns, such as the Mediterranean and the Mediterranean–DASH Intervention for Neurodegenerative Delay (MIND) diets, characterized by specific foods (e.g., vegetables and fruits) and dietary nutrients (e.g., n-3 fatty acids, B vitamins, and carotenoids) have shown potential benefits on cognitive health. However, inconsistencies across study findings necessitate further investigation. We review how the gut microbiota may mediate or moderate the diet-cognition association, or serve as a marker for cognitive health, particularly through mechanisms involving metabolic, immune, and neuroinflammatory pathways. Finally, we highlight key methodological challenges, including variability in exposure assessment, study design, and population heterogeneity, and propose a roadmap for future research, advocating for large-scale, multi-omics studies across diverse populations. These efforts are expected to facilitate the development of precision nutrition strategies for the prevention of cognitive decline and dementia.

INTRODUCTION:Longitudinal diagnostic and prognostic validity of plasma phosphorylated tau217 (p-tau217) in Alzheimer's disease (AD) remains uncertain. METHODS:In this multi-cohort study of 2117 individuals, we established baseline plasma p-tau217 thresholds for amyloid-β-positron emission tomography (Aβ-PET) and assessed their longitudinal classification stability and prognostic relevance for AD-related outcomes. RESULTS:Baseline-defined cutoffs achieved high and sustained accuracy (86%-95%) for Aβ-PET positivity over up to 5 years of follow-up. Longitudinally, most p-tau217-positive individuals remained stable (93%-98%), whereas the intermediate zone group progressed more to positive (44%-78%) than p-tau217-negative individuals (4%-21%). Participants with stable-positive and progress-to-positive p-tau217 profiles more frequently exhibited Aβ abnormalities (90%-100% and 64%-96%, respectively) and experienced accelerated tau accumulation, hippocampal atrophy, and incident dementia compared to those with a stable-negative p-tau217 profile. DISCUSSION:These findings support the high stability and Aβ-PET classification performance of longitudinal plasma p-tau217 monitoring in AD, providing a scalable tool for risk stratification and disease monitoring.

BACKGROUND AND PURPOSE:Lacunar stroke is a complex, multifactorial disease with significant genetic underpinnings. However, the mechanisms through which genetic predispositions and risk factors contribute to its pathogenesis remain poorly understood. We investigated whether genetically predicted white matter (WM) microstructure mediates causal relationships between risk factors and lacunar stroke. METHODS:Data from genome-wide association studies were used to perform two-sample Mendelian randomisation (MR) analyses. Genetic variants associated with risk factors (n=34 461-898 130), lacunar stroke (n=232 596) and eight MRI-derived WM microstructural metrics across 48 tracts (n=20 859-20 860) were analysed. Univariable MR assessed causal effects of risk factors on lacunar stroke. Two-step MR analysis evaluated mediation roles of WM microstructure, whereas multivariable MR accounted for confounders. RESULTS:Hypertension was identified as the strongest risk factor for lacunar stroke (OR=1.38; 95% CI: 1.28 to 1.50, p=4.43×10-15). Only hypertension showed a significant causal association with genetically predicted WM microstructure. Elevated mean diffusivity (MD), isotropic volume fraction (ISOVF) and the tertiary eigenvalue in the anterior limb of the internal capsule (ALIC) were independently linked to increased lacunar stroke risk, beyond the influence of WM hyperintensities, dilated perivascular spaces and brain volume. Mediation analysis suggested that hypertension-induced lacunar stroke was partially mediated through bilateral MD and left ISOVF in the ALIC, with mediation proportions of 23.70%-33.44%. CONCLUSIONS:Hypertension may contribute to lacunar stroke pathogenesis in part through WM microstructure alterations, particularly in the ALIC. MD and ISOVF in the ALIC may serve as structural brain reserves and early biomarkers of hypertension-induced pathophysiology associated with lacunar stroke.

Accurate assessment of consciousness in patients with disorders of consciousness (DoC) remains a major clinical challenge in both specialized neurorehabilitation and acute care settings, where behavioral evaluations alone can lead to misdiagnosis rates of up to 40

Choline plays key roles in neurotransmitter synthesis and membrane integrity, processes fundamental to brain function. However, evidence from population studies on the association of dietary choline intake with dementia risk is mixed. We analyzed data of 5,301 dementia-free participants (mean age = 68.6 years; 59

BACKGROUND:The role of different adjunctive tirofiban administration routes during endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) due to large artery atherosclerosis (LAA) remains controversial. We evaluated the efficacy and safety of intravenous (IV) alone and combined intra-arterial and intravenous (IA + IV) tirofiban in patients with LAA-related AIS. METHODS:This individual patient data pooled analysis included 850 anterior circulation large vessel occlusion (LVO) patients due to LAA from two Chinese randomized trials (RESCUE BT and MARVEL). Patients were categorized into three groups: EVT alone ( n = 360), Tirofiban-IV ( n = 385), and Tirofiban-(IA + IV) ( n = 105). The primary outcome was 90-day functional independence [modified Rankin Scale (mRS) 0-2]. Safety outcomes included symptomatic intracranial hemorrhage (sICH) within 48 hours, any ICH, and 90-day mortality. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were used for baseline adjustment. RESULTS:Among 850 eligible patients included in this analysis, the median age was 66 years, and 70.9% ( n = 603) were male. Both tirofiban regimens were associated with improved functional independence compared to EVT alone: Tirofiban-IV group [51.9 vs. 37.2%; adjusted odds ratio (aOR) = 1.90, 95% CI 1.39-2.59; P < 0.01] and Tirofiban-(IA + IV) group (46.7 vs. 37.2%; aOR = 1.97, 95%CI 1.22-3.17; P < 0.01). Notably, both tirofiban strategies enhanced successful recanalization rates [expanded thrombolysis in cerebral infarction (eTICI) ≥ 2b]. The Tirofiban-IV group achieved 92.5% versus 83.3% in the EVT-alone group (aOR = 2.43, 95% CI 1.51-3.92; P < 0.01), with comparable efficacy in the Tirofiban-(IA + IV) group (91.4 vs. 83.3%; aOR = 2.47, 95%CI 1.15-5.30; P = 0.02). Moreover, neither the Tirofiban-IV group (sICH: aOR = 0.75, 95% CI 0.44-1.27, P = 0.29; mortality: aOR = 0.77, 95% CI 0.52-1.14, P = 0.20) nor the Tirofiban-(IA + IV) group (sICH: aOR = 0.49, 95% CI 0.20-1.23, P = 0.13; mortality: aOR = 0.64, 95% CI 0.35-1.18, P = 0.15) showed increased risks of sICH or mortality compared to the EVT-alone group. These results remained robust in PSM sensitivity analyses. CONCLUSIONS:In patients with anterior circulation LVO secondary to LAA undergoing EVT, adjunctive tirofiban, whether administered IV or via a combined IA + IV approach, was associated with superior 90-day functional outcomes and enhanced recanalization efficacy, without an increased risk of sICH or mortality.

BACKGROUND AND OBJECTIVES:Smoking cessation is universally prioritized for the prevention of cardiovascular disease and cancer, but its impact on dementia risk remains uncertain. We aimed to evaluate the associations of smoking cessation and postcessation weight gain with long-term risk of dementia and cognitive trajectories. METHODS:We conducted a prospective cohort study using data from the US Health and Retirement Study (1995-2020). A total of 32,802 dementia-free adults (mean age 60.5 years [SD 10.7]; 57.1% female) were included. Smoking status and body weight were assessed biennially through structured interviews. The primary outcome was incident dementia identified using the Langa-Weir algorithm, and the secondary outcome was cognitive function measured on a 27-point scale. RESULTS:Over 25 years of follow-up (median 9.9 years, interquartile range 4.4-16.4 years), 5,868 dementia cases were documented. Compared with current smokers, individuals who quit during follow-up had a lower dementia risk after quitting (hazard ratio 0.84, 95% CI 0.73-0.95), similar to those who had quit before baseline (0.79, 0.72-0.87) and to never smokers (0.75, 0.69-0.83). The benefits of cessation were largely limited to participants with no or modest 2-year postcessation weight gain (≤5 kg). By contrast, the association of quitting accompanied by >10-kg weight gain was not statistically significant (1.33, 0.87-1.82). Restricted cubic spline analysis showed decreasing dementia risk with longer time since quitting, and the risk approached that of never smokers and plateaued at around 7 years after cessation. Cognitive trajectory analyses showed that quitting was associated with long-term slower cognitive decline (slope difference 0.19 points per decade, 95% CI 0.00-0.38) but no transient cognitive change (0.57; 95% CI -0.69 to 1.83), especially among those with minor weight gain (slope difference 0.23 per decade, 95% CI 0.03-0.43). DISCUSSION:Smoking cessation was associated with a sustained lower dementia risk and slower cognitive decline, comparable to never smokers and those without short-term risk increase. However, postcessation weight gain may attenuate these advantages, highlighting the need for weight management in cessation programs. These findings should be interpreted cautiously, given the potential residual confounding and measurement error.

Background: Previous studies have observed an association between cigarette smoking and lower risk of Parkinson’s disease (PD), but whether this association varies by genetic susceptibility, and its biological basis, remain unclear. Methods: The study was conducted among 495,255 participants (mean age: 56.5 years; 54.5% female) without PD at baseline in the UK Biobank. Cox regression was used to examine associations of smoking with incident PD and its interaction with PD polygenic risk score (PD-PRS). Among 52,130 participants with plasma proteomic data, smoking-associated and PD-associated proteins were identified using linear and Cox regression models, respectively. Mediation analyses prioritized candidate intermediate proteins jointly associated with smoking and PD. External supportive analyses were conducted in the Parkinson’s Progression Markers Initiative (PPMI, N=23,824). Findings: During a median follow-up of 14.1 years, 3,579 participants developed PD. Ever smoking was associated with lower PD risk than never smoking (hazard ratio [HR] 0.89, 95% CI 0.83–0.95), with a stronger association for current smoking (HR 0.72, 95% CI 0.62–0.82). This association varied by PD-PRS (P interaction=0.041), with HRs (ever versus never smoking) of 0.62 (0.45–0.85), 0.91 (0.84–1.00), and 0.82 (0.69–0.97) in the lowest decile, deciles 2–9, and highest decile, respectively. Ever smoking was associated with 1,556 of 2,920 proteins, of which 93 were also associated with incident PD and 61 showed significant positive mediation effects, including CTSD, EZR, and AGRN. Candidate proteins were enriched in extracellular recognition, membrane-associated communication, and proteolytic processing. TNFRSF10A further showed a significant interaction with PD-PRS in relation to incident PD. Interpretation: Smoking was associated with lower PD risk, with evidence suggesting variation by genetic susceptibility. This associations were potentially mediated by pathways related to extracellular recognition, membrane-associated communication, and proteolytic processing.

Neurons and glia are distinct in their morphology, development and function, possessing unique transcriptomes and proteomes, but little is known about their metabolomes. The challenge of brain cell metabolic profiling is to obtain a large number of cells for reliable analysis. Here we purified microglia, astrocytes and neurons from mouse brains, identifying >70 metabolites through targeted metabolomics and 9,854 metabolite features via untargeted metabolomics. We systematically characterized cell type-enriched metabolites and metabolic pathways, revealing an enrichment of glutathione (GSH) and polyamine metabolism in microglia. This enrichment was validated in vivo and showed significant decreases with ageing and in an Alzheimer's disease model. Notably, GSH and polyamine metabolism correlated strongly with chemokine-related gene expression. Disrupting the GSH pathway in microglia resulted in downregulation of chemokine-related genes, aberrant morphogenesis and β-amyloid deposition. Our results provide a valuable resource ( https://metabolismocean.org/braincell ) for metabolic studies related to ageing, Alzheimer's disease and other neurological diseases.

Diet is an essential factor influencing biological aging, yet few exsiting dietary indices were specifically developed to target biological aging. We developed a data-driven food-based Empirical Dietary Index for Slower Epigenetic Aging (EDISEA) in the US Health and Retirement Study (HRS, n=7,398), which predicted deceleration of GrimAge, an established DNA methylation-based epigenetic clock. Participants in the highest versus lowest EDISEA quintile had 4.65-year deceleration in GrimAge (P value <0.001). We externally validated EDISEA in an independent US cohort (n=23,830), where it showed consistent associations with several epigenetic clocks and lower all-cause mortality risk. In HRS and a UK aging cohort (n=4,895), EDISEA was associated with lower risks of several aging-related diseases and functional limitations. Outcome-wide analyses in the UK Biobank (n=187,035), together with integrative proteomic, metabolic, and neuroimaging assessments, revealed biological signatures of EDISEA implicating broad vascular, inflammatory, metabolic, and brain-structural pathways through which EDISEA was associated with biological aging. EDISEA provides a scalable, biologically anchored tool to inform the development of precision nutrition strategies aimed at slowing epigenetic aging and mitigating aging-related disease burden. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by the Fundamental Research Funds for the Central Universities (2025ZFJH01, to BL). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study used ONLY openly available human data that were originally located at: The Health and Retirement Study (HRS) data are available through the University of Michigan and the National Archive of Computerized Data on Aging (NACDA) subject to their data use policies. NHANES data are publicly available from the U.S. Centers for Disease Control and Prevention. English Longitudinal Study of Ageing (ELSA) data are available via the UK Data Service under standard access procedures. The UK Biobank data are available through application to the UK Biobank (application ID: 816009). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data used in this study are available from the respective cohorts under data access agreements and restrictions. The Health and Retirement Study (HRS) data are available through the University of Michigan and the National Archive of Computerized Data on Aging (NACDA) subject to their data use policies. NHANES data are publicly available from the U.S. Centers for Disease Control and Prevention. English Longitudinal Study of Ageing (ELSA) data are available via the UK Data Service under standard access procedures. The UK Biobank data are available through application to the UK Biobank (application ID: 816009).

Increasing evidence indicates that blood-based biomarkers, particularly phosphorylated tau (pTau) 217 and the pTau217/amyloid‑β (Aβ) 42 ratio, demonstrate strong diagnostic performance for Alzheimer’s disease (AD) and may offer a minimally invasive alternative to cerebrospinal fluid (CSF) assays and Aβ PET imaging. There is an urgent need to develop local plasma pTau217 and pTau217/Aβ42 ratio assay and to establish population-appropriate diagnostic cutoffs tailored to Chinese populations. This study included 831 individuals from a community-based memory screening cohort and 301 patients from a hospital-based cohort with confirmed Aβ pathology. Plasma pTau217, pTau181, and their ratios to Aβ42 were measured using a high-sensitivity direct chemiluminescence (DCL) immunoassay incorporating proprietary China-developed antibodies. Data-driven Gaussian mixture modeling (GMM) was applied to the community cohort to derive biomarker cutoffs; the diagnostic performance of these cutoffs was validated in the patients with confirmed Aβ pathology. A two-cutoff approach was established in the hospital-based cohort. Multivariate regression analysis was performed to assessed potential confounding effects from routine blood biochemical parameters. GMM identified cutoffs of 4.380 pg/mL for pTau217 and 0.670 for the pTau217/Aβ42 ratio. These values closely matched cutoffs derived from the maximum Youden index (4.296 pg/mL for pTau217 and 0.706 for pTau217/Aβ42) and achieved high diagnostic accuracy (up to 89

INTRODUCTION:Detecting and monitoring cognitive performance in older adults is critical. In this study, we evaluated the validity of an eye-tracking tool in diagnosing cognitive impairment. METHODS:We recruited 119 cognitively unimpaired (CU) individuals and 157 cognitively impaired (CI) patients who completed digital eye-tracking tests and cognitive scales. Of them, 154, 120, 53, and 146 underwent plasma biomarker tests, amyloid-β positron emission tomography (Aβ-PET) scans, tau-PET scans, and magnetic resonance imaging (MRI) scans. The diagnostic performance of eye-tracking markers and their relationships to Alzheimer's disease biomarkers and cognition were examined. RESULTS:The eye-tracking panel exhibited better performance (area under the curve [AUC] = 0.865) in classifying CI from CU compared to plasma Aβ42/40 (AUC = 0.699), p-Tau217 (AUC = 0.769), p-Tau217/Aβ42 (AUC = 0.801), glial fibrillary acidic protein (GFAP; AUC = 0.804), and neurofilament light chain (NfL) (AUC = 0.826). DISCUSSION:These findings demonstrate the validity of digital eye-tracking markers for screening patients with cognitive impairment, providing a novel digital marker for detecting cognitive decline in older adults.