Background Transcranial magnetic stimulation (TMS) is an effective therapy for patients with Alzheimer’s Disease (AD), potentially modulating aberrant functional connectivity. Electroencephalography (EEG) microstates represent transient large-scale resting networks and have emerged as candidate markers for AD. However, their modulation by repetitive TMS (rTMS) and intermittent theta burst stimulation (iTBS) protocols remains to be elucidated. Methods Resting-state EEG was recorded from 28 AD patients at baseline and following the 1st, 7th, and 14th sessions of rTMS or iTBS treatment. Polarity-insensitive modified k-means clustering was used to segment EEGs into constituent microstates, which were then subjected to source localization to identify their corresponding cortical regions. Longitudinal changes within subjects in clinical status and microstate parameters (duration, occurrence, coverage, transition probability) were evaluated with one-way repeated-measures analysis of variance, and differences between rTMS and iTBS groups were assessed using t-tests. Results Four microstates (MS A-D) were identified from EEG data. rTMS predominantly induced sustained suppression of MS-B, whereas iTBS elicited early-phase increases in MS-C activity. Clinical symptoms improvement following TMS correlated with increased MS-C and decreased MS-B activity. Source localization revealed rTMS predominantly modulated MS-B generators in the occipital cortex (impacting visual and dorsal attention networks), while iTBS preferentially engaged MS-C generators in the parietal cortex (affecting sensorimotor and frontoparietal networks). Conclusions We identified distinct EEG microstates and their underlying cortical generators associated with clinical improvement in AD following treatment with rTMS and iTBS protocols. The results demonstrate protocol-specific spatiotemporal modulation profiles and temporal dynamics, highlighting differential neural mechanisms of rTMS and iTBS.

Alzheimer's disease (AD) is molecularly heterogeneous, yet routine clinical practice lacks tools to resolve this heterogeneity into actionable subtypes, limiting early mechanism-based intervention. Here we propose a prior-rule-driven stratified plasma FTIR framework that resolves AD heterogeneity into three pathogenic pathway subtypes: protein misfolding, oxidative stress and glycation. From plasma FTIR spectra (1800-900 cm⁻¹) of 735 participants, we derived three independent first-derivative absorbance ratios that stably assign each individual to one of three AD subtypes: protein-dominant, oxidative-stress-dominant or glycation-dominant. Internally, the subtype-specific models outperformed the global model on identical test samples, achieving AUCs of 0.860-0.909 versus 0.671-0.787 on their respective subsets. External validation on a subsequently enrolled cohort of 125 samples confirmed the superiority of subtype models over the global model. The subtype models achieved AUCs of 0.939 (protein), 0.871 (oxidative stress), and 0.884 (glycation), all substantially higher than the global model’s 0.742 and exceeding those of random-partition controls. These models also delivered balanced sensitivity and specificity in the external cohort, each ranging from 80% to 90%. Subtype assignment proved highly reproducible, with 98.7% bootstrap agreement and an adjusted Rand index of 0.96. Moreover, each subtype differed significantly from healthy controls and from the other subtypes in its own defining ratio (all p < 0.001). Critically, these ratio-based metrics make plasma FTIR a clinically accessible, deterministic spectrochemical framework for clinical translation; diagnostic decisions are driven directly by interpretable biomolecular ratios, avoiding the risks inherent to black-box algorithmic models.

Background Cerebral amyloid angiopathy (CAA) is associated with a high risk of recurrence of intracerebral hemorrhage (ICH). This study aimed to identify risk factors of CAA-related ICH recurrence, especially focused on CAA-characteristic neuroimaging markers.Methods Consecutive survivors of spontaneous lobar ICH for probable CAA, possible CAA, and mixed cerebral small vessel disease (CSVD) were enrolled at Tianjin Huanhu Hospital between 2017 and 2024. Baseline clinical data and magnetic resonance imaging (MRI) findings were collected. Posterior confluent white matter hyperintensities (WMH-PC), which means WMHs predominantly posterior to the ventricular horns, extending more than 5 mm in the deep white matter. Other MRI features included multispot white matter hyperintensities (WMH-MS), cortical superficial siderosis (cSS), perivascular spaces (PVS), and acute convexity subarachnoid hemorrhage (cSAH) in the present study. Participants were prospectively followed for recurrent symptomatic ICH or death. Kaplan-Meier and Cox-regression models were used to assess associations with ICH recurrence risk.Results The cohort included 254 survivors of spontaneous ICH, with median age of 68.5 years (interquartile range [IQR]: 63.0-76.0) and 63.0% male. WMH-PC was present in 124 patients (48.8%). Hundred and seventy patients (66.9%) were probable CAA-related ICH. Over a median follow-up period of 20.0 months (IQR: 8.0-38.0), 53 patients (20.9%) experienced recurrent ICH. In the probable CAA-related ICH group, WMH-PC (adjusted hazard ratio [aHR]: 2.548; 95% confidence interval [CI]: 1.251-5.193); cSS (aHR: 2.340; 95% CI: 1.126-4.860); and CSO-PVS (aHR: 2.751; 95% CI: 1.219-6.207) were associated with increased risk of ICH recurrence; after adjusted for the MRI features, only CSO-PVS (aHR: 2.278; 95% CI: 1.075-4.828) remained independently associated with an increased risk of ICH recurrence. The effect of combined WMH-PC and cSS on the recurrence of ICH in cases of probable CAA was synergistic (aHR: 3.160; 95% CI: 1.579-6.325).Conclusions WMH-PC, cSS and CSO-PVS are risk factors associated with ICH recurrence and WMH-PC in combination with cSS demonstrates a synergistic effect on increased ICH recurrence risk in patients with probable CAA.

This study investigated the effects of repetitive transcranial magnetic stimulation (rTMS) on theta and alpha band dynamics within brain networks in Alzheimer’s disease (AD) patients. We analyzed cognitive task state data during rTMS, focusing specifically on changes across the encoding, maintenance, and retrieval phases of working memory (WM). Dynamic functional connectivity (dFC) matrices were used to analyze graph-theoretic topological properties of brain networks. Furthermore, we examined the correlation between alterations in the topological properties of these dynamic brain networks and changes in WM performance metrics as well as clinical scale scores. Based on our results, we provide a comprehensive discussion on how rTMS influences the dynamic characteristics of WM brain networks in AD patients. This work offers a theoretical foundation for understanding the mechanisms by which rTMS may improve WM performance in AD, highlighting its potential therapeutic implications.

Background:Growing evidence suggests that both ApoE genotype and metabolic disturbances including insulin resistance (IR) and obesity constitute risk factors for Alzheimer's disease (AD). However, large-scale studies investigating whether ApoE genotype interacts with metabolic abnormalities to indirectly impair cognitive function in AD remain scarce. Objective:This cross-sectional study aimed to explore the associations between ApoE genotype, metabolic disturbances [IR assessed by triglyceride-glucose (TyG) index and body mass index (BMI)], and cognitive function in AD patients. Methods:We analyzed 1,162 clinically diagnosed probable AD patients from the Cognitive Impairment Clinic at Tianjin Huanhu Hospital. Participants were categorized by ApoE ε4 carrier status. Metabolic parameters were evaluated using the TyG index and BMI. Mediation effect models were employed to assess the relationships between ApoE genotype, metabolic indices, and cognitive function. Results:ApoE ε4 carriers exhibited significantly lower BMI (P < 0.001) and higher TyG index (P < 0.001) compared to non-ApoE ε4 carriers. Significant TyG index elevation in ApoE ε4 carriers was observed in AD patients with Mini-Mental State Examination (MMSE) > 20 (P = 0.0036) and MMSE 10-20 (P = 0.009). Mediation analysis revealed that ApoE ε4 exerted 73.4% of its negative effect on cognition through direct pathways, while 9.7 and 16.9% were mediated through BMI reduction and TyG elevation, respectively. Conclusion:ApoE ε4 carriers demonstrate a distinct metabolic profile characterized by lower BMI and elevated TyG index, associated with poorer cognitive performance. Our findings suggest that ApoE ε4 may indirectly influence AD cognition through metabolic pathways, highlighting early interventions targeting ApoE-related metabolic dysregulation as potential strategies to delay AD progression.

BackgroundEmerging evidence supports the clinical utility of music therapy for Alzheimer's disease (AD), yet robust clinical evidence remains limited.ObjectiveThis study aimed to systematically evaluate the multidimensional effects of music therapy on individuals with AD and to identify optimal intervention parameters and cumulative duration thresholds to guide clinical implementation.MethodsWe conducted a systematic review using RevMan 5.4, analyzing 24 randomized controlled trials (n = 2316) from Chinese and English databases up to January 2025.ResultsCompared to controls, music therapy significantly improved cognition (MD = 2.14, 95%CI = 0.88∼3.41, p = 0.0009), reduced neuropsychiatric symptoms (SMD = -0.55, 95%CI = -0.99∼-0.12, p = 0.01) and anxiety (MD = -4.37, 95%CI = -6.68∼-2.06, p = 0.0002), enhanced quality of life (SMD = 0.51, 95%CI = 0.02∼1.01, p = 0.04), and alleviated caregiver burden (SMD = -0.75, 95%CI = -0.94∼-0.55, p < 0.00001). The optimal regimen involved: frequency >3 sessions/week (p = 0.002), duration <40 min/session (p = 0.03), and intervention period ≥12 weeks (p = 0.002). A staged care model progressing from individual to group-based approaches is recommended (all p < 0.05). Minimum cumulative intervention durations for symptom improvement were: ≥1440 min for quality of life, ≥1800 min for behavioral and psychological symptoms, and ≥3360 min for cognition (all p < 0.05).ConclusionsMusic therapy demonstrates multidimensional benefits for persons living with AD, with distinct cumulative dose thresholds required for improving specific clinical symptoms, providing valuable guidance for clinical practice.

The diagnostic criteria for Alzheimer's disease (AD) has undergone the fundamental shift, moving from clinical symptom-based approach to the focus on precise pathological changes. This paper focuses on the diagnostic advances and future prospects of cerebrospinal fluid biomarkers, blood biomarkers, and molecular imaging biomarkers for Alzheimer's disease, aiming to provide guidance for the early and accurate diagnosis of the disease.

Alzheimer's disease (AD) is associated with impaired connectivity in critical functional networks. This study investigated the effects of 20 Hz transcranial magnetic stimulation (TMS) on brain network mechanisms in 25 patients with AD, including 17 in the TMS group and 8 in the sham group. We analyzed resting-state functional magnetic resonance imaging data, using the amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) to quantify neural activity and identify regions of interest. Subsequently, changes in static and dynamic functional connectivity were analyzed based on these regions. The results showed that: (1)In the TMS group, significant increases in ALFF/fALFF were observed specifically in the right dorsolateral superior frontal gyrus (SFGdor.R) and the left anterior cingulate gyrus (ACG.L); (2)Enhanced static functional connectivity between the SFGdor.R and the right middle temporal gyrus was positively correlated with improvements in Montreal Cognitive Assessment scores, while reduced static functional connectivity between the ACG.L and the left inferior temporal gyrus was associated with gains in Boston Naming Test scores; (3)Improvements in both Montreal Cognitive Assessment scores and Mini Mental State Examination scores were linked to decreased dynamic functional connectivity variability between the ACG.L and the middle occipital gyrus. These findings suggest that TMS improves cognitive and behavioral performance in patients with AD through multiscale regulatory effects, and that this improvement may be associated with alterations in functional integration among brain regions as well as reduced variability of abnormal network dynamics, providing new insights into the mechanism of action of TMS in AD.

Early screening of Alzheimer's disease (AD) and its prodromal stage, mild cognitive impairment (MCI) faces core obstacles. These primarily include the minute spectral differences between disease stages, limited clinical sample sizes, and severe class imbalance. To overcome these challenges, a robust diagnostic framework for small-scale datasets termed Multi-View Spectral Contrastive Learning (MV-SCL) using blood-based attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy is proposed. Multi-view two-dimensional spectral images are constructed via Gramian Angular Fields (GASF/GADF) and Markov Transition Fields (MTF), explicitly encoding sequence dynamics through a feature fusion method based on Principal Component Analysis (PCA). A Siamese network based on the Vision Transformer architecture is then employed to optimize intra-class compactness and inter-class separability via contrastive learning, followed by an XGBoost classifier for non-linear decision-making. Evaluated on a clinical cohort of 429 subjects (277 AD, 152 MCI), the proposed method achieved a sensitivity of 73.91% and a specificity of 76.32%, significantly outperforming baseline models including SVM and 1D-CNN. The results demonstrate that the MV-SCL paradigm effectively mitigates the impacts of minute spectral differences, limited sample sizes, and severe class imbalance, providing a novel, low-cost, and non-invasive approach for the intelligent community screening of neurodegenerative diseases.

INTRODUCTION:We evaluated lecanemab's safety and cognitive outcomes in Chinese patients with Alzheimer's disease (AD) and the utility of blood-based biomarkers (BBMs) for treatment guidance. METHODS:A multicenter, real-world cohort enrolled 1042 patients receiving lecanemab, with 453, 359, 97 patients followed up at 3, 6, 12 months, respectively. Safety outcomes included amyloid-related imaging abnormalities (ARIA) and infusion-related reactions (IRRs), and the main clinical outcome was Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) score change. RESULTS:Of 1,042 patients, ARIA occurred in 7.87%, and IRRs in 16.12%. Discontinuation was 16.51%, mainly due to financial burden. CDR-SB did not change at 12 months overall or in any subgroup. High-accuracy BBMs were the sole AD biomarker assay in 5.28%, with comparable outcomes. DISCUSSION:Lecanemab exhibited favorable 12-month safety, with no clear evidence of cognitive decline, and BBMs hold potential for treatment guidance. Further studies using a control group are now warranted.

While Transcranial Magnetic Stimulation (TMS) shows therapeutic potential for Alzheimer’s Disease (AD), its mechanisms of action remain unclear. This study investigated TMS-induced brain network restructuring in 17 AD patients by analyzing resting-state fMRI before and after 20 Hz treatment, identifying regions of interest (ROIs) based on ALFF and fALFF changes. Subsequently, functional connectivity (FC) analyses were conducted based on these ROIs. At a global level, topological properties and FC between sub-networks were also analyzed. Our findings revealed increased ALFF and fALFF in the right dorsolateral prefrontal gyrus and the left anterior cingulate gyrus. Using the right dorsolateral prefrontal gyrus as a seed, we observed enhanced FC with the right middle temporal gyrus, which was related to improved cognitive performance. Similarly, using the left anterior cingulate gyrus as a seed, we found decreased FC with the left inferior temporal gyrus, correlating with improvements in semantic understanding. From a global perspective, AD patients exhibited a significant increase in clustering coefficient and strengthened FC between the dorsal and ventral attention networks (DAN/VAN). These results suggest that TMS may regulate cross-regional functional collaboration, enhance the integration of key subnetworks, and promote comprehensive improvement in patients’ cognitive abilities.

BackgroundThe rapid increase in the global aging population poses a major public health challenge due to the prevalence of stroke. Constipation represents a significant complication of stroke, significantly impacting quality of life. The objective of this study is to investigate the incidence of constipation in acute stroke and to identify the factors that contribute to new-onset constipation (defined as constipation developing after stroke in patients with no prior history) after stroke.MethodsA total of 600 acute stroke patients were recruited for a cross-sectional study, with a questionnaire administered to each participant. This study included demographic characteristics, stroke type and focus, medical history, sleep quality, psychological problems, and the NIHSS and Barthel index (BI). Participants with constipation were evaluated for severity, medications, and stroke outcomes at discharge by the investigators.ResultsOf the 600 acute stroke patients, 126 (21%) reported a history of constipation. Furthermore, 278 patients (46.3%) demonstrated post-stroke constipation (PSC), while 184 patients (38.8%) experienced new-onset constipation following their stroke. The results indicated that hemorrhagic stroke, posterior circulation stroke, diabetes, osmotic diuretics, antacids, use of bedpans, Difficulty falling asleep, depression, and a higher NIHSS score at admission were significant risk factors for new-onset constipation. In patients demonstrating moderate severity, PSC correlated with adverse stroke outcomes at discharge.ConclusionThe incidence of constipation in acute stroke patients is higher than that in the general population. The results suggest that depression and Difficulty falling asleep may increase the risk of new-onset constipation. Moreover, after adjusting for confounders, new-onset constipation was independently associated with poor discharge outcome, particularly in patients with moderate stroke severity. Early identification of constipation risk in stroke patients can improve the development and optimization of rehabilitation protocols.Clinical trial registrationIdentifier ChiCTR2400080663.

Background:Post-stroke cognitive impairment (PSCI) is common and imposes a significant burden upon both families and society. There is limited information on biomarkers for PSCI. This study investigated the correlation between blood biomarkers and post-ischaemic stroke cognitive impairment, to identify potential blood biomarkers and their efficacy in predicting the disorder. Methods:This prospective study enrolled patients who had experienced their first acute ischaemic stroke between January 2024 and March 2025. Patients underwent blood tests within 24 h of admission, which measured plasma levels of Aβ1-40, Aβ1-42, glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL), p-Tau181, p-Tau217, Aβ42/40, and p-Tau217/Aβ1-42. The cognitive function of the patients was assessed at the three-month follow-up visit using the Montreal Cognitive Assessment (MOCA) scale. Participants were divided into a cognitive impairment group and a cognitively normal group with a MoCA cutoff score of 22. Results:A total of 128 patients who had experienced a first ischaemic stroke were included in the analysis. At the three-month post-stroke follow-up, 69 patients (53.9%) were allocated to the PSCI group, with 59 patients (46.1%) in the cognitively normal group. After univariate and multivariate logistic regression analyses, plasma GFAP (OR = 1.0027, 95% CI = 1.0002-1.0053, p = 0.038) and plasma NFL (OR = 1.0046, 95% CI = 1.0006-1.0086, p = 0.025) were identified as independent risk factors for cognitive impairment following ischaemic stroke. Receiver operating characteristic (ROC) curves indicated area under the curve (AUC) values of 0.779 (95% CI = 0.700-0.858, p < 0.001) for plasma GFAP and 0.809 (95% CI = 0.733-0.885, p < 0.001) for plasma NFL, indicating good predictive performance for both parameters. The AUC for GFAP+NFL was 0.855 (95% CI = 0.792-0.918, p < 0.001), indicating superior predictive performance of the GFAP and NFL combination for PSCI post-ischaemic stroke cognitive impairment. Conclusion:Elevated plasma GFAP and NFL levels are associated with an increased risk of post-ischaemic stroke cognitive impairment. Plasma GFAP and NFL may represent potential biological markers for PSCI. The combination of the two parameters showed superior predictive efficacy for PSCI.

Objective.High accuracy in medical classification tasks does not ensure that neural networks reason in ways consistent with clinical or neurobiological understanding. This study examines whether a Transformer-based model trained on resting-state electroencephalography (EEG) infers cognitive impairment through physiologically meaningful mechanisms.Approach.A lightweight Transformer was trained on resting-state EEG to detect mild cognitive impairment. The model's probabilistic outputs were interpreted as continuous cognitive risk scores. Knowledge distillation and spatial perturbation analyses were performed to identify the electrophysiological features and cortical regions underlying the model's predictions.Main results.The model achieved an average accuracy of 75.4% in five-fold cross-validation, and generalized to Alzheimer's disease cohorts and an external clinical center. The derived risk scores correlated with Montreal Cognitive Assessment subdomains, particularly memory, language and orientation. Key drivers included increased autocorrelation, reduced Lempel-Ziv complexity and changes in power spectral density. Perturbation analyses highlighted strong contributions from the insular cortex and the transverse temporal regions.Significance.The model's decision process reflects physiologically and anatomically interpretable patterns consistent with clinical reasoning, supporting EEG-based modeling as an objective tool for quantifying cognitive function.

BackgroundDementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) are common types of dementia, however, diagnosis is challenging. An innovative MR method called neurite orientation dispersion and density imaging (NODDI) is used to assess different microstructural alterations between the conditions.ObjectiveTo assess microstructural white matter (WM) changes in DLB and AD using NODDI.MethodsDiffusion images were acquired from 26 DLB patients, 36 AD patients, and 37 normal controls (NCs). The diffusion tensor imaging (DTI) was used to generate fractional anisotropy (FA), mean diffusivity (MD), and NODDI was used to generate neurite density index (NDI), orientation dispersion index (ODI), and volume fraction of isotropic water molecules (Viso), these parameters were compared among groups applying Tract-based spatial statistics (TBSS). We also analyzed the correlations between altered parameters and cognitive scores and investigated the diagnostic efficacy of different parameters using k-nearest neighbor (KNN).ResultsCompared with NC, FA, ODI, and NDI significantly decreased, while MD and Viso significantly increased in both DLB and AD. Compared with DLB, ODI and NDI significantly decreased in AD. The diffusion parameters of multiple fibers were strongly correlated with cognition. NDI exhibited a relatively larger AUC value in differentiating between groups.ConclusionWidespread disruption of white matter microstructure is evident in both DLB and AD, with differences in these alterations between the two conditions. NDI holds promise as a neuroimaging biomarker for distinguishing DLB from AD.

Background:Pisa syndrome (PS) is well recognized in Parkinson's disease (PD) but has been less studied in dementia with Lewy bodies (DLB), and direct comparisons are scarce. The aim of this study is to compare the clinical expression of PS across PD and DLB. Methods:In this multicenter cross-sectional study, patients were classified as PD without PS (n = 50), PD with PS (n = 41), DLB without PS (n = 45), or DLB with PS (n = 35). Standardized assessments covered cognition, neuropsychiatric symptoms, caregiver burden, motor severity, gait, falls, daily function. Two-way models, disease-specific logistic regression, and mediation analyses were performed. Results:In both disorders, PS was associated with longer disease duration, worse daily functioning, and more recurrent falls. Significant disease × PS interactions were observed across cognitive, neuropsychiatric, gait, and fall outcomes. DLB-PS carried the heaviest cognitive and neuropsychiatric burden, whereas PD-PS showed the greatest motor and gait impairment. In PD, PS was independently associated with disease duration, MDS-UPDRS-III score, gait symmetry, and stride length. In DLB, PS was independently associated with lower attention and visuospatial/executive scores, greater hallucination severity, and a higher CDR stage. Attention/visuospatial dysfunction partly mediated the association between PS and recurrent falls in DLB, whereas gait asymmetry/stride impairment partly mediated the same association in PD. Conclusion:PS is not a uniform phenotype across Lewy body disorders. Our findings suggest that it behaves relatively more like a cognition-neuropsychiatry-associated axial syndrome in DLB, whereas in PD, it shows stronger associations with motor and gait features. The effect sizes are modest, indicating that PS is a multifactorial clinical sign rather than a strong predictor of any single domain.

The burden of cerebral microbleeds (CMBs) is greater in patients with dementia with Lewy bodies (DLB) than in those with Parkinson disease dementia (PDD), while few studies have been carried out in a large sample size, or focused on the prodromal stage. Thus, we investigated the clinical prevalence of CMBs and its relationship to clinical features in patients with DLB, PDD, mild cognitive impairment with Lewy bodies (MCI-LB) and Parkinson’s disease with MCI (PD-MCI) in this study. In this retrospective multicenter cohort study, the study population consisted of 486 patients with DLB, 262 cases with PDD, 74 cases with MCI-LB and 107 cases with PD-MCI from 22 memory clinics between January 2018 and June 2022 in China. Demographic and clinical information were collected by reviewing medical records. CMBs were classified as “present” or “absent” in the Gradient Recalled-Echo or Susceptibility Weighted Imaging. The prevalence of CMBs was significantly greater in patients with DLB with 24.69

ObjectiveThis study aimed to evaluate the diagnostic and prognostic value of the Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) Score, the Pan-Immune-Inflammation Value (PIV), and the Systemic-Immune-Inflammation Index (SII) in Alzheimer’s disease (AD), exploring their association with dementia severity and their potential utility in diagnosis and monitoring disease progression.MethodsIn a retrospective case-control study, 261 AD patients and 176 healthy controls were enrolled. Propensity score matching (PSM) generated a balanced cohort of 176 patient-control pairs. Demographic, clinical, and hematologic variables were collected, including HALP, PIV, and SII, and dementia severity was assessed using the mini-mental state examination (MMSE). Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for AD, while spearman’s correlation and receiver operating characteristic (ROC) curve analysis with bootstrap internal validation were used to evaluate the biomarker’s performance.ResultsFollowing matching, AD patients exhibited significantly lower HALP and higher PIV and SII levels indicating a chronic pro-inflammatory state. HALP, PIV, and SII showed gradual but non-significant changes with dementia severity. HALP exhibited inverse correlation trend with dementia severity, though it did not reach statistical significance. Logistic regression identified education level and elevated neutrophil counts as independent risk factors of AD. ROC analysis revealed modest diagnostic performance for indices (AUC from 0.627 to 0.655), while combination of them did not significantly improve the diagnostic power.ConclusionHALP, PIV, and SII are promising blood-based biomarkers for AD diagnosis and progression monitoring. HALP may help track disease progression. These low cost, accessible composite inflammatory indices offer potential as adjunct tools for early detection and severity assessment in AD, especially in resource limited settings.

BackgroundThe apolipoprotein E ε4 allele (APOE ε4) is a genetic risk factor for neurodegenerative diseases. The potential of lipid metabolism as a biomarker in conjunction with APOE ε4 for the evaluation of dementia with Lewy bodies (DLB) warrants further investigation.ObjectiveThe study aimed to investigate the association between APOE ε4 and lipid metabolism in DLB.MethodsThis was a cross-sectional observational study that included a total of 171 DLB patients diagnosed based on established clinical consensus criteria. Strict inclusion and exclusion criteria were used in this study. APOE genotypes and blood lipid levels were determined using unified standards. IBM SPSS Statistics software was used for statistical analysis.ResultsIn patients with mild and moderate CDR, APOE ε4 carriers had significantly higher CHOL and LDL-C levels compared to non-carriers. In the 70-79 age group, APOE ε4 carriers demonstrated higher LDL-C (2.94 ± 0.83 mmol/L versus 2.47 ± 0.97 mmol/L, q = 0.0480) and CHOL (4.88 ± 1.05 mmol/L versus 4.25 ± 1.18 mmol/L, q = 0.0453) levels compared to non-carriers. In the 70-79 age group, ROC curve analysis showed that TG (AUC = 0.65, 95%CI = 0.514-0.785, p = 0.046), LDL-C (AUC = 0.663, 95%CI = 0.526-0.801, p = 0.03) and CHOL (AUC = 0.692, 95%CI = 0.557-0.827, p = 0.011) had certain reference value for diagnosis. Among patients presenting with rapid eye movement sleep behavior disorder, fluctuating cognition, and parkinsonism, APOE ε4 carriers exhibited higher levels of APO B, CHOL, and LDL-C compared to non-carriers.ConclusionsPeripheral blood lipid level as a metabolic biomarker, combined with APOE ε4 gene detection, has potential value for disease monitoring and prognosis evaluation.

Caregivers' decisions have a significant impact on the progression of Alzheimer's disease (AD). However, research exploring the benefits of disease-modifying therapy (DMT) from the perspective of caregivers is limited. This study conducted a questionnaire survey among informal caregivers in families using lecanemab in China, aiming to explore their attitudes towards the diagnostic methods of AD and the application of lecanemab. This cross-sectional survey included 345 informal caregivers of Lecanemab-treated patients. A 36-item questionnaire was utilized to gather baseline information from caregivers, as well as their comprehension of AD and treatment decisions, and feelings following Lecanemab administration. We collected online questionnaires from 37 tertiary hospitals across 31 provinces/autonomous regions/municipalities in China (2024/06/24-2024/12/24). Multivariate analysis was conducted by ordered logistic regression. The participants' average age was 50.84, with an annual household income of ¥390,000 ($53,196). The average duration of care provided by caregivers is 2.37 years. In the selection of diagnostic methods for AD, 91.3% of caregivers chose PET, 20% chose blood, and 17.7% chose cerebrospinal fluid. However, caregivers still had insufficient understanding of AD disease and anti-amyloid protein therapy. Approximately 94.5% of caregivers reported that the use of Lecanemab did not exacerbate their caregiving burden. After using Lecanemab, 64.0% of the caregivers held the opinion that the drug had reached the anticipated therapeutic efficacy, and 86.3% of the caregivers manifested their willingness to continue its application. Among them, the groups with higher annual household income ( p  < 0.001) and where the caregivers are the patients' children ( p  = 0.040) were significantly more satisfied with the efficacy of Lecanemab (Table 1). Compared with younger caregivers ( p  = 0.038) and those with an annual income below ¥200,000 ($27,280) ( p  = 0.006), elderly caregivers and those with an annual income ranging from ¥400,000 to ¥590,000 ($54,560 - $80,476) were more inclined to continue using Lecanemab (Table 2). Most caregivers hold a positive attitude towards Lecanemab, particularly those with higher household incomes and when the caregivers are the patients' children. Elderly caregivers and those with an annual income of ¥400,000 to ¥590,000 were more inclined to continue using Lecanemab.