non-AD Group Research Articles

Heart rate variability stands up to bedside tests and composite autonomic symptom score-31 (COMPASS-31) questionnaire: Diagnostic tools for autonomic dysfunction in systemic sclerosis patients

BackgroundSystemic sclerosis (SSc) is an autoimmune disease that affects skin, cardiovascular, pulmonary, and gastrointestinal affection. Autonomic dysfunction (AD) was observed early and even preceded fibrosis. Researchers are looking forward to evolving tools to detect subclinical AD. Aim of the work: This study aimed to evaluate parasympathetic dysfunction in SSc patients using R-R interval variation (RRIV) during both rest and deep breathing compared to control group, compare it with different tools used to assess AD and explore its relation to clinical characteristics of SSc patients. Patients and methods: This work included 40 subjects; 20 SSc cases and 20 healthy controls. All were subjected to RRIV at rest and at deep breathing, composite autonomic symptom score-31 (COMPASS-31) questionnaire for autonomic dysfunction symptoms, bedside autonomic function tests (active standing and Valsalva maneuver).Results: The mean age of patients was 35.36 ± 10.24 years, disease duration 54.12 ± 54.32 months and were 16 females and 4 males (F:M 4:1). There was a significantly higher RRIV at deep breathing in SSc (26.7 ± 23.3) compared to controls (11.4 ± 6.1)(p = 0.017). There was no significant difference in the results of bedside tests between SSc and control. The AD groups detected by bed side tests tended to have higher RRIV values at rest and during deep breathing compared to the non-AD groups. There was no correlation between RRIV measurements and COMPASS score. SSc patients with arthralgia had significantly lower RRIV at deep breathing (p = 0.042). Conclusion: The RRIV is a promising noninvasive and simple cardiovascular test for detection of early parasympathetic dysfunction in SSc patients.

Association Between Atopic Dermatitis and Meniere's Disease: Nationwide Cohort Study.

Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by relapsing and remitting episodes. Although AD is well-known for its association with other allergic conditions, its relationship with Meniere's disease has not been thoroughly investigated. This study aimed to explore the potential correlation between AD and Meniere's disease. This study utilized data from the National Health Insurance Service-National Sample Cohort, a nationwide population-based database. The AD group was selected from a cohort of 1 million individuals randomly extracted from database. A non-AD group was obtained through Propensity Score Matching. The AD group comprised 84,579 individuals, with an equal number of individuals in the non-AD (control) group. The overall hazard ratio (HR) for Meniere's disease in the AD group was 1.44 (95% confidence interval (CI): 1.31-1.6). Subgroup analysis showed an adjusted HR of 0.42 (95% CI: 0.38-0.48) for Meniere's disease in males, 4.99 (95% CI: 4.45-5.62) in the middle-aged group (40-59 years), and 8.21 (95% CI: 7.21-9.35) in the older age group (≥60 years). Additionally, the adjusted HRs for developing Meniere's disease were higher in patients with comorbidities, including allergic rhinitis (1.18 [95% CI, 1.07-1.32]), allergic contact dermatitis (1.32 [95% CI, 1.19-1.48]), and allergic conjunctivitis (1.54 [95% CI, 1.32-1.82]). Long-term follow-up revealed that the prevalence of Meniere's disease was 1.44 times higher in the AD group compared to the control group. Moreover, older age, female sex, allergic rhinitis, allergic contact dermatitis, and allergic conjunctivitis were identified as factors that increase the risk of developing Meniere's disease. 3 Laryngoscope, 2024.

Comparing the frequency, antifungal susceptibility, and enzymatic profiles of the oral fungal composition in patients with and without Alzheimer's disease admitted to a neurology clinic.

Studies have shown that changes in the frequency of oral microorganisms may play a key role in the development of Alzheimer's disease (AD). However, no research has been conducted on the oral fungal composition in AD-patients. The present study aimed to investigate the changes in the frequency of oral fungal composition, the antifungal susceptibility, and the enzymatic profiles of oral fungal composition in patients suffering from AD compared to non-AD individuals. In the present analytical cross-sectional study during 12 months, 76 hospitalized patients with AD were matched with 76 individuals without AD. A sterile serum physiology-moistened cotton-tipped swab was used to sample the mouth area. All swabs were cultured on Sabouraud Chloramphenicol Agar. Fungal identified were confirmed through the PCR-sequencing techniques. Enzyme activity index (EAI) for important pathogenic factors including proteinase, esterase and hemolysin was measured using relevant protocols. The susceptibility to 8 antifungal agents (nystatin, voriconazole, itraconazole, fluconazole, posaconazole, amphotericin B, 5-fluorocytosine, and caspofungin) against fungal strains obtained from AD-patients was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines, document M38-A2 for filamentous fungi, and document M27-A4 for yeasts. The results showed that compared to the non-AD individuals, the prevalence of oral fungal composition in AD group was 1.6 times higher. Candida albicans was the most common fungal species isolated from oral swab samples of AD group (n=53, 80%) and non-AD group (n=28, 40%), and the diversity of the oral fungal composition in AD-patients were lower than non-AD individuals. Among the 3 investigated virulence factors, a statistically significant difference was shown in terms of hemolysin activity level between the two studied groups (p<0.05) and the activity level of esterase and proteinase enzymes did not show a significant difference in the two studied groups (p>0.05). The results showed that almost all of the tested isolates were susceptible to nystatin, the most widely prescribed antifungal to treat superficial infections, and only 1.69 % (2/118) of the Candida isolates were resistant to this antifungal drug. Understanding the changes in the frequency of oral fungal composition the antifungal susceptibility, and the enzymatic profiles of oral fungal composition in patients suffering from AD compared to non-AD individuals makes it possible to better understand the etiology of this disease.

Comparative accuracy of CA-153 and KL-6 as diagnostic and prognostic biomarkers for interstitial lung disease

BackgroundsTo discern the potential of KL-6 and CA-153 as diagnostic tools for interstitial lung disease (ILD), understand their relationship with GAP (Gender, Age, and Physiology) stage, and analyze their predictive capacities alongside CT features. This research aims to enhance ILD detection and management in autoimmune patients, emphasizing the diagnostic utility of these biomarkers. MethodsFrom Mar 2017 to Mar 2024, 398 patients from Taichung Veterans General Hospital’s Division of Allergy, Immunology, and Rheumatology with autoimmune diseases were prospectively enrolled. ILD diagnoses were confirmed using High-Resolution Computed Tomography (HRCT) or lung biopsy and characterized by radiologists. GAP scores were calculated for IPF prognosis. 583 serum samples were collected and tested for KL-6, CA-153, CA-199, and CA-125 using specific assays. Statistical analyses compared patients, assessed variables, determined missingness, and predicted ILD, with tools like ROC analysis and logistic regressions. Analyses were performed with IBM SPSS and MedCalc. ResultsILD patients were older, predominantly male, and had more smokers compared to non-ILD. Both KL-6 and CA-153 were higher in ILD and showed a significant, but non-interchangeable correlation. Age, BMI, smoking, and biomarker levels influenced ILD odds, with KL-6 and CA-153 being the strongest predictors. HRCT imaging highlighted these markers’ roles, especially in detecting specific features. Both markers also strongly associated with GAP stages. Stratified analyses emphasized KL-6′s significance in predicting ILD across both AD and non-AD groups. Complete data sensitivity analysis reinforced KL-6 and CA-153 as key ILD predictors. ConclusionsThis research emphasizes CA-153 as a feasible, cost-effective alternative to KL-6 in diagnosing and monitoring ILD. Both CA-153 and KL-6 levels were notably elevated in ILD patients, displaying a strong correlation, especially at CA-153 levels of ≤100 U/ml. They both also have significant associations with CT characteristics and GAP stages. The study reinforces the potential of CA-153, particularly in settings where KL-6 testing might be inaccessible or expensive.

Assessment of De-Escalation of Empirical Antimicrobial Therapy in Medical Wards with Recognized Prevalence of Multi-Drug-Resistant Pathogens: A Multicenter Prospective Cohort Study in Non-ICU Patients with Microbiologically Documented Infection.

Antimicrobial resistance poses a major threat to human health worldwide and the implementation of antimicrobial stewardship programs (ASPs), including antimicrobial de-escalation (ADE), is a multifaceted tool for minimizing unnecessary or inappropriate antibiotic exposure. This was a prospective observational study of 142 non-Intensive Care Unit (ICU) patients with microbiologically documented infection who were initially administered empirical antimicrobial therapy and admitted to the medical wards of 6 tertiary-care hospitals in Greece from January 2017 to December 2018. Patients were divided into two groups, the ADE and non-ADE group, based on whether ADE was applied or not, respectively. Exploratory end-points were ADE feasibility, safety and efficacy. ADE was applied in 76 patients at a median time of 4 days (IQR: 3, 5). An increased likelihood of ADE was observed in patients with urinary tract (OR: 10.04, 95% CI: 2.91, 34.57; p < 0.001), skin and soft tissue (OR: 16.28, 95% CI: 1.68, 158.08; p = 0.016) and bloodstream infections (OR: 2.52, 95% CI: 1, 6.36; p = 0.05). Factors significantly associated with higher rates of ADE were clarithromycin administration, diagnosis of urinary tract infection (UTI), isolation of E. coli, age and symptoms type on admission. Mortality was lower in the ADE group (18.4% vs. 30.3% p < 0.1) and ADE was not significantly associated with the probability of death (p = 0.432). ADE was associated with favorable clinical outcomes and can be performed even in settings with high prevalence of multi-drug resistant (MDR) pathogens without compromising safety.

The Alzheimer's Association Global Biomarker Standardization Consortium (GBSC) plasma phospho-tau Round Robin study.

Phosphorylated tau (p-tau) is a specific blood biomarker for Alzheimer's disease (AD) pathology. Multiple p-tau biomarkers on several analytical platforms are poised for clinical use. The Alzheimer's Association Global Biomarker Standardisation Consortium plasma phospho-tau Round Robin study engaged assay developers in a blinded case-control study on plasma p-tau, aiming to learn which assays provide the largest fold-changes in AD compared to non-AD, have the strongest relationship between plasma and cerebrospinal fluid (CSF), and show the most consistent relationships between methods (commutability) in measuring both patient samples and candidate reference materials (CRM). Thirty-three different p-tau biomarker assays, built on eight different analytical platforms, were used to quantify paired plasma and CSF samples from 40 participants. AD biomarker status was categorised as "AD pathology" (n=25) and "non-AD pathology" (n=15) by CSF Aβ42/Aβ40 (US-FDA; CE-IVDR) and p-tau181 (CE-IVDR) methods. The commutability of four CRM, at three concentrations, was assessed across assays. Plasma p-tau217 consistently demonstrated higher fold-changes between AD and non-AD pathology groups, compared to other p-tau epitopes. Fujirebio LUMIPULSE G, UGOT IPMS, and Lilly MSD p-tau217 assays provided the highest median fold-changes. In CSF, p-tau217 assays also performed best, and exhibited substantially larger fold-changes than their plasma counterparts, despite similar diagnostic performance. P-tau217 showed the strongest correlations between plasma assays (rho=0.81 to 0.97). Plasma p-tau levels were weakly-to-moderately correlated with CSF p-tau, and correlations were non-significant within the AD group alone. The evaluated CRM were not commutable across assays. Plasma p-tau217 measures had larger fold-changes and discriminative accuracies for detecting AD pathology, and better agreement across platforms than other plasma p-tau variants. Plasma and CSF markers of p-tau, measured by immunoassays, are not substantially correlated, questioning the interchangeability of their continuous relationship. Further work is warranted to understand the pathophysiology underlying this dissociation, and to develop suitable reference materials facilitating cross-assay standardisation. Alzheimer's Association (#ADSF-24-1284328-C).

Association of Atopic Dermatitis and Risk of Glaucoma Surgery: A Global Population-Based Study

Précis: Severe atopic dermatitis (AD) in patients with glaucoma heightens the risk of requiring surgical intervention, necessitating prompt specialist care and strict surveillance. Objective: The impact of AD on the prognosis of patients with glaucoma is rarely studied. This study aims to assess the risk of requiring glaucoma surgery among patients with glaucoma with and without AD. Materials and Methods: In this retrospective cohort analysis, we assessed patients with glaucoma initially diagnosed from December 5, 2003 to December 3, 2018 using the TriNetX database, dividing them into AD and non-AD cohorts. 1:1 propensity-score matching created balanced groups for baseline traits and comorbidities. We compared the cohorts’ risk and cumulative incidence of needing glaucoma surgery (minimally invasive glaucoma surgery, trabeculectomy, aqueous shunt, or transscleral cyclophotocoagulation). A subgroup analysis was also conducted for patients with severe AD. Results: Out of 528,469 patients with glaucoma, 2624 were in the AD group. Among the AD group, 584 had severe AD. The AD group showed a comparable risk of requiring surgery to the non-AD group (hazard ratio: 1.03; 95% CI: 0.72, 1.47). In contrast, the severe AD group demonstrated a significantly greater risk and cumulative incidence of surgery (hazard ratio: 2.80; 95% CI: 1.37, 5.73; log-rank P = 0.003) compared with the non-AD group. Conclusion: Patients with glaucoma with severe AD are significantly more likely to need surgical intervention, with AD severity being a correlating factor for increased risk.

Anatomical distribution of histone H3 acetylation in human hippocampus

In recent years, the role of histone acetylation in the brain has been studied from different aspects. However, the anatomical distribution of histone H3 acetylation in the human hippocampus and its potential relevance to triple synaptic circuits are unknown. As one of epigenetic remodeling ways, the modification of histones is involved in multiple aspects of neuronal function and development and is a key process in the onset and development of Alzheimer’s disease (AD). In our study, we compared acetylation levels of histone H3 at different regions of the hippocampus in AD and non-AD patients. We found that histone H3 acetylation can be detected in the dentate gyrus (DG), CA4, CA3, CA2, CA1, and lower Toya regions of the human hippocampus. The highest degree of acetylation in the hippocampus is in DG, and the level of acetylation changes gradually and systematically along the triple synaptic circuit. Besides, there were no significant differences in histone acetylation between AD and non-AD groups.

Role of fronto-limbic circuit in neuropsychiatric symptoms of dementia: clinical evidence from an exploratory study.

Neuropsychiatric symptoms (NPSs) are a distressful aspect of dementia and the knowledge of structural correlates of NPSs is limited. We aimed to identify associations of fronto-limbic circuit with specific NPSs in patients with various types of cognitive impairment. Of 84 participants, 27 were diagnosed with mild cognitive impairment (MCI), 41 with Alzheimer's disease (AD) dementia and 16 with non-AD dementia. In all patients we assessed regional brain morphometry using a region of interest (ROI)-based analysis. The mean cortical thickness (CT) of 20 cortical regions and the volume (V) of 4 subcortical areas of the fronto-limbic system were extracted. NPSs were rated with the Neuropsychiatric Inventory (NPI). We used multiple linear regression models adjusted for age and disease duration to identify significant associations between scores of NPI sub-domains and MRI measures of brain morphometry. All significant associations found were negative, except those between irritability and the fronto-opercular regions in MCI patients (corresponding to a 40-50% increase in CT) and between delusions and hippocampus and anterior cingulate gyrus (with a 40-60% increase). Apathy showed predominant involvement of the inferior frontal regions in AD group (a 30% decrease in CT) and of the cingulate cortex in non-AD group (a 50-60% decrease in CT). Anxiety correlated in MCI patients with the cingulate gyrus and caudate, with a CT and V decrease of about 40%, while hallucinations were associated with left enthorinal gyrus and right amygdala and temporal pole. Agitation showed associations in the AD group with the frontal regions and the temporal pole, corresponding to a 30-40% decrease in CT. Euphoria, disinhibition and eating abnormalities were associated in the MCI group with the entorhinal, para-hippocampal and fusiform gyri, the temporal pole and the amygdala (with a 40-70% decrease in CT and V). Finally, aberrant motor behavior reported a significant association with frontal and cingulate regions with a 50% decrease in CT. Our findings indicate that specific NPSs are associated with the structural involvement of the fronto-limbic circuit across different types of neurocognitive disorders. Factors, such as age and disease duration, can partly account for the variability of the associations observed.

334 Identification of novel plasma protein biomarkers for diagnosis and prediction of Alzheimer’s disease in African Americans

OBJECTIVES/GOALS: To identify novel panel of plasma protein biomarkers to improve prediction and diagnosis of Alzheimer’s disease (AD) for African Americans (AA), who are at greater risk of developing AD compared to non-Hispanic White individuals but are underrepresented in AD research. METHODS/STUDY POPULATION: Pre-existing plasma samples from 460 AA individuals with clinical diagnoses of AD, cognitively unimpaired (CU), mild cognitive impairment (MCI), or dementia with Lewy bodies (DLB) will undergo untargeted proteomics using the SomaScan assay, where modified single stranded DNA aptamers bind to protein targets which are quantified by DNA microarray. Protein expression levels will be compared between diagnostic groups to identify differentially expressed proteins. Additional clinical, genetic, and lifestyle factors will be compared with protein expression when available. Proteins of interest, identified by differential protein expression analysis results, will be included in receiver operating characteristic analyses to identify the optimal set of proteins for diagnostic classification. RESULTS/ANTICIPATED RESULTS: A pilot experiment utilizing plasma from 40 individuals identified multiple differentially expressed proteins (DEPs) between AD and non-AD groups. Eight proteins were nominated from the differential protein analysis into a receiver operating characteristic (ROC) analysis based on pvalue and previous implication in AD genome wide association studies. Proteins involved in microglial activation, neuronal adhesion, cell proliferation, and innate immunity were nominated. The ROC model achieved 100% classification accuracy of AD and CU groups using age, sex, and the eight nominated proteins. It is expected that there will be more significant associations when utilizing the full cohort of 460 AA and that DEPs between AD, CU, MCI, and DLB will be identified. DISCUSSION/SIGNIFICANCE: The nomination of a novel panel of plasma biomarkers developed from an AA cohort will directly serve the AA community by improving access to an early and accurate diagnosis of AD. Access to improved prediction and diagnosis will likely improve disease management, thus improving patient outcomes and decreasing burden on families and caregivers.

Identifying patients with acute aortic dissection using an electrocardiogram with convolutional neural network

BackgroundThe potential of utilizing artificial intelligence with electrocardiography (ECG) for initial screening of aortic dissection (AD) is promising. However, achieving a high positive predictive rate (PPR) remains challenging. Methods and resultsThis retrospective analysis of a single-center, prospective cohort study (Shinken Database 2010–2017, N = 19,170) used digital 12-lead ECGs from initial patient visits. We assessed a convolutional neural network (CNN) model's performance for AD detection with eight-lead (I, II, and V1-6), single-lead, and double-lead (I, II) ECGs via five-fold cross-validation. The mean age was 63.5 ± 12.5 years for the AD group (n = 147) and 58.1 ± 15.7 years for the non-AD group (n = 19,023). The CNN model achieved an area under the curve (AUC) of 0.936 (standard deviation [SD]: 0.023) for AD detection with eight-lead ECGs. In the entire cohort, the PPR was 7 %, with 126 out of 147 AD cases correctly diagnosed (sensitivity 86 %). When applied to patients with D-dimer levels ≥1 μg/dL and a history of hypertension, the PPR increased to 35 %, with 113 AD cases correctly identified (sensitivity 86 %). The single V1 lead displayed the highest diagnostic performance (AUC: 0.933, SD: 0.03), with PPR improvement from 8 % to 38 % within the same population. ConclusionsOur CNN model using ECG data for AD detection achieved an over 30% PPR when applied to patients with elevated D-dimer levels and hypertension history while maintaining sensitivity. A similar level of performance was observed with a single-lead V1 ECG in the CNN model.

A comparison between radial artery compression devices for patent hemostasis after transradial percutaneous interventions.

Patent hemostasis (PH) is essential for preventing radial artery occlusion (RAO) after trans-radial procedures; however, it remains unclear how it should be obtained. The aim of this multicenter randomized study was to evaluate whether the use of an adjustable device (AD), inflated with a pre-determined amount of air (AoA), was more effective than a non-adjustable device (non-AD) for achieving PH, thereby reducing the incidence of RAO. We enrolled a total of 480 patients undergoing transradial procedure at 3 Italian institutions. Before the procedure, a modified Reverse Barbeau Test (mRBT) was performed in all patients to evaluate the AoA to be eventually inflated in the AD. After the procedure, patients were randomized into 2 groups: (1) AD Group, using TR-Band (Terumo) inflated with the pre-determined AoA; and 2) non-AD Group, using RadiStop (Abbott). An RBT was performed during compression to demonstrate the achievement of PH, as well as 24 hours later to evaluate the occurrence of RAO. PH was more often obtained in the AD Group compared with the non-AD Group (90% vs 64%, respectively, P less than .001), with no difference in terms of bleedings. RAO occurred more often in the non-AD Group compared with the AD Group (10% vs 3%, respectively, P less than .001). Of note, mRBT was effective at guiding AD inflation and identifying high-risk patients in whom PH was more difficult to obtain. The use of AD, filled with a predetermined AoA, allowed PH significantly more often compared with non-AD, providing a significantly reduced incidence of RAO.

Lens capsule pathological characteristics in cases of intraocular lens dislocation with atopic dermatitis.

To explore lens capsule pathological characteristics in intraocular lens (IOL) dislocation after cataract surgery in patients with atopic dermatitis (AD). University hospital department of ophthalmology. Case series with clinicopathological correlations. Lens capsules and surrounding tissues excised during surgery from eyes with AD (AD group) and eyes without AD (non-AD group) with IOL dislocation were histologically evaluated. Hematoxylin and eosin staining was used to assess abnormal changes in lens epithelial cells (LECs). Masson trichrome staining distinguished the fibrous metaplasia around the lens capsule into high-density and low-density fibrosis. Capsular splitting (thinning) was identified in both stained preparations. The IOL dislocation morphology in the AD group (10 eyes of 10 patients) included 7 cases of capsular bag dislocation (CBD) and 3 cases of dead bag syndrome (DBS), with an average duration to IOL dislocation of 11.5 ± 5.6 years. All patients in the non-AD group (12 eyes of 12 patients) had CBD, averaging 10.2 ± 5.7 years to dislocation. Abnormal LECs, low-density fibrosis, and capsular splitting were observed in 9 (90), 9 (90), and 6 (60) of the patients in the AD group compared with 6 (50), 3 (25), and 2 (18), respectively, in the non-AD group (total n [%]). Compared with the non-AD group, the AD group exhibited higher frequencies of morphological changes in LECs, low-density fibrosis around the lens capsule, and capsular splitting characteristics of DBS. These results suggest LEC degeneration and increased lens capsule fragility occurred in patients with AD.

Abstract TP257: Atherogenic Dyslipidemia Advances Crucially the Aortic Complicated Lesion in Cryptogenic Stroke

Background and purpose: The aortic complicated lesion (ACL) is a notable embolic source of cryptogenic stroke (CS) observed in 10-60 % of patients. Although the antithrombotic and statin therapy are certainly effective, the recurrence of aortogenic stroke is not rare. Atherogenic dyslipidemia (AD) is regarded as the significant residual risk of cardiovascular diseases even under the statin remedy and characterized by low high-density lipoprotein (HDL) and high triglyceride (TG). In the present study, we aimed to clarify the underlying association between ACL and AD. Methods: Clinical data of CS patients admitted between April 2014 and December 2016 in Japanese 8 institutes and underwent transesophageal echocardiography (TEE) were analyzed in the present study. Low HDL was defined as ≤ 40 mg/dl and high TG was defined as ≥ 150 mg/dl in the fasting condition, respectively. Furthermore, AD must satisfy both cut-off values. Based on these criteria, patients were divided into 4 groups as AD group, HDL group, TG group, and non-AD group to compare the clinical features. Results: Of 664 CS patients, 68 (57 men, 68.6 ± 11.1 years) met the criteria of AD (AD group), and 108 (90 men, 68.5 ±13.7 years) fulfilled the low HDL only (HDL group), 115 (76 men, 66.9 ± 11.7 years) merely met the high TG (TG group), 373 (223 men, 69.4 ± 13.1 years) satisfied the neither (non-AD group). In a univariate analysis, ACL in arch revealed with TEE was significantly more frequent in AD group (55.9 vs 38.0 vs 39.1 vs 33.8 %, p=0.007). In a multiple regression analysis, male (OR 2.57, 95%CI 1.23-5.38, p=0.012), body mass index (unit OR 1.16, 95%CI 1.08-1.25, p&lt;0.001), diabetes (OR 2.52, 95%CI 1.41-4.53, p=0.002), ACL in arch (OR 2.12, 95%CI 1.19-3.80, p=0.011) were independently, and past history of stroke (OR 0.35, 95%CI 0.14-0.90, p=0.030) was inversely associated with AD group. Conclusions: Although the previous study exhibited that AD was predominantly associated with intracranial stenosis in atherothrombotic brain infarction, AD was also crucially related to ACL in CS in the present study. Concerning the aortogenic stroke, more intensive and pleiotropic lipid-lowering therapy would be efficacious for further treatment.

Abstract TP142: Perfusion Profiles to Identify Acute Extracranial Internal Carotid Artery Atherosclerosis-Related Stroke Prior to Endovascular Therapy

Introduction: Perfusion imaging has been used to assess collateral status in patients with acute ischemic stroke secondary to anterior large-vessel occlusion. We aimed to evaluate the hypoperfusion intensity ratio (HIR), a surrogate of collateral status, in acute stroke secondary to extracranial atherosclerosis disease (AD) compared with extracranial non-AD etiologies prior to EVT. Methods: We retrospectively reviewed the data of consecutive EVT stroke patients in our prospectively collected registry from January 2019 to December 2022. Inclusion criteria: patients with anterior circulation stroke with concomitant extracranial internal carotid artery (ICA) disease with 70-100% stenosis per NASCET criteria and patients who underwent computed tomography perfusion (CTP) before EVT. Patients were divided into those with extracranial AD and non-AD based on clinical and radiological characteristics. HIR was calculated as the volume of ischemic brain tissue with a Tmax&gt;10s divided by a Tmax&gt;6s. A relative CBF&lt;30% was also obtained. Multivariable regression was used to identify the HIR independently associated with extracranial ICA AD-related stroke; adjusted odds ratio with 95%CIs were calculated using the non-AD group as a reference. Results: Among all 624 EVT patients, 79 met inclusion criteria. Of these patients (21 women [36.2%]; median age 67 [60-75] years), 58 (72.5%) had extracranial ICA AD. Patients in the AD group had significantly lower CBF&lt;30% (median 8ml [0-17] vs 19ml [9-36]), lower Tmax&gt;10s (median 29ml [11-69] vs 68ml [38-117]), and lower HIR (median 0.27 [0.13-0.45] vs 0.49 [0.42-0.59]). There was no significant difference in time from last know well to CTP between groups. Lower HIR was independently associated with AD after adjusting for variables related to AD (Figure1). Conclusions: Low HIR values was a predictor of stroke secondary to extracranial ICA AD and could be helpful to differentiate from other non-AD etiologies prior to EVT.

Atopic Dermatitis Severity and Risk for Psoriasis: A Nationwide Population-Based Study

Introduction: As research on the role of the Th17/IL-23 pathway gains importance, the relationship between atopic dermatitis (AD) and psoriasis is becoming elucidated. Objective: The objective of this study wasto evaluate whether AD and its severity affect the risk for psoriasis. Methods: This retrospective population-based study used the database from the 2009 National Health Insurance Services-Health Screening Cohort in Korea. A total of 3,957,922 adult subjects were included and observed until 2018. The primary outcome was newly diagnosed psoriasis. Results: After adjusting for possible confounding factors, the moderate-to-severe AD group had the highest hazard ratio (HR) for psoriasis (HR = 2.50; 95% confidence interval (CI), 2.40–2.61), followed by the mild AD group (HR = 2.31; 95% CI: 2.19–2.44) compared with the non-AD group during a median 8.11 ± 1.19 years of follow-up. Limitations: It is difficult to define AD, which is not standardized, using a claims database and exclude patients who were misdiagnosed with AD. Conclusion: Patients with severe AD showed an increased risk for psoriasis compared to controls, and the risk for psoriasis was increased according to AD severity. This suggests that psoriasis and AD could share inflammatory, immune, and genetic features.

Prognostic value of plasma Aβ1-40 for Alzheimer's disease.

To investigate the clinical significance of plasma p-amyloid 1-40 (Aβ1-40) in patients with Alzheimer's disease (AD). In this retrospective study, the clinical data of 305 patients, with or without Alzheimer's disease (AD), who were treated at the Affiliated Hospital of Youjiang Medical University for Nationalities and the People's Hospital of Baise between January 2018 and December 2021 were analyzed. Patients were divided into two groups: an AD group (n=147) and a non-AD group (without AD, n=158 cases). Blood test indices, including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CRE), high-sensitivity C-reactive protein (hsCRP), and plasma β-amyloid 1-40 were collected and compared between the two groups. The plasma β-amyloid 1-40 in the AD group was (3.71±3.45) mol/L, which was significantly higher than (2.8±1.35) mmol/L in the non-AD group (P<0.05). Similarly, hsCRP expression was significantly higher in the AD group than that in the non-AD group (P<0.05). There were no significant differences in AST, ALT, UA, T-tau, NFL or Cr levels between the two groups (all P>0.05). Moreover, univariate regression analysis showed that plasma β-amyloid 1-40 and hsCRP were significantly correlated with AD. Multiple regression analysis demonstrated that plasma p-amyloid 1-40 (P<0.0001) and hsCRP (P=0.002) were independent predictors of AD. Plasma p-amyloid 1-40 and hsCRP are closely related to AD, and may serve as important clinical predictors of AD.

Diagnostic Performance Using a Combination of MRI Findings for Evaluating Cognitive Decline.

We investigated potentially promising imaging findings and their combinations in the evaluation of cognitive decline. This retrospective study included 138 patients with subjective cognitive impairments, who underwent brain MRI. We classified the same group of patients into Alzheimer's disease (AD) and non-AD groups, based on the neuropsychiatric evaluation. We analyzed imaging findings, including white matter hyperintensity (WMH) and cerebral microbleeds (CMBs), using the Kruskal-Wallis test for group comparison, and receiver operating characteristic (ROC) curve analysis for assessing the diagnostic performance of imaging findings. CMBs in the lobar or deep locations demonstrated higher prevalence in the patients with AD compared to those in the non-AD group. The presence of lobar CMBs combined with periventricular WMH (area under the ROC curve [AUC] = 0.702 [95% confidence interval: 0.599-0.806], p < 0.001) showed the highest performance in differentiation of AD from non-AD group. Combinations of imaging findings can serve as useful additive diagnostic tools in the assessment of cognitive decline.

Tau-neurodegeneration mismatch reveals vulnerability and resilience to comorbidities in Alzheimer's continuum.

Variability in relationship of tau-based neurofibrillary tangles (T) and neurodegeneration (N) in Alzheimer's disease (AD) arises from non-specific nature of N, modulated by non-AD co-pathologies, age-related changes, and resilience factors. We used regional T-N residual patterns to partition 184 patients within the Alzheimer's continuum into data-driven groups. These were compared with groups from 159 non-AD (amyloid "negative") patients partitioned using cortical thickness, and groups in 98 patients with ante mortem MRI and post mortem tissue for measuring N and T, respectively. We applied the initial T-N residual model to classify 71 patients in an independent cohort into predefined groups. AD groups displayed spatial T-N mismatch patterns resembling neurodegeneration patterns in non-AD groups, similarly associated with non-AD factors and diverging cognitive outcomes. In the autopsy cohort, limbic T-N mismatch correlated with TDP-43 co-pathology. T-N mismatch may provide a personalized approach for determining non-AD factors associated with resilience/vulnerability in AD.

Neuroinflammatory biomarkers in neurodegenerative disease: Insights from the ONDRI Cohort

AbstractBackgroundNeuroinflammation (NI) has been implicated in both the pathogenesis of and neuroprotection against neurodegenerative diseases (NDs)(Psenicka et al., 2021). Plasma glial fibrillary acidic protein (GFAP), and Neurofilament light (NFL) are measures of astrogliosis and neurodegeneration, respectively. Amyloid beta (Aβ)42/40 ratio (Aβ42 concentration to total Aβ concentration) below 0.068 is associated with AD pathology (Baldeiras et al., 2018). Neuroimaging‐based inflammatory biomarkers have been proposed, including free‐water diffusion (FWD)(Pasternak et al., 2009). Here we investigated FWD as a candidate biomarker for NI in AD compared to non‐AD dementia using Aβ42/40 ratio in a subset of data from the Ontario Neurodegenerative Disease Research Initiative (ONDRI).MethodFWD maps were generated in 370 subjects (126 non‐AD and 244 AD). MRI processing included ICVmapp3r for brain extraction and bias field correction, Synb0, Topup and Eddy for dMRI preprocessing and MATLAB for freewater mapping. Plasma Aβ42, Aβ40, GFAP and NFL were measured using the Simoa Human Neurology 4‐Plex E assay, and cognition was estimated using the Montreal Cognitive Assessment (MoCA). Linear regression was used to estimate the ability for FWD in the left (LcGM) and right (RcGM) cortical grey matter to predict GFAP, NFL and MoCA score in AD and nonAD based on Aβ42/40 threshold of 0.068.ResultFWD correlated with GFAP (LcGM; R = 0.4, p = 0.0013 and RcGM; R = 0.37, p = 0.0069), and MoCA total score (LcGM; R = ‐0.29, p = 0.001 and RcGM; R = ‐0.27, p = 0.001), but not with NFL across the whole group. This relationship was largely driven by the AD group wherein FWD predicted GFAP (LcGM: R = 0.12, p = 0.02, RcGM approaching significance R = 0.1, p = 0.06), and MoCA Total score (LcGM: R = ‐0.33, p&lt;0.0001), RcGM: R = ‐0.25, p&lt;0.0001). The nonAD group did not show this relationship. FWD did not predict NFL in the AD and nonAD group.ConclusionIn patients with Aβ42/40&lt;0.068, suggestive of AD, FWD in cGM was more strongly related to GFAP than NFL, and predicted cognition, a pattern that was not observed in nonAD patients. Our results suggest distinct patterns of NI in AD compared with nonAD that can be detected with FWD and with a multi‐modal approach could further understanding of differences in pathophysiology across NDs.