bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting Mild Cognitive Impairment in Amyloid Beta Biomarker Positive Individuals Using Automated Speech‐Based Testing Procedures
Authors: Skirrow Caroline , Meepegama Udeepa , Ropacki Michael T. , Weston Jack , Fristed Emil 
Published: January 2025

AbstractBackgroundNew disease modifying treatments for Alzheimer’s Disease (AD) require confirmation of amyloid biomarkers and evidence of clinical and/or cognitive AD symptoms. Blood tests for AD biomarkers are poised to enter routine care. However, at‐risk individuals with positive biomarkers vary in their level of cognitive impairment, raising the need for sensitive and scalable cognitive assessments. Fully automated speech‐based testing to screen for Mild Cognitive Impairment (MCI) has shown promise to bridge this gap, but its efficacy specifically within amyloid beta positive (Aβ+) individuals is yet to be fully established.MethodData from Aβ+ participants in the AMYPRED‐UK (NCT04828122) and AMYPRED‐US studies (NCT04928976) with Clinical Dementia Score (CDR‐G) between 0‐0.5 were analyzed. Speech recordings from Storyteller, a test battery leveraging two immediate and one delayed recall conditions from Automated Story Recall Task (ASRT), were collected from 84 Aβ+ individuals (n=38 MCI; n=46 unimpaired) who completed in‐clinic visits. A subsample of 46 Aβ+ participants (n=17 MCI; n=29 unimpaired) also completed Storyteller in a separate optional remote assessment session. Spoken responses were automatically transcribed and analysed to obtain a measure of proportional recall, “G‐match”, averaged over the three recall trials separately for in‐clinic and remote sessions. Analyses included T‐test for quantifying group differences, and prediction of MCI using the Area Under the Receiver Operating Characteristic curve (AUC). Correlations with the Wechsler Logical Memory Delayed Recall (LMDR) test and the Preclinical Alzheimer’s Cognitive Composite with semantic processing (PACC5) were also evaluated.ResultG‐match scores differed between MCI and cognitively unimpaired participants with large effect sizes for both in‐clinic (Cohen’s d=1.36) and remote assessments (d=2.07), Figure 1. Predictive ability for MCI was shown with AUC of 0.83 and 0.92 for in‐clinic and remote assessments respectively (Figure 2). Moderate‐to‐high correlations were observed between G‐match, LMDR, and PACC5 outcomes (r=0.73‐0.84).ConclusionSpeech‐based screening shows good sensitivity for detecting MCI in at‐risk populations. This approach could support at‐scale screening for suitability for new disease modifying treatments and for new treatment and prevention trials, with assessments incorporated into routine clinical visits or completed remotely at home.
Ultra‐widefield retinal imaging in Down syndrome: A high‐risk population for Alzheimer's disease
Authors: Lengyel Imre , Mitchell Jamie , Threlfall Adam , Beresford‐Webb Jessica , Walpert Madeleine , Holland Tony , MacGillivray Tom , Peto Tunde , Csincsik Lajos 
Published: January 2025

AbstractBackgroundPeople with Down syndrome (pwDS) have a high prevalence of early‐onset Alzheimer’s disease (AD). With the two‐fold increase in life expectancy for pwDS, identifying early biomarkers for AD in this patient population is needed (PMID: 32593336). Previously we have shown that phenotyping using ultra‐widefield retinal imaging (UWFI) has the potential to identify peripheral retinal biomarkers for AD, such as higher prevalence of peripheral hard drusen (pHD) and lower peripheral retinal vascular fractal dimension (RVFD) compared to controls (Ctrl) (PMID: 29621759, PMID: 34458553). In this cross‐sectional, case‐control study, the feasibility and the utility of UWFI in pwDS was investigated.MethodUWFI was performed on 24 pwDS and 17 cognitively healthy, age‐ and sex‐matched Ctrl. The images were graded for central and peripheral retinal vascular changes using the VAMPIRE software.ResultAfter quality control, 39 images of 20 patients and 34 images of 17 Ctrl were included in the study. pHD were detected on most of the images across both groups with no significant difference between pwDS and Ctrl. There was a higher arterial RVFD in the central zone (P<0.001) but no difference was observed in the peripheral zone. The venular RVFD were higher in the central zone (P<0.005) but lower in the peripheral zone (P<0.001) in pwDS compared to Ctrl. These results were the same with those diagnosed with and without AD. The arteriolar and venular width gradients were both significantly decreased in pwDS compared to Ctrl (P<0.02). This difference was only present in those with AD diagnosis.ConclusionThis study proved that UWFI is feasible in pwDS, and there are vascular changes that are associated with DS, especially in those with the diagnosis of AD. Therefore, we propose that peripheral retinal vasculature changes may hold a potential to monitor the progression of AD in this patient population.
Reducing the Use of Physical Restraints in the care of Persons with Delirium and Dementia: A Quality Improvement Project
Authors: Houston Elizabeth Reaves , Mournighan Kimberly , Lynch David H 
Published: January 2025

AbstractBackgroundHospitalized older adults, especially those with Alzheimer’s Disease and Related Dementias (PwD), are at high risk for delirium and distressing behaviors. Using physical restraints leads to functional decline and increased mortality. Our project aims to reduce restraint use by implementing a 4Ms approach for enhanced delirium management.MethodsOur interdisciplinary team used the Plan‐Do‐Study‐Act methodology over a 7‐month period (including 8 weeks of training) to introduce the 4Ms (Mentation, Mobility, Medication, what Matters) model in our 25‐bed Acute Care for Elders (ACE) unit. Nurses were trained in the Confusion Assessment Method (CAM) for delirium assessment, CAM‐S for delirium severity, and Six‐item Cognitive Impairment Test (6CIT) for cognitive impairment. Staff conducted the 6CIT per admission and CAM/CAM‐S per shift for patients aged ≥65, with electronic score documentation. Physical therapy assessed mobility within 24 hours of admission and during medical rounds. Medication reviews, led by the medical team and a geriatric pharmacist, occurred for new admissions. What Matters considerations were addressed through comprehensive geriatric assessments. Chart review collected data. An electronic record quantified physical restraint orders for six months pre‐ and post‐intervention, by patient days and distinct patients per month.ResultsIn the 19 weeks following data collection initiation, ACE unit patients (n = 362) averaged 81 years old, 60% female, 83% white, 14% Black, 18% were PwD, and 24% had significant cognitive impairment (6CIT score). Twenty‐two percent experienced incident delirium during a mean 6‐day stay. Documentation improved: CAM (68% to 86%), CAM‐S (0% to 79%), 6CIT (0% to 89%). A 4Ms checklist achieved a 96% completion rate with 37.5% receiving a geriatric assessment, 25% were discharged with an ADL disability, and 12.5% had medication deprescribed. Restraint use decreased from 7.7 patient days per month to 2.2, distinct patients with restraints decreased from 2.7 to 1.7.ConclusionsIn a high‐risk older adult population, a low‐resource quality improvement intervention effectively implemented the 4Ms model of care, showing a positive trend in reducing restraint use.
Traditional Japanese Kampo Medicine Yokukansan decreases phosphorylated tau and oligomeric tau
Authors: Mori Chika , Yamamoto Ryota , Shirafuji Norimichi , Asano Rei , Sasaki Hirohito , Yamaguchi Tomohisa , Kitazaki Yuki , Endo Yoshinori , Enomoto Soichi , Hamano Tadanori 
Published: January 2025

AbstractBackgroundOne of the pathological hallmarks in Alzheimer’s disease (AD) brain is neurofibrillary tangles (NFTs) composed of highly phosphorylated tau protein. Clinical benefit of traditional Japanese Kampo Yokukansan for dementia patients, including AD was suggested. In this study, we investigated whether yokukansan participates in the degradation of phosphorylated tau and toxic oligomeric species of tau by using cell culture model of tauopathy, M1C cells.MethodNeuronal cellular model of tauopathy, M1C cells which expresses wild type tau protein (4R0N) via tetracycline off induction (TetOff induction) was used in this study. M1C cells were treated with Ten to fifty ug/mL of Yokukansan and analyzed by Western blot analysis. Various phosphorylated tau antibodies (AT 180, AT270, and PS199/202) were used to detect phosphorylated tau. Oligomeric tau was examined by anti‐oligomeric tau specific antibody (TOC‐1) by dot blot analysis.ResultUp to 100 µg/mL of Yokukansan has no cytotoxic effects on M1C cells examined by morphological study, and ATP assay. WB analysis disclosed that of 10 to 50 µg/mL of yokukansan decreased phosphorylated tau detected by AT180, AT270, and PS199/202. Oligomeric tau detected by TOC1 also decreased by Yokukansan treatment. Major tau phosphatase GSK3β was inactivated by Yokukansan treatment. Autophagy marker P62 was downregulated by Yokukansan treatment.ConclusionThese results suggest that phosphorylated tau and oligomeric tau was reduced by Yokukansan via tau kinase inactivation and autophagy activation. Although the exact mechanisms of yokukansan on tau phosphorylation and oligomerization should be explored, these results shed light on the therapeutics of tauopathy, including AD.
Predicting Future Entorhinal Tau Levels through Amyloid PET Patterns: A Longitudinal Machine Learning Approach in Preclinical Alzheimer’s disease
Authors: Vahid Amirali , Zamani Jafar , Hosseini Hadi 
Published: January 2025

AbstractBackgroundAmyloid‐β (Aβ) plaques and tau tangles represent pivotal hallmarks of preclinical Alzheimer's disease (AD). Accumulating studies highlight a potential association between Aβ and tau, suggesting that the progressive deposition of Aβ may significantly contribute to build up of tau in the entorhinal cortex which subsequently result in neurodegeneration and cognitive decline. However, pattern of Aβ depositions that would result in tau development or propagation remains elusive. This study aims to leverage advanced machine learning along with longitudinal PET measures of brain Aβ and tau load to identify the most critical brain regions where the presence of Aβ is predictive of levels of future entorhinal tau levels.MethodAn Elastic‐Net model was applied to baseline Aβ SUVR data to predict entorhinal tau levels across multiple tau‐PET acquisition time points (0 to 5 years from baseline). The study focused on 80 subjects (41 female, mean (SD) age 71.8 (6.7) years) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) who had longitudinal data at all specified time points. Additionally, explainable AI, particularly SHapley Additive exPlanations (SHAP), was utilized to discern the model's learning process and identify brain regions significantly contributing to predicting the longitudinal entorhinal tau levels.ResultThe R‐scores between actual and predicted entorhinal tau value for time points 0 to 5 were: 0.36, 0.42, 0.47, 0.38, 0.47, and 0.40 (all p‐values < 0.001), as depicted in Figure 1. Notably, SHAP measures revealed that Aβ load in the rostral middle frontal, superior frontal and frontal pole regions contributed the most to prediction of future entorhinal tau 0 to 4 years later (Figure 2). These regions accompanied with the left inferior parietal lobe as most significant predictors of entorhinal tau at time point 5 (Figure 2).ConclusionOur findings suggest that Aβ loud in the medial and rostral frontal regions are highly predictive the development of tau in the entorhinal cortex within four years and may signal progression to clinical AD, considering that entorhinal tau is the most proximal correlate of neurodegeneration and future cognitive decline
Blood‐based plasmatic aminoacid profiles as potential biomarkers for dementia
Authors: Palmeira André Luiz Rodrigues , Fernandez Liana Lisboa , Pachado Mayra Pacheco , de Paula Leonardo Martins , Fontela Carolina , Oliveira Tiago Gil , Eller Sarah 
Published: January 2025

AbstractBackgroundThe study of new blood biomarkers in addition to amyloid beta and hyperphosphorylated tau is fundamental to expanding the understanding of the pathophysiology of dementia, especially Alzheimer`s disease, in search of therapeutic approaches.MethodIn this study, we included individuals diagnosed with Alzheimer disease (AD), Mixed‐type dementia (MD), Vascular dementia (VD) and a control group of cognitively healthy individuals. Demographics, clinical characteristics, neuroimages and plasma samples were collected. We performed a metabolomic aminoacid analysis using High‐Performance Liquid Chromatography‐Mass Spectrometry (HPLC‐MS/MS). Analyses were performed with GraphPad Prism 9.0 (GraphPad Software, San Diego, USA) or SPSS v. 18 software. Depending on the group comparison type, one‐way analysis of variances with post‐hoc Tukey‐HSD test or independent samples t‐tests. We compared aminoacid levels between the different groups (controls, AD, MD or VD) and dementia severity, assessed by Clinical Dementia Rating (CDR) score.Result135 individuals were clinically assessed as 33 controls, 42 AD, 41 MD and 19 VD. There was a statistically significant difference between controls and individuals with dementia in the following amino acids: aspartic acid (p<0.0001), arginine (p<0.0001), glutamic acid (p<0.0001), glutamine (p<0.0001), isoleucine (p<0.0008), leucine (p<0.0001). However, only arginine proved to be a biomarker capable of differentiating AD from DV (p<0.0003)ConclusionThese preliminary analyses show that leucine, isoleucine and glutamine were reduced in the plasma of patients with dementia, while aspartic acid, glutamic acid and arginine were increased. These markers can help us identify the underlying metabolic dysfunctions of different signaling pathways relevant to neuroprotection and vascular function.
Alzheimer's Disease cerebrospinal fluid Biomarkers and kidney function in normal and cognitively impaired older adults
Authors: Neal Reem M. , Yang zhiyi , Lah James J. , Hajjar Ihab 
Published: January 2025

AbstractBackgroundRecent Alzheimer’s disease (AD) clinical trials have used CSF biomarker levels for screening and enrollment. Preliminary evidence suggests Alzheimer’s Disease (AD) risk may be related to impaired renal function but the association of variation in levels of biomarkers commonly used AD biomarkers with kidney function is unknown.MethodWe conducted an analysis using data from participants enrolled in two research protocols at the Goizueta Alzheimer’s Disease Research Center that had simultaneous measurements of serum creatinine at the time of their Cerebrospinal fluid (CSF) collection (N=970). The participants had a mean age of 66.5 years, with 52% showing mild cognitive impairment (MCI). Among them, 31% were of African American ethnicity, and 62% were women. Estimated glomerular filtration rate (eGFR) was obtained from chronic kidney disease‐epidemiology Collaboration. All participants had similar CSF collection procedures. Aβ42, Tau, or pTau were measured on the Luminex ALZBIO platform. General linear models and individual data were used to assess relationships between biomarkers and eGFR.ResultThe analysis revealed significant associations between all three biomarkers and eGFR. The slopes per unit of eGFR were as follows: 0.75 (p=0.002) for Aβ42, ‐0.39 (p<0.0001) for Tau, and ‐0.13 (p=0.0002) for pTau. The association between eGFR and AD biomarkers was independent of cognitive status. However, there was a notable interaction between MCI and eGFR, where the impact of eGFR on AD biomarker levels was more robust in individuals with cognitive impairment (interaction p‐values: MCI*GFR: 0.005, Tau: 0.04, pTau: 0.04)ConclusionWe found a significant association between eGFR with CSF levels of Aβ42, tau, and pTau that were stronger in those with mild cognitive impairment. This suggests that kidney function should be considered in the context of interpreting the positivity of AD biomarkers in clinical evaluations and clinical trials, especially in those in the early symptomatic stage of AD. Future studies need to further explore the impact of kidney function and other comorbidities on the interpretation of AD Biomarkers.
Longitudinal Association of Perceived Stress with Cerebrospinal Fluid Alzheimer's Disease Biomarkers in a Biracial Cohort
Authors: Trammell Antoine R , Goldstein Felicia , Lah James J. , Parker Monica W , Davis Crystal P , Dorbin Cornelya D , Saleh Sabria , Murphy‐Tchivzhel Elizabeth , Rose Alecia Michella , Osborne Amber , Ahmad Adiva , Al‐Amin Jahmila , Hajjar Ihab 
Published: January 2025

AbstractBackgroundAfrican American (AA) persons have a higher Alzheimer's disease (AD) prevalence and report more perceived stress than White persons. Our previous cross‐sectional study (JAD, 2020, 77:843‐853) demonstrated an association between self‐reported stress levels and cerebrospinal fluid (CSF) AD biomarkers. Using a biracial cohort, the current study investigates the association between stress and longitudinal CSF AD biomarkers over time.MethodWe analyzed data from a biracial cohort of community‐dwelling adults 50 years or older who completed baseline, Year 1, and Year 2 visits at the Emory Goizueta Alzheimer’s Disease Research Center. Participants underwent a lumbar puncture and cognitive testing and completed the perceived stress scale (PSS) questionnaire at each visit. We created 4 groups by self‐reported race (AA vs. White) and cognitive classification (normal vs. impaired). Using ANOVA or chi‐square, we compared baseline characteristics, cognitive classification status, and CSF AD biomarkers in the 4 groups (white/normal, white/impaired, AA/normal, and AA/impaired). Next, we tested associations between baseline PSS scores (predictor) and CSF AD biomarkers (outcome) over time using mixed models adjusted for factors confounding racial differences in AD. The significance level for all tests was p < 0.05.ResultData for 583 participants were analyzed (mean age:64.2; AA:49.7%; female:61.1%; impaired:68.6%). The AA participants were younger (63.6 vs. 67.7, p=.004) than white participants and had less neuropathology (Aβ42: 278 vs. 249, p<.0001; T‐tau: 47.9 vs. 74.7, p<.0001; P‐tau: 16 vs. 23.3, p<.0001; TAR: .21 vs. .37, p<.0001; PTAR: .07 vs. .11, p<.0001). AA/impaired participants reported higher stress (PSS=23.1, p=.04) than other groups. Regression, after adjusting for age, sex, education, BMI, and vascular comorbidities, showed higher baseline PSS scores were associated with higher P‐tau (F=8.22, p=.008) and PTAR (F=9.29, p=.005) over time in AA/impaired participants.ConclusionHigher baseline PSS scores were associated with Tau accumulation in the AA/impaired group over time. These results confirm previous findings and further suggest a biological connection underlying the stress‐AD link and its racial disparity. Future work exploring potential mechanisms is needed.
Differential Patterns of Brain and Body Aging on MR Imaging
Authors: Raji Cyrus A. , Meysami Somayeh , Hashemi Sam , Garg Saurabh , Akbari Nasrin , Gouda Ahmed , Chodakiewitz Yosef Gavriel , Nguyen Thanh Duc , Niotis Kellyann , Merrill David A. , Attariwala Rajpaul 
Published: January 2025

AbstractBackgroundComparative information on how whole‐body organs are linked with age and the brain is lacking.MethodOverall, 7,149 healthy participants from four sites (Mean age 53.06 ± 12.95 years, 18‐97 years; 48% women; 52% men; 38% non‐white) were scanned on 1.5T MR machines with a whole‐body protocol. Whole body sequences utilized in the quantitative analyses were coronal T1 for organ, fat and muscle segmentation. Deep learning with FastSurfer on MPRAGE trained on 134 participants aged 27‐66 and segmented 96 brain regions. Partial correlation analysis was done controlling for sex and total intracranial volume for brain regions and total abdominal organ volume for abdominal organs. Multiple comparisons were accounted for using the Bonferroni method.ResultAge negatively correlated with gray matter (rp = ‐0.38, p = 6.31×10−244) and white matter (rp = ‐0.263, p = 4.03×10−112). Age positively correlated to cerebral ventricle volume (rp = 0.493, p < .001). Increasing age was also inversely correlated with the lobar structural volumes: frontal lobe (rp = ‐0.420 p = 2.70×10−302), temporal lobe (rp = ‐0.378 p = 4.50×10−240), parietal lobe (rp ‐0.373 with p = 2.22×10−233), occipital lobe (rp = ‐0.259; p = 1.58×10−108). Age negatively correlated with AD risk regions: hippocampus (rp = ‐0.288 and p = 9.79×10−136), posterior cingulate (rp = ‐0.338, p = 4.37×10−189), precuneus (rp = ‐0.321, p= 1.44×10−169). Beyond the brain, the kidney and psoas muscle showed significant negative correlations with age (kidney; rp= ‐0.114, p = 1.23×10−211) and the psoas muscle (rp = ‐0.353, p= 1.13×10−208). Strikingly, visceral fat (vfat) was found to have a strong positive correlation with age, (rp = 0.416, p= 8.81×10−297). Subcutaneous fat (sfat), by contrast, showed a null correlation (rp = ‐0.01, p=1.0). Increasing age showed negative correlations with liver volumes (rp = ‐0.226, p = 2.21×10‐82), spleen (rp = ‐0.262, 5.46×10‐112) and total muscle volume (rp = ‐0.317, 3.17×10‐165).ConclusionDifferential patterns of brain and body organ aging may lend insight into how age can increase the risk for common brain disorders in the elderly such as Alzheimer’s.