bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Study of PET‐validated EEG‐machine learning algorithm predicting brain amyloid pathology in pre‐dementia Alzheimer’s disease
Authors: Kim Nam Heon , Park Ukeob , Wang Min Jeong , Lee Chunghwee , Jeong Jee Hyang , Park Kee Hyung , Hong Yun Jeong , Shim Yong Soo , Kim SangYun , Choi Seong Hye , Yang Dong Won , Kang Seung Wan 
Published: December 2023

AbstractBackgroundCurrently positron emission tomography (PET) is used as the initial or sole biomarker of β‐amyloid (Aβ) brain pathology, which may inhibit Alzheimer’s disease (AD) drug development and clinical use due to cost, access, and tolerability. Machine learning (ML)‐based EEG biomarkers may address these challenges. Previous studies have confirmed their ability to accurately discriminate between normal, mild cognitive impairment (MCI) and Alzheimer’s dementia. However, few quantitative EEG (QEEG) biomarkers have been validated with Aβ PET. We developed a QEEG‐ML algorithm to predict brain Aβ pathology among subjective cognitive decline (SCD) and MCI patients, and validated it using Aβ PET.MethodEEG (19‐channel, eye‐closed, resting‐state) and Aβ PET data were collected from 160 human subjects with MCI (77 Aβ+, 83 Aβ‐). We excluded 45 data (23 Aβ+, 22 Aβ‐) for test verification. QEEG absolute power, relative power, power ratio, and connectivity between channels (iCoherence) comprised the input features, from which the most relevant predictive features were identified using four methods (Random Forest Importance (GBM, XGB), ElasticNet, Whitney‐Mann). We then trained six ML algorithms (SVM, Logistic, KNN, Naive Bayes, Random Forest(GBM/XGB)) using each relevant feature set, yielding 24 models (4 sets * 6 algorithms). The 45 test data sets were input into each model to compare their performance. Then, 111 MCI data (56 Aβ+, 55 Aβ‐) and 165 SCD data (31 Aβ+, 134 Aβ‐) were classified by the model for 3rd validation.ResultIn test validation, the best‐performing model showed 77.8% accuracy, 81.8% sensitivity, 73.9% specificity in discriminating Aβ+ from Aβ‐. In 3rd data validation, the best‐performing model showed 72.1% accuracy, 71.4% sensitivity, 72.7% specificity in MCI. In SCD, it showed, 69.1% accuracy, 64.5% sensitivity, 70.2% specificity.ConclusionThese findings suggest that our novel ML‐based QEEG biomarker can accurately predict the presence of brain Aβ plaque. Additional benefits of such a biomarker include reduced expense, wide availability, and high‐throughput screening and response monitoring. Future studies will assess utility as primary AD screens, adjunctive use with PET, and as a support in clinical rationales for Aβ PET and treatment choice in AD.
Investigation of tau post‐translational modification based on T217 and T231 in human plasma as new biomarkers
Authors: Yoon Hyosang , Kwon SunSang , Jeong Seongeun , Kim Han‐Kyeol , Cho Hanna , Lee Soo Hyun 
Published: December 2023

AbstractBackgroundPost‐translational modification (PTM) of human tau protein is of high importance as an indicator for predicting the progress of Alzheimer’s disease (AD). Particularly, phosphorylation and O‐glycosylation on tau have been observed at relatively high levels in Alzheimer’s disease (AD) patients and healthy controls, respectively [1]. Recently, a study reported that an increase in the level of phosphorylation at T217 and T231 was observed in the initial stages of the preclinical Alzheimer’s continuum [2]. Reference: [1] C. Alquezar et al. Frontiers in Neurology, 11 (2021) 595532. [2] Marc Suárez‐Calvet et al. EMBO Molecular Medicine, 12 (2020) e12921.MethodTo investigate the PTM of tau protein in human blood plasma, an electrochemical sensor with 1 µm gap between working and counter electrodes was performed and obtained Taumeter indicating the ratio of phosphorylation and O‐glycosylation on the surface of tau protein, where antibodies for phosphorylated T217 and T231 were used [3]. To explore the clinical association, standardized uptake value ratio (SUVR) of amyloid‐positron emission tomography (PET), mini‐mental state examination (MMSE), and clinical dementia rating scale sum of boxes (CDR‐SB) were also investigated and compared to Taumeters. Reference: [3] Yoon et al. Alzheimer’s & Dementia, 18 (2022) e061465.ResultA total of 43 participants (normal control (NC, n = 15), mild cognitive impairment (MCI, n = 14), and AD (n = 14) were investigated. Taumeters for T217 (p = 0.00423, AUC = 0.82667) and T231 (p = 0.00034, AUC = 0.86222) were obtained and analyzed through one‐way analysis of variance (ANOVA) between NC and AD groups (Figure 2). In regression analysis, Taumeter for T217 (r = 0.23824, p = 0.12394) was more correlated with amyloid‐PET SUVR than Taumeter for T231 (r = 0.28072, p = 0.06824) (Figures 3a‐b). Taumeter for T217 (r = ‐0.51246, p = 0.00044) was also more correlated with MMSE score than Taumeter for T231 (r = ‐0.07186, p = 0.64701) (Figures 3c‐d). Taumeter for T217 (r = 0.57937, p<0.0001) was more correlated with the CDR‐SB score than Taumeter for T231 (r = 0.16254, p = 0.29768) (Figures 3e‐f).ConclusionIn this study, we investigated the correlation between Taumeters for T217 and T231, amyloid‐PET SUVR, MMSE score, and CDR‐SB score. As a result, Taumeter for T217 indicates more strong correlation with analytical results of amyloid‐PET SUVR, MMSE score, and CDR‐SB score than Taumter for T231.
Association between Auditory Impairment and the Onset of Alzheimer’s Disease: The LIFE Study
Authors: Fukuda Haruhisa , Fujii Takayuki , Maeda Megumi , Murata Fumiko , Ono Rei 
Published: December 2023

AbstractBackgroundThe prevalence of Alzheimer’s Disease (AD) has seen an upward trend due to the demographic shift towards an aging population in Japan. The possible association between auditory impairment and the onset of AD has been previously proposed, however, it remains a subject of ongoing discussion. This study aimed to investigate this association using data from 13 municipalities in Japan.MethodFrom the LIFE Study, 13 municipalities that possessed both long‐term care certification questionnaire and medical claims data were identified as eligible for inclusion. The study population consisted of individuals who had newly applied for long‐term care certification between April 2013 and October 2021. The study population consisted of individuals who displayed no cognitive impairment at the time of application and had not been diagnosed with dementia within the preceding six months, inclusive of the month of application. The month succeeding the application was established as the index month, and the interval from this month to the onset of AD (ICD‐10 codes F00 or G30) was assessed. The Cox proportional hazards model was utilized to examine the risk of AD onset in relation to auditory status as reported on the long‐term care certification questionnaire.ResultThe study cohort consisted of 33,067 participants, with a mean follow‐up duration of 21.0 months. At the index month, 60.2% of the patients were female, and the mean age was 79.5 years. In the course of the follow‐up period, 1,827 (5.53%) individuals developed AD. Auditory impairment was not found to be correlated with the incidence of AD. The hazard ratio (HR) for the development of AD in relation to auditory impairment was 1.31 (95% Confidence Interval: 0.65 ‐ 2.64).ConclusionThe examination of the long‐term care certification questionnaire data did not reveal any correlation between auditory function and the onset of AD. The limitations of this study include the inability to determine the use of hearing aids or the timing of onset of auditory impairment. Further investigations are necessary to clarify the relationship between auditory function and dementia.
Molecular hallmarks of Alzheimer’s disease with a multimodal single cell atlas of the cortex
Authors: Travaglini Kyle J , Gabitto Mariano I , Ariza Jeanelle , Ding Yi , Mahoney Joseph T , Casper Tamara , Chakrabarty Rushil , Clark Michael , Crane Paul K , Dee Nick , Ferrer Rebecca , Gatto Nicole M , Gloe Jessica , Goldy Jeff , Grabowski Thomas J , Guilford Nathan , Guzman Junitta , Hawrylycz Michael J , Hodge Rebecca D , Jayadev Suman , Kaplan Eitan S , Keene C Dirk , Larson Eric B , Latimer Caitlin S , Levi Boaz P , Melief Erica J , Meyerdierks Emma , Mukherjee Shubhabrata , Pham Thanh , Rachleff Victoria M , Smith Kimberly , Torkelson Amy , Lein Ed S , Miller Jeremy A 
Published: December 2023

AbstractBackgroundThe Seattle Alzheimer’s Disease Cell Atlas (SEA‐AD, https://sea-ad.org) is a large‐scale effort to identify, at single cell resolution, the cellular and molecular mechanisms that cause AD and facilitate its progression. SEA‐AD brings together quantitative neuropathology (QNP) derived from classic histopathological and cell type stains with single nucleus transcriptomics, epigenetics, and spatial transcriptomics on a cohort of 84 aged donors that span the pathological and cognitive disease spectrum, including unaffected controls.MethodWe ordered SEA‐AD donors based on QNP using a Bayesian latent space model to construct a model‐estimated “pseudo‐progression” (PS). We then used a general linear mixed effects model to test for gene expression changes along the PS in each of the BRAIN initiative’s 139 cell types present in SEA‐AD’s single nucleus RNA sequencing dataset (∼1.2 million nuclei) from the middle temporal gyrus. By separately fitting models to donors with lower and higher pathology, we obtained two beta coefficients for each gene that enabled distinction between early, late, and consistent up‐ and down‐regulation along PS. We then tested whether the betas for each gene were different across all cell types or in only certain ones to measure specificity. We curated gene modules from biological processes potentially relevant to AD, identified in gene‐set enrichment analyses and prior studies, and categorized each gene within them based on their dynamics and specificity.ResultRoughly one‐third of genes had differential expression across neuronal cell types (mean betas > 0.2), split evenly between up‐ and down‐regulation, while a smaller subset were changed in specific cell types. Modules enriched in broadly changed genes that had increased expression early in PS included those involved with the microtubule cytoskeleton, vesicle adaptors, and neurotransmitter receptors, while those with decreased expression included those involved with cholesterol synthesis, glycolysis, mitochondrial function, and neurofilaments. Among the genes changed only in specific cell types were NOTCH2 in Somatostatin and Parvalbumin interneurons selectively vulnerable to pathology, PTPRG in disease associated microglia, and COL21A1 in disease associated astrocytes.ConclusionBroadly affected modules identified by SEA‐AD suggest most neurons are affected by disease pathology and cell type‐specific differences may provide clues to selective vulnerability.
Prevalence and recognition of cognitive impairment in hospitalized older patients: a flash mob study
Authors: Visser Fleur C.W. , van Eersel Marlise E.A. , van Munster Barbara C. , Consortium Flashmob Cognition 
Published: December 2023

AbstractBackgroundIt is estimated that over one‐third of hospitalized older patients have cognitive impairment. Cognitive impairment directly impacts care during and after hospitalization. Recognition of cognitive impairment is important to provide person‐centered care, involve relatives, prevent adverse outcomes, and identify people that need support or diagnostic evaluation for dementia after discharge. Previous studies of medical records suggested under‐recognition of cognitive impairment in hospitalized older patients by healthcare professionals. The aim of this study is to investigate the prevalence of cognitive impairment in hospitalized older patients and the recognition of cognitive impairment by healthcare professionals.MethodA cross‐sectional, observational study was conducted in three university hospitals and ten general hospitals in the Netherlands on a single day in 2022, following a flash mob design. The study was an initiative of Alzheimer Center Groningen as part of ABOARD (A Personalized Medicine Approach for Alzheimer’s Disease). Cognitive impairment, indicated by a Mini‐Cog score of <3 (out of 5), was assessed in Dutch‐speaking, hospitalized patients aged ≥ 65 years old. Patients were excluded if they were unable to perform the Mini‐Cog due to sensory impairment or severe delirium, required medical isolation, or were not willing to participate. The nurses and physicians that took care of the patient that day were asked whether they thought the patient had cognitive impairment.ResultA total of 1,318 potentially eligible patients were available. Of these patients, 374 (28%) were excluded because they were unable to perform the Mini‐Cog or were isolated, and 187 (14%) were excluded because they were not willing to participate. Finally, a total of 757 patients (58%) were included (median age, 77 years [71‐82]; male, 386 [51%]). Of the included patients, 347 patients (46%) had cognitive impairment. Cognitive impairment was recognized by their nurse in 137 of 323 patients (42%) and by their physician in 156 patients (48%). In 135 patients (42%) cognitive impairment was not recognized by either the nurse or physician.ConclusionCognitive impairment is common in older hospitalized patients, and is poorly recognized by healthcare professionals. This study highlights the need for quality improvement of cognitive impairment recognition to provide person‐centered care.
Serum biomarkers for prognosis and monitoring in asymptomatic Alzheimer’s Disease
Authors: De Meyer Steffi , Blujdea Raluca , Schaeverbeke Jolien , Reinartz Mariska , Luckett Emma S. , Adamczuk Kate , Gabel Silvy , Van Laere Koen , Dupont Patrick , Teunissen Charlotte E. , Vandenberghe Rik , Poesen Koen 
Published: December 2023

AbstractBackgroundPrognostic and monitoring capabilities of blood‐based biomarkers for early cognitive decline, amyloid‐β (Aβ) accumulation and grey matter (GM) loss in the asymptomatic phase of Alzheimer disease require further investigation over extended time periods. This longitudinal study investigated serum glial fibrillary acidic protein (GFAP), neurofilament light (NfL) and Aβ1‐42/Aβ1‐40 as potential prognostic and monitoring biomarkers in cognitively unimpaired (CU) elderly.MethodWe included 184 CU older adults (Table 1) who underwent baseline serum sampling and 2‐yearly neuropsychological assessment for up to 10 years (median: 6 years, Figure 1). A subset (N = 109) underwent serial blood sampling, Aβ‐PET and structural MRI at 2 (N = 73), 3 (N = 34), or 4 (N = 2) time points (time interval: 2‐10 years, median: 6 years). Cognition was evaluated in memory, language and executive functioning domains through conversion of neuropsychological tests scores to standardised z‐scores and subsequent averaging per domain. Aβ‐accumulation and GM loss were analysed in a voxelwise manner using Voxelstats with cluster‐level p
RFT<.05 and voxel‐level puncorrected<.001 significance thresholds.[1] Aβ1‐42/Aβ1‐40 was inverted to facilitate biomarker comparison. Linear‐mixed effects models were used to (i) identify the predictive value of serum biomarkers for longitudinal cognitive decline, Aβ‐accumulation and GM loss, (ii) calculate annual serum biomarker rates of change and (iii) investigate associations between longitudinal biomarker changes and longitudinal changes in cognition, Aβ‐PET and GM volume.ResultHigh baseline GFAP and NfL predicted a longitudinal decline in memory (βGFAP*time = ‐0.020, pFDR
= 0.03; βNfL*time = ‐0.031, pFDR = 0.002) and language (βGFAP*time = ‐0.025, pFDR<0.001, βNfL*time = ‐0.017, pFDR = 0.04), and longitudinal GM loss within the hippocampus. Low Aβ1‐42/Aβ1‐40 predicted memory decline (βAβ1‐42/Aβ1‐40*time = ‐0.022, pFDR = 0.03) as well as Aβ accumulation within Aβ‐vulnerable regions (Figure 1). Serum GFAP (βtime = 0.022, pFDR<.001) and NfL (βtime = 0.040, pFDR<.001) increased over time. Longitudinal serum NfL increases were associated with a concomitant decline in memory (β∆NfL*time = ‐0.031, pFDR= .004), language (β∆NfL*time = ‐0.022, pFDR= .01) and GM volume (Figure 2). Serum GFAP increases were associated with precuneal Aβ accumulation. Aβ1‐42/Aβ1‐40 decreases were stronger in Aβ‐ subjects (pFDR<.001) and did not associate with Aβ accumulation, nor any other longitudinal marker.ConclusionSerum GFAP, NfL and Aβ1‐42/Aβ1‐40 are prognostic and/or monitoring biomarkers providing complementary information by reflecting different Aβ‐dependent or ‐independent pathophysiological processes.REFERENCE[1] Mathotaarachchi et al. Front Neuroinform 2016.
Consumption of coffee and tea and the risk of dementia – role of sex and vascular comorbidities
Authors: Hou Kuan‐Chu , Chen Yen‐Ching , Chen Ta‐Fu , Sun Yu , Wen Li‐Li , Yip Ping‐Keung , Chu Yi‐Min , Chiou Jeng‐Min , Chen Jen‐Hau 
Published: December 2023

AbstractBackgroundCoffee and tea consumption has been shown to associate with the risk of dementia. However, little is known about how sex and vascular comorbidities (type 2 diabetes, hypertension, and hypercholesterolemia) modify this association.MethodThis is a multi‐center case‐control study. We recruited 278 Alzheimer’s disease (AD) and 102 small‐vessel vascular dementia (VaD) patients aged 60 or older from three teaching hospitals in Taiwan from 2007 to 2010; controls (n = 468) were recruited from the health checkup program during the same period of time. The outcomes of this study are clinically diagnosed AD and VaD. Information on coffee and tea consumption and the history of type 2 diabetes, hypertension, and hypercholesterolemia were collected based on questionnaires and medical charts. A multinomial logistic regression model was utilized to evaluate 1) the association of coffee and tea consumption with dementia risk, and 2) how sex and vascular risk factors modified these associations.ResultDifferent combinations and quantities of coffee and tea consumption protected against AD and VaD. Our analyses demonstrated consumption of three or more cups of coffee or tea per day was associated with a decreased risk of AD [adjusted odds ratio (aOR) = 0.42; 95% confidence interval (CI) = 0.22‐0.78)] and VaD (aOR = 0.42; 95% CI = 0.19‐0.94). After stratification, these associations became more evident in females for AD (aOR = 0.15; 95% CI = 0.05‐0.46) and in males for VaD (aOR = 0.06; 95% CI = 0.01‐0.50). Similarly, hypertensive participants consuming higher quantities of coffee and tea had a decreased risk of AD (aOR = 0.30; 95% CI = 0.11‐0.78). Moreover, hypercholesterolemia significantly modified the association of coffee or tea consumption with the risk of dementia (Pinteraction < 0.001).ConclusionCoffee and tea consumption was associated with a decreased risk of AD and VaD. Sex and vascular comorbidities differentially modified the association of coffee and tea consumption with the risk of dementia.
Chronic Exposure with 5‐Alpha Reductase Inhibitor Ameliorates Anxiety and Depression‐like Behaviors By Reducing Systemic Oxidative Stress in D‐galactose‐Induced Aging Male Rats
Authors: Pintana Hiranya , Saengmearnuparp Thiraphat , Apaijai Nattayaporn , Chunchai Titikorn , Lojanapiwat Bannakij , Chattipakorn Nipon , Chattipakorn Siriporn C 
Published: December 2023

AbstractBackgroundThe most common geriatric psychiatric disorders are anxiety and depression. The 5‐alpha reductase inhibitor (5‐ARIs), finasteride (Fin), is a standard medication used to treat benign prostatic hyperplasia (BPH), that often occurs in the elderly. However, the effects of Fin on mental health in aged population are still unclear. D‐galactose (D‐gal)‐induced aging has been recognized worldwide, as a model to mimic natural aging in rodents. Therefore, we investigated the effect of Fin on anxiety and depression‐like behaviors in D‐gal‐induced aging male rats.MethodTwenty‐male Wistar rats (8‐week‐old) were randomly divided into two groups (n = 10/group) to receive either vehicle as control or D‐gal (150 mg/kg/day via subcutaneous injection) for 18 weeks. At week 13, rats in each group were divided into two subgroups (n = 5/subgroup) in order to receive either vehicle (drinking water) or Fin (5 mg/kg/day) via oral gavage. At the end of the treatment, elevated‐plus maze (EPM), and splash test (ST) were performed for quantifying anxiety and depression‐like behaviors, while open‐field test (OFT) to determine locomotor activity. In addition, blood in each rat was collected for determining the metabolic profiles.ResultD‐gal‐treated rat showed no effect on metabolic disturbance, but increased systemic oxidative stress (Figure 1A‐C). Anxiety and depression‐like behavior were observed in D‐gal‐treated rats, as indicated by a decrease % preference index in the open arm of EPM and grooming time in ST (Figure 1D‐E). Fin‐treated control rats demonstrated hypercholesterolemia (Figure 1A‐B), and depression‐like behavior was observed (Figure 1E). Anxiety and depression‐like behaviors were attenuated in Fin‐treated D‐gal rats (Figure 1D‐E). Regarding the locomotor activity, no significant difference was found among all groups. (Figure 1F).ConclusionFIN exposure induced metabolic disturbance, and depression‐like behaviors in male rats. In contrast, Fin ameliorated anxiety and depression‐like behaviors in D‐gal‐induced aging rat, which may due to a reducing systemic oxidative stress. The findings in this study provide information for future clinical applications such as the use of Fin for therapeutic approach for anxiety/depression‐like behaviors in the elderly. However, caution is advised when using Fin in young men since it may induce depressive‐like behaviors.
Analysis of the effect of adult onset increase of neurotrophic factor GDNF expression in APP‐NL‐G‐F AD mouse model
Authors: Olfat Soophie , Andressoo Jaan‐Olle 
Published: December 2023

AbstractBackgroundGradual decline in cholinergic transmission and cognitive function occurs during normal aging, whereas pathological loss of cholinergic function is a hallmark of different types of dementia, including Alzheimer’s disease (AD), Lewy body dementia (LBD), and Parkinson’s disease dementia (PDD). Glial cell line‐derived neurotrophic factor (GDNF) is known to modulate and enhance the dopamine system. However, how endogenous GDNF influences brain cholinergic transmission has remained elusive.MethodRecently we showed that two fold increase in endogenous GDNF expression in Gdnf hypermorphic mice, Gdnf wt/hyper, attenuated age‐associated decline in the cholinergic index and cognitive function observed in Gdnf wt/wt animals. Biochemical analysis revealed that the level of nerve growth factor (NGF), which is important for survival and function of central cholinergic neurons, was significantly increased in several brain areas of old Gdnf wt/hyper miceResultOur results identified endogenous GDNF as a potential enhancer of cholinergic transmission upon aging (11). Here we propose to follow up those results by analyzing the effect of adult onset increase in endogenous GDNF expression on cholinergic index, A‐beta load, NGF expression and cognition in APP‐NLGF mouse model of AD. To accelerate AD onset and to facilitate future studies we have also generated and propose characterization of APP‐NLGF conditional Hypermorph mouse model.ConclusionOur goal is to conclude therapeutic potential of enhanced endogenous GDNF signaling on AD associated cholinergic and cognitive decline to pave way to new dementia treatments based on GDNF mimetics currently under development by several academic and industrial laboratories.