bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation analysis of ApoB, ApoA1 and ApoB/ApoA1 with cortical morphology in patients with memory complaints
Authors: Wang Jiayu , Chen Lei , Wang Ziqi , Duan Mingjun 
Published: January 2025

AbstractBackgroundApolipoproteins and cortical morphology are closely associated with memory complaints, and both may contribute to the development of Alzheimer’s disease.MethodA total of 97 patients from the University of Electronic Science and Technology (UESTC) (n=42) and the Fourth People's Hospital of Chengdu (FPHC) (n=55) were grouped based on recruitment location, and underwent neuropsychological tests. ApoB, ApoA1, ApoB/ApoA1, plasma Alzheimer’s biomarker, apolipoprotein E (ApoE) genotyping, 3T magnetic resonance imaging. The CAT12 toolbox (SPM12) was performed for the calculation of each patient's cortical morphology index based on structural MRI data, and the cortical morphology index and apolipoproteins were analyzed by multiple regression analysis.ResultSignificant positive correlations were found between ApoB and sulcal depth in the lateral occipital cortex for the UESTC and total sample groups (p<0.0001). Sulcal depth in the lateral occipital cortex showed negative correlations from the Shape Trails Test Part A and B in the UESTC, the FPHC and total sample groups. In the FPHC group, the delayed recall of Auditory Verbal Learning Test, Animal Fluency Test and Boston Naming Test were positively correlated with the sulcal depth.ConclusionApoB is associated with the sulcal depth in the lateral occipital cortex, potentially relating to speed/executive function in individuals with memory complaints.
Exploring the current approach to reablement for community‐dwelling people living with dementia: preliminary practitioner‐led goals and targets for practice change
Authors: O'Connor Claire , Poulos Christopher , Kurrle Susan , Anstey Kaarin J. 
Published: January 2025

AbstractPeople living with dementia have a range of functional, physical, cognitive, and behaviour needs. Reablement (and/or ‘rehabilitation’) is an important multidisciplinary approach, such as using occupational therapy and exercise, to address each person’s needs. People with dementia in Australia are being referred to community aged care teams for everyday living support, and an evidence‐informed reablement handbook is freely available (www.hammond.com.au/reablement). Despite this, evidence‐informed reablement is still not routinely available. This project aims to explore how reablement is currently provided for people with dementia in the community, and to identify practitioner perspectives around potential goals and targets for practice change. The preliminary outcomes from this research (presented here) will feed into a broader project that seeks to understand how to implement evidence‐informed reablement for people with dementia in Australia.To explore how reablement is currently provided for people with dementia, a retrospective file audit was conducted with two community aged care providers in New South Wales, Australia. At the time of data collection, the providers had not implemented the evidence‐informed reablement handbook into practice. Data from the clinical file notes from each provider were compared against the reablement handbook. Site‐specific outcomes were then presented back to the respective allied health teams from each provider via focus groups; through this process, practitioners identified potential goals and targets for practice change.Data from 10 clients with cognitive impairment or dementia were included in the audit. There was partial alignment with the handbook in terms of interventions delivered (e.g. personally prescribed multicomponent exercises; provision of compensatory strategies), and some areas where discrepancies existed (e.g. very few written support plans provided to clients). Twelve allied health professionals (occupational therapy, physiotherapy, social work, dietetics) participated in the focus groups. A range of potential targets for practice change were identified, such as better tailored information for clients’ cognitive/physical functioning, and more structured functional cognition assessment.Although some alignment with the reablement handbook existed, there was room for improvement in provision of reablement for people with dementia. Moving forward, broad consultation with a range of stakeholders is needed to determine the best implementation approach on a national scale.
Novel piperazine‐benzoquinone derivative as a possible lead molecule selectively targeting AChE for the management of dementia in Alzheimer’s disease
Authors: Silakari Pragati , Piplani Poonam , Kumar Amit , Grewal Amarjot Kaur 
Published: January 2025

AbstractBackgroundThe present study recapitulates the potency of the novel synthesized piperazine‐benzoquinone derivative as a lead molecule selectively targeting AChE along with the antioxidative potential for the management of cognitive decline in Alzheimer’s disease.MethodNovel piperazine‐benzoquinone derivative was synthesized implementing appropriate synthetic procedures and was characterized by various spectral and elemental techniques. The purity of this synthetic analogue was ascertained by TLC, melting point determination and elemental analyses. Further, the compound was evaluated for its selective in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory potential at different concentrations using mice brain homogenate as the source of the enzyme. The analogue further evaluated for their antioxidant potential using DPPH radical scavenging and hydrogen peroxide radical scavenging protocols at five different concentrations and further studied against behavioural alterations using step down passive avoidance and escape learning protocol at a dose of 0.5 mg/kg with reference to the standard drug donepezil. Scopolamine at a dose level of 2.0 mg/kg was used as an inducer of dementia in the animal model. The ex vivo acetylcholinesterase (AChE) inhibition using mice brain homogenate as the source of the enzyme were also performed. Biochemical estimation of the markers of oxidative stress (lipid peroxidation, superoxide dismutase, glutathione and catalase) has also been carried out to determine the role of the synthesized molecule on the scopolamine induced oxidative damage.ResultA synergistic effect of two structural components viz. the benzoquinone moiety and the cyclic secondary amino subunits on the inhibitory activity against AChE has been anticipated. The compound exhibited selective acetylcholinesterase activity (IC50 06.795 µM), appreciable selectivity index value (0.353) and significant antioxidant potential. The ex vivo AChE inhibition assays were also in conformity with the behavioural studies data along with the docking results showing important interactions with AChE protein (Figure 1)ConclusionOutcomes depicted the anti‐amnesic effect of the synthesized conjugate on scopolamine‐induced memory impairment probably related to mediation of cholinergic system and their effective antioxidant activity. Results obtained were found to be appreciable and provided promising lead which can be further explored structurally and pharmacologically, presenting a favourable scenario for the development of selective AChE inhibitors.
Magnetic resonance imaging‐negative cerebral amyloid angiopathy: cerebrospinal fluid amyloid‐β42 over amyloid positron emission tomography
Authors: Pyun Jung‐Min , Kang Min Ju , Baek Seung Jin , Lee Kyungbok , Park Young Ho , Kim SangYun 
Published: January 2025

AbstractBackgroundCerebral amyloid angiopathy (CAA) pathology is becoming increasingly important in Alzheimer’s disease (AD) because of its potential link to amyloid‐related imaging abnormalities, a critical side effect observed during AD immunotherapy. Identification of CAA without typical magnetic resonance imaging (MRI) markers (MRI‐negative CAA) is challenging, and novel detection biomarkers are needed.MethodWe included 69 participants with high neuritic plaques (NP) burden, with and without CAA pathology (NP with CAA vs. NP without CAA) based on autopsy data from the Alzheimer’s Disease Neuroimaging Initiative. Two participants with hemorrhagic CAA markers based on MRI were excluded and the final analysis involved 36 NP without CAA and 31 NP with CAA. A logistic regression model was used to compare the cerebrospinal fluid (CSF) amyloid‐β42 (Aβ42), phosphorylated tau181, and total tau levels, the amyloid positron emission tomography (PET) standardized uptake ratio (SUVR), and cognitive profiles between NP with and without CAA. Regression models for CSF and PET were adjusted for age at death, sex, and the last assessed clinical dementia rating sum of boxes score. Models for cognitive performances was adjusted for age at death, sex, and education level.ResultNP with CAA had significantly lower CSF Aβ42 levels when compared with those without CAA (110.5 pg/mL vs. 134.5 pg/mL, p‐value = 0.002). Logistic regression analysis revealed that low CSF Aβ42 levels were significantly associated with NP with CAA (odds ratio [OR]: 0.957, 95% confidence interval [CI]: 0.928, 0.987, p‐value = 0.005). However, amyloid PET SUVR did not differ between NP with CAA and those without CAA (1.39 vs. 1.48, p‐value = 0.666). Logistic regression model analysis did not reveal an association between amyloid PET SUVR and NP with CAA (OR: 0.360, 95% CI: 0.007, 1.741, p‐value = 0.606).ConclusionCSF Aβ42 is more sensitive to predict MRI‐negative CAA in high NP burden than amyloid PET.
what do reactive astrocytes (really) do?
Authors: Liddelow Shane A. 
Published: January 2025

AbstractBackgroundAstrocytes, a major glial cell in the central nervous system (CNS), can become reactive in response to inflammation or injury, and release toxic factors that kill specific subtypes of neurons. Over the past several decades, many groups report that reactive astrocytes are present in the brains of patients with Alzheimer’s disease, as well as several other neurodegenerative diseases. In addition, reactive astrocyte sub‐types most associated with these diseases are now reported to be present during CNS cancers of several types. Given the active role some of these reactive astrocyte sub‐states in these contexts, it suggests that targeting astrocyte reactivity may be a novel therapeutic strategy for multiple disorders. Here we explore the link between astrocyte reactivity and brain cancer, and found that some brain tumors can induce a similar form of reactive astrocytes that promote tumor growth and invasion.MethodWe used a combination of single cell/nuclei RNAseq, ATACseq, spatial transcriptomics, protein and lipid analyses, in both rodent primary and human iPSC‐derived astrocytes, as well as behavioral assays in mice that lack key components of astrocyte reactivity pathways.ResultMultiple sub‐states of reactive astrocytes first described in the context of acute inflammatory responses, or chronic neurodegenerative disease, are present in the brains of rodent models of cancer. This includes oligodendroglioma and melanoma metastases.ConclusionAstrocytes while being very heterogeneous at the measurable 'omics level and with respect to functional output WITHIN an individual disease, can have sub‐states that are homogenous across multiple disease states. This means that functional/dysfunctional outcomes learning in one model may be translatable to further out understanding of disease pathogenesis in another model. This has been historically reported in the comparison of (say) spinal cord injury and stroke ‐ both of which produce a proliferative border/scar formed by reactive astrocytes, but is now appreciated at multiple pro‐inflammatory reactive states including neurotoxic reactive astrocytes, interferon‐responsive reactive astrocytes, and likely many more.
Functional Connectivity and Longitudinal Changes in Amyloid Pathology in Cognitively Healthy Older Adults
Authors: ten Kate Mara , Lorenzini Luigi , Tijms Betty M. , Wink Alle Meije , Konijnenberg Elles , Tomassen Jori , van der Landen Sophie M. , de Geus Eco J.C. , Coomans Emma M. , Collij Lyduine E. , Scheltens Philip , van de Giessen Elsmarieke , Visser Pieter Jelle , den Braber Anouk , Barkhof Frederik 
Published: January 2025

AbstractBackgroundAccumulation of amyloid beta in the brain is one of the first events in Alzheimer’s disease (AD) and starts decades before symptoms arise. It has been hypothesized that brain areas with higher levels of neuronal activation (‘hubs’) are more prone to amyloid deposition. In this study, we examined the regional relationship between cortical hubs and longitudinal changes in amyloid pathology in a sample of cognitively healthy older subjects.MethodParticipants were included from the EMIF‐AD PreclinAD cohort, a longitudinal study in cognitively healthy older monozygotic twins. Standard resting state functional MRI pre‐processing was performed with fMRIprep. Individual connectivity matrices were generated as the pairwise timeseries correlation between 100 regions in the Schaeffer atlas, and binarized using a proportional threshold of 0.25. Regional degree, the number of connections of each region, was taken as a continuous measure of functional 'hubness'. Degree was computed within the 100 individual regions, and averaged within 7 resting state networks. Dynamic [18F]Flutemetamol PET scans were used to visually assess amyloid status, and to quantify global and regional binding potential (BPND) at baseline and follow‐up (mean 4.4±0.5 years). We first assessed whether baseline regional degree could predict change in amyloid status using GEE to account for familial clustering. Next, we performed ROI‐wise analyses, assessing the relationship between group‐average regional values of degree and quantitative BPND (baseline and change) in the whole sample and according to amyloid subgroups (negative stable, converter, positive stable).ResultWe included 124 subjects (age 68.3±6.4, female 54%). In baseline amyloid visually negative subjects (n=111), a lower mean degree in the default mode network (β=‐0.26, p=0.008) was associated with higher chance of conversion from negative to positive amyloid status. In the ROI‐wise analyses, a lower degree was associated with higher baseline BPND and larger rate of increase over time (Figure 1). This relationship was most pronounced in the converter group (Figure 2).ConclusionWe found that in cognitively healthy individuals, decrease rather than increase in functional hubness is associated with amyloid load and accumulation. Possibly in this population of older adults, functional hubs are already affected by ageing, or early pathology.
Atrial function: Association with cerebrovascular disease and cognitive dysfunction
Authors: Tan Eugene , Hilal Saima , Chan Siew‐Pang , Sim Ming Ann , Lai Mitchell Kim Peng , Chong Joyce R , Robert Caroline , Hazli Hazliza , Gong Lingli , Berboso Josephine , Venketasubramanian Narayanaswamy , Tan Boon Yeow , Richards Arthur Mark , Chen Christopher , Lieng‐Hsi Ling 
Published: January 2025

AbstractBackgroundThe relationships of left atrial (LA) dysfunction with cognition are poorly understood. We investigated the associations of LA function with cognitive impairment, etiologic‐subtype (neurodegenerative vs. vascular[VCI]), neuroimaging markers of cerebrovascular disease (CeVD) and circulating biomarkers, in subjects without AF.MethodIn this prospective cohort study of subjects recruited from memory clinics with brain magnetic resonance imaging (MRI), neuropsychological assessments, circulating biomarker measurements, LA strain (reservoir [LASr], conduit [LAScd], contractile) was determined using 2D speckle‐tracking echocardiography. VCI was defined as vascular dementia or cognitive impairment no dementia(CIND)/Alzheimer’s dementia with significant CeVD, and neurodegenerative defined as CIND/dementia without significant CeVD on neuroimaging.ResultAmong 251 subjects (age 75±8years, 59% female, 178(71%) had cognitive impairment (37% dementia, 14% moderate CIND, 20% mild CIND), of which 58% were VCI and 42% neurodegenerative. LAScd was the only LA strain parameter independently associated with more severe (moderate CIND/dementia vs. mild CIND/no cognitive impairment) grades of cognitive impairment (lowest vs. highest tertile: adjusted odds ratio[AOR] 2.50, p=0.015), and worse MMSE scores, visuomotor construction and memory on neuropsychological testing (p<0.05). LAScd was independently associated with VCI (vs. neurodegeneration) (lowest vs. highest tertile: AOR 3.16, p=0.006), and showed no associations with markers of neurodegeneration, including circulating pTau‐181 and strictly lobar cerebral microbleeds (p>0.05). LAScd and LASr were both associated with increased burden of CeVD including intracranial stenoses, cortical infarcts, lacunes, cerebral microinfarcts, microbleeds and white matter hyperintensities and correlated with cardiac‐specific biomarkers (p<0.05), but LAScd correlated additionally with a broader range of circulating biomarkers reflecting inflammation, neurotrophic processes and neuronal damage (p<0.05).ConclusionReduced LA conduit function was associated with more severe cognitive impairment, primarily due to CeVD. LA strain, particularly LAScd, may be a useful biomarker of cognitive impairment in at‐risk subjects without AF.
Simple fully convolutional network to detect Alzheimer’s Disease
Authors: Aithal Ninad , Sinha Neelam 
Published: January 2025

AbstractBackgroundDeep Neural Networks (DNNs) have emerged as powerful tools in the biomedical field, particularly for the early detection of neurodegenerative diseases. Despite their complexity and data‐intensive nature, simpler fully connected Convolutional Neural Network (SFCN) architectures have shown effectiveness in accurately discerning between subjects affected by Alzheimer’s disease (AD) and healthy controls (HC). This model draws inspiration from the work of Peng H et al. and is trained on the openly available Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset.MethodIn this study, RAW 3T T1‐weighted MPRAGE MRI images with a sagittal acquisition plane and 3D acquisition type were carefully selected, amounting to 807 MRI images categorized into AD and CN classes. These images underwent brain extraction and linear registration (12 degrees of freedom) to a standard 2mm MNI template using FSL, resulting in uniform‐shaped scans of dimensions 1 × 91 × 109 × 91. The model comprises 5 blocks, each incorporating 2 × 3D CNN blocks, 3D batch normalization, and ReLU activation functions. A single MaxPooling layer doubles the channels at each CNN block, followed by a 3D pointwise CNN block reducing channels from 1024 to 256 while introducing non‐linearity. The final block includes 3D adaptive average pooling with a kernel size of 1, dropout set to 0.5, and 2 × 3D point‐ wise CNN layers acting as fully connected layers. This 13‐layer deep network is trained using Weighted Cross Entropy as the loss function and the Adam optimizer with a learning rate initialized to 0.00001. Training involved 100 epochs with a batch size of 16 and a 70‐10‐20 train‐validation‐test split.ResultThe voxel‐based DNN, trained on 278 AD and 288 CN MRI images, achieves a remarkable 95% accuracy on a test dataset of 161, exhibiting precision and recall values of 0.96 and 0.94, respectively.ConclusionThe promising 95% classification accuracy on the ADNI dataset, encompass‐ ing over 800 subjects, underscores the efficacy of the SFCN in distinguishing between AD and NC subjects based on T1‐weighted MRI scans. This ap‐ proach holds potential for robust early detection of Alzheimer’s disease, con‐ tributing to advancements in neuroimaging‐based diagnostic methodologies.
Resting state EEG Abnormalities and their Relationship with TMS‐EEG induced Cortical Excitability in Alzheimer's Dementia
Authors: Alhabbal Hiba , Asare Gifty , Lawson Renee P , Azami Hamed , Zomorrodi Reza , Chen Robert , Blumberger Daniel M. , Mulsant Benoit H. , Pollock Bruce G. , Rajji Tarek K. , Kumar Sanjeev 
Published: January 2025

AbstractBackgroundPrevious literature has identified slowing of resting state electroencephalography (EEG) rhythm and abnormal cortical excitation in Alzheimer’s Dementia (AD). However, the relationship between these two divergent functional abnormalities and cognitive symptoms of AD are not well understood.MethodResting state EEG signal was recorded in participants with AD and HCs for 5 minutes with eyes closed. Relative resting state EEG power was measured for the five frequency bands. Participants underwent a single pulse transcranial magnetic stimulation (TMS) combined with EEG. Cortical evoked activity (CEA) was assessed using TMS‐evoked potential (TEP) rectified area under the curve (AUC) from 25 to 80 ms post‐TMS stimulus, and the TEPs peak amplitudes were calculated by taking the maximal peak in the following time windows: 25 – 35 ms (P30), 40 – 50 ms (N45), and 55 – 65 ms (P60).ResultCompared to 32 HC (18 females; mean ± SD age: 69.3 ± 7.9 years), 52 participants with AD (32 females; 74.2 ± 8.5 years) had higher relative theta power than HCs (t(66.6) = 5.34, p<0.001). AD participants also had a significantly lower alpha power (t(76) = ‐3.03, p=0.003) and beta power (t(76) = ‐2.51, p=0.014) than HCs. Controlling for sex, age and years of education, AD participants showed a positive association between theta power and CEA (rpartial=0.573, p=0.008); and an inverse association between alpha power and CEA (rpartial=‐0.471, p=0.036). Theta power in AD participants showed a positive association with P60 (rpartial=‐0.637, p=0.003) and an inverse association with N45 (rpartial=‐0.512, p=0.025), while alpha power was inversely associated with P60 (rpartial=‐0.531, p=0.016).ConclusionThis study showed a positive association between resting state EEG slowing and increased cortical excitability in AD, indicating a possible shared mechanistic pathway between these abnormalities.
DNA methylation signatures can predict amyloid‐beta burden
Authors: Vacher Michael 
Published: January 2025

AbstractBackgroundA growing body of research has confirmed the presence of epigenetic alterations in Alzheimer’s disease (AD). While the causal relationship between these changes and AD remains uncertain, they offer a novel avenue to explore potential treatments. In this study, we aimed at characterising the methylation signatures of amyloid beta (Aβ) deposition, one of the main hallmarks of AD.MethodThe cohort consists of 654 participants (mean age = 72.8 years (±6.83), N(male/female) = 293/361) with genome‐wide DNA methylation data (Illumina Infinium EPIC 850k array), drawn from the Australian Imaging Biomarkers and Lifestyle (AIBL) study. We used a centiloid (CL) threshold of 20CL to dichotomise amyloid status of participants (Aβhigh N = 290, Aβlow N = 364). Two methods, Partial Least Square Discriminant Analysis (PLS‐DA) and Elastic Net (EN) regression, were employed to identify methylation signatures characterising Aβ status. The overlapping set of features between the two methods were then used to build a logistic regression model to predict amyloid burden.ResultThe PLS‐DA and Elastic Net models allowed the identification of 5 key methylation probes specific to low and high amyloid burden. These main features include (cg18032014 and cg17889682, DYNC1; cg06561607, SMYD3; cg03161454, NXPH4, cg06311780). Individually, all these features were significantly differentially methylated between high and low participants. Assessing the collective effect of these biomarkers in a logistic regression model resulted in 71% Area Under Curve (AUC) performance. The AUC increased to 83% when controlling for the main risk factors of AD, age and APOE ε4 genotype of participants.ConclusionThis study demonstrates the possibility to use a small set of methylation markers as a non‐invasive way to predict Aβ burden. In addition, the features identified could help shed some lights on the mechanisms underpinning Aβ accumulation. Further validation in independent cohorts is required to validate and refine the results presented in this study.