bluuebunny/crossref_metadata_2025_split huggingface dataset:
CSF Biomarkers and [18F]flutemetamol PET‐Derived Centiloids in Patients with SCD or MCI
Authors: Battle Mark R , Buckley Chris J , Farrar Gill , Janelidze Shorena , Palmqvist Sebastian , Ossenkoppele Rik , Smith Ruben , Hansson Oskar 
Published: December 2023

AbstractBackgroundCSF biomarkers are well characterised as surrogate markers for amyloid deposition and neurofibrillary tau tangles reflecting pathological features of Alzheimer’s disease. Amyloid PET images provide a visual and quantitative assessment of brain amyloid burden. In diagnostic workup these biomarkers are considered interchangeable, however their relationship is not fully understood.MethodsCentiloid (CL) values for 387 [18F]flutemetamol images from the Swedish BioFINDER I study were derived following the methods of Klunk et.al. (Alzheimer’s & Dementia, 2015). Subjects, comprising Controls, SCD and MCI (Table 1), were ranked by Centiloid values (lowest to highest) and the average for each consecutive group of 30 subjects calculated. Corresponding CSF biomarker values (Aβ42/40 and pTau181) were plotted for each group.ResultsSubjects in groups averaging ‐7.7 CL to 29.0 CL had a mean(±SD) Aβ 42/40 ratio of 0.144 (±0.033, range 0.051 to 0.236, n = 240) with no statistically significant differences between groups (Fig. 1A). A statistically significant fall in CSF Aβ42/40 ratio between the 29.0 CL and 47.3 CL groups (from 0.134 (±0.041, 0.066 to 0.236) to 0.088(±0.031, 0.045 to 0.183), p<0.0001) was observed. The average CSF Aβ42/40 ratio value for all subjects ranging from 66.3 Cl to129.8 CL was 0.072 (±0.017, 0.030 to 0.127, n = 117) with no statistically significant difference in CSF levels across these CL bands.Subjects in the groups averaging ‐7.7 CL to 29.0 CL had a mean(±SD) pTau181 value of 48.9 pg/mL (±15.9, 22 to 138) with no statistically significant difference between groups (Fig. 1B). A statistically significant (p<0.05) increase between 29.0 CL (47.3±19.3, 24 to 116 pg/mL) and 47.3 CL groups (67.8±29.4, 24 to 175 pg/mL) was observed. For all Subjects from 66.3 CL to129.8 CL mean pTau181 levels were 79.6 (±30.3, 32 to 209 pg/mL) with no statistically significant difference across these CL bands.ConclusionsComparison of [18F]flutemetamol image quantitation and CSF biomarkers indicates CSF Aβ42/40 and pTau181 starts to show amyloid positivity at approximately 30‐40 CL units. Recent comparisons between visual rating and Centiloids from PET imaging indicate visual positivity from approximately 20 CL units indicating sensitivity of amyloid PET imaging for the detection of early amyloid deposition.
Ex vivo identification of transcriptional regulation landscape and potential therapeutic targets against ER stress using Alzheimer’s disease patient‐derived dermal fibroblast: findings from BICWALZS cohort
Authors: Son Sang Joon , Kim Yeojin , Yoon Sunwoo , Park Sunghong , Cho Yong Hyuk , Nam You Jin , Roh Hyun Woong , Hong Chang Hyung , Hong Sunhwa 
Published: December 2023

AbstractBackgroundEndoplasmic reticulum (ER) stress is considered as a central pathophysiology for neurodegeneration in Alzheimer’s disease (AD). Many studies using in vitro cell line or in vivo mouse model have shown the possible association between ER stress and neurodegeneration. However, that connection was not elucidated well in AD patient‐derived cell or brain organoids. In this study, we aimed to identify transcriptional regulation landscape and potential therapeutic targets against ER stress using AD dementia patient‐derived dermal fibroblast.MethodFor the purposes of ex vivo research, we performed skin biopsy and stabilized dermal fibroblasts in vitro. Total of 20 AD dementia patients and 22 cognitively normal older adults were assessed. All of AD dementia patients were amyloid positive on PET imaging, APOE e4 carrier, and cognition was imparied. On the contrary, all of cognitively normal older adults were amyloid negative on PET imaging, and APOE e4 non‐carrier. We applied thabsigargin (10 nM) to dermal fibroblast for 24 hours to promote ER stress. After that, to identify transcriptional regulation landscape against ER stress, RNA sequencing was performed.ResultTotal of 252 transcripts (up = 162, down = 90) were commonly differentially expressed in both of AD dementia and cognitively normal older adults derived dermal fibroblast by ER stress‐thabsigargin. These transcripts were enriched in GO categories related to protein folding in ER, response to ER stress, and ERAD pathway. Interestingly, 80 transcripts (up = 33, down = 47) were only differentially expressed in AD dementia dermal fibroblast by ER stress‐thabsigargin. These transcripts were enriched in GO categories related to cell division, miotic cell cycle, and microtubule‐based movement. Total of 60 transcripts (up = 41, down = 19) were only differentially expressed in cognitively normal older adults dermal fibroblast by ER stress‐thabsigargin. These transcripts were enriched in GO categories related to cholesterol biosynthesis process, DNA replication checkpoint, and cAMP‐mediated signaling.ConclusionWe identified transcriptional regulation landscape by ER stress‐thabsigargin in AD dementia and cognitively normal older adults dermal fibroblast. Further bioinformatic analysis with computational tools and validation experiments will be performed to find potential therapeutic targets against ER stress.
Longitudinal Associations of Social Support and Gait Speed Decline
Authors: Pollak Chava , Emmeline Ayers , Verghese Joe , Blumen Helena M 
Published: December 2023

AbstractBackgroundSocial support predicts functional and cognitive decline and is associated with brain regions that are important for both cognitive, and motor functions. Gait speed declines years before dementia onset, but the associations between social support and gait speed decline in aging is not well understood. This study examined longitudinal associations between social support and gait speed in older adults without dementia.MethodSocial support and gait data from 592 older adults without dementia (Mdn age 75 years, IQR 71,80, 55.3% female, 79.1% Caucasian) enrolled in the Central Control of Mobility in Aging (CCMA) study was examined. Overall support, emotional support, tangible support, affectional support, and positive social interactions, from the Medical Outcomes Study Social Support Survey at baseline were the predictors of interest. Annual change in simple (walking at normal pace) and complex (walking while reciting alternate letters of the alphabet) gait speed (cm/s) were the primary outcomes. Linear mixed effects models were used to examine the associations between change in single and complex gait speed and baseline social support, adjusting for gender, race, depression, overall cognition, comorbidities, and marital status.ResultThe mean annual change in gait speed was 1.9 cm/s during the simple walking condition and 1.07 cm/s during the complex walking condition. Tangible support was the only social support measure that predicted decline in simple and complex gait speed over a median follow up of 3 years. The annual decline in gait speed was 0.52 cm/s (p = 0.008, CI ‐0.91, ‐0.13) and 0.51 cm/s (p = 0.02, CI ‐0.95, ‐0.07) greater among those with low tangible support than among those with high tangible support during simple and complex walking conditions, respectively.ConclusionTangible support is a potentially modifiable risk factor for gait speed decline Further study is needed to examine the mechanisms behind the observed associations and potentials for intervention.This research was supported by NIH/National Center for Advancing Translational Science (NCATS) Einstein‐Montefiore CTSA Grant Number KL2 TR002558
Progressive alterations in lipid distribution and composition in a murine Alzheimer’s disease model visualized by label‐free Raman microscopy
Authors: Haessler Annika , Jung Nathalie , Windbergs Maike 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is accompanied by severe alterations in the brain lipid profile, affecting both the type and the distribution of lipids in the tissue. Moreover, literature also suggests a close association of Aβ plaques and lipids, exacerbating amyloidogenesis and plaque deposition. Thus, a spatially resolved approach is eminently important to understand the chemical nature of the progressive relationship between Aβ plaques and surrounding lipids. In the here presented study, Raman microscopy, a label‐free, chemically selective technique, was used in combination with state‐of‐the‐art statistics to analyze Aβ plaques and the surrounding tissue in a murine Alzheimer’s disease model. By encompassing differently aged diseased and healthy mice, this study aimed to generate knowledge on the alterations of Aβ plaque surrounding lipids during disease progression, whilst advancing the application of Raman microscopy within a neurodegenerative context.MethodRegions of interest in brain sections of APP/PS1 (Amyloid‐Precursor‐Protein / Presenilin‐1) mice aged 50 days, 5 months, and 10 months, as well as healthy non‐transgenic mice were imaged using a confocal Raman microscope (WITec GmbH, Ulm, Germany). The hyperspectral Raman data sets were processed using Project 4 software (WITec GmbH, Ulm, Germany), in‐house written Matlab scripts (The Mathworks, Inc., Natick, USA) and the Matlab‐integrated RamanLight App.ResultUsing multivariate analysis, Raman signatures of the Aβ plaques, cell nuclei, mitochondria, and lipids were identified in the tissue, characterized, and compared to each other (Figure 1). Subsequently, the lipid signal was semi‐quantitatively analyzed. The results of this analysis indicate an increasing, massive abundance of lipids in the direct vicinity of the Aβ plaques with disease progression, and the biochemical Raman spectra also reveal the growing presence of long‐chained lipids around the Aβ plaque. Overall, a distinct shift of the lipid spectra and abundance, starting with disease manifestation, is observed in the proximity of the plaques.ConclusionThe presented study shows progressive alterations in the distribution and type of lipids surrounding Aβ plaques in an AD model, spatially resolving lipid alterations and providing valuable additional biochemical insight to more established imaging methods such as fluorescence microscopy.
Access to support groups for people with Alzheimer’s Disease since the COVID‐19 pandemic in the Province of Quebec : an action research approach
Authors: Lapierre Nolwenn , Huet‐Fiola Caroline , Gaied Nouha Ben , Labrie Dylane , Côté Claudie , Vincent‐Blouin Emilie , Lamontagne Marie‐Eve , Pageau Felix , Best Krista , Poulin Valérie , Tawbi Nadia , Routier Francois 
Published: December 2023

AbstractBackgroundPeople with Alzheimer’s Disease (PWAD) face reduced social participation and community engagement. Community organizations have developed resources to address these challenges. During the COVID‐19 pandemic, many of them closed, and developed online resources to avoid further increasing the social isolation of PWAD (Armitage and Nellums, 2020). However, there is no consensus regarding their effects and questions remain about the way to implement them (Fields et al., 2020; Xie et al., 2020). Therefore, this study aims to: 1) describe the online support groups implemented by community organizations (e.g., Alzheimer Society) to support PWAD during the COVID‐19 pandemic; 2) Explore the ethical aspects, the safety and respect of privacy of these online groups; 3) Evaluate the engagement of PWAD in relation to these groups and their impact on social participation; 4) Develop methods to expand these resources and make them sustainable.MethodsThis four‐stage iterative research‐action study is conducted in partnership with the Federation of Quebec Alzheimer Societies (Creswell, 2009; Rauch et al., 2014). Stage 1: involves a qualitative study to identify important factors for the development of online support groups. Stage 2: will consist of co‐creation workshops with our partners to identify areas of improvement for the different support groups offered across the province of Quebec. Following the implementation of these enhanced online support groups. Step 3: will be a sequential mixed‐methods study to evaluate the process of implementing these resources and its effects on the social isolation of PWAD. Step 4: In order to identify ways to expand these resources to other communities, co‐creation workshops will be conducted.Expected resultsFacilitators and barriers to implement online support groups that respect the safety and privacy of PWAD will be identified. The effects of these online support groups on the social isolation and the engagement of PWAD will be measured to identify best practices for online services.ConclusionThe knowledge developed will enable community organizations to expand and refine online resources dedicated to PWAD in the community. Finally, the main social implication of this project is to provide access to safe, ethical and best practices for online support groups for PWAD.
A composite measure of atrophy using volumetric T1‐weighted and T2‐FLAIR imaging using the Boundary Shift Integral
Authors: Prosser Lloyd , Malone Ian B , Sudre Carole H , Barkhof Frederik , Fox Nick C , Cash David M , Barnes Jo , Carrasco Ferran Prados 
Published: December 2023

AbstractBackgroundWhole‐brain volume loss using T1‐weighted imaging is an established measurement of neurodegeneration. The Boundary Shift Integral (BSI) produces reliable metrics of longitudinal volume loss, used in research studies and clinical trials. With the increased acquisition of volumetric T2‐FLAIR imaging in studies, there is opportunity to produce atrophy metrics using a composite atrophy measure (T1‐weighted and T2‐FLAIR) that is more precise than either modality alone.MethodData from Alzheimer’s Disease Neuroimaging Initiative (ADNI3) were used. Volumetric T1 and T2‐FLAIR weighted imaging were obtained (n = 269), for baseline and follow‐up; Table 1. T1‐weighted images were bias corrected and underwent Geodesic Information Flow (GIF), producing probabilistic brain masks. Masks were resampled to T2‐FLAIR space. The BSI was performed on serial T1‐weighted (gBSI), and T2‐FLAIR (fBSI) separately. We tested differences by diagnosis (control (CN), mild cognitive impairment (MCI) and Alzheimer’s disease (AD)) between indirect volume change, gBSI, fBSI, and composite BSI, using linear regression and effect size. We further compared metric differences within diagnosis, using pairwise correlation, paired samples t‐test, and Pitman’s test of variance.ResultDemographic information is reported in Table 1. fBSI showed good Pearson’s correlation (r) with both gBSI (CN 0.7, p < 0.001; MCI 0.8, p < 0.001; AD 0.9, p < 0.001), and indirect change (CN 0.6, p < 0.001; MCI 0.6, < 0.001; AD 0.7, < 0.001). The composite BSI further showed good correlation with indirect change (CN 0.8, p < 0.001; MCI 0.8, p < 0.001; AD 0.8, 0.004). Mean values by diagnosis are shown in figure 1, along with paired samples t and variance tests. Pairwise comparisons reported in table 2, highlight good diagnostic group separation in all BSI metrics, with overall strong effect sizes for fBSI, composite BSI, and gBSI respectively.ConclusionCalculating atrophy using T2‐weighted imaging is possible using fBSI. This can be used in a composite atrophy measure using fBSI and gBSI. Both fBSI and composite BSI perform well with group separation, and with good correlations with classical atrophy metrics. Future work will explore the influence of White Matter Hyperintensities on BSI.
Therapeutic Evaluation of Thermal Heat Shock Response in Mouse Model of Alzheimer’s disease
Authors: Sharma Lalit , Sharma Rishabh 
Published: December 2023

AbstractBackgroundThe accumulation of toxic amyloid‐ß protein in brain is a hallmark of Alzheimer’s disease. The accumulation of such toxicants is prevented by a cellular protein quality control system. Molecular chaperons, which further prevent proteins from misfolding and aggregating, are produced by this system, which is mostly activated in response to acute thermal stress. This study aims to determine the therapeutic effect of frequent thermal shock on the development of Alzheimer’s diseaseMethodThe induction of Alzheimer’s disease was caused by the intracerebroventricular (ICV) injection of the Aß (1‐42) peptide into the ventricular system of the mouse brain. The animals were divided into four groups: normal control (NC), disease control (DC), sham control (SC), water immersion/no heat group (NH), and hot water immersion/high heat group (HH). The ICV‐Aß injection was given to the DC, NH, and HH groups to induce dementia and AD‐like symptoms. The animals in the HH treatment group were given heat shock in the form of hot water immersion for a period of 4 weeks, where each session lasted for 20 minutes. The animals in the NH group were also exposed to water immersion for 20 minutes daily for a period of 4 weeks, but the water temperature was maintained at room temperature. After the completion of the treatment period, the behavioural and biochemical parameters of the animals were assessed for learning and memory defects. The enzyme‐linked immunosorbent assay (ELISA) was carried out for the Aß estimation.ResultBehavioural assessments in the Y‐maze and morris water maze showed that the animals given daily heat exposure for a period of 4 weeks resisted the detrimental memory effects of the ICV‐Aß injection and had better memory than the water immersion group with no heat treatment given. Increased levels of lipid peroxidation and decreased levels of glutathione were significantly (p<0.05) antagonised by hot water immersion treatment. ELISA showed the lower level of Aß in hot water immersion/high heat group animals when compared to the disease control animals.ConclusionThe study concluded that frequent heat exposure from hot baths and saunas may reduce the risk of developing dementia and Alzheimer’s‐like symptoms in old age.
Prediction of Mild Cognitive Impairment Using a Hybrid Audio‐Visual Approach: An I_CONECT Study
Authors: Poor Farida Far , Alsuhaibani Muath , Fard Ali Pourramezan , Mahoor Mohammad , Dodge Hiroko H 
Published: December 2023

AbstractBackgroundCognitive decline can affect speech, language, head pose, eye gaze, and facial expressions in older adults. Artificial Intelligence (AI) can assist in automated prediction and monitoring of the progress of cognitive decline. Our previous work shows that utilizing unimodal linguistic features or facial features separately can lead to the prediction of cognitive impairment. We hypothesize that utilizing multimodal features from both audio and video can lead to a more accurate AI algorithm in differentiating those with mild cognitive impairment (MCI) from those with normal cognition (NC).MethodWe utilize deep learning methods (DL), specifically Transformers to extract both linguistic and facial features to predict whether an older subject is MCI or NC. Data is collected through Internet‐Based Conversational Engagement Clinical Trial (I‐CONECT) (NCT02871921) aiming to determine the effects of social interactions (video chats) on cognitive functions. Videos and respective transcribed audios of three themes; Summertime (30 participants), Halloween (32 participants), and Self‐care (30 participants) are selected based on “Good” video qualities. Dataset is balanced (half are diagnosed with MCI).Facial features are extracted from video frames through a convolutional Autoencoder, and then a Bidirectional Encoder Representations from Transformers (BERT) model captures temporal facial information. Linguistic features are generated by the DistilBERT language model being deployed on the transcribed audio. We used a 10‐fold cross‐validation approach to train and test the models separately. For each modality, the probability scores given by the transformers are fused using a majority voting method.ResultAccuracy, F1 score, precision, recall and area under the curve (AUC) are the evaluation metrics in this study. Score‐level fusion outperforms previous non‐hybrid methods of MCI prediction. Audio‐visual fusion leads to promising results for Summertime, Halloween and Self‐care with accuracy of 84.8%, 85%, and 84.5% and AUC of 86%, 86.1%, and 85.7%,respectively, which are marked improvements from the previous findings (48% accuracy using linguistic features alone and 67.8% using facial features alone).ConclusionThe results of our study show that the proposed multimodal approach improves the accuracy of the AI/ML model in distinguishing MCI from NC. That is, audio‐visual fusion could outperform other single methods.
Quantifying caregiver sleep disturbances using a dyadic model of dementia
Authors: Quigg Mark S , Youngkin Anna E , Manning Carol A 
Published: December 2023

AbstractBackgroundSleep disturbances including insomnia, poor sleep quality, and sleep fragmentation appear to play a role in the development and progression of Alzheimer’s disease (AD) in older adults, but may also affect the health of caregivers. The purpose of this pilot study was to objectively quantify daily rest: activity patterns and polysomnography of the sleep of people with dementia (PWD) and their caregivers (CGS).MethodParticipants: Six dyads with PWD and their primary CGS. Actigraphy: Wrist actigraphy recorded for 14 days divided into fixed rest (2200‐0600) and activity (0600‐2200) periods. Polysomnography: recorded and scored for 1 night for each dyad member separately. Variables: sleep onset latency (SOL), total sleep time (TST).ResultAverage activity measures showed no differences within dyads for average daytime or nighttime activity, indicating the activity levels of CGS are highly reflective of the activity of their PWD partners. Despite similar activity levels, CGS displayed sleep deficits compared to their partners, with significantly increased SOL (p = 0.004). Additionally, with the exclusion of one outlier, all CGS received less TST than their demented partners. These deficits were present even when sleeping separately from their partners.ConclusionThe main findings of this pilot dyadic study reveal that the daily rest:activity patterns of CGS reflect that of their partners. Importantly, despite similar day‐ and nighttime activity, CGS had worse overall sleep than their demented partners, with lowered TST and significantly increased SOL. These findings occurred even when dyads were sleeping separately, indicating that sleep disruptions in CGS cannot be exclusively attributed to nighttime activity of the PWD. Our dyadic model currently is being applied to studies with larger sample sizes in order to determine the impacts of caregiving on sleep.