bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlations between APOE4 status and regional amyloid and tau burdens in cognitively normal older individuals
Authors: Hong Yun Jeong , Kim Chan‐Mi , Lee Jae‐Hong , Sepulcre Jorge 
Published: June 2023

AbstractBackgroundThe correlations between apolipoprotein epsilon 4 (APOE4) status and regional Alzheimer’s disease–related biomarkers in cognitively normal elderly are not fully understood. Our cross‐sectional study compared clinical characteristics, amyloid/tau burden, and cortical thickness according to APOE4 carrier status to assess correlations between APOE4 and regional biomarker burdens.MethodWe analyzed 185 cognitively normal participants from the ADNI 3 cohort study. Participants aged 55‐90 with normal cognitive function were eligible. We divided participants into Aß+ APOE4 carriers (group 1, n = 27), Aß+ APOE4 non‐carriers (group 2, n = 29), and Aß‐ normal controls regardless of APOE4 carrier status (group 0, n = 129). We compared clinical characteristics, cerebrospinal fluid (CSF) amyloid β42 & phosphorylated tau, florbetapir positron emission tomography (PET), flortaucipir PET, cortical thickness, and cognitive scores among the 3 groups. Quantitative imaging analyses were performed using the standardized uptake value ratio (SUVR). We additionally assessed correlations between APOE4 carrier status and imaging biomarkers.ResultThe baseline characteristics except age were similar among the groups. The participants in group 2 were oldest. The regional amyloid/tau SUVRs did not differ between groups 1 and 2, but the amyloid/tau SUVRs in most regions were numerically higher in group 1 than group 2 after adjusting for age difference. The regional amyloid and tau SUVRs in the younger (<70) group were higher in group 1 than group 2. APOE4 carrier status showed significant association with amyloid burden in diffuse cortical areas after adjustment for age and sex, but it was not associated with regional tau burden or cortical thickness.ConclusionWe identified that cognitively normal APOE4 carriers showed similar but numerically greater amyloid and tau burdens than did APOE4 non‐carriers after adjusting for age. APOE4 carrier status might be more highly associated with amyloid deposition than with other AD‐related biomarkers such as tau or cortical thickness, especially in the younger group below 70.
Individual analysis of changes in a single reminiscence session from nostalgic music videos using text mining
Authors: Urabe Mie , Miyata Chiharu , Fukuda Hiroko , Yoneda Sho , Sakai Katsumi , Kato Yuka , Kitajima Kengo , Sawada Chikao 
Published: June 2023

AbstractBackgroundThis study conducts an intervention using nostalgic music videos and reminiscence, which provide stimulation to the emotions of a person with dementia. This study found the occurrence of positive emotions. In AAIC, we provided a presentation on this intervention and its analysis using text mining (Urabe et al., 2020, 2021).As we proceeded with this intervention, we found that nostalgic music or words led the person with dementia to mention stories from memory even after only one session.The purpose of this study is to clarify the individual changes and important music or words in the narrative of one reminiscence session of a person with Alzheimer’s disease using text mining.MethodThe participant with Alzheimer’s disease was a female aged over 80 years old (MMSE: eight points) and is in a psychiatric hospital in Japan due to behavioral and psychological symptoms of dementia. We intervened two times using nostalgic music videos that she liked and listened to her memories of youth. We recorded her narrative and analyzed the words of her stories using text mining. Moreover, we divided the time points where we noted changes in the narrative from a single session and compared these changes.ResultAfter 10 min and 23 sec from the start of the first session, we noted a change in the content of the narrative (Point A).In the second session, the change appeared after 4 min and 53 sec. (Point B)In the co‐occurrence network, the number of connected co‐occurrence words increased clearly after Point A and Point B.In the first session, the number of sentences was 61 (before Point A) and 159 (after Point A), the number of paragraphs was 39 (before Point A) and 68 (after Point A).In the second session, the number of sentences was 33 (before Point B) and 269 (after Point B), the number of paragraphs was 22 (before Point B) and 164 (after Point B).ConclusionNostalgic music and important words for persons with dementia hold the potential to increase memory and the number of utterances even after one session of intervention.
The association of physical activity and cognitive decline has become important with the increase in dementia prevalence. These systematic review and meta‐analysis of longitudinal studies demonstrate that association
Authors: Eissa Elissa Abou 
Published: June 2023

AbstractBackgroundDementia is increasing in prevalence across our globally ageing population. In absence of disease modifying therapy, the need to assess the effectiveness of preventative measures becomes important. It is becoming clear that intervention before disease manifests is crucial. Physical activity (PA) is the most influential risk factor for dementia, examining impact on cognitive decline is important to discern.MethodOur search criteria involved conducting a database search through MEDLINE (Ovid) as well as examining two prior reviews, with protocol registered with PROSPERO (registration number: CRD42019129449). Longitudinal studies on population ≥18 years of age with cognition measured at both baseline and follow‐up were included. Included studies were assessed for their methodological quality.ResultOverall, 42 studies were included, with literature showing evidence of an association between increase PA and reduced cognitive decline. Components of PA were reported on as follows: frequency in 37 studies, intensity in 28 studies, duration in 25 studies, and type in 22 studies. Meta‐analysis showed PA of greater frequency and duration, and more vigorous intensity, was significantly associated with reduced cognitive decline (relative risk 0.72, 95% confidence interval 0.62, 0.82; p<0.001).ConclusionData available to date suggests that a wide range of different types of activity may be important on influencing preventive impact. In addition frequency, duration and intensity of PA are each significantly associated with reduced cognitive decline where greater frequency and duration of PA are associated with reduced cognitive decline, as is increased average intensity. PA recommendations are required to increase adherence in order to delay the onset of cognitive decline. It is important that future studies examine these details as this review revealed a paucity of research on key components to guide adherence to recommendations.
Trail Making for electronic touchscreen self‐administration (eTrails) as used in the remote iPACES neuro‐exergaming trial for Mild Cognitive Impairment (MCI): An initial validation report
Authors: Roque Nelson A , Ferguson Irelee , Saulnier Emilie T , Anderson‐Hanley Cay 
Published: June 2023

AbstractBackgroundTo enable brief and integrated serial assessment across a national sample, we developed an electronic version of the Trail Making test (eTrails) for remote self‐administration on digital devices. eTrails, a digital, web‐based assessment, mimicking the traditional paper version of Trails B (see demo: https://bit.ly/33DCPGP), in which participants draw a line from a number to a letter in alternating, ascending order, was integrated into the iPACES app. Herein we report on initial validation of eTrails, as compared with the paper Trail Making Test.MethodThis initial validation report examined digital trail making data (n = 34 sessions) serially collected from ten MCI and caregiver participants in the iPACES v3 clinical trial (mean age = 70.2, mean years of education = 16.9). Included in analyses were eTrails data for traditional metrics (i.e., overall completion time) and novel digital biomarkers extracted from event‐level data (e.g., # of lifts and pause time). After a baseline tele‐neuropsychological evaluation in which paper Trail Making was administered (Forms A&B), at predetermined study intervals (typically weekly), participants were automatically prompted to complete the eTrails on their iPACES tablet. In the eTrails, participants were presented with one of four randomly selected alternate forms of trail making stimuli (i.e., different spatial configurations of Form B).ResultOverall completion time from eTrails was moderately correlated with both forms of paper‐based trail making completed at baseline (correlation with Paper Trails A: r = .37, p = .030; correlation with Paper Trails B: r = .41, p = .017). Novel digital biomarkers (i.e., # lifts, pause time) were moderately correlated (r’s = 0.59‐0.6, p’s < .001) with the traditional scoring of the eTrails (i.e., assessment completion time in seconds), and though non‐significant, weakly correlated with completion time of paper Trails A (r = 0.20, p = 0.25).ConclusionThese preliminary data provide initial evidence of validity, that eTrails as a serial assessment of subtle cognitive decline can serve as a remote self‐administered digital test for serial assessment of executive function and will be further evaluated in our ongoing iPACES study. Future research may explore the sensitivity of novel digital biomarkers extractable from event‐level data.
Stroop for electronic touchscreen self‐administration (eStroop) as used in the remote iPACES neuro‐exergaming trial for Mild Cognitive Impairment (MCI): An initial validation report
Authors: Roque Nelson A , Ferguson Irelee , Saulnier Emilie T , Anderson‐Hanley Cay 
Published: June 2023

AbstractBackgroundIn collaboration with the Mobile Monitoring of Cognitive Change (M2C2; 1‐U2C‐AG060408‐01) Project, our team developed a tablet‐based electronic Stroop (eStroop) task. Initial development explored direct translation of the paper‐Stroop (pStroop) often used in clinical settings, and found that this resulted in ceiling effects. Herein we report on initial validation of the eStroop task from the iPACES v3 clinical trial.MethodInitial validation examined eStroop data (n = 59 sessions) serially collected from ten MCI and caregiver participants in the iPACES v3 clinical trial (mean age = 70.2, mean years of education = 16.9). Included in analyses were eStroop data for both traditional metrics (i.e., overall accuracy by block condition), response time, as well as typically constructed difference/ratio scores (i.e., AC ratio). After a baseline tele‐neuropsychological evaluation in which paper Stroop was administered, at predetermined study intervals (typically weekly), participants were automatically prompted to complete the eStroop on their iPACES Android tablet. In the eStroop, participants were presented with four blocks of 40 trials: (1) color words in black font, (2) congruent word and font color; (3) incongruent words with font color; (4) mixed congruent and incongruent trials.ResultThe paper Stroop AC Ratio (total seconds to complete paper A, divided by time to complete paper C), was moderately negatively correlated (r = ‐0.52, p < .001) with average response time on block three of eStroop (incongruent words with font color). The pStroop AC Ratio was also significantly negatively correlated with number of errors on block one (r = ‐0.42, p < .001), two (r = ‐0.26, p = 0.04), three (r = ‐0.39, p = 0.002), and four (r = ‐0.26, p = .049). A weak, significant positive correlation (r = 0.44, p < .001) was observed between the AC ratio from pStroop and eStroop. Very weak non‐significant correlations between paper Stroop AC Ratio and average response time on blocks one, two, and four of eStroop were observed.ConclusionThese pilot data provide preliminary evidence that the eStroop can serve as a remotely and self‐administered digital test for serial assessment of executive function and will be further evaluated in our current iPACES study.
Prevalence of anti‐egg albumin antibodies in cerebrospinal fluid of patients with mild and severe Alzheimer’s Disease. Correlation with gender and incidence of anti‐casein antibodies and AGEs.
Authors: Amanatidou Dionysia , Tsolaki Magda , Fili Maria , Anastasiou Anna , Papageorgiou Athanasia , Bourmas George‐Marios , Eleftheriou Phaedra 
Published: June 2023

AbstractBackgroundAlzheimer’s Disease (A.D.) is a multifactorial process. Advanced glycation end products (AGEs) have been correlated with disease development1. Additionally, high concentrations of antibodies against the food derived antigens egg‐albumin and bovine casein, have been detected in patients with Alzheimer’s disease in preliminary research presented by our team, previously (AAIC 2018).In the present study, antibodies against egg‐albumin and bovine casein as well as AGEs were detected in the cerebrospinal fluid of 36 patients with mild and 35 patients with severe Alzheimer’s Disease and 13 healthy individuals and a correlation between the measured parameters and sample properties was attempted.MethodELISA plates pre‐treated with highly hydrophilic microlon resin were used for the purpose of this study2. Egg‐albumin or bovine casein antigens were attached at the ELISA plates for the measurement of antibodies. Additionally, polyclonal antibodies against multiple AGE products were used to detect attached sample CSF AGEs.ResultAccording to the results, 48,6% of of the samples of patients with severe AD had anti‐egg albumin concentration higher than mean concentration of healthy idividuals+2SD (characterized as positive) compared to 8.3% of positive samples in patients with mild disease. An overall 265% increase in mean concentration was observed in severe compared to mild patients, indicating association with severity. The observed difference was significant at p = 0.01 according to mann witney U test. Lower anti‐egg albumin concentrations were observed in female samples of either mild or severe disease (Figure 1). Much lower incidence of anti‐casein antibody positive samples was found in in severe AD (5.7% positive in severe versus 0% in mild AD). A slight, not statisticaly significant, increase in mean anti‐casein antibodies concentration (23.7%) and AGEs (16.2%) was observed in severe compared to mild disease with the higher concentrations also detected in the most positive to anti‐egg albumin samples.ConclusionThe results indicated a potential correlation of antibodies against egg‐albumin with the severity of Alzheimer’s disease with increased incidence in male patients. A lower correlation was observed in case of anti‐casein antibodies and AGEs.References:1. Takeuchi et al., Current Pharmaceutical Design, 14(10), 2008, 973‐978.2. P. Eleftheriou, etal. Biomed. Res. Int., 2014.
The niacin receptor HCAR2 induces a protective response of microglia to amyloid pathology.
Authors: Moutinho Miguel , Puntambekar Shweta S , Tsai Andy Po‐Yi , Coronel Isarel , Lin Peter Bor‐Chian , Casali Brad T , Martínez Pablo , Oblak Adrian L , Reeves Cristian A Lasagna , Lamb Bruce T , Landreth Gary E 
Published: June 2023

AbstractBackgroundDietary intake of niacin correlates with reduced risk of Alzheimer´s disease (AD). Niacin is a ligand for the niacin receptor HCAR2, which, in the brain, is expressed by microglia. HCAR2 ligands have been shown to modulate microglia functions and exert neuroprotective effects in different models of neuronal injury. Therefore, we hypothesized that HCAR2 modulates a protective microglial phenotype in AD, which can be stimulated by HCAR2 agonists.MethodTo assess the role of HCAR2 in amyloid pathology, the brains of the AD animal model 5xFAD and 5xFAD mice lacking Hcar2 gene (5xFAD‐KO) were subjected to transcriptomic, immunohistochemistry and biochemical analysis. Furthermore, to activate HCAR2, 5 month‐old 5xFAD mice were treated with a FDA‐approved formulation of niacin (Niaspan®) daily, by oral gavage for 30 days with 100 mg niacin/kg. Treated animals were sacrificed and the brains were collected for immunohistochemistry and biochemical analysis. To validate that Niaspan® effects were dependent on HCAR2, we performed the same treatment paradigm and analysis using 5xFAD‐KO mice.ResultOur results indicate that microglia significantly induce HCAR2 expression in the AD brain. Lack of Hcar2 in the 5xFAD mice leads to a deficient response of microglia to amyloid pathology, which is accompanied by an increase in plaque load and exacerbation of the amyloid‐associated neuropathology. Niaspan® treatment increased the response of microglia to amyloid pathology, decreased plaque burden in 5xFAD, and exerted a neuroprotective effect evidenced by reduced neuronal loss in the subiculum, accompanied by a rescue of working memory deficits. Niaspan® did not induce these beneficial effects in 5xFAD‐KO mice.ConclusionThese data suggest that HCAR2 induces a protective microglial phenotype in AD. Furthermore, activation of HCAR2 by Niaspan® treatment has neuroprotective effects in AD, even after the onset of severe amyloid pathology, possibly through the stimulation of a protective microglia response. Niaspan® is a FDA‐approved drug, thus there is a translational potential of this strategy into clinical practice, supporting further study of this therapeutic approach.
Music as a trigger for specific memories
Authors: Pillay Jayendran 
Published: June 2023

AbstractBackgroundThis study uses the expertise of an ethnomusicologist who uses preexisting music in the brain music as the cue to trigger the autobiographical memories of her own mother struggling with dementia.MethodBy adapting a methodology in Ethnomusicology involving the autobiography of one’s music history, I set up the experiment for another ethnomusicologist to conduct. Dividing the study into discrete music time periods (infancy, childhood, teenager, young adult, older adult), I delineated specific songs or pieces of music with powerful meanings to the patient in those time periods to be played. The responses of the patient on video was then recorded.ResultEach of those pieces of music had some level of recognition by the Alzheimer’s patient, some stronger than others. Other attendant contextual memories surfaced during the experiment, suggesting autobiographical recall, despite a weakened sense of time and space after the onset of Alzheimer’s.ConclusionThis single case study needs to be broadened into a larger scale experiment involving many participants to assess the efficacy of this ethnomusicological‐derived approach to improve autobiographical recall abilities among the Alzheimer’s patients. This approach also makes it possible for families to engage in the autobiographical recall process using the preexisting music in the patients’ neural pathways. This study also offers collaborative efforts between Ethnomusicology and Neurology in running clinical trials to develop autobiographical memory recall processes for therapy.
TREM2‐H157Y Increases Soluble TREM2 Production and Reduces Amyloid Pathology
Authors: Qiao Wenhui 
Published: June 2023

AbstractBackgroundThe p.H157Y variant of TREM2 (Triggering Receptor Expressed on Myeloid Cells 2) has been reported to increase Alzheimer’s disease (AD) risk. This mutation in the extracellular domain of TREM2 localizes at the cleavage site and was shown to enhance shedding and impair phagocytosis in vitro by ectopic expression of TREM2‐H157Y in HEK293 cells. However, the physiological and AD‐related outcomes of TREM2 H157Y mutation in vivo remain unknown.MethodWe generated a novel Trem2 H157Y knock‐in mouse model through CRISPR‐Cas9 technology and investigated how Trem2 H157Y mutation impacts TREM2 proteolytic processing, synaptic function, and AD‐related amyloid pathology by conducting biochemical assays, immunofluorescent staining, hippocampal electrophysiology, and in vivo micro‐dialysis in awake, free‐moving animals.ResultConsistent with previous in vitro findings, TREM2‐H157Y increases the amount of soluble TREM2 (sTREM2) in the cortex and serum of mutant mice compared to the wild type controls. Interestingly, the Trem2 H157Y variant enhances synaptic plasticity without affecting microglial density and morphology. In the presence of amyloid pathology, TREM2‐H157Y surprisingly accelerates Aβ clearance and reduces amyloid burden and microgliosis.ConclusionTaken together, our findings support a beneficial effect of the Trem2 H157Y mutation in synaptic function and in mitigating amyloid pathology. Considering the genetic association of TREM2 p.H157Y with AD, we speculate TREM2‐H157Y might increase AD risk through an amyloid‐independent pathway, as such its effects on tauopathy and neurodegeneration merit further investigation.
The role of FUT8‐catalyzed core fucosylation in Alzheimer’s amyloid‐β oligomer‐induced activation of human microglia
Authors: Jin Lee‐Way , Lucente Jacopo Di , Schindler Ryan , Tena Jennyfer , Mendiola Ulises R , Tang Xinyu , Zivkovic Angela M. , Lebrilla Carlito B. , Maezawa Izumi 
Published: June 2023

AbstractBackgroundA previous RNA‐seq study of human Alzheimer’s disease (AD) brain samples revealed significant upregulation of FUT8 coding for α1‐6 fucosyltransferase in parahippocampal gyrus, suggesting a role of FUT8 and the core fucosylation it catalyzes in early AD. Despite the well‐recognized roles of core fucosylation in immune regulation, its significance in microglial function, especially in neurodegenerative conditions such as AD, has rarely been studied.MethodHuman microglia derived from induced pluripotent stem cells (iMG) were used as the model system. To simulate microglia in the early stage of AD, we stimulated iMG derived from a subject of APOE3/3 genotype with amyloid‐β oligomer (AβO, 3 μM). The degree of microglia activation was determined by cytokine induction and MAPK phosphorylation. Lectins were used in flow cytometry, cytochemical staining, and lectin blotting to determine the changes in core fucosylation. Fucosylation was also examined by MS/MS‐based N‐glycan analysis. FUT8 expression in brain or cell samples was determined by quantitative PCR and Western blotting. FUT8 inhibition was induced by siRNA‐mediated gene silencing. The transcriptional regulation of FUT8 was investigated by ChIP‐PCR using p53 antibodies.ResultHuman iMG responded to AβO with a pattern of pro‐inflammatory activation within 24 hours. Using two lectins specifically recognizing α1,6 core fucose, AAL and LCA, in flow cytometry and fluorescence staining, we showed that such an activation was associated with increased core fucosylation. This observation will be further verified by N‐glycomic analysis. Inhibition of fucosylation by two inhibitors, 2FF and 6‐Alk‐Fuc, as well as FUT8 knockdown by specific siRNAs suppressed AβO‐induced iMG activation. AβO‐activated iMG also showed increased protein levels of FUT8 and p53. Because p53 was previously shown to be a direct transcriptional activator of FUT8 in tumor cells, we will test whether p53 is responsible for FUT8 upregulation by ChIP‐PCR. The in vivo relevance of our results is supported by qPCR results showing increased levels of FUT8 transcript in human temporal cortex, 5xFAD mouse cortex, and microglia isolated from 5xFAD mice.ConclusionOur data suggests that FUT8‐catalyzed α1‐6 core fucosylation is required for AβO‐induced microglia activation and may play a role in the pathogenesis of AD.