bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does amyloid moderate practice effects in language measures in a cognitively unimpaired at‐risk sample?
Authors: Basche Kristin E , Jonaitis Erin M. , Betthauser Tobey J , Christian Bradley T. , Hermann Bruce P , Johnson Sterling C , Mueller Kimberly D , Langhough Rebecca E 
Published: December 2023

AbstractBackgroundLack of practice effects (PE) in common cognitive tests has been associated with increased risk of dementia. Previous studies have found connections between recall of proper names (PN) and amyloid positivity in cognitively unimpaired adults at risk for Alzheimer’s Disease (AD; Mueller et al., 2020). For several language‐related tests, including PN, we compared PE modeling options and then examined whether amyloid status moderated PE.MethodParticipants with language tasks and C‐Pittsburgh Compound‐B (PiB) amyloid positron emission tomography (PET) were selected from the Wisconsin Registry for Alzheimer’s Prevention (WRAP; n = 377). PE operationalizations included: number of language task exposures – 1 (“PEnvis‐1”), the square root of PEnvis‐1 (“PEsqrt”) and categorical PE (“PEcat”; reference = 0 (baseline) vs 1, 2, or 3+ follow‐up assessments). Language outcomes variables included letter fluency (CFL), animal naming, and logical memory (LM). From LM, we utilized item‐level data to create immediate and delayed PN recall. We used linear mixed effects models to identify the best fitting PE operationalization for each outcome and ran subsequent models examining amyloid*PE interactions (covariates: age at assessment, gender, and WRAT‐III reading score; random effects for intercept).ResultSample characteristics are shown in Table 1 overall and by amyloid status. AIC fit statistics were best overall for PEnvis‐1. In subsequent models, the PE*amyloid interaction was significant for LM Total Score (β = ‐0.08, 95% CI = (‐0.15, ‐0.01), p = 0.02) and PN immediate recall (β = ‐0.22, 95% CI = (‐0.38, ‐0.05), p = 0.01). For both outcomes, predicted Z‐scores increased with more practice for amyloid positive participants, but decreased for amyloid negative participants (Table 2; Figure 1). The main effect of PE was significant for CFL (β = 0.12, 95% CI = (0.08, 0.15 p<0.001) and Animal Naming (β = 0.07, 95% CI = (0.03‐0.11), p = 0.002).ConclusionPEnvis‐1 was generally the best‐fitting PE operationalization. In our relatively young sample (baseline mean age = 54.1; mean years between baseline and most recent LM = 9.12), improvements with practice for animal naming and CFL were not modified by amyloid status. In contrast, those with amyloid negative biomarkers showed practice‐related improvements on LM while those with positive amyloid showed decreased performance with more practice.
3D chromatin structure and massively parallel reporter assays in hiPSC‐derived microglia and human macrophages identifies novel putative Alzheimer’s Disease risk genes
Authors: Quiroga Ivana Yoseli , Bond Marielle L , D'Costa Susan , Bell Jessica L , McAfee Jessica C , Reed Kathleen S Metz , Sahasrabudhe Isha R , Patrucco Mary , Won Hyejung , Phanstiel Douglas H 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) genome‐wide association studies (GWAS) identified 75 disease‐associated loci; however, interpretation of these results has proven difficult for two primary reasons. First, linkage disequilibrium between nearby variants makes it difficult to identify the causal variant(s) at each locus. Second, because the vast majority of OA risk variants are non‐coding and can regulate genes from distances of greater than one million base pairs, the genes impacted by AD risk variants are largely unknown. Recently developed genomic approaches can address these hurdles but must be applied to the correct cell types and biological contexts.MethodWe quantified the impact of 3,576 AD‐associated genetic variants on enhancer activity by performing massively parallel reporter assays (MPRAs) in resting and activated human macrophages. To map these variants to the genes they regulate we built regulatory networks by mapping 3D chromatin structure (Hi‐C), chromatin accessibility (ATAC), histone K27 acetylation (CUT&RUN), and gene expression (RNA‐seq) in both resting and activated iPSC‐derived microglia.ResultIn total we identified 20,992 chromatin loops across resting and activated iPSC‐derived microglia. Among these, 9,544 loops linked 14,576 enhancers to 11,487 genes. 58 loops connected 414 AD‐risk variants queried by our MPRA assays to 85 genes. 212, 19,256, and 2,790 of these loops, enhancers, and genes (respectively) changed in response to activation, providing further insight into their regulatory mechanisms and highlighting the need to study these events in the correct biological context.ConclusionOngoing analyses and data integration should reveal further mechanistic details and provide novel AD risk genes for further research and therapeutic development. By intersecting our MPRA results and dynamic regulatory networks with AD GWAS, we were able to identify novel putative genes regulated by non‐coding AD risk variants in a cell‐type and condition‐specific manner.
The role of experiential avoidance and cognitive fusion in the development of anxiety symptoms among family carers of people with dementia
Authors: Van Hout Elien , Contreras Milena L , Mioshi Eneida , Kishita Naoko 
Published: December 2023

AbstractBackgroundDespite the high prevalence of anxiety symptoms among family carers of people with dementia (Kaddour & Kishita, 2020), current carer interventions are considered to be not as effective for anxiety as they are for depression (Kishita et al., 2018). Therefore, understanding the mechanism by which a common stressor (i.e. carer subjective burden) and underlying psychological processes influence anxiety symptoms among this population is critical to inform future interventions. In this study, the roles of two psychological processes known to be associated with mental health problems were explored: experiential avoidance in caregiving (an attempt or desire to control or suppress distressing thoughts and feelings related to caregiving) and cognitive fusion (the tendency for one’s behaviour to be overly regulated and influenced by thoughts).MethodWith a sample of seventy‐seven family carers (mean age of 63.47 years (SD = 10.64) and 73% female), this study examined the indirect effect of carer subjective burden (ZBI‐12) on anxiety symptoms (GAD‐7) through experiential avoidance in caregiving (EACQ) and cognitive fusion (CFQ) using a path analysis approach.ResultThe whole sample model showed a good fit to the data. The indirect effect of carer subjective burden on anxiety symptoms through its effect on cognitive fusion (β = .17), and its combined effect on experiential avoidance in caregiving and cognitive fusion (β = .01) were significant. Examined variables accounted for 54% of the variance in anxiety symptoms.ConclusionGiven the higher explanatory value demonstrated for the indirect effect of cognitive fusion alone, facilitating cognitive fusion through psychological interventions may be critical for preventing clinically significant levels of anxiety symptoms, particularly among those carers experiencing high levels of carer subjective burden. The results also demonstrated that family carers with higher experiential avoidance in caregiving may be prone to cognitive fusion, which in turn could lead to higher levels of anxiety symptoms. Therefore, an early intervention targeting experiential avoidance may be beneficial for preventing increased cognitive fusion and anxiety symptoms.
The role of Tau‐seed interactome in Alzheimer’s disease and other tauopathies
Authors: Martinez Pablo , Patel Henika , You Yanwen , Garfe Nur Jury , Zhang Jie , Troncoso Juan C , Reeves Cristian A Lasagna 
Published: December 2023

AbstractBackgroundPathological tau aggregation is a defining histopathological feature of Alzheimer’s disease (AD) and other neurodegenerative diseases collectively known as tauopathies. The propagation of pathological forms of tau in AD patient brains has been shown to follow neuronal networks. However, the cellular mechanisms involved in tau propagation and the nature of the tau species involved in spreading remain unclear.MethodWe performed an unbiased quantitative mass spectrometry‐based study to identify the proteins that specifically interact with this tau seed.ResultHerein, we report the identification of bassoon (BSN), a scaffolding presynaptic protein, as an interactor of the tau seed isolated from a mouse model of tauopathy, and from AD and progressive supranuclear palsy (PSP) postmortem samples. We show that BSN exacerbates tau seeding and toxicity in vivo. Furthermore, BSN downregulation significantly decreases tau spreading and overall disease pathology in vivo, rescuing synaptic and behavioral impairment and reducing brain atrophy.ConclusionOur findings improve the understanding of tau seeds and highlight the importance of identifying interactors, such as BSN, that could stabilize these seeds. Inhibiting tau‐seed interactors is a potential new therapeutic approach for neurodegenerative tauopathies.
Neuroticism is associated with entorhinal cortex volume in cognitively unimpaired older adults
Authors: Akbarian Niki , Vandermorris Susan , Verhoeff Nicolaas Paul L.G. , Herrmann Nathan , Mah Linda 
Published: December 2023

AbstractBackgroundNeuroticism, the tendency toward negative mood states, is associated with Alzheimer’s Disease (AD) and tau pathology within entorhinal cortex (EC) in mild cognitive impairment and healthy older adults. However, studies of the link between neuroticism and structural neurodegeneration of EC have been negative. This may result from failure to account for subsyndromal affective symptoms or previous psychiatric history, as neuroticism is closely related to mood conditions that in turn, affect similar brain regions vulnerable to AD. We examined the association between neuroticism and EC volume while accounting for cognition, affective symptoms, and other personality traits in cognitively unimpaired (CU) older adults without history of major psychiatric conditions.Method42 CU adults (age = 71.1 years, 27 females) with normal neuropsychological test performance and no known neurological conditions and current or past psychiatric disorders completed Geriatric Depression Scale, State‐Trait Anxiety Inventory, NEO Five‐Factor Inventory‐3 which assesses neuroticism, openness, conscientiousness, extraversion, and agreeableness, Montreal Cognitive Assessment (MoCA), and structural magnetic resonance imaging of whole brain at 3T. Regression analyses examined the unconditional ability of neuroticism to predict bilateral EC volume, and while considering the potential contribution of cognition (MoCA, California Verbal Learning Test Delayed Recall), affective state, other personality traits, and age, gender, and education. P<.10 was set as the significance threshold for β estimates.ResultIn univariable modelling, neuroticism was predictive of left EC volume (β = ‐17.4, p = .025), explaining 9.8% of its variability [F(1, 40) = 5.45, p = .025]. Neuroticism remained a significant predictor of left EC volume (β = ‐1.9, p = .045) after factoring in demographic, cognitive and affective/personality variables. Additional left EC predictors were extraversion and state anxiety (β = ‐2.61, p = .01; β = 1.71, p = .045 respectively). Neuroticism was not predictive of right EC in univariable or multivariable modelling, but agreeableness emerged as a significant predictor (β = ‐1.68, p = .091).ConclusionNeuroticism was predictive of left EC volume in CU adults without current or past history of psychiatric disorders, independent of cognition, affect, and other personality traits. These findings, which have not been previously reported, extend previous epidemiological evidence of increased AD risk due to neuroticism and suggest the importance of considering the impact of mood symptoms and psychiatric history in this context.
Glucocorticoid excess and insulin resistance in rat models of vascular contributions to cognitive impairment and dementia
Authors: Lansdell Theresa A , Ojeda‐Henaiz Angel , Lewis Ally , Dorrance Anne M 
Published: December 2023

AbstractBackgroundHypertension and insulin resistance are major risk factors for the development of dementia. While insulin resistance is considered an important risk factor for the development of hypertension and dementia, little consideration has been given to the idea that vascular disease could initiate insulin resistance and fuel a destructive cycle that hastens dementia. We previously showed that bilateral carotid artery stenosis results in HPA‐axis dysfunction and insulin resistance (Lansdell et al., 2022). We hypothesized that hypertension would also cause glucocorticoid excess and insulin resistance.MethodTo test this hypothesis, we measured fecal corticosterone and the expression of steroid biosynthetic genes in the adrenal glands of six‐month‐old spontaneously hypertensive rat/stroke‐prone (SHRSP) and normotensive Sprague Dawley (SD) rats. To assess glycemic control, rats were subjected to glucose and insulin tolerance tests.ResultSHRSP were hypertensive and cognitively impaired. Corticosterone was elevated in hypertensive compared to normotensive rats (Male SD vs. SHRSP: 167±29 pg/g vs.1091±166 pg/g, P<0.0001; Female SD vs. SHRSP: 134±19 pg/g vs. 376±47 pg/g, P = 0.0017). Adrenal CYP11B1 mRNA expression was increased in SHRSP (Males 14.44±1.44, P = 0.0009; Females 710±59, P = 0.0016). STARD1 mRNA expression provided a marker of HPA negative feedback. Male SHRSPs had decreased STARD1 mRNA expression (0.56±0.09, P = 0.0217). However, female SHRSPs had increased STARD1 mRNA expression (12.5± 2.25, P = 0.0028). Female, but not male, hypertensive rats had increased fasting blood glucose, decreased fasting insulin, and reduced rates of glucose clearance (female SD vs. SHRSP: 73±6 vs. 92±4 mg/dL glucose, P = 0.0045; 33±2.0 vs. 12±5 pmol/L insulin, P = 0.0111; AUC 185±37 vs. 279±27 mg/dL/h, P = 0.0368). When fasting rats were challenged with insulin, both male and female hypertensive rats had decreased clearance of glucose compared to normotensive rats (Male SD vs. SHRSP AUC 87 ± 2 vs. 58 ± 4 mg/dL/h, P< 0.0001, Female SD vs. SHRSP AUC 82 ± 2 vs. 68 ± 3 mg/dL/h, P = 0.0007).ConclusionThese results indicate that hypertension is associated with impaired HPA function and insulin resistance, with female hypertensive rats developing hyperglycemia at an earlier age than males.
A multicenter validation study on the diagnostic and prognostic value of CSF Neurogranin and BACE1
Authors: Wang Xiao , Freiesleben Silka Dawn , Schneider Luisa Sophie , Gabelin Tatjana , Preis Lukas , Priller Josef , Schneider Anja , Fließbach Klaus , Wiltfang Jens , Jessen Frank , Düzel Emrah , Buerger Katharina , Perneczky Robert , Teipel Stefan , Laske Christoph , Spottke Annika , Heneka Michael T. , Peters Oliver 
Published: December 2023

AbstractBackgroundCerebrospinal fluid (CSF) biomarkers have immense diagnostic and prognostic potential for Alzheimer disease (AD). Currently, AD is still mostly diagnosed relatively late in the disease process, sometimes even years after the initial manifestation of cognitive symptoms. Disease‐modifying treatments should be most effective in the earliest stages, before amyloid plaques and neurodegeneration become prevalent. Thus, further identification of biomarkers is required that can detect AD in the predementia stage. This study aimed to assess the clinical utility of synaptic proteins neurogranin and beta‐secretase 1 (BACE1) in the diagnosis and prognosis of AD.MethodWe enrolled 530 participants from DELCODE, a multicenter prospective cohort study, including healthy controls (HC), subjective cognitive decline (SCD) subjects, mild cognitive impairment (MCI) subjects, mild AD dementia and first‐degree relatives of AD patients. Based on amyloid and tau status, we divided the participants into four groups: A−T−; A−T+; A+T−; A+T+. Neurogranin and BACE1 levels across groups were assessed by ANCOVA after adjusted for age and sex. To test the correlation of the biomarkers to cognitive performance, we used linear mixed models to model baseline biomarker levels and 7 years longitudinal MMSE and PACC5 scores.ResultRegardless of amyloid status, CSF neurogranin and BACE1 levels were significantly higher in T+ group compared with T‐ (all p < 0.0001). Furthermore, for participants with negative tau status, neurogranin and BACE1 levels were lower in A+ group compared with A‐ (both p < 0.0001). After adjusting for covariates (Age, Sex, Education, APOEε4), linear mixed‐effect models indicated that higher neurogranin predicts faster decline in MMSE (β = ‐0.14, p < 0.01) and PACC5 (β = ‐0.03, p < 0.05) over 7 years.ConclusionThis study reveals that neurogranin and BACE1 could offer insight into identifying patients at early stages of AD and improve prediction of cognitive decline.
Late positive potential component and cognitive functioning in occipital area of Mild Cognitive Impairment
Authors: Zhang Zhenyu , Aleman André , Opmeer Esther , De Deyn Peter Paul , Reesink Fransje E , Spikman Jacoba M , Herrmann Christoph S , Wardana Nido Dipo , Enriquez‐Geppert Stefanie , Lejko Nena , Ćurčić‐Blake Branislava 
Published: December 2023

AbstractBackgroundMild Cognitive Impairment (MCI) is a prodromal stage of Alzheimer’s disease and other dementias (Langa & Levine, 2014). It has been suggested that a late event‐related potential (ERP) called the late positive potential (LPP) is related to cognitive functioning including sustained attention and reaction time in people with MCI (Waninger et al., 2018). The LPP in the occipital area was also suggested to be a biomarker of MCI (Liu et al., 2022). However, it remains unclear whether LPP in the occipital area is related to cognitive functioning.MethodWe collected EEG of 50 people with MCI (mean age 72.44±7.96; education: 5.52±1.07) by using a 20‐channel EEG recording system while participants performed the simple vigilance task (SVT). Their reaction time (ms) was taken as a measure of sustained attention. Vienna Reaction Time Task (VRTT) (Schuhfried GmbH, Moedling, Austria) was used to measure processing speed and inhibition while separating motor action (measured as a motor time) and cognitive processing (measured as a reaction time). Mini‐Mental State Examination (MMSE) was used to measure the severity of cognitive impairment (mean score: 26.20±2.44). Correlation analysis was used to analyze the liner relationship between the average LPP amplitude in the occipital areas (Oz, O1, and O2; time window: 400 to 800 ms after stimulus presentation), reaction time on the three versions of the VRTT, and reaction time on the SVT.ResultWe found significant correlations between reaction time on the SVT and motor time on VRTT (S1: p = 0.015; S2: p = 0.075; S3: p = 0.021;), but we found no significant correlations between reaction time on the SVT and VRTT (ps > 0.193), no significant correlations between LPP amplitude in the occipital areas and reaction time on any of the tasks (SVT: p > 0.056, VRTT: ps > 0.288) or between LPP amplitude and motor time on any version of the VRTT (ps > 0.500).ConclusionOur preliminary results indicate that LPP amplitude measured over the occipital area was not significantly associated with sustained attention or inhibition.
NIA Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS): 2023 Update
Authors: Nicaretta Heather Issen , Kuzma Amanda B , Valladares Otto , Manuel Joseph , Greenfest‐Allen Emily , Gangadharan Prabhakaran , Katanic Zivadin , Kirsch Maureen , Armus Lauren , Saravanan Naveensri , Wilk Andrew , Zhao Yi , Qu Liming , Moon Michelle K , Rose Alexis Lerro , Keskinen Peter , Cifello Jeffrey , Chou Shin‐Yi , Lee Wan‐Ping , Leung Yuk Yee , Naj Adam C. , Schellenberg Gerald D. , Wang Li‐San 
Published: December 2023

AbstractBackgroundNIAGADS is a national genomics data repository that facilitates access of genotypic and sequencing data to qualified investigators for the study of the genetics of Alzheimer’s disease (AD) and related neurological diseases. Collaborations with large consortia and centers such as the Alzheimer’s Disease Genetics Consortium (ADGC), Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, the Alzheimer’s Disease Sequencing Project (ADSP), and the Genome Center for Alzheimer’s Disease (GCAD) allow NIAGADS to lead the effort in managing large AD datasets that can be easily accessed and fully utilized by the research community.MethodNIAGADS is supported by National Institute on Aging (NIA) under a cooperative agreement. All data derived from NIA funded AD genetics studies are expected to be deposited in NIAGADS or another NIA approved site. NIAGADS manages a Data Sharing Service (DSS) that facilitates the deposition and sharing of genomic data and association results with approved users in the neurodegenerative research community. In addition, researchers are able to freely use the NIAGADS Alzheimer’s Genomics Database (www.niagads.org/genomics/) to search annotation resources that link published AD studies to AD‐relevant sequence features and genome‐wide annotations.ResultAs of January 2023, NIAGADS houses 93 datasets comprised of >149,000 samples including GWAS, sequencing, gene expression, annotations, deep phenotypes, and summary statistics. Qualified investigators can retrieve ADSP sequencing data with ease and flexibility through the NIAGADS DSS. To date, the ADSP and other contributing studies have completed whole exome sequencing (WES) of 20,503 samples and whole genome sequencing (WGS) of 36,361 samples. Raw WES and WGS files, quality controlled VCF files, and phenotype data files are available via qualified access. The next round of sequencing currently underway will generate around 30,000 additional genomes to be released in late 2023.ConclusionNIAGADS is a rich resource for AD researchers, with the goal of facilitating advances in Alzheimer’s genetics research. By housing datasets from many projects and institutions, NIAGADS enables AD researchers to meet their research goals more efficiently. Datasets, guidelines, and features are available on our website at https://www.niagads.org.