bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implicit response incompatibility slowed down asymptomatic individuals with Alzheimer’s disease pathology
Authors: Hung Shao‐Min , Wu Daw‐An , Harrington Michael G , Shimojo Shinsuke , Arakaki Xianghong 
Published: December 2020

AbstractBackgroundAlzheimer patients exhibit explicit decline of cognitive abilities. However, such decline, by definition, does not appear pre‐symptomatically. Here we introduced a subliminal incompatibility paradigm where a masked word was either congruent or incongruent to the response to the subsequent target stimulus. We examined if implicit response incompatibility led to performance decline in asymptomatic individuals with Alzheimer’s disease pathology, serving as a possible early marker of the disease.MethodCognitively healthy (CH) participants (demographically matched) were recruited from the local community, consisting of two subgroups based on cerebrospinal fluid (CSF) proteins: with normal amyloid/tau ratio (CH‐NAT, n = 20) or pathological amyloid/tau ratio (CH‐PAT, pre‐symptomatic AD, n = 20). A task‐switching Stroop task was implemented. Each trial contained two stimuli, and participants had to name the color or word of a colored word for each stimulus with button press. If the two stimuli involved different task demands (e.g. color naming and word naming), it was a switching trial. Otherwise it was a non‐switching trial. In‐between the two stimuli, a forward‐ and backward‐masked word congruent (i.e. same button press) or incongruent to the response to the subsequent stimulus was inserted.ResultFinal analysis included only the trials with both stimuli correctly responded. On average, participants had near‐ceiling performance with ∼95% accuracy. In a mixed ANOVA with one between‐subject factor (CH‐PAT/CH‐NAT) and three within‐subject factors (word/color naming, switching or non‐switching, and masked word congruent or incongruent), we analyzed the reaction time of the target (second) stimulus. We found significant main effects of word/color and switching. That is, participants responded significantly slower (1) to color of the stimulus (typical Stroop effect) and (2) when they had to switch attention across different stimulus features in a trial (color to word or vice versa). Critically there was an interaction between switching and congruency. Further analysis showed that during switching, incongruent trials slowed down significantly. Such effect was only evident in CH‐PATs (p = 0.00005), but not CH‐NATs (p = 0.1).ConclusionDuring a challenging task‐switching condition, the behavioral performance of asymptomatic individuals with Alzheimer’s disease pathology was significantly affected by implicit response incompatibility.
Does feature binding account for functional decline in patients with mild cognitive impairment? Evidence from the Details of Function of Everyday Life Questionnaire (DoFEL)
Authors: Calia Clara , O'Donal Freddie , Pickett Eleanor , Parra Mario A. 
Published: December 2020

AbstractBackgroundAvailable functional scales used to discriminate normal and abnormal ageing are informative of basic abilities (e.g., bathing, grooming, feeding, etc.). These are complex functions and the tools used to assess them lack theories from cognitive ageing. These features have rendered them insensitivity to the early stages of dementia such as that caused by Alzheimer’s disease (AD). To overcome these limitations, we need to improve our understanding of the cognitive underpinnings of functional decline. The ability to bind information in memory (i.e., feature binding) declines from the preclinical stages of AD. It remains unknown whether such subtle cognitive deficits can underpin decline of instrumental activities of everyday life (IADL, e.g., managing finances, using technologies, shopping) found in the prodromal stages of AD. To address this need we have developed a theory‐driven scale namely Details of Function of Everyday Life Questionnaire (DoFEL). We used DoFEL to investigate if cognitive constructs such as memory binding can account for impairment of specific abilities that support instrumental functions.MethodsParticipants (N=168) completed a neuropsychological test battery, comprising of a set of novel and traditional neuropsychological tasks known to be useful in the early detection of AD. Binomial logistic regression was utilised to evaluate the predictive effect of DoFEL relative to other scales such as the Addenbrooke's cognitive examination (ACE).ResultsA stratified model incorporating the Shopping and Money, Work and Social Life and Domestic Chores domains of the DoFEL, X2(3)=48.57, p < 0.001, R2 = 0.70, AUC=0.94, demonstrated comparable accuracy to that of the ACE‐R scores, X2(1)=47.61, p < 0.001, R2 = 0.71, AUC=0.94. The DoFEL scores informing on conjunctive binding abilities had a moderately high accuracy and Nagelkerke's R2 results, indicating a higher predictive power to discriminate between healthy older adults and individuals with MCI.ConclusionsFunctional composite measures integrating feature binding constructs within measures of IADL impairment are plausible future indicators of early cognitive decline in prodromal AD. Further research is required to evaluate the validity of DoFEL and its sensitivity across the whole AD continuum.
Disparities in brain‐behavior relationships among Latinos and white non‐Latinos
Authors: Calcetas Amanda , Smirnov Denis S. , Salmon David P. 
Published: December 2020

AbstractBackgroundWith a growing racial and ethnic disparity in the aging population, it is important to understand factors that could influence relationships between neurodegeneration and cognitive decline. Differences in early socioeconomic exposure, educational background, and/or lack of culturally and linguistically appropriate testing protocols could impact the ability to see or interpret such relationships. We examined this issue by comparing the association between MRI‐derived measures of cortical thickness and performance on tests of global cognitive function, memory and language in elderly Latino and Non‐Latino White (NLW) individuals before and after adjustment for education.MethodsParticipants were 36 Latino and 126 NLW elderly individuals with cognitive impairment (i.e., Mild Cognitive Impairment, Alzheimer Dementia), and 33 Latino and 95 NLW cognitively normal controls (NC). Participants were evaluated annually at the Shiley‐Marcos Alzheimer's Research Center (ADRC) where they received cognitive assessment that included measures of global cognitive function (i.e., MMSE), memory (Logical Memory Test, Word List Learning) and language (Category Fluency Test). MRI scans were performed within 6 months of testing and measures of hippocampal volume and cortical thickness were determined using Freesurfer procedures.ResultsDemographically, the Latino NC group was younger (71.0+7.9) than the Latino‐Impaired group (73.2+10.8) and both NLW groups (NLW NC=72.8+5.7; NLW‐Impaired: 74.4+7.7; p < 0.01). Latino‐Impaired (9.9+4.8) had fewer years of education than Latino NC (13.8+3.2), and both Latino groups fewer than the NLW groups (NC=16.5+2.2; Impaired: 16.2+2.9). Regression analyses showed that MMSE, Word List Learning, Logical Memory, and Category Fluency were associated with entorhinal cortical thickness or hippocampal volume in the Latino and NLW groups. Furthermore, these associations were stronger in the Latino‐Impaired group than in the NLW Impaired group (all p’s < 0.05). However, these latter differences no longer reached significance when adjusted for education (i.e., in regression analyses or when the overall Latino group was restricted to the education range of the NLW group.ConclusionsThe large education gap between elderly Latinos and NLWs can influence perceived differences in the association between measures of neurodegeneration and cognitive decline. Further investigation of cultural and ethnic influences on the manifestation of dementia and its underlying causes is needed.
Risk factors for falls in preclinical and prodromal Alzheimer’s disease and dementia due to Alzheimer’s disease: Findings from the Australian Imaging, Biomarker and Lifestyle study of ageing (AIBL)
Authors: Huynh Andrew , Woodward Michael , Zeimer Henry , Zisis Georgios , Martins Ralph N , Rainey‐Smith Stephanie R , Brown Belinda M , Fernando Warnakulasuriya , Gardener Samantha L , Rowe Christopher C , Masters Colin L , Yates Paul A 
Published: December 2020

AbstractBackgroundLiterature suggests that preclinical Alzheimer’s disease (AD) is associated with increased falls risk1. Falls are a major cause of morbidity and mortality in older people, particularly people living with dementia. We aimed to identify factors associated with falls in older Australians with baseline Aβ PET imaging.MethodParticipants from the Australian Imaging, Biomarker and Lifestyle Study of Ageing (AIBL), with baseline 11C‐PiB PET and 18‐monthly review for 6 years, including self‐reported falls. Participants with severe illness, alcohol abuse and cerebrovascular disease were excluded. Multivariable logistic regression was used to identify factors associated with falls, including Aβ PET status (elevated/not elevated as previously published).Result293 participants (mean age 72.6 years, 52% female, 62% cognitively‐normal, 20% Mild Cognitive Impairment, 18% AD) reported 50 falls during the study period. Female gender (adjusted odds ratio [aOR] 3.17, 95% CI 1.53‐6.58, p=0.002), impaired vision (aOR 2.32, 95% CI 1.08‐4.99, p=0.031) and an education greater than 12 years (aOR 2.40, 95% CI 1.20‐4.82, p=0.014) were associated with incident falls. Age (p=0.172), elevated Aβ (p=0.549) and cognitive status (p=0.799) were not associated with falls.ConclusionWhile our findings that female gender and visual impairment are associated with increased risk of falls are consistent with prior reports, the association with higher education is intriguing and warrants further investigation. Recruitment methods and reporting biases may contribute to the lack of observed association between falls and Aβ or cognitive diagnosis compared with other studies. Future analyses should also include cerebrovascular disease, physical activity, medications and alcohol intake. 1 Stark SL et al. Preclinical Alzheimer disease and risk of falls. Neurology. 2013 Jul 30; 81(5): 437–443.
Description of longitudinal cranial imaging and cognitive changes in the Strong Heart Study
Authors: Suchy‐Dicey Astrid M , Verney Steven P , Nelson Lonnie A , Grabowski Thomas J , Buchwald Dedra 
Published: December 2020

AbstractBackgroundLittle is known about cognitive impairment and dementia in American Indians, who are underrepresented in most studies of Alzheimer’s disease and related dementias.MethodThe Strong Heart Study recruited 4,549 American Indians aged 45‐75 from 3 major geographic regions in 1989‐1991. In 2010‐2013 and again in 2017‐2019, all eligible surviving participants were recruited for comprehensive cranial magnetic resonance imaging, cognitive, and clinical examinations. Neurological data collected included history of stroke and neurological symptoms. Cognitive data included Modified Mini Mental Status Examination, Weschler Adult Intelligence Scale, Controlled Word Association Test, California Verbal Learning Test, Wide Range Achievement Test, Montreal Cognitive Assessment, Craft Story Recall, Benson Figure Copy, Number Span test, Category Fluency, Trail Making test, Multilingual Naming Test, Functional Activities Questionnaire. Physical function tests included Short Physical Performance Battery, dynamometric grip strength, and Halstead finger tapping test. Mood and quality of life tests included Short Form 36 and Centers for Epidemiologic Studies Depression scale. Clinical examination included anthropometric measures, blood pressure, and basic blood and urine laboratory assays including serum glucose, lipids, creatinine, and albumin. Neuroradiologists blinded to clinical data examined MRI for vascular and structural findings, including presence and location of infarcts, hemorrhages, white matter hyperintensities, sulcal widening, ventricle enlargement, and volumetric estimates of hippocampus, parahippocampal gyrus, thalamus, and frontal lobe. Neuropsychologist panels adjudicated cognitive impairment and dementia by case review.ResultThis report describes the structure and methods used to collect these longitudinal data, including the cognitive examinations, the neuropsychological data cleaning, and the panel‐based case reviews. We also include basic epidemiologic description of the data, including changes in cranial imaging findings and cognitive and functional examinations between the two neurological examinations (approximate follow‐up time: 7 years).ConclusionThis report adds to existing literature with the first longitudinal description of cranial imaging and cognitive testing data in American Indian elders, as well as the first cognitive measurements related to Alzheimer’s disease, in this population. These data may be used to estimate incidence and prevalence of vascular brain injury, structural atrophy, imaging markers related to Alzheimer’s disease, and cognitive function in this understudied population.
The amyloid plaque proteome in different subtypes of Alzheimer’s disease
Authors: Drummond Eleanor , Pires Geoffrey , Kanshin Evgeny , Askenazi Manor , Ueberheide Beatrix , Wisniewski Thomas 
Published: December 2020

AbstractBackgroundAmyloid plaques contain many proteins in addition to beta amyloid (Aß). Previous studies examining individual plaque‐associated proteins have shown that the presence of these proteins is important: they provide insight into Alzheimer’s disease (AD) pathogenesis, and they are potential biomarkers and/or therapeutic targets for AD. However, a comprehensive analysis of all proteins enriched in amyloid plaques has not yet been done. Therefore, the aim of this study was to use an unbiased proteomic approach to identify all proteins consistently enriched in amyloid plaques in different subtypes of Alzheimer’s disease.MethodWe used label‐free quantitative mass spectrometry to identify all proteins significantly enriched in microdissected amyloid plaques in comparison to surrounding, non‐plaque tissue in two subtypes of AD; sporadic early onset AD (EOAD; age at death <65; n = 5) and Down syndrome with AD (DS; n = 5). Validation was performed using immunohistochemistry and by comparison with published proteomics databases.Result116 proteins were consistently enriched in plaques in EOAD and DS in addition to Aß. The five most highly enriched proteins in plaques were the same in both subtypes of AD; COL25A1 (136 fold enriched in plaques), SMOC1 (87 fold enriched), MDK (59 fold enriched), NTN1 (55 fold enriched), and HTRA1 (49 fold enriched). Amyloid plaques were most significantly enriched in vesicle proteins (predominantly endosomal/lysosomal proteins; enrichment FDR = 5.71 × 10−19), therefore suggesting that the endosomal/lysosomal system may have an important role in amyloid plaque formation. We also identified 53 novel proteins enriched in plaques: 12 of these proteins have been previously associated with either Aß or APP, but not yet known to be present in plaques, while 41 of these proteins have not yet been associated with Aß. Immunohistochemistry validated the enrichment of selected novel plaque proteins such as all ERM family members (ezrin, radixin, moesin), which interact with the actin cytoskeleton and have important roles in endosome transport and maturation.ConclusionAmyloid plaques are enriched in >100 proteins in addition to Aß. We have identified many novel amyloid plaque proteins, which may be potential therapeutic targets and/or biomarkers for AD.
Leveraging mouse genetic diversity to investigate the role of brain myeloid cells in Alzheimer’s disease
Authors: Yang Hongtian Stanley , Onos Kristen , Choi Kwangbom , Keezer Kelly , Diemler Cory , Hewes Amanda , O'Rourke Rita , O'Rourke Sarah , Gastoukian Nils , Harder Jeffrey , Skelly Daniel , Sasner Michael , Carter Gregory W. , Howell Gareth 
Published: December 2020

AbstractBackgroundMyeloid cells have been strongly implicated in Alzheimer’s Disease and related dementias (ADRDs). Our previous study showed genetic diversity significantly modified brain myeloid cell responses and AD‐relevant phenotypes in mice. Therefore, incorporating natural genetic variation into mouse models is indispensable to understand the role of myeloid cells in AD. This study aims to characterize brain myeloid cells in our genetically diverse AD panel to determine their functions in ADRDs.MethodsBrain myeloid cells were isolated from 8‐9 months‐old female mice from our genetically diverse AD mouse panel [C57BL/6J (B6), PWK/PhJ, WSB/EiJ and CAST/EiJ strains, each carrying APP/PS1] using magnetic activated cell sorting and were subjected to single‐cell RNA‐sequencing (scRNA‐seq). Data were processed using a customized pipeline allowing strain‐specific genome alignment followed by downstream analyses using Seurat and edgeR packages. Differences in myeloid cell responses between strains are being validated using functional assays in primary microglial cultures and immunofluorescence. To identify the putative genetic variations that drive and/or modify differences in myeloid cell responses, quantitative trait locus mapping of microglia number and morphology is being performed in brains from 120 Diversity Outbred (DO) mice, derived from eight mouse strains including those listed above.ResultsscRNA‐seq uncovered heterogeneous clusters of myeloid cells that vary significantly in cell abundance and gene expression between both wild‐type and APP/PS1 of B6, PWK, WSB and CAST mice. There was a significantly lower percentage of disease‐associated microglia in WSB.APP/PS1 mice and a significantly higher percentage of interferon‐responding microglia in PWK.APP/PS1 mice, compared to other AD strains. These data agreed with previously determined phenotype differences between strains. Differential gene expression analyses (all data compared to the B6 strain) revealed robust APP/PS1‐responding genes unique to strain background (strain by genotype effect) including Rpl29, Irf7, Cd36, H2‐Eb1, Lag3 and Cd34 in CAST; Ramp, Tmem176a, Tmem176b, Sepp1 and Inpp5d in PWK, and Ccl6, Slamf8, Nme1 and Pcna in WSB strain. Validation by primary culture and analyses of DO mice are underway.ConclusionAs in humans, mouse genetic diversity significantly impacts the landscape and dynamics of brain myeloid cells in AD. These studies will improve the translatability of myeloid‐based therapies for ADRDs.
Idiosyncratic neurolinguistic presentations of Chinese speaking primary progressive aphasia individuals
Authors: Tee Boon Lead , Tempini Maria Luisa Gorno , Chen Ta‐Fu , Lo Raymond Y. , Wong Adrian 
Published: December 2020

AbstractBackgroundPast research on Primary Progressive Aphasia(PPA) has been centered around English language, thus there is limited knowledge to the presentations of linguistic features that differ from the English language. Chinese language possesses numerous linguistic features that contrast significantly from the English language. Chinese language is a tonal and numeral classifier language; hence tones are lexically contrastive and numeral cannot quantify a noun without classifiers. As more than 40% and 20% of living languages worldwide are tonal and numeral classifier languages, investigating these idiosyncratic neurolinguistics features in non‐English speaking PPA individuals may refine the clinical practice paradigm to be more adaptable worldwide.MethodThe CLAP (Chinese Language Assessment for PPA) project aims to investigate the neurolinguistics features of Chinese speaking PPA individuals. The CLAP battery consists of fourteen speech and language tasks and this presentation focuses on the tonal and numeral classifier performances as they are idiosyncratic traits of the Chinese language. The tonal perception function is assessed via tonal identification, tonal discrimination, tone‐picture matching, and tone‐word matching tasks. The tonal production performance is evaluated through serial tone reading, repetition of tonal tongue‐twisters, and multi‐tone multi‐repetition tasks. To illustrate classifier function, participants are tasked with producing the accurate classifiers after visual and auditory stimuli of the nouns.ResultThe CLAP project recruited 13 healthy controls and 20 PPA individuals (5 nfvPPA, 6 svPPA, and 9 lvPPA) that are native Chinese speakers. Individuals with svPPA were noted to perform significantly lower in the tone‐picture matching task (p=0.024) and classifier task (p<0.0001). Volumes in left inferior temporal and bilateral temporal poles were significantly correlated with the performance in the tone‐picture matching and classifier task respectively. Conversely, individuals with nfvPPA scored substantially lower than healthy controls in all three tone production tasks (p<0.0001, p=0.024, p<0.0001) and lower than other PPA variants in tonal tongue‐twisters tasks. Performance in tonal tongue‐twister tasks was found to correlate with the degree of atrophy in left inferior and superior frontal regions.ConclusionTone and classifier tasks can potentially serve as diagnostic and classification tools for PPA individuals that speaks Chinese language and other tonal and numeral classifier languages.
Comparative proteomic analysis of skin fibroblasts of patients with familial Alzheimer's and healthy controls: Searching for new therapeutic targets
Authors: Lopez‐Toledo Gustavo , del Carmen Silva‐Lucero Maria , Arias‐Montaño Jose Antonio , del CCardenas‐Aguayo Mariaarmen 
Published: December 2020

AbstractBackgroundAlzheimer's disease (AD) is a neurodegenerative disorder characterized by memory loss, neuronal degeneration and synaptic dysfunction, resulting in atrophy of the affected regions. The identification of early biomarkers for AD diagnosis has been a challenge due to the high individual variability in markers expression, thus the use of peripheral cells other than neuronal cells such as bone marrow or dental pulp mesenchymal cells, blood cells and fibroblasts represents an opportunity for the detection of early pathological changes of Alzheimer's disease patients. Moreover, neuronal cells differentiated from reprogram somatic cells, recapitulate brain cell pathological associated changes.MethodWe study the proteome using 2D‐PAGE and protein identification by mass spectrometry. Skin fibroblasts were cultured from patients with a mutation in Presenilin‐1 (A246E or M146L) and from control individuals of the Coriell Institute cell repository in Earl MEM salts medium with 15% non‐inactivated Fetal Bovine Serum. Fibroblast phenotype was confirmed by immunodetection of vimentin and S100A4 markers. We use Western Blot and qPCR techniques to evaluate changes in the expression of genes and proteins of particular pathways involved in the neurodegeneration of AD.ResultDifferences in protein expression in fibroblasts were identified between affected individuals and controls, related to cell adhesion, cytoskeleton, energy and glucose metabolism, ubiquitin‐proteasome pathway, autophagy and signal transduction, which have been previously found affected in neurons from AD patients.ConclusionOur results indicate that samples derived from fibroblasts from AD patients have a unique protein profile with respect to controls, both at expression level and proteins patterns, showing that peripheral cells can be useful in modeling degenerative pathways and biomarker identification for Alzheimer's disease.