bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repeated concussions associated with worsened working memory, attention and processing speed, but preserved delayed memory: A PROTECT study
Authors: Lennon Matthew J , Thayanandan Tony , Corbett Anne , Aarsland Dag , Ballard Clive , Raymont Vanessa 
Published: December 2021

AbstractBackgroundApproximately 5% of all dementia diagnoses may be attributable to traumatic brain injuries (TBI), but the precise pathway and required thresholds for increased dementia risk remain unclear. TBI can cause disparate degrees of damage to parts of the brain and thus may affect different subdomains of cognitive function differently. This study examined the strength of associations between traumatic brain injuries and cognitive subdomains in a healthy cohort of older adults.MethodCognitive and demographic data was collected from individuals aged 50 ‐ 93 (n = 12,041) participating in the PROTECT study, a large online cohort study. Self reported, cross sectional data on head injury were collected through the Brain Injury Screening Questionnaire (BISQ). Cognitive tests were standardised and grouped into four domain scores using the FLAME composite (Working Memory, Delayed Memory, Processing Speed and Attention) based on a principle components analysis (KMO test = 0.724). Regression analyses were performed, examining the association between numbers of head injuries, episodes of loss of consciousness and the cognitive domain scores.Result62.8% of participants reported a previous head injury and 33% of those had at least one episode of subsequent loss of consciousness (21% overall). There was a significant association between the self‐reported historical number of head injuries and poorer working memory, attention and processing speed (B = ‐0.005, ‐0.007, ‐0.014 and p=0.004, <0.001, <0.001 respectively). Self‐reported historical episodes of head injuries followed by loss of consciousness (LOC) demonstrated similar, albeit stronger, associations with working memory, attention and processing speed (B = ‐0.019, ‐0.024, ‐0.024 and p = 0.002, <0.001, <0.001). Neither numbers of head injuries or LOC were associated with poorer delayed memory performance.ConclusionThe PROTECT study is one of the largest, healthy older adult cohorts to examine the link between TBI and cognitive outcomes. Although it is cross sectional the increasing effect sizes seen for increasing severity of head injury indicates a dose‐response relationship suggestive of causation. Our results suggest that TBI may differentially impact particular brain areas and functions and that cognitive impairment in those with a history of TBI has a distinct pathological and clinical phenotype.
Associations between obstructive sleep apnea, Alzheimer’s disease pathology, and objective daytime sleepiness measured by the psychomotor vigilance task in cognitively unimpaired adults
Authors: Plante David T , Tran Kieulinh Michelle , Cook Jesse D , Hagen Erika W , Peppard Paul E , Kollmorgen Gwendlyn , Suridjan Ivonne , Blennow Kaj , Zetterberg Henrik , Carlsson Cynthia M , Johnson Sterling C. , Bendlin Barbara B 
Published: December 2021

AbstractBackgroundDaytime sleepiness is common among individuals with obstructive sleep apnea (OSA), and has been reported among individuals with Alzheimer’s Disease (AD) pathology. However, objective measures of decreased alertness have not been examined in the context of AD. Here, we examined performance on the psychomotor vigilance task (PVT) in relation to AD pathology as indexed by AD biomarkers in cerebrospinal fluid (CSF), among individuals with and without OSA.MethodForty‐eight cognitively unimpaired adults (32 women), mean age 66.3±7.9 years, enrolled in the Wisconsin Alzheimer’s Disease Research Center (ADRC) completed a multifaceted sleep assessment. Presence and severity of OSA was evaluated using WatchPAT at‐home overnight recordings. Habitual sleep‐wake patterns were assessed using actigraphy. Neurobehavioral alertness was quantified using the 10‐minute PVT. CSF biomarkers were quantified using the exploratory Roche NeuroToolKit assays, a panel of automated robust prototype immunoassays (Roche Diagnostics International Ltd). Generalized linear models examined associations between AD biomarkers, apnea‐hypopnea index (AHI), and PVT performance. Primary AD biomarkers of interest were phosphorylated‐tau (p‐tau), total tau (t‐tau), and amyloid‐beta (Aβ) 42/40 ratio, measured in CSF. The primary PVT variable of interest was the mean response time of the 10% slowest responses, which is associated with daytime sleepiness and default mode network activity. Log transformations for PVT and AHI+1 were utilized for analysis. Covariates included age, sex, body mass index, total sleep time, sleep efficiency, APOEε4 status, years of education, and parental history of AD.ResultAHI was associated with lower Aβ 42/40 (β=‐0.005,p=0.03) and higher p‐tau (β=2.22,p=0.03), but not t‐tau (β=20.28,p=0.20). Significant AHI*PVT interactions were observed for p‐tau (p=0.0002) and t‐tau (p=0.02), but not for Aβ 42/40 (p=0.18). Specifically, among individuals with OSA (AHI>5/hour;n=20), PVT performance was correlated with p‐tau (r=0.68,p=0.0009) and t‐tau (r=0.39,p=0.09), an association that was not observed in those without OSA in this preliminary dataset.ConclusionOSA was associated with amyloid and tau pathology, in individuals without cognitive impairment. Furthermore, PVT performance may be an objective measure of sleepiness associated with elevated p‐tau and t‐tau among individuals with OSA. Replication and expansion of these findings in larger and longitudinal datasets are indicated. Funding: Supported by R03AG063274 and P30‐AG062715.
The effect of bilingualism on the brain is modulated by language experience
Authors: Calabria Marco , Voits Toms , Rothman Jason , Robson Holly , Marín Lidón Marín , Costumero Víctor , Aguirre Naiara , Pliatsikas Christos 
Published: December 2021

AbstractBackgroundResearch has shown that lifelong bilingualism may contribute to cognitive reserve in neurodegenerative diseases as shown by a delay of the age at symptom onset in bilinguals with different types of dementia. However, the study of the neural mechanisms behind this bilingual advantage is limited, especially for the preclinical stages of dementia, such as Mild Cognitive Impairment (MCI). Additionally, most of the studies have operationalised bilingualism as a dichotomous variable, despite the fact that language experience results from a combination of different factors (language usage, frequency of language switching, age of second language acquisition, and language proficiency).MethodIn the present study we investigated cortical and subcortical grey matter structure volume, and episodic memory performance, in a group of bilingual individuals with MCI by considering their linguistic profile. Specifically, we compared active bilingual speakers of Spanish and Catalan and bilinguals who have good knowledge of their second language but without any active usage of it. This classification is based on the results of a previous study in which we found that actively speaking the two languages promotes the delay of symptoms in individuals with MCI.ResultThe results reveal that active bilingualism significantly delays the onset of MCI symptoms. Additionally, active bilingualism is also shown to result in increased cortical grey matter in the right supramarginal gyrus, increased bilateral hippocampal volume and reshaping of the right amygdala and right caudate nucleus.ConclusionThese results are compatible with the hypothesis that bilingualism protects against cognitive decline via neural compensation mechanisms and by increasing neural efficiency in individuals with MCI.
Using a multi‐staged translation method to develop socio‐culturally and language‐sensitive study materials: Lessons learned from an Asian cohort for Alzheimer’s disease
Authors: Lee Haeok , Tzuang Marian , Tee Boon Lead , Li Clara , Gu Yian , Lu Anna T , Lee Sang A , Seo Eun Hyun , Kang Younhee , Kim Kyungmin , Tran Binh , Chae Wonjeong , Nguyen Dat , Nguyen Dam , Vuong Quyen , Jun Gyungah R , Wang Li‐San , Yu W. Haung , Park Van Ta ,   The Asian Cohort for Alzheimer's Disease Study
Published: December 2021

AbstractBackgroundAlzheimer’s disease (AD) is a global health crisis on multiple levels. A major impediment to AD research is the availability of socio‐culturally and language appropriate study materials and instruments and inclusion of under‐represented minorities. To fulfill this need, we apply best practices and lessons learned to translate study materials for use in the Asian Cohort for Alzheimer’s Disease’s (ACAD) study of AD in Asian Americans and Asian Canadians (ASAC) with the overarching goal in inclusivity of these populations to better understand the etiology of AD.MethodOur multi‐stag translation process is guided by the World Health Organization’s (WHO) process of translation (forward and reverse translation, consensus verification and reconciliation) to achieve parity with the English materials for our target groups (Chinese (simplified and traditional; Mandarin and Cantonese), Korean and Vietnamese). ACAD’s collective experience partnering with aging Asian adults has revealed not only a language barrier, but also issues with socio‐cultural communication traits, and literal translations that stigmatize AD and dementia. Consequently, we have taken into account the varying perceptions and expressions of words in a social context. The translation process was implemented by a team of multi‐lingual researchers/clinicians/community leaders with extensive practical translation experience. Since language influences how a speaker views the world, we employed a cross‐section of translators and emphasized conceptual (vs. literal) culturally appropriate translations for the community.ResultsTo date, we have developed Asian language versions of ACAD documents (informed consent, data collection, community and social media outreach materials, website) for all our target groups and continue the process of beta‐testing our study materials (including the cognitive assessment instruments).ConclusionThe multi‐stage translation process accounts for distinctive Asian socio‐cultural‐language backgrounds, providing an important guideline for AD researchers to promote health literacy in the health and general community in an effort to reduce health disparities in underrepresented groups, like Asians. In order to ensure fidelity across languages, we will continue validating the original English version in Chinese, Korean, and Vietnamese versions in the ACAD study.
Treatment for anomia in bilingual speakers with progressive aphasia
Authors: Grasso Stephanie M , Kazemi Nina , Mirzapour Haideh , Neupane Rozen , Peña Elizabeth , Bonakdarpour Borna , Tempini Maria Luisa Gorno , Henry Maya L 
Published: December 2021

AbstractBackgroundAnomia is an early and prominent feature of primary progressive aphasia (PPA) and other neurodegenerative disorders. Research investigating treatment for lexical retrieval impairment has focused primarily on monolingual speakers.The purpose of this study was to examine the benefits of a naming intervention administered to bilingual speakers with PPA. We predicted that participants would show improved naming for trained stimuli, with maintenance at follow‐ups. In addition, we predicted that cognate pairs (e.g., rose and rosa) would demonstrate advantages in cross‐linguistic transfer.MethodIn this case series, treatment was administered to ten bilingual speakers with PPA using a single‐subject multiple‐baseline design. Treatment was administered in two phases, with one language targeted per phase. Cognates were included as treatment targets to investigate their potential to facilitate cross‐linguistic transfer. Participants spoke a variety of languages (Table 1), and underwent cognitive‐linguistic testing at pre‐treatment (Table 2). Performance on trained and untrained stimuli was evaluated before, during, and after treatment, and at 3‐, 6‐, and 12‐months post‐treatment.The Lexical Retrieval Cascade (Henry et al., 2013; 2019) was used to target individually tailored and matched word sets. The intervention targets naming by leveraging relatively spared cognitive‐linguistic abilities, with the goal of retraining specific vocabulary as well as instilling word‐retrieval strategies more broadly. Treatment sessions occurred twice weekly (Table 3) and were complemented with daily home practice. Participants’ performance was analyzed via d‐statistics (Beeson & Robey, 2006) and simulation analysis.ResultParticipants demonstrated significant treatment effects in each of their treated languages, with maintenance up to one‐year post‐treatment for the majority of participants (Figure 1). Most individuals in the cohort showed a significant cross‐linguistic transfer effect for trained cognates in both the dominant (8/10) and nondominant (7/10) language, with fewer than half of participants showing a significant effect for noncognates.ConclusionFindings support the implementation of dual‐language intervention approaches for bilingual speakers with PPA, irrespective of language dominance. In addition, our findings indicate that monolingual clinicians may select cognates to support gains across languages. Further research is needed to determine whether measures related to disease severity or language history are predictive of treatment and transfer effects.
Developing best practices for outreach for the Asian Cohort for Alzheimer’s Disease (ACAD) study
Authors: Yu W Haung , Tzuang Marian , Thomas Carlos , Vogel Briana , Lu Anna T , Lee Haeok , Chow Tiffany W , Jun Gyungah R , Wang Li‐San , Park Van Ta ,   The Asian Cohort for Alzheimer’s Disease (ACAD) Study
Published: December 2021

AbstractBackgroundAlzheimer’s disease (AD) is a leading cause of death worldwide. Despite the global impact, clinical research in AD and, in particular, clinical trials, biomarker and genome‐wide association studies are underrepresented for racial/ethnic minorities such as Asian Americans and Asian Canadians (ASAC). The Asian Cohort for Alzheimer’s Disease (ACAD) is the first large AD cohort for ASAC to address this disparity, building on best practices in community recruitment and outreach strategies with the goal of identifying genetic and non‐genetic risk factors of AD in populations of Asian descent. ACAD will include individuals of Chinese, Korean and Vietnamese ancestry, representing the first multi‐cultural Asian cohort analysis for AD.MethodCommunity‐Based Participatory Research (CBPR) principles are embedded through all activities as a fundamental strategy to increase research participant engagement of ASAC. CBPR engages the community in all phases of research (i.e., recruitment; resource sharing; study design; data interpretation) as a collaborative process between the community and researchers that leverages each other’s strengths/assets, and requires commitment to sustainability. ACAD’s Recruitment and Outreach Workgroup aims to: a) coordinate and monitor recruitment activities across all 8 recruiting sites in the US and Canada; b) develop and disseminate recruitment and community outreach/education material; c) work with ACAD’s community advisory board (CAB) to address community partner needs; d) work with AD and Asian community partners; and e) develop best practices for community outreach in Asian and immigrant populations.ResultWe have gathered local/regional/national leaders representing the three target ASAC cultural groups (Chinese, Korean, and Vietnamese) of ACAD as our CAB. Four significant activities thus far include: curation of information for public use; translation of ACAD educational/outreach materials; development and dissemination of social media information; and, identifying outreach and enrollment metrics as enduring documents for the research and community stakeholders.ConclusionThe overarching goal of ACAD is to include this underserved and underrepresented group, reducing health disparities, while increasing our knowledge about the risk of AD among ASAC. Our multifaceted outreach and recruitment strategies will help to optimize ACAD’s success in recruitment and engagement with the ASAC community.
Decorin is an early CSF biomarker of Alzheimer’s Aβ amyloidosis
Authors: Jiang Richeng , Smailovic Una , Haytural Hazal , Haret Robert Mihai , Shevchenko Ganna , Tijms Betty , Gobom Johan , Abelein Axel , Johansson Jan , Zetterberg Henrik , Winblad Bengt , Frykman Susanne , Jelic Vesna , Bergquist Jonas , Visser Pieter Jelle , Nilsson Per 
Published: December 2021

AbstractBackgroundAlzheimer’s disease (AD) brains are characterized by extracellular amyloid‐beta (Aβ) deposition and autophagy dysregulation. Here we aimed at deepening the understanding of these brain pathologies and how they translate to the CSF using App knock‐in mice.MethodAD postmortem brain tissues and App knock‐in mouse models (AppNL‐F
and AppNL‐G‐F
) were used for autophagy characterization. The cerebrospinal fluid (CSF) from App knock‐in mice was analyzed by label‐free mass spectrometry (MS) and compared with previously reported CSF MS results from patients. The expression of decorin in the mouse brains was analyzed by immunohistochemistry and western blot. The autophagy‐activating effect of decorin was measured in the mouse primary neurons.Resultp62 and LC3 II levels were increased in AppNL‐G‐Fmice similar to the marked accumulation of p62 in AD brains. Several extracellular matrix (ECM) proteins, including decorin, were significantly increased in the CSF of both AppNL‐F mice and amyloid‐positive/tau‐negative subjects with normal cognition. Decorin was decreased in parvalbumin‐positive interneurons but increased in choroideus plexus of AppNL‐Fmice, both of which correlated with Aβ pathology. Decorin‐treated mouse primary neurons exhibited lowered p62 and LC3 II levels.ConclusionAutophagy is similarly inhibited in the brains of AppNL‐G‐Fmice and AD patients. The similar increase of decorin in CSF of AppNL‐F mice and amyloid‐positive/tau‐negative subjects with normal cognition indicates a potential of decorin as an early biomarker of Aβ amyloidosis. In addition, decorin activates neuronal autophagy by increasing autophagosomal‐lysosomal degradation linking changes in ECM to autophagy.
iLoF: a blood‐based optical fingerprinting tool for Alzheimer’s disease screening
Authors: Mumtaz Mehak , Faria Simão , Santos Paulo , Carpinteiro Cristiana , Pinto Vanessa , Rodrigues Sandra , Marques Filipe , Rocha Sara , Sampaio Paula , Paiva Joana S. ,   iLoF
Published: December 2021

AbstractBackgroundThe high cost and invasiveness of state‐of‐the‐art ATN diagnostic methods underscore the need for alternative approaches for Alzheimer's Disease (AD) patient screening. Blood‐based biomarkers have opened unrivalled opportunities to make AD diagnostics cost‐ and time‐efficient. However, single biomarkers are failing to provide accurate diagnosis/prognosis information for patients suffering from this heterogenous disease, hence the need to combine multiple biomarkers to generate disease‐specific signatures. Here, we present a blood‐based optical fingerprinting tool as a unique ‘holistic’ cost and time efficient solution for frontline AD diagnostics.MethodPlasma samples from 96 subjects with AD (n=33), mild cognitive impairment due to AD (MCI, n=29), and nondemented controls (n=33) were analyzed with the iLoF technology to generate an optical fingerprint of each sample. Briefly, samples were exposed to a fixed wavelength light‐beam guided through a single mode optical fibre and their back‐scattered signal was acquired and processed to calculate signal‐associated features. The combination of optical features was computed by supervised machine learning algorithms, and four‐fold validation was done to fit the best model. Spike‐and‐recovery experiments for amyloid‐β42, total/phospho‐tau were performed to derive their specific optical fingerprints in blood samples.ResultThe iLoF method classified AD, MCI, and nondemented subjects with an AUC of 0.83. The iLoF measurements correlated with amyloid‐β42 (r=0.783, p>0.0001), total tau (r=0.815, p>0.0001), and phospho‐tau (r=0.782, p>0.0001) concentration in CSF, MMSE score (r=0.759, p>0.0001), and amyloid‐PET scan results (p>0.0001). Additionally, spike‐recovery experiments showed that iLoF technology can identify and quantify relevant AD biomarkers in blood at pathophysiological concentrations. A coefficient of determination between predicted and real concentrations of r2=0.968, r2=0.996 and r2=0.984 was obtained for amyloid‐β42, total tau and phosphor‐tau, respectively. These biomarker‐directed optical fingerprints can be used to further improve the classification model.ConclusionIn conclusion, blood optical fingerprinting provides a rapid, low‐cost, and convenient tool to enable agnostic screening of AD patients. This disruptive and agnostic technology is expected to become a front‐line screening tool to empower AD diagnosis and may deliver simultaneous screening for multiple diseases underlying dementia. Further work will focus on expanding testing to larger cohorts and addition of other common forms of dementia.
The risk of cognitive impairment in spouses of patients with cognitive impairment
Authors: Park Hee Kyung , Jeong Jee Hyang , Kim Geon Ha 
Published: December 2021

AbstractBackgroundWe aimed to investigate demographics, neuropsychological performance, and amyloid pathology in spouses of people with cognitive impairment.MethodA total of 30 patients and 30 spouse controls were enrolled in a prospective cohort for Alzheimer’s disease between June 2018 and December 2020. All subjects had a comprehensive interview, laboratory findings, formal neuropsychological test battery, brain computed tomography or magnetic resonance imaging, and 18F‐ Florbetaben positron emission tomography (FBB PET).ResultThere were no differences in age, sex, education level, family history of dementia, and vascular risk factors between the patient group and spouse group. APOE e4 carriers were more common in the patient group (40.0%) than in the spouse group (10.0%). Although none of the spouses complained of impaired cognition, 40.0% of them were shown to have mild cognitive impairment. Visual analysis of FBB PET showed that 24.1 % of spouses showed amyloid deposition.ConclusionForty percent of spouses of people with cognitive impairment showed mild cognitive impairment and about 24% of them had amyloid pathology. This finding implicates high risk of cognitive impairment in spouses of people with cognitive impairment, which may be associated with shared environmental factors and psychosocial burden as a caregiver. Early diagnosis and intervention for spouses of people with cognitive impairment may be necessary for both patients and spouses. In the future, further investigations in a larger cohort is warranted to confirm findings from this study.