bluuebunny/crossref_metadata_2025_split huggingface dataset:
ADSP Phenotype Harmonization Consortium
Authors: Hohman Timothy J. 
Published: December 2023

AbstractBackgroundThe Alzheimer’s Disease Sequencing Project Phenotype Harmonization Consortium (ADSP‐PHC) was assembled in 2021 to provide large‐scale harmonization of 40+ deeply phenotyped cohorts included in the ADSP. Harmonization spans from markers of amyloid, tau, neurodegeneration, concomitant pathways of injury, and cognitive decline. This presentation will provide an overview of the methods and results of our first data release (October 2022) and provide a preview for upcoming data release in the coming years.MethodA team of domain experts was established to provide statistical harmonization. The outcome of these specialized harmonization procedures includes longitudinal composite measures of executive function, language, and memory performance leveraging latent variable modeling, longitudinal biomarker measurement of Aβ42, total tau, and phosphorylated tau leveraging a distribution based harmonization, longitudinal amyloid positron emission tomography (PET) harmonization accounting for different ligands and scanner protocols across sites, longitudinal magnetic resonance imaging (MRI) harmonization including diffusion imaging leveraging image‐based harmonization and statistical harmonization with COMBAT, and both vascular risk factor and neuropathology harmonization leveraging a detailed variable mapping approach. All data, scripts, and documentation are made freely available to qualified investigators on dss.niagads.org.ResultThe first data release (October of 2022) and is described in detail here: https://dss.niagads.org/datasets/ng00067/#phenotype-harmonization. This release included longitudinal cognitive data from >50k individuals covering more than 100k longitudinal data points, with more than 15k individuals also having full sequencing data. Moreover, the release included >6k individuals with harmonized neuropathology and genetic data, and >3k individuals with harmonized fluid biomarker and genetic data. Full data dictionaries and data availability are publicly available here: https://vmacdata.org/adsp-phc. In our next release coming late summer 2023 we will extend the available data in all three of these domains while also including longitudinal neuroimaging (released jointly by NIAGADS and LONI) and vascular risk factor data from 17 cohorts in the ADSP.ConclusionThe deeply phenotyped cohort studies within the ADSP provide an unprecedented opportunity to explore the genetic architecture of amyloid, tau, neurodegeneration, and cognitive decline. The ADSP‐PHC will deliver an unparalleled resource of harmonized data across domains to facilitate novel genomic discovery and provide AI‐ready resources to better understand drivers of disease heterogeneity.
Association between lifestyle at different life periods and brain integrity in older adults
Authors: Turpin Anne‐Laure , Felisatti Francesca , Ourry Valentin , Mézenge Florence , Landeau Brigitte , Vivien Denis , la Sayette Vincent De , Chetelat Gael , Gonneaud Julie ,   Medit‐Ageing Research Group
Published: December 2023

AbstractBackgroundIncreasing evidence suggests that lifestyle factors are related to cerebral markers of aging and Alzheimer’s disease (AD) in older individuals. However, most studies addressed the association between current lifestyle and neuroimaging, providing little information on the relative effect of lifestyle at different life periods on older adults’ brain integrity. We proposed to determine the life period(s) at which lifestyle factors have the greatest influence on older adults’ brain health.MethodWe included baseline data of 135 cognitively unimpaired older adults (aged>65) from the Age‐Well study (NCT02977819). They underwent multimodal neuroimaging providing measures of Gray Matter volume (GMv), glucose metabolism, perfusion (early‐Florbetapir‐PET) and beta‐amyloid burden. The Lifestyle Experiences Questionnaires (LEQ) was used to assess complex mental activities during early‐ (13‐30y), mid‐ (30‐65y) and late‐life (>65y). To evidence the effect of activities at each life period controlling for the others, multiple regressions were conducted including the three LEQ sub‐scores to predict each neuroimaging modality, both 1) focusing on AD‐signature regions and 2) voxel‐wise. In the presence of significant associations, complementary analyses were realized to directly compare the effect of life periods between them. All analyses were controlled for age and sex.ResultsLEQ scores were not associated with AD‐signature regions. Voxel‐wise analyses revealed that higher LEQ score at midlife were positively associated with GMv, including the anterior cingulate cortex (Fig.1a), and negatively associated with amyloid burden, notably in the precuneus (Fig.1b). When compared with the other periods, these associations were statistically stronger for midlife. On the other hand, late‐life activities were positively associated with perfusion (Fig.2a) and glucose metabolism (Fig.2b), mainly in medial frontal regions, and these associations were stronger for late‐life than for any other life period.ConclusionOur study suggests that complex mental activities at midlife are more strongly associated with structural and molecular markers of brain integrity in older adults, while late‐life (i.e. current) activities are more strongly correlated with brain function. Interestingly, these associations were not found on AD‐signature regions but in brain regions relevant to reserve and aging. Lifestyle at different life periods might have an influence on distinct markers of brain health in late‐life.
Neuro‐immune markers, socioeconomic inequalities, and neurodegenerative disorders in older age
Authors: Gireesh Aswathikutty , Sacker Amanda , McMunn Anne , Cadar Dorina 
Published: December 2023

AbstractBackgroundAccumulating evidence suggests that the neuro‐immune markers of inflammation may be involved in the onset of neurodegenerative disorders (Bostancıklıoğlu, 2019; Park et al., 2020). However, immune mechanisms linking socioeconomic adversities in later life and neurodegenerative disorders have yet to be fully explored. This study has used a large longitudinal study to investigate the mediating effects of neuro‐immune markers in the socioeconomic disparities of neurocognitive disorders in older adults.MethodData of 4815 participants aged 50 and above from the English Longitudinal Study of Ageing (ELSA) across three waves of data collection. Socioeconomic position was assessed in 2008/9 and neuro‐immune markers in 2012/2013. Neurocognitive disorders were ascertained using cognitive variables available in 2018/2019 using a well‐accepted consensus criterion (Richardson et al., 2019). It was categorised into no cognitive impairment, cognitive impairment, no dementia (CIND) and dementia. Mediation analysis was carried out to investigate the mediation effect of c‐reactive protein (CRP), fibrinogen and white blood cell (WBC) count in the association between socioeconomic position and different subtypes of neurocognitive disorders. All models were adjusted for age, sex, marital status and baseline cognitive status.ResultAfter accounting for potential confounders, CRP, fibrinogen, and WBC partly mediated the association of education, occupation, and wealth with cognitive impairment. Results on dementia were all non‐significant.ConclusionAdverse socioeconomic environment were related to early stages of neurocognitive disorders partly via elevated biomarker levels in later life. Neuroinflammation might be one of the immunobiological mechanisms underlying socioeconomic disparities in cognitive impairment. Further research should explore other plausible biological mechanisms to develop interventions to delay the onset of neurodegeneration.
Predictive value of BMI in Cognitive Outcome in Mild Cognitive Impairment
Authors: Jeong Jee Hyang , Lee Eun Hye , Kim Geon Ha , Choi Seong Hye 
Published: December 2023

AbstractBackgroundThis study aimed to determine the association between neuropsychological performance and body mass index (BMI) in patients with mild cognitive impairment (MCI). In addition, this study investigated the effects of the APOE genotype and sex in the relationship between the BMI and cognition in MCI.MethodsA total of 3,038 subjects with MCI aged 65‐90 were enrolled from the Clinical Research Center for Dementia of South Korea (CREDOS) cohort and a dementia cohort of the Ewha Womans University Mokdong Hospital (EUMC). MCI patients were classified into three subgroups (normal‐weight, overweight and obesity) according to the Asian standard of BMI. Cognitive performances between groups were compared by one way analysis of variance. To investigate the effects of the age, education, APOE genotype and sex, multivariate linear regression models after adjusting for possible confounders were used.ResultsEven‐though normal BMI groups were younger, had more males and less comorbidities, higher BMI groups (Overweigh and Obese) were associated with better performance in cognitive functions, scores of all neurocognitive tests were significantly increased (RCFT copy, p = 0.047; animal fluency, p = 0.039; phonemic fluency, p = 0.013; SVLT delay recall, p = 0.005; RCFT delay recall, K‐MMSE, p = 0.001; K‐BNT and Stroop test, p<0.001), and CDR‐SB (p = 0.001) was decreased. The APOE ε4 carriers showed positive relationship between the BMI and the memory tasks: SVLT delay recall (p = 0.017) and RCFT delay recall (p = 0.002). And comparing between APOE ε4 carrier gender groups, significant positive relationship was shown only with visual memory task as BMI increases.ConclusionsOur findings suggested that higher BMI in patients with MCI were associated with better cognitive performance. The effects of the APOE genotype and sex in the associations between BMI and cognition were distinguishing. Therefore, according to physical status, APOE ε4 genotype, and sex‐specific strategies in the assessments and treatments may be necessary in elderly patients with MCI.
Identifying Cognitive Resilience Related Genes Among Genetic Risk Loci of Alzheimer’s Disease
Authors: Carrigan Maria , Van der Lee Sven J , van Loenhoud Anna C. , Bocancea Diana I. , Groot Colin , Barkhof Frederik , Krugers Harm J. , Lucassen Paul J. , van der Flier Wiesje M. , Ossenkoppele Rik 
Published: December 2023

AbstractBackgroundCognitive resilience (CR) in the context of Alzheimer’s disease (AD) describes the ability to maintain cognitive function despite the presence of neuropathology (Hohman et al., 2016). While most studies have focused on investigating genetic risk factors for developing AD, we here examined the association of most robust risk loci (Bellenguez et al., 2021) with CR using a neuroimaging‐based approach that incorporates measures of brain atrophy and cognition into a quantitative CR metric (van Loenhoud, 2017).MethodWe performed magnetic resonance imaging (3T) and DNA testing on n = 440 amyloid‐positive individuals in different clinical stages of AD. Employing a global cognitive composite score, we predicted gray matter volume (GM) in each voxel, adjusted for sex, age, premorbid intracranial volume, disease stage, and scanner type. To operationalize CR, W‐scores were computed for each individual based on the standardized individual difference between predicted and observed GM within temporoparietal (TP) and whole brain (WB) masks. In this approach, positive W‐scores reflect low CR, while negative W‐scores reflect high CR. A total of 83 genetic risk variants for AD (Bellenguez et al., 2021) were each tested for their association with W‐scores in a linear regression model corrected for population substructure (PC1‐5).ResultWe found an association for 6 genetic loci, of which variants rs113706587 in gene RASGEF1c and rs6943429 in gene UMAD1 were associated with higher CR (TP: p<0.01, p<0.02; WB: p<0.02, p<0.01). As expected, APOEe4 was associated with low CR (TP: p<0.01, WB: p<0.01), as were genetic markers of genes CLU, MINDY2 (WB: p<0.04, p<0.04), and BCKDK (WB: p<0.05, TP: p<0.04). Importantly, no association was found between APOEe2 and CR (WB: p = 0.195, TP: p = 0.139).ConclusionAmong genetic risk‐loci for AD, we identified two genetic variants associated with cognitive resilience in amyloid‐positive individuals. Interestingly, APOEe4 associated with low CR, as did genes CLU, MINDY2, and BCKDK, indicating anti‐resilience – possibly through accelerating mechanisms. In addition, our results suggest that CR against AD is independent of the protective relationship found between APOEe2 and developing AD, highlighting the relevance of investigating the mechanisms behind CR.
Realizing the Representative Reach: How Digital is Enabling Engagement of Hispanic Participants from a Semi Rural County in the United States
Authors: Cantú Jessica A. , Falcon James A , Gonzalez Daniella , Garcia Laura , Falcon Cindy , Griffith Dora Y , Devine Sherral A. , Ume Chisom , Ames Hailey Grace , Jain Shubhi , Sunderaraman Preeti , Brown Christina M. , Low Spencer , Au Rhoda 
Published: December 2023

AbstractBackgroundEarly detection of brain‐related disorders is key to prevention of Alzheimer’s disease (AD), and research on Hispanic populations is severely lacking. Obstacles to recruitment include the lack of trust in research and researchers and requirements for English proficiency, which excludes many potential Hispanic participants.MethodsResearchers from El Faro Health and Therapeutics in Starr County, Texas and the Framingham Heart Study are teaming up on a digital phenotyping study and incorporating “trust” as a central theme for recruitment/retention of Hispanic participants. Study materials are in both English and Spanish. The smartphone tasks are presented in two formats: “in‐clinic” using an iPad and “remote” utilizing participants’ smartphones. Activities include voice tasks, gait and balance, and game‐like cognitive tasks. Longitudinal data will be collected every three months for one year.ParticipantsRecruitment is for anyone aged 18+ in Starr County, which is approximately 98% Hispanic. To maximize inclusivity, there are no other inclusion/exclusion criteria. Study procedures are customized to accommodate individuals. Recruitment goal is 500 participants within one year, with planned expansion to 5,000+ over 5 years.ResultsRecruitment approach includes several components: (1) El Faro investigators have been providing clinical services to community members for decades, and are respected and trusted members of the community. (2) All participant‐facing study materials are available in both English and Spanish, with most translated into the specific local dialect. (3) Community fliers include text in both English and Spanish. (4) Social media outreach has sparked a great deal of interest for participating in research, and the team attends community events to further spread the word. (5) Multi‐generational families are encouraged given family decision‐making culture; (6) Word‐of‐mouth within the Starr County community is expected to be an important contributor to recruitment.ConclusionsAlthough data collection will begin in February 2023, already more than 150 participants have expressed interest in being involved. Leveraging resources to enable highly respected and trusted local researchers to conduct the research, and using participant‐centric design approaches will result in greater success in recruitment and retention of this underrepresented population.
Carers' perspective on adapting the iSupport in New Zealand
Authors: Sani Tara P , Cheung Gary , Peri Kathy , Yates Susan , Whaanga Hēmi , Cullum Sarah J 
Published: December 2023

AbstractBackgroundThe World Health Organisation (WHO) has developed ‘iSupport for Dementia’, a self‐paced training for family carers of people with dementia. Empowering Dementia Carers in an iSupport Virtual Assistant (e‐DIVA) project aims to develop a website based on iSupport to support carers in Aotearoa New Zealand (NZ), Australia, Indonesia, and Vietnam. We aim to understand carers’ perspectives on iSupport to inform the NZ adaptation.MethodWe recruited primary unpaid carers through a local non‐government dementia support organisation. We included carers who were aged 18 years old or over, caring for a person living with dementia for at least six months, able to speak English and use internet for video conference. Participants were provided with the original iSupport manual to review for a month. We conducted online focus group discussions with the carers (3‐4 per group) who provided feedback on the original manual. Each group met twice for two hours. The meetings were recorded, transcribed verbatim, and analysed thematically. We then used the results of the thematic analysis to inform the development of the iSupport‐VA NZ website and supporting materials such as videos.ResultSeven carers participated in this study. We identified common feedback which could be grouped into content, delivery, and potential use beyond immediate family carers. Based on the feedback, we split Module 1 into four sections, adding contents on optimising brain health, person‐centred care, and planning for the future. We also rearranged Modules 4 and 5 to start with information that all carers need then moving on to information more relevant to mid‐to‐late stage dementia. We also made changes in the illustration and language used. We amended the school‐like features (right‐or‐wrong approach), but kept the reflective activities. Carers also discussed the possibility of using iSupport as resources for extended family not involved in care and for care professionals.ConclusionSeveral changes were required to adapt iSupport for use in NZ. This tool has some potentials for wider use beyond unpaid family carers. A separate research with Māori carers using a similar method started in 2023.
Establishing National Social Exposome Alzheimer’s Disease and Related Dementias (ADRD) Infrastructure
Authors: Kind Amy J. 
Published: December 2023

AbstractThe exposome, comprising the variety of life‐course exposures and influenced by structural inequities such as systematic racism, is theorized to interact with biological, behavioral, sociocultural, and economic mechanisms as a modifiable factor influencing Alzheimer’s Disease and Related Dementias (ADRD) risk and resilience. The disparities‐aligned exposome is optimally linked to biologic health outcomes using participant residential history– denoted by US privacy law as ‘protected health information’ or PHI and subject to stringent regulation. The complicated legal, administrative, and technical research infrastructure challenges with multi‐site PHI‐data have formed substantial barriers to ADRD‐aligned exposome study, leading to a present state in which most national biologic repositories and resources curate only non‐PHI data thus prohibiting direct disparities‐aligned exposome metric linkage. Due to data security concerns including the substantial cybersecurity risk an institution assumes in storage of PHI‐data from outside the home institution, there are few existing resources to link geo‐specific exposures to ADRD outcomes on a national scale. This project will remove barriers in exposome science by addressing the infrastructure expansion needed to connect key NIA national data and biorepository resources to PHI‐requiring exposome metrics while shielding these NIA research infrastructures from the burden of PHI management. Our goal is to build infrastructure across the 22 ADRCs in the Neighborhoods Study (R01AG070883), including developing data intake and linkage processes for new exposome metrics. The project is directly responsive to the Congressional language that led to the allocation of these funds; specifically, to support infrastructure that enables the linkage of life‐course exposure factors to biological outcomes, characterized through a mechanistic health disparities lens. In this presentation we will outline the specific plans to enhance, refine and establish enduring, ethical and community‐aligned administrative and legal agreement, process and coordination infrastructure for on‐going PHI and exposome data flow intake and non‐PHI exposome data outflow; and to enact data acquisition, intake, linkage and management processes for additional ADRD disparities‐aligned exposome metrics (e.g., pollution).
The speech‐to‐song illusion in frontotemporal dementia and Alzheimer’s disease
Authors: Jiang Jessica , Requena‐Komuro Mai‐Carmen , Benhamou Elia , Johnson Jeremy , Sivasathiaseelan Harri , Chokesuwattanaskul Anthipa , Hardy Chris JD , Warren Jason D 
Published: December 2023

AbstractBackgroundPerceptual plasticity depends on dynamic, coordinated synaptic tuning across neural circuits and is therefore likely to be vulnerable to neurodegenerative pathologies. However, the nature and limits of perceptual plasticity in dementia are largely unknown. Here we addressed this issue using a dramatic instance of auditory perceptual plasticity ‐ the speech‐to‐song illusion discovered by Diana Deutsch (2011), whereby a spoken phrase is perceived as sung after a few repetitions.MethodWe studied patients representing all major syndromes of frontotemporal dementia (FTD) (N = 22) and Alzheimer’s disease (AD) (N = 25) versus healthy age‐matched controls (N = 21). We asked each participant whether they experienced the Deutsch illusion, and separately assessed their ability to discriminate spoken and sung phrases. In patients who reported experiencing the illusion, we verified this using a forced‐choice procedure.ResultThe Deutsch illusion was reported by 76% of healthy controls, and by 44.4% with progressive non‐fluent aphasia (PNFA), 42.9% of patients with semantic dementia (SD), 20% with typical AD, 20% with logopenic aphasia (LPA), and none with behavioural variant FTD (bvFTD). Mean scores for speech/song discrimination were as follows: healthy controls, 99%; SD, 97.6%; AD, 95%; LPA, 94.7%; PNFA, 94%; bvFTD, 87%. bvFTD performed significantly lower than healthy controls at discrimination.ConclusionPerception of the speech‐to‐song illusion is reduced in canonical FTD and AD syndromes compared with healthy older people and stratifies dementia syndromes disproportionately to any underlying perceptual deficit. The illusion presents an interesting new model for assessing perceptual plasticity in these diseases.