bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma‐based biomarkers of Alzheimer’s Disease in a multi‐ethnic population: A Cross‐Sectional analysis from the WHICAP Study
Authors: Bahl Aanya , Honig Lawrence S. , Kang Min Suk , Sanchez Danurys , Reyes‐Dumeyer Dolly , Lantigua Rafael A. , Dage Jeff L. , Brickman Adam M. , Manly Jennifer J. , Mayeux Richard , Gu Yian 
Published: December 2023

AbstractBackgroundBlood‐based biomarkers have the unique potential to make diagnoses along the Alzheimer’s Disease (AD) continuum. The value of these plasma‐based biomarkers in AD among different race and ethnicity, sex, and genetic status groups needs to be evaluated.MethodThe study included 603 participants of the Washington Heights Inwood Columbia Aging Project, a community‐based cohort study. We measured six AD biomarkers, including phosphorylated Tau‐181 (PTau181), total Tau, Amyloid Beta (Aβ) 40, Aβ42, Glial Fibrillary Acid Protein (GFAP), and Neurofilament Light Chain (NfL). We compared the biomarker levels among 95 individuals clinically diagnosed with AD, 167 individuals with Mild Cognitive Impairment (MCI), and 341 cognitively unimpaired individuals using linear regression models, adjusting for age, sex, race and ethnicity, years of education, APOE ɛ4 status, and sample storage time. We further examined whether the association between biomarkers and clinical diagnosis differed by racial and ethnic groups, sex, and APOE ɛ4 status.ResultThe participants were on average 80.23 (SD = 6.77) years old. Participants self‐identified as non‐Hispanic White (24.03%), non‐Hispanic Black (24.70%), or Hispanic (51.21%), with 414 women (68.66%). AD participants had elevated total tau levels (β = 0.303, p = 0.029), NfL (β = 0.472, p <0.001), and GFAP (β = 0.467, p < 0.001) compared to cognitively unimpaired participants. Individuals with MCI also had higher levels of total tau (β = 0.258, p = 0.016), NfL (β = 0.234, p = 0.035), and GFAP (β = 0.248, p = 0.02) than controls. Stratified analyses showed that men with MCI had higher NfL levels than cognitively unimpaired individuals (β = 0.123, p = 0.008). In women, there were no observable differences in NfL levels between individuals with MCI and controls (β = 0.014, p = 0.669). Among APOE e4 carriers, individuals with MCI had higher levels of NfL than unimpaired controls (β = 0.157, p = 0.006). This was not observed in APOE e4 non‐carriers (β = 0.025, p = 0.397).ConclusionConsistent with the literature, we found plasma AD biomarkers including total tau, NfL, and GFAP were higher in MCI and AD compared with cognitively unimpaired individuals. Among men and APOE e4 carriers, we found higher NfL levels in MCI individuals than in cognitively unimpaired individuals.
Strategies to inform public policies while studying diverse older adults living alone with cognitive impairment in the United States
Authors: Portacolone Elena 
Published: December 2023

AbstractBackgroundBridging research and policy allows research findings to have a lasting impact in the wellbeing of vulnerable population such as the estimated 4.3 million older adults living alone with cognitive impairment in the United States. For example, a lasting impact comes from healthcare and social services provided by Medicare and Medicaid tailored to address unmet needs of these populations identified via rigorous research. Despite the importance of bridging research with policy, researchers seldom collaborate with policy makers, thus missing the opportunity of influencing policies. Reasons for these limited collaborations include limited knowledge on methods for researchers to collaborate with policy makers. This session will draw from the expertise gained by the research team of the 5‐year Living Alone with Cognitive Impairment Project to involve policy experts in the design of their mixed‐method study.MethodAt the very start of the 5‐year project (2020) we convened a Policy Advisory Group and then conducted 17 one‐on‐one interviews and 4 plenary meetings with its 17 members which include diverse policy experts at national and federal level.ResultRegular interactions between the research team and the Policy Advisory Group led to: 1) a mixed‐method design aligned with policy priorities; 2) a report highlighting the priorities of PAG members with regard to policies to enhance the wellbeing of older adults living alone in the US; 3) a series of policy briefs highlighting key findings and related policy recommendations.ConclusionThe oversight, and regular engagement, of a Policy Advisory Group has allowed the Living Alone with Cognitive Impairment Project to focus research activities that are most likely to be translated into policy solutions, thus likely to mostly benefit older adults living alone with cognitive impairment, with emphasis on communities of color. These practices can be easily replicated by researchers in studies supporting underserved populations.
Auditory Gamma Entrainment Leads to Theta Oscillations Asymmetric behavior in both Alzheimer’s Disease and Healthy Participants
Authors: Sedghizadeh Mohammad Javad , Aghajan Hamid , Vahabi Zahra 
Published: December 2023

AbstractBackgroundBrain oscillations known for handling various information across brain. The gamma rhythms observed in high‐level cognitive process (Fries et al., Trends in neurosciences 2018) and theta cycle observed to process sensory information and interact with gamma oscillations (Amemiya et al., Cell Reports 2018). Disruption in synchronization of gamma oscillations have been observed in Alzheimer’s disease patients (Uhlhaas et al., Neuron 2006). Gamma stimulation had been shown to reduce the mentioned dysfunction and reported to have therapeutic results (Martorell et al., Cell 2019; Suk et al. Alzheimer’s and Dementia 2020). This study examines the effect of gamma band activity induced by auditory chirp stimulation as a driver for other frequency sources. The chirp signal is designed to entrain 40Hz which had been shown to have therapeutics effects.Method33 participants were included in this study including 17 mild AD, 6 MCI and 10 healthy elderlies. A session consists of interleaved periods of forty second stimulation and twenty second silence. The stimulation is a 5kHz tone modulated by a 40Hz chirp at 0.1 duty cycle. EEG data were collected by a 10/20 system. Relative magnitude of the 40Hz oscillations with respect to neighbors’ magnitude during the stimulation was measured as an indicator of the entrained gamma oscillations. Total participants are categorized into entrained and not‐entrained group based on the indicator. Phase locking Value (PLV) is then calculated in theta frequency band.Result40Hz entrainment have been observed in healthy participants and also some Alzheimer’s disease patients. Based on the power spectral density (PSD) at forty hertz 23 entrained and 10 not‐entrained participants are separated and PLV analysis have been calculated for the two groups. Theta oscillatory asymmetry have been observed in posterior temporal cortex during auditory stimulation.ConclusionEntraining gamma oscillations using auditory stimulation results in cross frequency variation. Phase‐amplitude or phase‐phase coupling measures the simultaneous correlation between specific oscillations. This study suggests that despite the concurrent association of theta‐gamma frequencies, some brain network changes occur in response to gamma oscillation which should be more discussed in related researches.
Executive functioning in low education contexts: evidence from a controlled clinical trial among illiterate adults
Authors: Friedlaender Clarisse Vasconcelos , de Faria Rocha João Victor , dos Santos Tomaz Kelle Luisa , Ruppert Emma Patrice , Lourandes Aida , de Castro Magalhães Assenção Joanna , Grinberg Lea T. , Rosen Howard J. , Rincon Luciana Paula , Ribeiro Norton Gray Ferreira , Constantina Dulce , Zacarias Ana Paula , Caramelli Paulo , Maciel Francisca Izabel Pereira , Resende Elisa de Paula França 
Published: December 2023

AbstractBackgroundEducation level is a well established modifiable risk factor for dementia prevention. Aiming to improve cognitive reserve and reduce dementia risk in vulnerable populations in Brazil, we created a literacy training program targeting low educated and illiterate adults. In this study, we intend to analyze how executive functioning and cognitive heterogeneity may interfere in the program’s effectiveness.Method130 adults attending classes for adult education were screened and 108 met inclusion criteria. The group was divided into control (regular classes, n = 51) and intervention (regular classes + program targeting literacy training) (n = 57). In addition to answering clinical and education history questions, all the subjects underwent an extensive neuropsychological assessment at baseline and at follow up (after six months of intervention), measuring global cognition, executive functioning (EF), memory and language.Result77 subjects completed all the assessments at the end of the study. Mean age (years) was 59.0 (±9.17), mean education level (years) 2 (±2.18), 79.2% women and 89.6% Blacks. No significant differences were found between control and intervention groups improvement on reading abilities (reading accuracy of isolated words) at follow up. Considering abandonment reasons of formal education in childhood, subjects with childhood history of learning disability (CHLD) had less improvement on reading abilities at follow‐up. The CHLD group also showed poorer performance on a composite score of EF tasks at baseline (F = 3.814, p = 0.021). EF level at baseline correlated with reading abilities at baseline (Spearman’s rho = 0.659, p<0.001) and follow‐up (Spearman’s rho = 0.703, p<0.001).ConclusionBoth control and intervention groups showed improvement on reading abilities, regardless of specific literacy training. EF seems to have an impact on reading skills progress. Subjects with CHLD currently display poorer EF and show very little improvement of reading skills, which might indicate an undiagnosed neurodevelopmental disorder (e.g. ADHD, dyslexia, dyscalculia): an uncared condition still harming cognitive reserve improvement to this day. Thus, there is greater risk of developing dementia. Inclusive learning environments must also be considered for low educated populations.
Spiritual Needs of Older Adults Living with Dementia: An Integrative Literature Review
Authors: Britt Katherine C , Boateng Augustine Cassis , Zhao Hui , Ezeokonkwo Francesca , Federwitz Chad , Epps Fayron 
Published: December 2023

AbstractBackgroundProviders report that persons living with dementia (PLWD) have greater spiritual needs compared to persons without dementia (Hermans et al., 2017), however, spiritual care for spiritual needs is minimally present in dementia care (van der Steen et al., 2014; Durepos et al., 2017). Encompassing connection, spirituality is positively associated with better health, including cognition, quality of life, sleep, behavioral expressions, and well‐being in older adults (Agli et al., 2015; Britt et al., 2022; Britt et al., 2023; Hosseini et al., 2019). Unmet spiritual needs may lead to depression (Puchalski, 2012), anxiety, and greater physical pain (Delgado‐Guay et al., 2016); thus, addressing the spiritual needs of PLWD is essential to support well‐being and inform personalized care.MethodsWe conducted an integrative literature review to identify the spiritual care needs of PLWD by searching five databases (ATLA Religion, CINAHL, PsychInfo, PubMed, and SocIndex) and identified 12 original research studies that focused on spiritual needs of PLWD, published between 2000‐2022 in English.ResultsConducted worldwide, included studies comprised PLWD across all stages (mild, moderate, severe) and contained multiple perspectives (PLWD, family, caregiver, healthcare providers, therapists, faith leaders); most studies were in long‐term care (N = 5) and qualitative in design (N = 9). Sometimes described as religious needs, spiritual needs can be individual or in community. Components of spiritual needs included the importance of maintaining connections in relationships and with religious and spiritual rituals and activities (mealtime grace, bedtime prayers, nature, art, music, communion). Supporting the spiritual needs of PLWD includes connecting them to past sources of meaning and supporting their dignity. Facilitating interaction for PLWD with meaningful sources and connections can promote a sense of peace, provide comfort in the loss of ability, help them retain some control, and support their coping mechanisms.ConclusionsA dimension of holistic care, spiritual care, may facilitate meaningful engagement for PLWD with self and others, supporting their identity and values and leading to a sense of peace. Healthcare providers may utilize complementary, low‐cost holistic care to promote personhood and well‐being among PLWD. Tailored and culturally sensitive spiritual care interventions are needed to support identified spiritual needs among PLWD.
ALLFTD: Identifying and Characterizing Frontotemporal Lobar Degeneration Participants in a Multi‐center North American Study
Authors: Heuer Hilary W. , Forsberg Leah K. , Mester Carly T. , Johnson Noah , Ramos Eliana Marisa , Kantarci Kejal , Kremers Walter K. , Petrucelli Leonard , Rosen Howard J. , Boeve Brad F. , Boxer Adam L. ,   ALLFTD Consortium
Published: December 2023

AbstractBackgroundThe ALLFTD (ARTFL‐LEFFTDS Longitudinal Frontemporal Lobar Degeneration) study is an NIH‐funded effort to prepare for clinical trials in sporadic (s‐FTLD) and familial (f‐FTLD) FTLD syndromes by characterizing cohorts, developing new clinical trial outcome measures, and evaluating disease progression. ALLFTD represents the merger and continuation of two prior studies: Advancing Research and Treatment of Frontotemporal Lobar Degeneration (ARTFL) and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS).MethodsALLFTD recruits participants with FTLD spectrum disorders (bvFTD, svPPA, nfvPPA, FTD‐ALS, CBS or PSP), with strong family histories of FTLD, or known FTLD‐associated genetic variants within the family. 26 sites in North America enroll participants for clinical and neuropsychological evaluations, MR Imaging, blood draws, and CSF collection in willing participants; participants are requested to return annually for follow‐up evaluation. All participants are genotyped for dementia‐associated mutations. Participants also enroll in the FTD Disorders Registry for follow‐up surveys. A subset of participants undergo remote assessment via the ALLFTD app. Visits conducted under ARTFL and LEFFTDS are included in the ALLFTD dataset.ResultsALLFTD has been successful in developing methods to conduct remote or hybrid visits and in actively evaluating participants. Since ALLFTD began in January 2020, 1034 participants (736 new; 298 previously enrolled in ARTFL or LEFFTDS) have been evaluated in the longitudinal arm; an additional 119 participants have been participated in a shortened, biofluid‐focused visit. 349 have returned for follow‐up visits. Including prior participants, the ALLFTD dataset contains 3871 visits from 2343 individuals. 1277 people have sporadic syndromes; 1045 were enrolled as familial. Among s‐FTLD, bvFTD is the most common phenotype (32.8%) followed by PSP (15.9%). 61.4% of f‐FTLD participants were clinically normal at first visit; bvFTD is the most common syndrome in symptomatic f‐FTLD (40%). 477 are confirmed carriers of FTLD‐associated genetic mutations. MRIs were obtained for 2594 visits; 3492 visits have associated blood biospecimens banked; 978 visits have associated CSF samples.ConclusionsThe ALLFTD consortium is actively evaluating participants across North America to better characterize FTLD syndromes and support the planning and development of FTLD clinical trials. Longitudinal datasets including clinical, genetic, and imaging data are available by request.
Translating dementia care to public health: implementation analysis of a community center for people with dementia and family caregivers in Chile
Authors: Gajardo Jean , Aubert Josefina , Moreno Ximena , Aravena Jose M , Navarrete Ignacia , Carcamo Felipe , Abusleme Maria T , Barrientos Carolina , Mascayano Franco 
Published: December 2023

AbstractBackgroundAs part of the National Plan of dementia in Chile, community centers for people with dementia have been developed (1). This program delivers support to the person living dementia and their family, integrating social and clinical aspects through a multicomponent interprofessional intervention, and has been highlighted as an innovative approach to dementia care (2‐4). There is limited knowledge on implementation aspects influencing its functioning as a public health initiative. This work seeks to analyze implementation outcomes of the first community center, called Kintun, in Santiago, Chile, 2013‐2022.MethodA qualitative study was conducted following a realistic approach (multiple data collection strategies and informants to analyze complex interventions). Key informants of program implementation were identified to participate in interviews or focus group, at different levels (macro‐level of centralized policy, meso‐level of intervention deliverers and coordinator, and micro‐level of user family caregivers). Table 1 summarizes informants, multiple data collection strategies, and implementation outcomes addressed. Interviews and focus group were audio‐recorded and transcribed. Deductive thematic analysis was used with predetermined codes describing implementation outcomes according to the Active Implementation Frameworks (Blanchard et al, 2017) and implementation outcomes by Proctor et al (2011).ResultThe Kintun program is on a full implementation stage. At a macro‐level, the program has not experienced significant administrative transformations, where fidelity is tensioned due to lack of updated centralized technical orientations. In contrast, at a meso‐level, program components have been locally modified or adapted. Several implementation drivers are identified, such as engagement with the local service network, tailoring according to context, and more recently, the COVID‐19 pandemic, and new policies (explicit health guarantee). The program is highly pertinent for all levels, however, the inception of new health policies challenges its place in the healthcare network.ConclusionIn the implementation of the first community center for people with dementia in Chile, at a policy macro‐level the program has been continuous and stable. Modifications and adaptations occurred at a meso‐level of implementation, informing of discrepancies in intervention fidelity. Due to the high influence of meso‐level on intervention implementation, it is necessary to explore the implementation processes of other eight centers.
Medial temporal lobe gray matter microstructure alterations provide improved sensitivity to detect neurodegeneration associated with Alzheimer’s disease biomarkers
Authors: Brown Christopher , Das Sandhitsu R. , Xie Long , Nasrallah Ilya M. , Detre John A. , McMillan Corey T , Yushkevich Paul A. , Wolk David A. 
Published: December 2023

AbstractBackgroundDespite the strengths conventional structural imaging measures to detect atrophy, cross‐sectional relationships between neurodegeneration and Alzheimer’s disease (AD) biomarkers in early stages is limited. Neurite orientation dispersion and density imaging (NODDI) measures microstructural alterations that are unique from conventional structural metrics. Alterations in microstructure have been detected in individuals with AD compared to cognitively normal individuals, but there is sparse data regarding the relationship between these metrics and AD biomarkers. Here we sought to characterize how NODDI metrics in the medial temporal lobe (MTL) are associated with plasma AD biomarkers.MethodOne‐hundred and sixty‐seven cognitively normal (CN) individuals, 47 individuals with mild cognitive impairment, and 16 individuals with AD underwent diffusion and T1w imaging. T1w images were segmented using the ASHS‐T1 protocol to form anterior and posterior MTL ROIs. Multi‐shell DTI data were collected in 113 non‐collinear directions with 1.5mm isotropic voxels, were pre‐processed using a custom pipeline, and fit with voxel‐wise NODDI models. ANTs was used to linearly register NODDI and T1w images to allow transformation of MTL ROIs to diffusion space. Stepwise‐regression models examined relationships between anterior and posterior MTL NODDI metrics with plasma biomarkers in CN and impaired (MCI/AD) groups after accounting for MTL volume.ResultNODDI metrics of intracellular volume fraction (icVf) and orientation dispersion index (ODI) were decreased, and isometric volume fraction (isoVf) was increased in cognitively impaired compared to CN. Amyloid positivity was associated with decreased ODI and increased isoVf in cognitively impaired individuals. While posterior MTL volume predicted plasma p‐Tau‐181, inclusion of NODDI metrics subsumed this effect (F‐change>7.54, p<0.0067), and reduced ODI was the best predictor of plasma pTau‐181 within cognitively impaired individuals, while isoVf best predicted pTau‐181 across all individuals. Posterior MTL volume did not predict plasma GFAP, but inclusion of ODI and icVf both significantly predicted plasma GFAP in both CN and impaired individuals (F‐change>12.68, p<.001). Anterior MTL icVf predicted both pTau‐181 and GFAP.ConclusionMicrostructural alterations measured by NODDI appear more closely linked to AD‐related molecular measures and, thus, may provide a more sensitive cross‐sectional measure of neurodegeneration of the MTL compared to conventional macrostructural metrics.