bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age of amyloid onset, but not amyloid accumulation rate, differs across APOE‐e4 carriers vs. non‐carriers in three cohorts and three methods
Authors: Betthauser Tobey J. , Bilgel Murat , Koscik Rebecca L. , Jedynak Bruno Michel , An Yang , Jonaitis Erin M , Christian Bradley T. , Engelman Corinne D. , Asthana Sanjay , Wong Dean F. , Albert Marilyn S. , Resnick Susan M. , Johnson Sterling C. 
Published: February 2022

AbstractBackgroundNew methods have recently been developed to model longitudinal amyloid biomarkers in AD. This work compares three methods in three different cohorts, and investigates associations of APOE‐e4 status with amyloid onset age and amyloid accumulation rates.MethodParticipants from ADNI (N=1213), BLSA (N=205) and WRAP (N=272) with available amyloid PET imaging and APOE genotype were included in the study (Table 1). Amyloid (A) burden was quantified using established methods (ADNI: BAI processed SUVR, WM reference region; BLSA: SRTM‐LRSC DVR, PVC, cerebellum GM reference region; WRAP: graphical analysis DVR, cerebellum GM reference region). Group‐based trajectory modeling (GBTM), ordinary differential equation‐Gaussian process (ODE‐GP) and sampled iterative local linear approximation (SILLA) methods were used to model longitudinal amyloid accumulation, estimate A+ onset age, and align amyloid values by years A+ for each cohort. Forward and backward SUVR/DVR prediction, estimated age of A+ onset, and associations of DVR/SUVR residuals with age, time from reference scan, and SUVR/DVR, were compared for each model and cohort. The impact of APOE genotype on A+ onset and amyloid PET accumulation trajectories was investigated using discrete rate sample, Kaplan‐Meier curves, and accelerated failure time models.ResultAll methods produced similar amyloid vs. years A+ curves for each cohort (Figure 1) with most notable discrepancies occurring in the A‐ range. DVR/SUVR prediction performance was similar across methods and was better for retrospective vs. prospective prediction. Amyloid accumulation rates and trajectories were similar for APOE‐e4+ and APOE‐e4‐ genotypes (Figure 2). Kaplan‐Meier curves were different between the APOE groups (log‐rank test, p<0.005 for each test; Figure 3), with the e4+ group exhibiting earlier A+ onset ages compared to e4‐ (Table 2) for all methods and cohorts.ConclusionThis work demonstrates similar performance of three novel methods for modeling longitudinal amyloid PET burden and estimating individualized A+ onset age. Results suggest that APOE‐e4 status affects the A+ onset age, but not the rate of amyloid PET accumulation. Ongoing work is investigating potential differences in amyloid accumulation trajectories and A+ onset age between APOE genotypes (e.g. e3e3, e3e4, e4e4,...) and is investigating relationships between A+ onset, APOE genotype and onset of cognitive impairment.
Alterations in white matter integrity in cognitively stable Down syndrome correlate with plasma neurofilament light chain: Evidence of early myelin breakdown
Authors: Rosas H. Diana , Hasimoglu Yasemin , Mercaldo Nathaniel , Lai Florence , Petersen Melissa , Brickman Adam M. , Keator David , Yassa Michael A. , Lott Ira T , Silverman Wayne , Schupf Nicole , O'Bryant Sid 
Published: February 2022

AbstractBackgroundAlterations in white matter (WM) integrity occur in adults with DS during the early stage of dementia. These changes may be documented by diffusion tensor imaging wherein increases in radial diffusivity (RD), a marker of dysmyelination or myelin breakdown, occur in commissural and limbic pathways in DS. Neurofilament light chain (NfL) is a support protein within large, myelinated axons specifically within the cerebral white matter and is released into blood following axonal damage and is increased in DS. In this study, we evaluated the association between plasma NfL concentrations and RD.MethodThirty cognitively stable adults with DS from the Alzheimer Disease in Down Syndrome (part of the ABC‐DS) study, (18 M, 12 F: mean age 47.1 years SD 5.2 years), underwent DTI and plasma NfL concentration measurements. Plasma NfL was assayed using the Simoa platform. Diffusion MRI connectometry was conducted using q‐space diffeomorphic reconstruction and a multiple regression model to assess the associations between plasma NfL and white matter radial diffusivity (RD). The Spearman correlation coefficient, and its 95% confidence interval (CI), was used to quantify the monotonic association between plasma NfL and RD.ResultConsistent with our hypothesis, we found positive associations between plasma NfL and RD increases, in several WM higher order association tracts, including the corpus callosum (0.46, 95% CI 0.11‐0.70, p=0.012), the cingulum bundle (L: 0.62, 0.34‐0.80, p<0.001; R: 0.54 0.23‐0.76, p=0.002) and the uncinate fasciculus (L: 0.17, ‐0.20‐0.50, p=0.367; R: 0.51, 0.18‐0.73, p=0.004).ConclusionOur findings support an important link between alterations in WM myelin integrity, particularly of higher order association areas, and axonal degeneration in cognitively stable adults with Down syndrome. These findings support an important role of WM alterations in adults with DS who are at risk for and who develop AD earlier than in sporadic AD cases. WM might provide an important and novel target for intervention. Additional research is needed to understand the underlying neuropathological processes, including the potential contribution of neuronal dysfunction and/or loss to our findings. Acknowledgements: NIH grant U01AG051412. We are grateful to our participants, families, the agencies serving individuals with ID, and our dedicated staff.
Evaluating the properties of intrinsic functional brain networks vulnerable to Alzheimer’s disease during development through connectomics analysis: Preliminary findings from the PRANK study
Authors: Phipps Connor J. , Sexton Jennifer N. , Behm Lillian , DeCesare Thomas A. , Heller Abi M. , Maerlender Arthur C. , Phatak Vaishali S. , Cramer Justin A. , Blair James , Murman Daniel L. , Warren David E. 
Published: February 2022

AbstractBackgroundThe organization of the brain’s intrinsic functional networks changes during healthy lifespan development, but pathologies such as Alzheimer’s disease (AD) alter the normative trends in functional network organization. Similarly, cognitive abilities such as memory change across the lifespan, but AD pathology causes memory deficits relative to normative expectations. While AD‐related changes in memory and brain networks are often observed in older adults, it is possible that vulnerability to AD is established through differences in early‐life brain and cognitive development including the periadolescent epoch. Here, we used a cross‐sectional approach to study the organization of AD‐vulnerable brain networks and memory in healthy periadolescent children. Data were drawn from the Polygenic Risk of Alzheimer’s Disease in Nebraska Kids (PRANK) study. The goal of our research is to evaluate whether early‐life functional brain development may create vulnerabilities to late‐onset AD.MethodTo better understand the relationship between network properties of the brain and hippocampal‐dependent memory, we studied cognitive and brain measures in a preliminary sample of periadolescent children (N=40) and healthy young adults (N=10) from the PRANK study. Cognitive assessment included a standardized paired associates learning task (CANTAB), a task that requires hippocampal‐dependent relational memory. Brain structure and function were assessed with MRI protocols adapted from the Human Connectome Project. Resting‐state fMRI data was used to measure resting state functional connectivity which supported our investigation of brain network properties. Analysis focused primarily on the measurement of whole‐brain network properties.ResultWe observed differences in brain variables between the PRANK participants and the dataset of healthy young adults. Between‐group differences were observed in modularity scores and other graph theoretical measures of network organization. We also observed relationship between the functional network properties of periadolescent children and their cognitive performance on the CANTAB task.ConclusionOur ongoing study measures the association of brain variables, cognitive performance, and AD polygenic risk score in periadolescent children. Our preliminary analysis of brain and cognitive measures illustrate functional network properties of the periadolescent brain with a focus on associations with cognitive performance. Future directions include examining the association between AD polygenic risk score and the same network properties.
Stroke and cardiovascular disease risk exacerbate brain aging among middle‐age and older Hispanics/Latinos: Preliminary findings from the Study of Latinos‐Investigation of Neurocognitive Aging‐MRI (SOL‐INCA‐MRI)
Authors: Stickel Ariana M. , Tarraf Wassim , Gonzalez Kevin A. , Paredes Alejandra Morlett , Zeng Donglin , Cai Jianwen , Isasi Carmen R. , Kaplan Robert , Lipton Richard B. , Daviglus Martha L. , Testai Fenando D. , Lamar Melissa , Gallo Linda C. , Talavera Gregory A. , Gellman Marc D. , Ramos Alberto R. , Gonzalez Hector M. , DeCarli Charles S. 
Published: February 2022

AbstractBackgroundHispanics/Latinos have high prevalence of cardiovascular disease (CVD) risk factors which increases risk for stroke. However, the downstream impacts of CVD risk and stroke on brain structure in aging Hispanics/Latinos remains largely unknown. We compared Hispanic/Latino brain aging by CVD risk and stroke.MethodHispanics/Latinos (nunweighted=1,156, 50‐85 years) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) underwent magnetic resonance imaging (MRI) as part of the Study of Latinos ‐ Investigation of Neurocognitive Aging‐MRI (SOL‐INCA‐MRI) ancillary study. Outcomes included global (gray matter, total brain) and regional (lobar cortices, hippocampal) brain, lateral ventricle (log‐transformed), and total white matter hyperintensity (WMH; log‐transformed) volumes residualized for total cranial volume. Ten‐year CVD risk at visit 2 (before MRI) was determined by Framingham Risk Score and recoded into three groups (Low (<10%), Medium (10‐<20%) and High (20+%)). Stroke (yes, no) was based on self‐report of ≥1 strokes or transient ischemic attacks at visit 1 and/or 2. Linear regression models tested 1) whether CVD risk or presence of stroke modified the relationship between age and MRI outcomes, and 2) whether CVD risk or stroke related brain aging differed by sex. All models adjusted for height and Hispanic/Latino background.ResultSample was 64.3± 7.1 years old on average (nunweighted=798 women). High CVD risk was inversely associated with total brain (standardized beta β=–0.26; p<0.001), total gray (β=‐0.23; p=0.006), frontal (β = ‐0.33; p<0.001) and parietal cortical gray (β =‐0.28; p=0.002) matter volumes and positively associated with (log) lateral ventricle (β log=0.23; p=0.006) and (log) WMH (βlog =0.42; p<0.001) volumes. Stroke/TIA (nunweighted=48) showed a similar profile of associations but only the associations with (log) lateral ventricle (βlog=0.27; p=0.049) and (log) WMH (βlog=0.44; p=0.001) reached significance. Accelerated brain aging (age slope modification) through CVD risk and stroke was evident for total brain volume but less so for other MRI outcomes, and equivalently so across sexes.ConclusionAmong Hispanics/Latinos, CVD risk and stroke are associated with poorer brain health across brain MRI indicators. Additionally, CVD risk and stroke may accelerate overall brain aging for both Hispanic/Latino men and women as determined by total brain volumes.
Characterizing machine learning studies on ADRD caregivers’ social media posts: A systematic review
Authors: Zou Ning , Wang Zhendong , luo Zhimeng , Xie Bo , He Daqing , Hilsabeck Robin C , Aguirre Alyssa B 
Published: February 2022

AbstractBackgroundSocial media have increasingly been used by ADRD caregivers to share and seek information. An emerging trend in the literature is using machine learning (ML) methods to understand caregivers’ information behaviors on social media. To date no systematic review exists on what ML methods have been used, what the findings are, and what needs to be improved in order to better understand ADRD caregivers’ information behaviors on social media. This systematic review addresses these gaps in the literature.MethodFollowing the PRISMA guidelines, during October and November 2020, we performed three rounds of screening. First, we searched predetermined keywords in ACM Digital Library, IEEE Xplore Digital Library, and PubMed. This step generated 324 results. After removing 92 articles that were not peer‐reviewed journal/conference proceedings and 2 duplicate articles, 230 results remained. Next, we screened the titles and abstracts of the 230 articles using predetermined inclusion/exclusion criteria; 200 articles were excluded, and 30 remained. Finally, we screened the full text of the 30 articles to ensure that they met the inclusion/exclusion criteria; 12 articles were excluded, leaving a final sample of 18 studies for analysis.ResultAll 18 studies covered at least two of the three focal areas: ADRD, ML, and social media; only 6 covered all three areas. Study aims of these 18 studies were in two groups: 1) 4 papers focused on characterizing ADRD caregivers’ behaviors on social media; and 2) 14 papers aimed to build ML models to predict ADRD related activities. Twitter was the data source for 14 studies; other sources included Reddit, Youtube, Weibo, and AskaPatient. The key features for modeling ADRD related activities included semantic representations of post content, positive/negative sentiments, and network structures representing posting/answering activities.ConclusionML provides promising tools for extracting useful information from large amounts of social media posts about ADRD caregivers’ information behaviors. Research in this area is still at its infancy, and much more attention is needed to understand how ML methods can be best utilized. Due to the interdisciplinary nature of the task, effective collaborations leveraging expertise from health sciences, information science and social sciences will be critical.
Structural covariance in the affective pain network in Alzheimer’s disease
Authors: Iversen Wm. Larkin , Monroe Todd B. , Failla Michelle D. 
Published: February 2022

AbstractBackgroundPain consists of both sensory and affective networks. Literature exploring the effect of Alzheimer’s disease (AD) on pain is limited. Some evidence suggests that the affective networks are impacted earlier while the sensory networks are preserved until late in the course of disease (Cole 2006). To examine the preservation of networks underlying pain perception in AD, we examined the structural covariance of regions in the pain network. Using structural MRI (sMRI) data, we investigated structural covariance by modeling a network from the correlation of volume between regions. In structural covariance, path length represents the minimum number of steps that must be taken to travel between two nodes and may serve as a proxy for structural brain integrity. Characteristic path length averages together the path lengths for all nodes in a given a priori network to create a global network metric (Paldino 2017). We hypothesized that there would be alterations in altered characteristic and nodal path length in individuals with AD.MethodAs part of a larger study, cortical volume measurements were obtained for 78 participants (39 AD, 39 HC) via Ma‐CRUISE mutli‐atlas segmentation (Huo 2016). The affective pain network consisted of bilateral: anterior and posterior insula, amygdala, anterior cingulate cortex (ACC), and dorsolateral pre‐frontal cortex (dlPFC, specifically the superior frontal and medial frontal gyri, Woo 2017). The analysis was conducted in BRAPH using a undirected weighted graph with negative correlations set to zero. (Mijalkov 2017). Only characteristic and nodal path length were included in this analysis as these metrics are more robust for discriminating differences in AD (Mårtensson 2018).ResultNo significant differences were found for characteristic path length between groups (p = > 0.05). Additionally, no significant differences were found in path length for any of the nodes analyzed following correction with the Benjamini‐Hochberg procedure (Q = 0.05).ConclusionPreservation of characteristic and nodal path length metrics in the affective pain network provides preliminary evidence that this network may be preserved in mild to moderate AD. This clinically meaningful finding provides further evidence indicate that affective pain may be preserved longer than originally thought during the course of AD.
α‐Synuclein in oligodendroglia and neuron‐derived blood exosomes distinguishes between synucleinopathies
Authors: Dutta Suman , Hornung Simon , Kruayatidee Adira , Maina Katherine M , del Rosario Irish , Paul Kimberly , Palma Jose Alberto , Perlman Susan L. , Poon Wayne W. , Gylys Karen H , Kaufmann Horacio , Fogel Brent L. , Bronstein Jeff M. , Ritz Beate , Bitan Gal 
Published: February 2022

AbstractBackgroundSynucleinopathies are neurodegenerative diseases characterized by aggregation and deposition of α‐synuclein in different brain cells. Diagnosis of these neurological disorders is very challenging due to overlapping complex clinical symptoms. Developing reliable biomarkers that can distinguish among the synucleinopathies is an urgent public health need. Recently, α‐synuclein was shown to transfer via exosomes between different brain cells suggesting that measuring α‐synuclein in specific brain cell‐derived exosomes could serve as a potential biomarker for synucleinopathies.MethodIn this study, we used antibody‐coated magnetic dynabeads to immunochemically enrich specific exosomes released by neurons or oligodendrocytes from serum of healthy individuals and patients with Parkinson’s disease (PD) and Multiple System Atrophy (MSA) and measured biomarker concentration in them by a sensitive electro‐chemiluminescence ELISA. CNS exosomes were isolated from serum/plasma from a discovery cohort and a validation cohort containing 50 patients with MSA, 50 patients with PD and 50 healthy controls in each cohorts.ResultSignificantly higher concentrations of α‐synuclein were observed in both neuronal and oligodendroglial exosomes from patients than in controls. The absolute values of α‐synuclein in neuronal and oligodendroglial exosomes provided moderate separation between the MSA and PD groups, yet the ratio between the two cell types derived exosomal α‐synuclein allowed separating the two disease groups with 90.0% sensitivity and specificity.Conclusionα‐Synuclein in CNS‐derived blood exosomes provides a sensitive biomarker for distinguishing these two synucleinopathies using a blood test and suggest that the method can be expanded further for other neurodegenerative diseases.
Psychological influences of architecture on the demented in the care homes of Kerala, India
Authors: Krishnan Kavya P 
Published: February 2022

AbstractBackgroundOur built environments have a direct relationship with our mental and physical health. The effects of this relationship are only heightened with age, especially when the process of ageing entails psychological, and physical decline of the human body. This is where the art of space making can elevate the quality of life of the fading. This paper discusses how an architect can create an environment that triggers positive neurological changes in its users in the context of Kerala, India through a set of design guidelines for care environments. Dementia, a public health priority, is largely prevalent in the state as it comprises of the fastest ageing population in the country. There are no designed living environments nor existing guidelines/protocols by which a care facility must abide in order to offer specialized care in this field.MethodUnderstanding the current context and background of dementia in the country and in Kerala. This defines the area of research and specifies the objectives to be achieved to formulate the design guidelines. It’s vitally important when designing a facility to understand the residents’ conditions, state of mind and the way they use or interact with the building. This is done through literature reviews which understands and studies dementia, the psychological impacts of home and existing design principles. To understand the theories in practice, five case studies are observed from around the world and compared along with survey responses from neurologists and caretakers.ResultThe analysis of the data manifests the efficacious relationship between designed spaces and standard of living ergo guiding the development of design strategies for dementia care facilities in Kerala. The guidelines are categorized under the following after data collection and research:‐ Spatial Quality: Layout and distribution, Communal Spaces and Communal Activities, Personal Space: (Lighting, Material and Colour), Landscape, Way finding, Security.ConclusionThe guidelines are designed to help architects, or any caretaker, make better, more informed design decisions. Establishing the design guidelines will help improve the quality of life and the living environment of the ageing with dementia.
It takes two: APOE4 and air pollution synergistically affect hippocampal volume in women
Authors: Ukraintseva Svetlana , Popov Vladimir , Arbeev Konstantin , Duan Matt , Yashin Anatoliy 
Published: February 2022

AbstractBackgroundThe APOE e4 allele (APOE4) is the strongest genetic risk factor for Alzheimer's Disease (AD), and exposure to air pollution is emerging as a major environmental AD risk factor. These factors, individually, do not explain most of AD cases though. It is possible that more than one “hit” is required for AD to develop, so different risk factors acting together might synergistically promote AD‐related pathology.MethodIn this study, we explored how different combinations of APOE4 carrier status and exposure to traffic‐generated air pollution may influence right hippocampal volume (RHV) in 10,623 females and 9,682 males aged 60‐75, using the UK Biobank Resource. The higher exposure to traffic pollution was approximated by closeness (50 meters or less) of subject’s primary residence to a major road. The APOE4 status was defined as carrying C allele of rs429358. The RHV was evaluated by the magnetic resonance imaging (MRI). We performed the analysis of variance (ANOVA) and Tukey's honestly significant difference (HSD) test.ResultThe RHV was significantly lower in female APOE4 carriers who live 50 meters or less from a major road (N=199) compared to non‐carriers living farther from the road (N=7195) (P‐Value=0.01). Separately, APOE4 or closeness to the road did not significantly influence RHV in females. No significant effects were found in males.ConclusionTwo hits (APOE4 and high exposure to car exhaust fumes) may be needed to cause brain changes associated with AD pathology, such as reduced RHV. A major component of car exhaust fumes is nitrogen oxides that have been linked to disruption of blood‐brain barrier and increased brain permeability to toxins. The APOE4 was previously associated with reduced myelin damage repair. A potential mechanism might, therefore, involve a synergistic effect of increased brain permeability to damaging factors and decreased brain ability to repair relevant damage. Results of this study also suggest that negative effects of the strongest genetic risk factor for AD (APOE4) on the brain may be attenuated by avoiding damaging exposures, such as to air pollution from car exhaust fumes.