bluuebunny/crossref_metadata_2025_split huggingface dataset:
APOE ε4 as a predictor of tauopathies independent of β‐amyloid
Authors: Thompson Kayla I. , Nunez Christina A. , Golden Charles , Stripling Ashley M. 
Published: February 2022

AbstractBackgroundDue to the failure of clinical trials that target amyloid β and findings that suggest tau’s role in Alzheimer’s Disease (AD) atrophy and cognitive decline, the investigation of tau‐pathology in AD is needed. While studies have investigated the effect of APOE ε4 on tau‐pathology in mouse models, few have examined the relationship in humans, as well as tau’s role on cognitive decline as a mechanism independent of amyloid β deposition. The aim will be to examine the roles of tau in AD, as an independent pathway.MethodUtilizing the National Alzheimer’s Coordinating Center (NACC) database, our sample included those determined with AD, as defined by NACC derived variables. Among participants (n= 5391,Mage= 73, SD=10.5) ε4 carriers accounted for 42%. A separate longitudinal sample (n=108, Mage= 70, SD=9.80) was used to determine cognitive decline as measured by the MoCA.ResultThe ANCOVA showed a significant effect of APOE carrier status on neurofibrillary tangles after controlling for neuritic plaques, F(1,5390) = 5643.617, p<.001, partial η2=.512 and separately, after controlling for Thal amyloid phases, F(1,2632) =4809.032, p<.001, partial η2=.646. The regression model showed covariates including sex, race, ethnicity, age, education, and language did not contribute significantly to the model, F(6,102) =2.051, p<=0.66 and accounted for 10.8% of the variation on MoCA scores. Introducing APOE carrier status explained 16.5% of the variation of MoCA and was significant in change, F(1,101) =6.891, p=.010. While addition of all neuropathies explained 32.9% of the model, F(3,98) =7.979, p<.001, post hoc T‐tests revealed that only neurofibrillary tangles had a significant effect on cognitive decline, demonstrating a negative relationship.ConclusionThese results indicate that the neuropathological effects of APOE ε4 are demonstrated with or without amyloid β deposition, suggesting that apoE may act through tau‐pathways independently. Additionally, while the relationship between APOE ε4 and neuropathology predicts cognitive decline, NFT is the primary driver of cognitive decline in Alzheimer's Disease, while amyloid β deposition has no significant effect.
Best practices in biomarker performance evaluation: Common tool and standards with neuropredict
Authors: Raamana Pradeep Reddy 
Published: February 2022

AbstractBackgroundThe need for standards in neuroimaging research has been clearly recognized recently in a number of research areas [1]. However, the recommendations made so far do not sufficiently address the complexities involved in the full PRedictive ANAlysis Workflow (PRANAW). In this presentation, I would like to highlight the need, and present some guidelines, towards standardizing generic predictive analysis, that is increasingly becoming common in many areas of neuroscience research. A key application to the Alzheimer’s community being the performance evaluation of biomarkers.MethodIncomplete/non‐standard reporting of the PRANAW prevents from engaging in any meaningful comparisons. Moreover, given its complexity, it's easy to make choices for individual steps (such as how one performs cross‐validation) in PRANAW, that may not fit well in the full workflow, or produce less accurate results as a whole (with variations in bias or variance). Lack of standards in PRANAW led to the publication of hundreds of papers without clear insight emerging towards whether there is a reliable biomarker for a particular application, and their relative performances.ResultI will present some ideas to facilitate standardized and easy predictive analysis: 1) A tool (accessible to all skill levels) to perform predictive analysis that implements the best practices, as well as standardized reports. A preliminary attempt in this direction is neuropredict [2]. 2) A cloud repository to receive various standardized reports (either using the tool above, or user's own). 3) A web portal (for visualization and comparison) which lets users and reviewers compare new methods to those in the database.ConclusionI believe the publicly available and openly validated tools/infrastructure is necessary now, and prove to be of great value in the long run. Moreover, this would enable a number of Alzheimer’s researchers without native expertise in machine learning or informatics to apply the best practices in biomarker performance evaluation and report more stable and reproducible results. References: [1] Nichols, Thomas E., et al. "Best practices in data analysis and sharing in neuroimaging using MRI." Nature neuroscience 20.3 (2017): 299‐303. [2] Raamana, Pradeep Reddy, “Easy and standardized predictive analysis with neuropredict”, github.com/raamana
The READyR intervention: Focus group feedback from case managers on the initial development of a remote assessment and dynamic response intervention for dementia‐related care needs
Authors: Miller Lyndsey M , Solomon Diane N , Hiatt Shirin , Wu Chao‐Yi , Harbison Sam , Steele Joel S 
Published: February 2022

AbstractBackgroundPrevious interventions to improve dementia care planning have relied upon self‐reported needs assessments, which are subject to bias and can be inaccurate, especially as dementia progresses, insight diminishes, caregiver burden increases, and needs change more frequently. The Remote Assessment and Dynamic Response (READyR) Program was created to deliver continuous objective in‐home assessments of dementia‐related care needs through a comprehensive sensor platform. The objective of this study was to refine and validate READyR for use by professional care managers of older adults with early‐stage dementia and their spouses/partners.MethodEvaluation of the READyR Program by 11 professional care coordinators and case managers for families with dementia (across three semi‐structured focus group interview sessions) was used to explore the utility of READyR for assessing dementia‐related needs. Conventional content analysis was used to iteratively code focus group data and to describe prevalent themes.ResultPrevalent themes included barriers to (e.g. family relationship strain, chaotic assessments, complex care needs) and facilitators of (e.g. proactive family caregivers, tailored assessments, upholding care values) the optimal process for assessing dementia‐related care needs by professional care managers, as well as advantages (e.g. providing new objective insights into safety, function, and routines) and disadvantages (e.g. bringing up new questions about care) for incorporating the READyR remote monitoring data into a values‐based needs assessment.ConclusionQualitative data supported the utility and validity of the READyR Program. Discussion will focus on the potential of READyR as a dynamically tailored needs assessment to improve preparation for future care, mitigate the stress process of dementia, and improve health and well‐being in the spousal care dyad.
Dementia family caregiving experience among Asian American older adults
Authors: Choi JiWon , Park Van Ta , Vuong Quyen , Cheng Joyce , Mukherjea Arnab , Tsoh Janice Y 
Published: February 2022

AbstractBackgroundAsian Americans are almost twice more likely to assume caregiving roles for their family than the general population. More Asian American dementia caregivers (DCGs) find their role highly stressful than African American or Hispanic DCGs. Research exploring the challenges and coping strategies for Asian American DCGs is limited. This qualitative study, entitled the SHARE (Share History, Activity, Resilience, and Experience) Project, was conducted to explore the challenges and coping strategies among Asian American DCGs.MethodsFocus groups and individual interviews were conducted with 29 Asian Americans in the Bay Area between July‐December 2020. The inclusion criteria were: 1) age ≥ 50 years 2) self‐identified as Chinese, Indian, Korean, or Vietnamese American; and 3) provide ≥ 5 hours of care/week currently or in the past for dementia care recipient. Participants were recruited through local community service agencies, the community advisory board of this study, online networks, and word of mouth. Interviews that were conducted in Cantonese, Korean, and Vietnamese were transcribed and translated in . Ethnically/linguistically matched moderators facilitated eight focus groups (six via zoom video and two via WeChat video; three in English, two in Cantonese, one in Korean, and two in Vietnamese) and two individual interviews via telephone (one in English and one in Vietnamese) using the structured interview guide.ResultsAbout two thirds were current DCGs. Participants reported care recipient’s behavior‐related challenges (e.g., arguing, forgetfulness, wandering) and dementia‐related challenges (e.g., uncertainty, helplessness, duty for 24/7). Across all focus groups, filial piety, love, or responsibility as a family were the main source of enduring. Participants reported exercise, distraction, positive thinking, and having time alone as coping strategies. Having multigenerational families or a care team approach for care recipients appeared to decrease caregiving burden. Not feeling guilty or shame about one’s limitation and using informal/formal support in a timely manner may also help. Some DCGs also expressed a need for social networking with other DCGs for information and emotional support.ConclusionsNeeds for affordable and/or culturally appropriate formal care services were found. Education and training for DCGs given by former DCGs may be useful to disseminate coping strategies.
Quality of life of Alzheimer’s disease patients during the Covid‐19 pandemic January ‐ December 2020 at the National Brain Center Hospital in Jakarta, Indonesia
Authors: Devicaesaria Asnelia 
Published: February 2022

AbstractBackgroundDuring the Covid‐19 pandemic, new habit adaptations applied. This affects the Alzheimer’s Disease patients quality of life who went to our Memory Clinic from January – December 2020.MethodThis study aims to describe the quality of life of Alzheimer's Disease patients based on 13 questions from the QOL‐AD questionnaire filled by the patient's family. A descriptive cross‐sectional study using QOL‐AD questionnaire google form sent by Whatsapp to 42 Alzheimer's disease patients, which was filled by the patient's family. Data collected in the form of gender, age, latest education level, MMSE score and MOCA‐INA score.ResultFrom 42 Alzheimer's Disease patients, 24 patient families (57%) responded to the questionnaire. Obtained 10 male (42%) and 14 female (58%) patients, age range 40‐50 years 1 person (4%), 51‐60 years 4 people (17%), 61‐ 70 years 8 people (33%), 71 ‐ 80 years 8 people (33%) and> 80 years 3 people (13%), education level <6 years 3 people (13%), 6‐9 years 2 people (8 %), 10‐12 years 11 people (46%) and> 12 years 8 people (33%), MMSE scores 0‐16 20 people (83%), 17‐23 4 people (17%) and 24‐30 0 people (0%) and MOCA‐INA scores 0‐17 23 people (96%), 18‐25 0 people (0%) and 26‐30 1 people (4%). Quality of life based on gender, age, education level, MMSE score and MOCA‐INA score, the most poor quality is found in the memory of 19 people (79%), the most fair quality is in the finances of 19 people (79%), the most good quality is in marriage with 13 people (54%) and the most excellent quality is in the marriage of 2 people (9 %).ConclusionThe quality of life of Alzheimer's Disease patients at National Brain Center Hospital during pandemic Covid‐19 is poor to fair.
Developing biomarkers of TDP‐43‐related splicing dysfunction in frontotemporal dementia
Authors: Seddighi Sahba , Hill Sarah , Brown Anna‐Leigh , Qi Andy , Hawrot James , Coon Steven , Petrucelli Leonard , Fratta Pietro , Ward Michael 
Published: February 2022

AbstractBackgroundFrontotemporal dementia (FTD) is a rapidly progressive neurodegenerative disorder characterized by prominent atrophy of the frontal and temporal lobes and marked language and/or behavioral disturbances. Mislocalization of the TAR DNA‐binding protein 43 (TDP‐43) – characterized by both its nuclear loss and its cytosolic accumulation – occurs in up to 50% of FTD cases. Recent evidence from our group and others demonstrates that loss of TDP‐43‐dependent splicing activity occurs in FTD patient brains, is an early disease phenomenon, and contributes directly to neuronal death. Monitoring the products of TDP‐43 related mis‐splicing may, thus, yield promising biomarker candidates of early cellular dysfunction in FTD.MethodWe propose a series of proteogenomic studies in human iPSC neurons, post‐mortem brain, and patient biospecimens to identify and develop protein‐based biomarkers of RNA mis‐splicing in FTD. First, we will identify pathologic RNA splicing changes and protein products of mis‐splicing that occur in the context of TDP‐43 depletion in iPSC‐derived neurons. We will next determine which of these predicted transcripts and de novo proteins occur in post‐mortem human FTD brains, as a crucial first step in biomarker development. Finally, we will develop CSF biomarkers of FTD‐related mis‐splicing through a combination of targeted proteomics and ELISA‐based assays of lead candidate biomarkers.ResultUsing CRISPRi knockdown of TDP‐43 in i3Neurons followed by total RNAseq, we detected cryptic exon formation in STMN2 as well as hundreds of additional transcripts. We developed a proteogenomic informatic pipeline to detect de novo protein products of mis‐spliced transcripts in TDP‐43 deficient i3Neurons, revealing two in‐frame de novo peptides in the MYO18A transcript. Furthermore, we detected 38 of these mis‐spliced transcripts in ALS/FTD post‐mortem cortex, including MYO18A.ConclusionThese preliminary studies indicate that our i3Neuron CRISPRi pipeline can predict disease‐relevant markers of TDP‐43 mis‐splicing and suggest a proteogenomic workflow for development of novel protein‐based biomarkers of mis‐spliced transcripts.Together, these efforts will yield early biomarkers of TDP‐43 related cellular dysfunction that can act as surrogate measures of disease onset and progression in FTD.
Preliminary results from the COVID caregiving project
Authors: Largent Emily A , Clapp Justin , Stites Shana D. , Peterson Andrew H , Abera Maramawit , Harkins Kristin , Karlawish Jason 
Published: February 2022

AbstractBackgroundIn the United States, family caregivers are the cornerstone of the support system for persons living with dementia (PLWD). This study examined how the coronavirus disease 2019 (COVID‐19) pandemic challenged caregivers’ capacity to deliver long term care services and supports to PLWD.MethodParticipants (expected N=40) in this qualitative study are family caregivers for PLWD who reside in either the community or a long‐term care facility. Family caregivers participate in semi‐structured, hour‐long telephonic interviews covering: (1) adequacy of caregiving supports; (2) social, emotional, physical, financial, and other effects of caregiving during the COVID‐19 pandemic on the caregiver; and (3) effects of the COVID‐19 pandemic on the person with dementia. Interviews are audio‐recorded, transcribed, and coded in NVivo. The University of Pennsylvania IRB approved this study.ResultsPreliminary results show that social distancing measures disrupted services and supports for PLWD (e.g., closure of adult day centers). Efforts to minimize the risk of COVID‐19 disease or death for the person with dementia increased caregiver work and feelings of burden. Many caregivers described making difficult tradeoffs. Some reduced their utilization of supports (e.g., forgoing having paid aides come into the home, limiting visits from other family members), but this has increased workload and limited opportunities for respite. Other caregivers reduced work hours or left the workforce entirely (e.g., because they deemed their risk of SARS‐CoV‐2 exposure on the job too high), but this has increased financial vulnerability and social isolation. A majority of caregivers expressed concern that social distancing has negatively affected the person in their care; many perceive a hastening of cognitive decline and feel their time with the person with dementia has been limited by the pandemic. Caregivers for long‐term care facility residents reported frustration with limited visitation opportunities as well as a perceived decrease in quality of care and lack of transparency.ConclusionOur results will help characterize the impact of the COVID‐19 pandemic on PLWD and their caregivers. They will inform ethical guidelines and policies to improve the delivery of services and supports for PLWD and the ability of people to perform the work of caregiving.
Effects of aerobic exercise on imaging biomarkers in Alzheimer’s disease
Authors: Yu Fang , Mathiason Michelle , Gunter Jeffrey L. , Jones David T. , Botha Hugo , Jack Clifford R. 
Published: February 2022

AbstractBackgroundIn animal models of Alzheimer’s disease (AD), aerobic exercise favorably modified the accumulation, degradation, and removal of Aβ and tau. However, human mechanistic randomized controlled trials (RCTs) are limited with mixed findings on hippocampal volume and biofluid Aβ and tau. Hence, an objective of the FIT‐AD Trial was to examine the effects of 6‐month aerobic exercise on magnetic resonance imaging (MRI) biomarkers in community‐dwelling older adults with AD dementia.MethodThe FIT‐AD Trial was a pilot RCT that first qualified participants for the main exercise study eligibility and then for MRI. Participants were randomized to moderate intensity cycling or low intensity stretching for 20‐50 minutes, 3 times a week for six months on a 2:1 ratio with three age strata (66‐75, 76‐85, and 85+ years of age) and followed up for another six months. MRI biomarkers included hippocampal volume, temporal meta‐regions of interest cortical thickness, white matter hyperintensity (WMH) volume, and network failure quotient (NFQ) measured at baseline, six months, and 12 months.ResultSixty participants met MRI eligibility, but one was excluded when this participant’s baseline MRI failed quality control. Among the 59 remaining participants, 38 were randomized to cycling and 21 to stretching. The sample characteristics (n=59) were 77.3±6.3 years old with 15.6±2.9 years of education and 53% men. Both groups experienced significant declines in hippocampal volume (2.64% in cycling vs. 2.89% in stretching) and cortical thickness (0.94% vs. 1.54%) over six months and over 12 months (hippocampal volume: 4.47% vs. 3.84%; cortical thickness: 2.27% vs. 1.79%). These declines didn’t differ between groups. WMH volume increased significantly, but the cycling group increased >50% less than stretching (10.9% vs. 24.5% over six months [f=4.47, p=.04]; 12.1% vs. 27.6% over 12 months [f=5.88, p=.02]). NFQ didn’t change significantly over time nor differed between group.ConclusionAerobic exercise may reduce hippocampal volume and cortical thickness declines during the intervention period; however, its effects are likely to be small and dose‐dependent and reverse after the intervention stops. Aerobic exercise is effective on reducing WMH progression but has no effect on NFQ.
Diffusion tensor imaging in mild cognitive impairment in community‐dwelling older adults in Taiwan
Authors: Chuang Yi‐Fang 
Published: February 2022

AbstractBackgroundMost structural magnetic resonance imaging studies of Alzheimer’s disease and mild cognitive impairment (MCI) have focused on volumes of gray matter structures in the medial temporal lobe. This study aims to investigate white matter microstructures using diffusion tensor imaging (DTI) in MCI and different types of MCI in a community‐based cohort of older adults in Taiwan.MethodThe DTIs of 372 older adults at baseline from a community‐based prospective cohort study, the Epidemiology of Mild Cognitive Impairment in Taiwan (EMCIT) were used. Among them, 74 were ascertained as MCIs including 53 amnestic MCIs and 21 non‐amnestic MCIs. Tract‐based spatial statistics (TBSS) were used to compare voxelwise fractional anisotrophy (FA) differences between MCI, amnestic (aMCI), non‐amnestic MCI (naMCI) and cognitively normal (CN) older adults.ResultMean age of participants was 70.7± 5.3 years. Older adults with MCI were older, have lower education and higher prevalence of diabetes and depression. The pattern of white matter integrity disruption tends to follow an anterior to posterior gradient with greater damage noted in posterior regions in MCI (Fig. 1). On further analysis, participants with aMCI showed disrupted integrity in multiple white matter tracts across the whole‐brain when compared with CNs (Fig. 2) whereas only few white matter regions with diffusion changes were found in aMCI as compared to CNs and with less significance.ConclusionThese findings indicate that the degeneration extensively exists in white matter tracts in MCI, especially naMCI. The results are consistent with the view that MCI is not a uniform disease entity and presents heterogeneity in the structural brain changes.
Characterizing white matter hemodynamic markers of lesion burden and cognitive function using arterial spin labeling MRI
Authors: Juttukonda Meher R. , Almaktoum Randa , Stephens Kimberly A. , Yochim Kathryn M. , Salat David H. 
Published: February 2022

AbstractBackgroundWhite matter lesions (WMLs) have been linked to cognitive decline in Alzheimer’s disease (AD), but physiological mechanisms associated with microvascular dysfunction in white matter remain incompletely understood. The purpose of this study was to investigate associations between arterial spin labeling (ASL) magnetic resonance imaging (MRI) markers of white matter hemodynamics and aging, cognitive function, and WML burden.Method
Study design. Participants (n=234) provided written consent for this IRB‐approved cross‐sectional study as part of the Human Connectome Aging Project. Participants underwent a range of health and cognitive assessments, including the Montreal Cognitive Assessment (MoCA), and 3 Tesla MRI.
Structural imaging. High‐resolution T1‐weighted images were acquired for co‐registration and were processed with FreeSurfer for calculation of white matter signal abnormalities as a measure of WML burden. Hemodynamic imaging. ASL data were acquired using a labeling duration=1500 ms and five equally spaced post‐labeling delays from 200‐2200 ms with spatial resolution=2.5x2.5x2.5 mm3. ASL images were corrected for distortion and for motion. Cerebral blood flow (CBF) and arterial transit time (ATT) were computed using a cross‐correlation approach and a two‐compartment model. Data analysis. Mean CBF and ATT values were calculated inside white matter masks derived using FreeSurfer for each subject and assessed as a function of age, WML burden, and MoCA score.ResultWe found an inverse association between white matter CBF and age (p<0.001) and a direct association between white matter ATT and age (p<0.001), where increasing age corresponded to lower CBF and longer ATT. After including age as a covariate, we found a trend for an inverse relationship between white matter CBF and WML burden (p=0.064), with lower CBF indicating higher WML burden (Figure 2). Lastly, we also found a trend for an inverse association between white matter ATT and MoCA score (p=0.097), with longer ATT indicating lower MoCA scores (Figure 3).ConclusionPreliminary results indicate that impaired hemodynamic properties (lower white matter CBF and longer white matter ATT) may be associated with elevated WML burden and poorer cognition. Further longitudinal studies are necessary to determine whether white matter hemodynamic may represent a prospective marker of WML burden and associated cognitive impairment.