bluuebunny/crossref_metadata_2025_split huggingface dataset:
Livestreaming, interactive, group movement classes to address social isolation and well‐being in people living with memory loss and their caregivers
Authors: Nicosia Francesca M , Lee Jennifer Ann , Chesney Margaret A , Mehling Wolf , Sudore Rebecca L , Barnes Deborah 
Published: February 2022

AbstractBackgroundNon‐pharmacologic programs can improve function and quality of life in people with memory loss (PWML), but in‐person programs are not available in many communities. We previously developed the interactive, livestreaming, group‐based, Moving TogetherTM program for PWML and their caregivers (CGs). This study assesses feasibility, satisfaction, and qualitative outcomes in four groups that participated during the COVID‐19 pandemic.MethodWe assessed feasibility based on number of participants and attendance. We administered an online survey at the end of the 12‐week program to assess satisfaction. The survey included a 6‐item Class Experience scale (e.g., feeling accepted, energized) and the 4‐item PROMIS Social Isolation scale, both using 4‐point Likert response scales. Open‐ended questions asked about changes noticed in themselves and others during the program. We used a previously established coding scheme informed by a biopsychosocial framework to code free‐text survey responses and refined codes as we identified new concepts.ResultsWe offered four 12‐week class series (1 hour, 2 days/week) from April to July 2020 that included 8 to 14 participants each (total N=39: 24 PWML, 15 CGs). Average attendance was 78% (range: 58% to 98%). Surveys were sent to 31 participants who completed the program, of whom 25 (16 PWML, 9 CGs) responded. Nearly all respondents reported that they often, mostly or always felt acceptance and well‐being during classes (6‐items, 88% to 100%), and most reported that they rarely or never felt social isolation (4 items, 50% to 100%). Qualitative analyses of free‐text responses identified self‐reported improvements in both PWML and CGs in several areas: 1) emotional well‐being, including better mood, lower stress, and increased relaxation; 2) social connection, such as friendship and camaraderie; 3) physical function, including more energy, increased activity, improved movement, and increased mind‐body awareness; and 4) cognitive function such as better focus.ConclusionThis study demonstrates that the interactive, livestreaming, group‐based, Moving TogetherTM program is feasible and associated with high satisfaction among both PWML and their CGs. Technology offers tremendous potential to increase accessibility to evidence‐based, non‐pharmacologic programs that people with memory loss (PWML) and caregivers (CGs) can participate in from the safety of their homes.
The effect of APOE4 on plasma and cerebrospinal fluid polyunsaturated fatty acids following DHA supplementation
Authors: Yassine Hussein N. , He Xulei , Lee Mitchell , Gomez‐Loarte Sol , Evans Jim E. , Oberlin Sarah , Abdullah Laila 
Published: February 2022

AbstractBackgroundPast studies indicate that APOE4 promotes a metabolic shift toward greater fatty acid usage. We have shown that APOE4 is associated with lower increase in cerebrospinal fluid (CSF) polyunsaturated fatty acids (PUFAs) following supplementation with triglyceride (TG) based DHA. The purpose of this study is to define the effect of APOE4 on plasma and CSF lipids using a comprehensive lipidomic analysis.MethodPlasma and CSF samples were obtained from the DHA Brain Delivery Pilot, a randomized clinical trial of DHA treatment (n=13) vs placebo (n=13) in non‐demented older participants (CDR ≤ 0.5, age> 55 years old) and stratified by APOE4. Participants were provided 2,040 mg DHA daily in the form of TG‐DHA for six months.ResultFollowing supplementation, levels of phosphatidylcholine DHA (PC 38:6) and cholesterol ester DHA (CE 22:6) had the largest increase in CSF (p<0.0001). Using principal component analysis, changes in plasma TG (56:8), TG (58:10), ePE (40:8), TG (56:9), PC (40:6) and PC (38:6) had the strongest correlations with changes in CSF PC (38:6, p<0.001). Figure 1 shows Pearson correlation coefficients of all plasma and CSF lipids. Among all lipid species, changes in PUFA enriched TGs were significantly correlated between CSF and plasma. APOE4 had a significant effect on CSF TG (52:6) changes, with the mean increase in E4 carriers significantly (0.039 units) less than in E4 non‐carriers (p=0.0072) after adjusting for baseline levels and treatment group.ConclusionOur findings demonstrate the first time the existence of PUFAs within a TG pool in CSF that correlates with the corresponding plasma TG pool, suggesting an exchange of TG particles at the CSF‐blood barrier. The effect of APOE4 on the metabolism of PUFAs is strongest on TG enriched PUFAs and supports their greater oxidation in APOE4. These findings help explain why APOE4 carriers are vulnerable to dietary omega‐3 deficiency, and less responsive to short term omega‐3 supplementation.
Examining the structural correlates of amyloid‐beta in people with DLB
Authors: Gajamange Sanuji , Yassi Nawaf , Chin Kai Sin , Desmond Patricia M. , Villemagne Victor L. , Rowe Christopher C. , Watson Rosie 
Published: February 2022

AbstractBackgroundDementia with Lewy bodies (DLB) is a neurodegenerative disorder characterized pathologically by the deposition of alpha synuclein. Many patients with DLB also have brain compatible with Alzheimer’s disease (namely Amyloid‐β and tau), which can lead to challenges with clinical diagnosis and management. In this study we aim to understand the influence of Aβ on brain atrophy in DLB patients.Method19 participants with probable DLB underwent 3T MRI T1‐weighted (voxel size=0.8x0.8x0.8mm3, TR=2400ms, TE=2.31ms) and β‐amyloid (Aβ) PET (radiotracer 18F‐NAV4694) imaging. Participants were grouped into Aβ negative (n=10; age=71.6±5.8 years) and Aβ positive (n=9; age=75.1±4.3 years) with a threshold of 50 centiloid units to identify neuropathological change (Amadoru et al. 2020). Brain volume measures (regional subcortical grey matter and global white and grey matter) were segmented from T1‐weighted images with FreeSurfer (Fischl et al. 2002, Fischl 2012). Given previous literature suggesting prominence of thalamic structural changes in DLB, we also specifically analysed changes in the thalamus by segmenting the thalamus into 25 nuclei, which were then grouped into six regions (anterior, lateral, ventral, intralaminar, medial and posterior) (Watson et al. 2017, Iglesias et al. 2018). All brain volumes were expressed as fractions of intracranial volume to account for differences in head size. Group comparison analyses were not controlled for age and sex as both these covariates did not statistically differ between groups.ResultBrain volume differed significantly between Aβ‐ and Aβ+ DLB patients in the left thalamus (Aβ‐:4.39±0.37x103, Aβ+:4.07±0.19x103, p=0.03) and right thalamus (Aβ‐:4.17±0.34x103, Aβ+:3.84±0.22 x103, p=0.03). Specifically, the ventral (LEFT; Aβ‐:1.78±0.15, Aβ+:1.63±0.14, p=0.03. RIGHT; Aβ‐:1.83±0.15, Aβ+:1.65±0.12, p=0.01) and posterior (LEFT; Aβ‐:1.30±0.12, Aβ+:1.17±0.10, p=0.04. RIGHT; Aβ‐:1.42±0.14, Aβ+:1.21±0.12, p=0.003) regions were significantly reduced in Aβ+ compared to Aβ‐ DLB patients.ConclusionWe demonstrated significant thalamic atrophy in Aβ+ patients compared to Aβ‐ DLB patients. We did not observe significant differences in grey matter and hippocampal volume between patient groups. This study showed that AD‐related processes in DLB patients are associated with thalamic atrophy, specifically in the ventral and posterior regions. Future studies would benefit a larger DLB cohort to further understand the association between AD‐related pathology and the regional thalamic correlates of clinical function.
Cortical microstructural associations with CSF amyloid and tau
Authors: Nir Talia M. , Reina Julio E. Villalon , Haddad Elizabeth , Zheng Hong , Thomopoulos Sophia I. , Maiti Piyush , Zhu Alyssa H. , Thompson Paul M. , Jahanshad Neda 
Published: February 2022

AbstractBackgroundMulti‐shell diffusion MRI (dMRI) biophysical models can estimate intracellular (ICVF), extracellular (ECVF) and free water (ISOVF) volume fractions (VFs) in brain tissue, and may offer insight into Alzheimer's disease pathological processes. These microstructural measures can be calculated in the cortex using a gray matter specific model that may be sensitive to amyloid and tau burden. Here, we evaluated relationships between regional cortical microstructural VFs and CSF amyloid and tau biomarkers.MethodMulti‐shell dMRI and CSF biomarker data were available for 50 ADNI‐3 participants (age: 72.4±6.4 yrs; 20 male; 36 cognitively normal, 12 MCI, 2 dementia). Cortical ICVF, ECVF and ISOVF were estimated with the multi‐tissue spherical mean technique (MT‐SMT). Mean cortical measures were extracted from 4 lobes and the cingulate cortex, parcellated with FreeSurfer. Random‐effects linear regressions tested associations between regional dMRI measures and CSF pTau or Aβ42/Aβ40 burden, adjusting for age, sex, education, and grouping by scanning site. FDR (q=0.05) was used to correct for multiple comparisons across 5 regions, 3 diffusion measures, and 2 tests.ResultHigher Aβ42/Aβ40 was associated with lower ISOVF throughout the cortex (Figure 1), and higher ECVF and ICVF in the cingulate, frontal and temporal lobes. Higher ICVF was also found in the parietal cortex. Higher pTau was associated with higher ISOVF in the occipital and parietal lobes, and lower ECVF in the frontal and parietal lobes (Figure 2). No pTau ICVF associations were detected.ConclusionLower ICVF and higher ISOVF with greater amyloid and tau may indicate neuronal loss or edema, while lower ECVF could reflect, for example, as neuronal swelling or an influx of activated microglia. Lower ECVF with greater amyloid and tau burden may also reflect accumulation of large hydrophobic amyloid plaques and neurofibrillary tangles in the extracellular space. These results are preliminary and, as many factors influence dMRI measures, should be interpreted with caution. Future work will incorporate multimodal imaging to map associations of diffusion measures with localized PET‐derived amyloid and tau measures.
Sex‐dependent age trajectories of subcortical brain volume: A UK Biobank study (N=39,544)
Authors: Ching Christopher , Muir Alexandra M , Santhalingam Vigneshwaran , Abaryan Zvart , Zhu Alyssa H , Thomopoulos Sophia I , Jahanshad Neda , Thompson Paul M 
Published: February 2022

AbstractBackgroundUnderstanding the normative variation in brain structure across life may provide insights into healthy aging as well as neurological disorders such as Alzheimer’s disease (AD). Women are at greater risk of developing AD, but men tend to show faster rates of subcortical atrophy across adulthood. Sex‐dependent differences in male and female brain aging trajectories may change over the adult lifespan, and could play a role in differential risk for neurological illness. The current study maps normative trajectories (nomograms) of subcortical volume across adulthood and quantifies the interaction between age and sex in a large, healthy sample.MethodT1‐weighted brain MRI from a sample of UK Biobank participants free from psychiatric/neurological illness (; N=39,544; 44.6‐82.8 years) were segmented using FreeSurfer 7.1 to derive average left and right thalamus, putamen, pallidum, hippocampus, amygdala, caudate, nucleus accumbens and ventricle volumes. Normative quantile regression models (nomograms) were created to visualize aging trajectories for each volume. Linear mixed models were fit in binned age groups to assess age‐by‐sex interactions across middle to late adulthood.ResultNomograms showed volumetric loss across adulthood, except for ventricular volume which was larger with increasing age (). Compared to females, males showed a steeper slope of volume change with increasing age in all regions across the full age range (Cohen’s d: ‐0.14 ‐ 0.12) (). Binned‐age analysis showed males to have steeper volume loss trajectories in middle adulthood, with fewer age‐by‐sex interactions detected later in life for most structures.ConclusionIn a large sample of healthy adults, we found a structure‐specific interaction between age and sex, with males tending to show steeper age‐related volume loss trajectories compared to females until later decades of life, where trends appeared similar for men and women. This study provides normative subcortical aging trends and identifies potential sex‐dependent variations across life that may be used to understand healthy brain aging and risk for disorders such as AD.
Does [18F]FDG and [18F]AV1451 PET predict neurodegeneration?
Authors: Nowell Joseph , Young Megan , Raza Sanara , Livingston Nicholas R , Crook Harry , Edison Paul 
Published: February 2022

AbstractBackground[18F]FDG PET is a well‐established and valuable biomarker in the assessment of neurodegenerative disorders, with high diagnostic utility, wide accessibility, and relatively low costs. Recent advances in PET imaging technology now allow for the in vivo exploration of tau deposition. However, it is still being debated which of [18F]FDG PET or [18F]AV1451 PET better predicts neurodegeneration. This study aimed to evaluate [18F]FDG PET and [18F]AV1451 PET imaging in predicting grey matter atrophy in patients with cognitive impairment.Method190 patients with mild cognitive impairment or Alzheimer’s disease (Mean age = 74.3 years, SD = 8.04) were evaluated from the Alzheimer’s Disease Neuroimaging Initiative (adni.loni.usc.edu). All participants completed a T1‐weighted MPRAGE MRI, [18F]AV1451 and [18F]FDG PET scans. Standard uptake ratio values were calculated in SPM12 to identify the glucose metabolic rate and tau deposition within the medial temporal lobe. Whole brain grey matter volumes were obtained from processed data from ADNI. Pearson’s correlation coefficients were calculated to assess the relationship between imaging modalities.ResultThere was a significant negative association between [18F]AV1451 uptake in the medial temporal lobe and whole brain grey matter volume (r = ‐0.288, p = 0.001). A stronger positive relationship was identified between medial temporal lobe [18F]FDG uptake and whole brain grey matter volume (r = 0.444, p < 0.001).ConclusionThis study demonstrated that regional FDG and tau tracer uptake in patients with cognitive impairment both display a significant relationship with total grey matter volume. Whilst both tracers show utility in predicting a patient’s level of neurodegeneration, glucose metabolism as indicated by [18F]FDG PET appears to have a closer relationship to grey matter atrophy than PET markers of tau deposition.
Impact of reduced injected dose on the quantification of [18F]RO948 and [18F]Flortaucipir PET for in vivo tau pathology
Authors: Young Peter , Thomas Wesley P. , Axelsson Jan , Himmelmann Jakob , Dominguez Pablo Aguilar , Ohlsson Tomas , Hansson Oskar , Lubberink Mark , Bohorquez Sandra Sanabria , Rieckmann Anna , Baker Suzanne L. , Schöll Michael 
Published: February 2022

AbstractBackgroundPrevious research has demonstrated that the injected dose in PET examinations can be reduced without substantial effects on quantitative outcomes. These reductions can lead to lower radiation burden for subjects, reduced costs for institutions and potential for additional research scans of the same subject. Here, we investigated the effect of reduced injected doses of [18F]RO948 and [18F]Flortaucipir (FTP) on standardised uptake value ratios (SUVRs) and associated outcomes.MethodImages were manipulated from list‐mode data to simulate injected doses of 70%, 50%, 25% and 12.5% of the true injected dose. Initial analyses were scan time reduction for RO948 and dose reduction for FTP with future harmonisation of processing intended. Inferior cerebellum‐grey was used to compute SUVRs in regions‐of‐interest (ROIs) corresponding to the in vivo Braak regions of tau spread. Differences between true and reduced injected doses (given as a percentage) were calculated in individual regions as the mean of [SUVRreduced – SUVRtrue] over the means of SUVRreduced and SUVRtrue values across subjects.ResultPreviously reported test‐retest variability for RO948 and FTP are 2‐6% (±6%) and 1.5‐3.3% (±3%) respectively. Regionally, RO948 remained below this TRT variability at 25% injected dose, with an average SUVR difference of 2.3% (±8%) (figure 2), whereas FTP remained below TRT variability only at 70% injected dose with an average SUVR difference of 2.9% (±3%). However, differences were above TRT variability for FTP at lower injected doses. FTP average SUVR differences were observed to be higher in CN compared to AD patients at reduced injected doses but with greater variability in AD than CN. There were no differences observed between Ab+ and Ab‐ controls.ConclusionPreliminary findings suggest that lower injected tracer‐doses for RO948 and FTP yield robust SUVRs. However, the degree to which injected doses can be reduced must be investigated further for different demographics and for different tracers. Ongoing work aims to harmonise the simulation list‐mode processing, add MCI/AD RO948 subjects, and evaluate dose reduction in [18F]GTP1 data. Further validation will be performed against demographic and clinical variables, as well as for longitudinal data.
Association of AD biomarker levels with functional connectivity within and between large‐scale brain networks among cognitively normal individuals
Authors: Soldan Anja , Pettigrew Corinne , Bilgel Murat , Kutten Kwame , Miller Michael I. , Hou Xirui , Lu Hangzhang , Albert Marilyn S. 
Published: February 2022

AbstractBackgroundIt is well documented that amyloid pathology accumulates many years prior to the emergence of clinical symptoms of Alzheimer’s disease (AD), when individuals are cognitively normal. Few prior studies have investigated the impact of AD pathology on brain connectivity among cognitively normal individuals. We investigated the impact of AD biomarkers on functional connectivity within and between large‐scale brain networks important for cognitive function.MethodAnalyses included 123 cognitively normal participants (mean age=69 years) from the BIOCARD Study who completed clinical and cognitive assessments, resting state functional magnetic resonance imaging (rs‐fMRI) scans, and cerebrospinal fluid (CSF) measures of AD biomarkers [abeta1‐42 (AB42), abeta1‐40 (AB40), total tau (ttau), and phosphorylated tau 181 (ptau)] during their annual visit. Among these, 106 participants also had 11C‐PiB PET imaging to assess amyloid burden. Functional connectivity within 7 large‐scale, non‐overlapping networks was measured and averaged to compute global within‐network connectivity. Between‐network connectivity was measured using graph theory‐based metrics of modularity and segregation. Linear regressions (covarying age, sex, education, whole brain volume, and vascular risks) tested the associations between the connectivity measures and the CSF and PET AD biomarkers.ResultOlder age was associated with reduced global connectivity within networks and reduced network modularity and segregation (all p’s <0.05), indicating reduced functional specialization with older age, consistent with prior studies. Amyloid positivity on PET, as well as lower AB42/AB40 and higher ttau/AB42 and ptau/AB42 ratios were associated with higher network modularity and segregation (all p’s <=0.01). When AB42/40, ttau, and ptau were simultaneously entered in the regressions, only AB42/AB40 remained significantly associated with modularity and segregation (p’s<0.01). There were no associations between the CSF or PET biomarkers and global within‐network connectivity.ConclusionAmong older individuals with normal cognition, more abnormal AD biomarker levels were related to greater network modularity and segregation. Given that higher modularity and segregation are important for maintaining cognitive function with age, these results suggest that the associations with rs‐fMRI connectivity may reflect a compensatory response of the brain to accumulating pathology. These findings are consistent with autopsy studies showing compensatory increases in neuronal size (neuronal hypertrophy) among asymptomatic individuals with AD pathology.
Courage in care planning: Advanced care planning readiness in caregivers of individuals living with dementia
Authors: Brandt Katherine , Quimby Megan , Wong Bonnie , Quintiliani Lisa M , Marchesano Amy , Howe Inola , Paasche‐Orlow Michael K , Krahn Erin , Krivensky Samantha , O’Chander Raseeka , Dickerson Brad C , Volandes Angelo 
Published: February 2022

AbstractBackgroundFamily caregivers of individuals living with dementia due to Alzheimer’s Disease, Frontotemporal Dementia and related diseases must make medical decisions and develop care plans for current and future needs of care recipients, often without a comprehensive understanding of those needs. Educational tools are available to help caregivers but little guidance is offered to healthcare providers about when and how to raise the topic of advanced care planning and present educational tools.MethodAs part of a larger study about the utility of video decision aids for advanced care planning in dementia, we conducted 16 focus groups, interviewing 28 caregivers of individuals living with dementia, separated into those with mild, moderate, or severe dementia. During each group, video decision aids about specific caregiving topics were shown. After each video, participants answered six questions about acceptability and then responded to open‐ended questions to explain their ratings. We coded the focus group transcripts using a qualitative content analysis method; similar codes were grouped into themes.ResultThe qualitative data support the following major themes, which did not differ across dementia severity stages. Caregivers like learning through videos even when serious illness topics are presented, and would like this opportunity at early stages and in an ongoing way. Caregivers would like to engage in care planning with loved ones who have dementia early in the process so that they may have a voice in planning.ConclusionThe evidence from this qualitative study revealed that caregivers of individuals with dementia like learning about advanced care planning topics through videos—including serious illness topics—and that access to such information at an early stage and in an ongoing way is desirable. We plan to evaluate whether empowering caregivers with information about anticipated medical decisions at an earlier stage promotes earlier care planning. We also plan to evaluate whether earlier care planning allows some individuals living with dementia to engage with caregivers in the process, and whether that increases caregiver confidence in planning for healthcare decisions. We believe that early dyadic engagement in care planning promotes dignity and person‐centered care planning for individuals living with dementia.