bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early outcomes of a community‐based participatory research (CBPR) approach to investigating brain health and ADRD phenotypes following traumatic brain injury
Authors: Dams‐O'Connor Kristen 
Published: January 2025

AbstractThis session is proposed for consideration to be presented as part of the Partnering with Research Participants Professional Interest Area (PIA), for AAIC 2024 FRS titled Participant and Public Involvement Across Alzheimer’s Disease Research Studies: Conceptual and Empirical Strategies for Equitable Participation. This session will focus on areas of opportunity in the involvement of research volunteers to further and enhance research design and practices in different aspects of AD and ADRD research studies. This session is specifically focused on conceptual and applied approaches for the involvement of research volunteers across all study designs. We will use a use‐case example to illustrate the implementation of a DoD CDMRP‐funded Focused Program Award designed to investigate brain health and ADRD phenotypes following traumatic brain injury. The ENRICH brain health study is founded in a community‐based participatory research (CBPR) approach, with one of the five studies focused on the formation and implementation of a Community Advisory Group for Brain Health (CAGE‐BH). The CAGE‐BH consists of individuals with lived experience of brain injury, neurodegenerative disease, military service history, leadership of or participation in local or national brain injury or dementia care advocacy groups, and veteran service organizations. The CAGE‐BH is involved in the development and implementation at all stages of the four research studies comprising the ENRICH Focused Program Award. The proposed session will share early outcomes of a community‐based participatory research (CBPR) approach to investigating brain health and ADRD phenotypes following traumatic brain injury.
An Usability and Acceptability Study for Immersive Virtual Reality Application in People With Alzheimer’s Disease: A Case Series
Authors: Menengiç Kübra Nur , Çelikçi Cengiz , Süzme Zeynep , Yeldan İpek 
Published: January 2025

AbstractBackgroundVirtual reality (VR), an emerging technology that is becoming increasingly widespread, shows promise as an effective rehabilitation strategy for various diseases. The aim of this study was investigating usability and acceptability of VR in people with Alzheimer’s Disease (AD).MethodNine people with early and middle stages of AD were included in the study. The immersive VR application was implemented via the BOBO® VR Z Headset. Selected YouTube VR films, such as relaxing animal and space videos, as well as museum tours, were watched. The VR experience of participants was assessed after a 15 minute application. The usability was evaluated with a survey prepared for this study, including questions evaluating aspects such as realism, comfort, enthusiasm, entertainment, and willingness to participate again. Participants' sickness symptoms were evaluated with the Simulator Sickness Questionnaire, and their moods were evaluated with the Brunel Mood Scale.ResultsAll participants found the application realistic and exciting. 4 of participants found the goggles uncomfortable and 2 of them stated that they would not want to apply it again. 4 of the participants experienced symptoms of general discomfort, fatigue, eye discomfort, and difficulty in concentrating.ConclusionWhile the application was found to be feasible and acceptable for some participants, it was not for others. The discomfort, especially in the nose part of the headset, appears to be caused by the design factors of the device. Additionally, some participants experienced sickness symptoms. VR has the potential to serve as an alternative, offering a different and enjoyable approach within rehabilitation practices for certain individuals. However, we are of the opinion that the results of the application show individual differences and the immersive VR may not be suitable for all individuals with AD.
Myelin water imaging with clinically feasible scan time: the accelerated BMC‐mcDESPOT (aBMC‐mcDESPOT) method
Authors: Bae Jonghyun , Gong Zhaoyuan , Guo Alex , Laporte John P , Faulkner Mary E , Bouhrara Mustapha 
Published: January 2025

AbstractBackgroundIn 2016, we introduced the Bayesian Monte Carlo analysis of multicomponent‐driven equilibrium observation of T1 and T2 (BMC‐mcDESPOT) MRI method for myelin water fraction (MWF) mapping, a surrogate of myelin content. While BMC‐mcDESPOT has been extensively applied to study brain aging, dementias, and risk factors influencing myelination, it still requires a lengthy acquisition time (∼17 min) which hampers its integration in clinical studies and trials. In this study, we aim to accelerate the BMC‐mcDESPOT method for whole brain, high‐resolution, MWF mapping within clinically feasible scan time of ∼6 min.MethodData Acquisition Reference data (ref‐BMC, no‐acceleration): Two subjects underwent the BMC‐mcDESPOT protocol consisting of SPGR and bSSFP images at 10 different FAs. For assessing reproducibility, three sets of fully‐sampled datasets were collected without any under‐sampling (total acquisition time = 17 min). Compressed sensing acceleration (cs‐BMC): Three sets of accelerated scans were acquired using compressed sensing (CS) with an acceleration factor of ∼2 (9 min) (Figure 1(a)). Image domain acceleration (du‐BMC): The undersampling in the data domain was retrospectively performed on the bSSFP images by selecting only 2 optimal images instead of the full 10 images (12 min) (Figure 1(b)). Combined accelerations (aBMC): The above two acceleration methods were combined and resulted in an acquisition time of ∼6min. (Figure 1(c)) Data Processing We estimated MWF maps from the different undersampling methods described above. The accuracy was evaluated between the MWF from the reference and those from each undersampled dataset. The reproducibility was measured with the coefficient of variations (CoV) across different measurements for each sampling method. We also performed Bland‐Altman analysis to quantify bias and limits of agreement (LOA).ResultFigure 2 shows a representative slice of MWF estimates from different sampling methods. The different acceleration methods showed similar regional patterns, with relatively low errors (du‐BMC/cs‐BMC/aBMC = 10.8/9.8/13.7%) and CoV (ref‐BMC/du‐BMC/cs‐BMC/aBMC = 9.0/14.3/10.7/15.3%). While a slight bias in the derived MWF values was observed (Fig.3), the LOA for aBMC was under 5% in white matter.ConclusionaBMC‐mcDESPOT is a practical MRI method for accurate determination of MWF within 6 min, offering unique opportunities to further integrate myelin imaging in clinical studies and trials.
Comparison of amyloid positron emission tomography, hippocampal volume, and plasma biomarkers in predicting conversion to mild cognitive impairment
Authors: Bilgel Murat , An Yang , Shah Ishaan , Walker Keenan A. , Moghekar Abhay , Ashton Nicholas J. , Kac Przemyslaw Radoslaw , Karikari Thomas K , Blennow Kaj , Zetterberg Henrik , Thambisetty Madhav , Resnick Susan M. 
Published: January 2025

AbstractBackgroundWe examined whether brain amyloid PET, hippocampal volume, or plasma biomarkers are better predictors of conversion to mild cognitive impairment (MCI).MethodIn the Baltimore Longitudinal Study of Aging (BLSA), plasma Aß42, Aß40, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) concentrations were measured using Quanterix Simoa Neurology 4‐plex E. Plasma p‐tau181 and p‐tau231 concentrations were measured using in‐house Simoa assays at University of Gothenburg. Brain amyloid was quantified using mean cortical 11C‐Pittsburgh compound B PET distribution volume ratio (mcDVR). Hippocampal volume was calculated from T1‐weighted MRI and adjusted for intracranial volume. Of 178 cognitively unimpaired (CU) participants with both plasma and neuroimaging measurements at baseline, 33 developed MCI during follow up (median time to MCI onset: 3.7 [interquartile range (IQR) 2.1‐6.2] years), 17 of whom had elevated brain PET amyloid at baseline. We used Cox proportional hazards models to examine the association between risk of conversion to MCI (time to conversion right‐censored at death or last visit for CU participants) and baseline plasma or neuroimaging biomarker, adjusting for age, sex, race, and education. To enable comparison of hazard ratios (HRs), we negated plasma Aß42/Aß40 and hippocampal volume, and standardized each biomarker using statistics calculated in a cross‐sectional dataset of CU individuals aged 60‐80 (preferring the visit closest to age 70 per participant) drawn from the larger BLSA. For standardization, we examined subtracting the median and dividing by the IQR and binarization (top tertile vs. not).ResultIn analyses using IQR normalized scores, mcDVR and plasma Aß42/Aß40 and GFAP had statistically significant HRs (Table 2). In binarized biomarker analyses, mcDVR and plasma GFAP, p‐tau181, and p‐tau231 were statistically significant. Using all plasma biomarkers together yielded the highest concordance: 0.877±0.026 and 0.861±0.026 for the continuous and binarized biomarker analyses, respectively.ConclusionPlasma biomarkers provide information beyond demographics regarding the prediction of MCI conversion within 4 years. Risk prediction conveyed by several individual plasma biomarkers exceeded that of brain amyloid PET. Plasma GFAP was consistently identified as contributing to the prediction of MCI conversion, with Aß42/Aß40 and p‐tau exhibiting statistically significant associations in a subset of analyses.
Elevated Blood Biomarkers of Neurodegeneration and Blood Brain Barrier Dysfunction Correlate with Lower MRI Regional Brain Volumes Two Years after COVID‐19
Authors: Frontera Jennifer A. , Ge Yulin , Boutajangout Allal , Ahmed Wajiha , Betensky Rebecca A , Debure Ludovic , Jiang Li , Links Jon , Masurkar Arjun V. , Sun Zhe , Thawani Sujata , Vedvyas Alok , Wisniewski Thomas 
Published: January 2025

AbstractBackgroundCognitive impairment is one of the most frequently reported post‐acute sequelae of COVID‐19, yet the pathophysiology underpinning this symptom remains unknown. We aimed to explore the correlation of blood markers of inflammation, BBB disruption and neurodegeneration with MRI volume measurements in COVID‐19 patients with and without cognitive impairment, and among patients with no prior history of COVID‐19.MethodWe conducted a prospective study of COVID‐19 patients (COV+; laboratory verified SARS‐CoV‐2 infection) and non‐COVID‐19 controls (COV‐; no history of SARS‐CoV‐2 infection and negative SARS‐CoV‐2 nucleocapsid antibody). All patients underwent neuropsychological testing using the Uniform Data Set Version 3 Cognitive Battery. Patients were coded as having cognitive impairment (COG+) based on neuropsychological testing (= 1 abnormal test result), and clinician interview with the patient and informant. 3T MRI (3D T1‐MPRAGE) sequences were utilized for regional volume measurements using MRICloud (Johns Hopkins University) segmentation software. The ratios of regional to total intracranial volume (SPM software) were reported to correct for differences in head size. Fasting plasma biomarkers of neurodegeneration, BBB dysfunction, and inflammation were measured concurrent with MRI testing. Bivariate Spearman correlation coefficients were calculated comparing MRI regional volumetric measures with blood biomarkers among COV+ versus COV‐ subjects with and without cognitive impairment (COG+ versus COG‐). Significance was set at P = 0.001 after Bonferroni correction.ResultA total of 90 subjects were included (N = 75 COV+ with median 724 days from index SARS‐CoV‐2 infection, N = 15 COV‐; N = 39 COG+, N = 51 COG‐). Among all COV+ subjects (N = 75), neurodegenerative biomarkers (NFL, amyloid‐ß‐40, GFAP, ptau‐181), BBB markers (hepatocyte growth factor) and TNF‐a were significantly negatively correlated with regional MRI volumes, most notably in the limbic and hippocampal regions (Figure 1, bold = P = 0.001); whereas this signature of correlations was not observed in COV‐ subjects (N = 15). Among COV+ subjects with cognitive impairment (COV+COG+, N = 33), significant negative correlations were observed between neurodegenerative biomarkers (NFL, amyloid‐ß‐40, GFAP, ptau‐181) and MRI volumes (particularly frontal, temporal and limbic), whereas COV+COG‐ subjects (N = 42) did not demonstrate this pattern (Figure 2).ConclusionTwo‐years post‐COVID‐19, signature correlations between neurodegenerative, BBB and cytokine blood biomarkers and MRI regional volumes differ between COVID‐19 subjects versus controls, particularly among those with cognitive impairment.
Cortical correlations of CSF Neurogranin, VILIP‐1, Alpha‐Synuclein and NFL in SCD and MCI according to amyloid status
Authors: Guimarães Emanuel R. , de Campos Brunno , Ribeiro Isadora Cristina , Aventurato Ítalo Karmann , da SIlva Marjorie Cristina Rocha , Rizzi Liara , Balthazar Marcio 
Published: January 2025

AbstractBackgroundAlzheimer’s disease (AD) pathophysiology is complex and not completely known. Emerging new biomarkers that evaluate synaptic function (VILIP‐1, neurogranin), co‐pathology (alpha‐synuclein), and neurodegeneration (NFL) are potential candidates to be incorporated into the early AD diagnosis. To better understand the relevance of these biomarkers, we evaluated the correlations between their CSF concentrations with whole‐brain grey matter volumes in SCD and MCI, according to their amyloid status (A‐ or A+).Method75 participants diagnosed with SCD or MCI were included, 30 A‐ and 45 A+. They all underwent comprehensive neuropsychological assessment, CSF analyses (Roche Elecsys), and volumetric 3T MRI (Philips Achieva). Voxel‐based morphometry was used to quantify brain volumes through CAT12 running on MATLAB 2019b. Partial correlation analysis between CSF biomarkers and cortical volumes was performed with SPSS 22, adjusting for age and sex.ResultSignificant correlations were found in the A‐ but not in the A+ group. NFL and hippocampus (r = 0.40, p = 0.028); VILIP‐1 and superior temporal gyrus (r = ‐0.38, p = 0.035), and superior frontal gyrus (r = ‐0.40, p = 0.025); alpha‐synuclein and hippocampus (r = ‐0.39, p = 0.036), middle frontal gyrus (r = ‐0.375, p = 0.049), and superior temporal gyrus (r = ‐0.478, p = 0.01).ConclusionWe found different patterns of correlations between brain anatomy and emerging biomarkers, according to amyloid status, in the very early stage of the neurodegenerative process. Interestingly, these correlations were found only in the amyloid‐negative group, which might suggest that different pathological processes involving synaptic function, neurodegeneration, and co‐pathology occur in suspected non‐Alzheimer pathophysiology cases.
Resting‐state activity across cortical hierarchies provides readiness for memorizing in aging humans
Authors: Han Feng , Chen Xi , Varghese Leah , Cassady Kaitlin , Chadwick Trevor , Mason Suzanne , Jagust William J. 
Published: January 2025

AbstractBackgroundThe neural basis of memory aging remains elusive. The default mode network (DMN) supports memory encoding and retrieval, and its connectivity decreases in aging. Young adults with larger differences in resting‐state functional connectivity (rsFC) between higher‐order DMN and lower‐order sensory/motor network (SMN) have better cognition and memory. We combined resting‐state and task‐based fMRI during an associative memory task to explore how this cross‐hierarchical contrast of rsFC is linked to memory aging.MethodWe included resting‐state prior to (an object‐scene‐pair encoding) task fMRI from 16 young adults (YA; 24.6 ± 3.6 years; 7 females) and 42 cognitively normal older adults (OA; 76.8 ± 6.9 years; 24 females) in the Berkeley Aging Cohort Study. We subtracted the averaged rsFC within lower‐order regions from higher‐order ones, and correlated the cross‐hierarchy contrast of rsFC with age and memory task performance. Brain function contrast between the higher and lower order regions may also manifest as the temporal difference/delay of cortical activation, seen in propagating waves between hierarchical cortices. The propagating number (i.e., frequency) in each direction (“High‐to‐low” or “Low‐to‐high”) was therefore also correlated with memory performance and activation in anterior‐temporal (AT), posterior‐medial (PM), and hippocampal (HPC) memory regions during task‐fMRI.ResultAmong OAs, cross‐hierarchy contrast of rsFC decreased with aging (Spearman’s ρ = ‐ 0.32, p = 0.040) and in females (p = 2.3 ×10‐3). OAs with lower rsFC contrast had worse memory during retrieval (ρ = 0.36, p = 0.019; Fig. 1). Memory scores were not correlated with mean rsFC within higher‐order regions or lower‐order ones. Propagating number along the “Low‐to‐high” direction decreased in OAs. More propagation was associated with better memory and lower task‐evoked activation in AT, PM, and HPC regions (all ρ strength > 0.35, p < 0.030; Fig. 2&3).ConclusionPatterns of resting‐state functional connectivity related to hierarchical cortical organization are associated with aging and memory decline. In particular, slow propagating waves of cortical activation transiting across these hierarchies may serve a preparatory function, readying the brain for memory formation, a process that is affected by aging.
Multi‐atlas fully automated segmentation of the locus coeruleus in in vivo neuromelanin‐sensitive MRI
Authors: de Flores Robin , Blanchard Thaïs , Foyard Emilie , Naveau Mikaël , Delcroix Nicolas , Landeau Brigitte , Yushkevich Paul A. , Chételat Gael 
Published: January 2025

AbstractBackgroundLocus coeruleus (LC) imaging using neuromelanin‐sensitive (NM) MRI sequences is a promising biomarker for detecting early Alzheimer’s Disease (AD). Although automatic approaches have been developed to estimate LC integrity by measuring its intensity, these techniques most often rely on a single template built in a standardized space and/or depend on a number of voxels to be accounted that is defined a priori. Thus, these algorithms make it impossible to perform direct volumetric analyses and do not properly account for inter‐individual anatomical variability. To fill this gap, our aim was to develop a new multi‐atlas fully automated segmentation method using the Automatic Segmentation of Hippocampal Subfields (ASHS) software.MethodWe used baseline data from 102 unimpaired older adults (mean age: 73.72 ± 3.5 years; mean education: 13.25 ± 3.1 years; 58 women, 44 men) from the Age‐Well randomized controlled trial for whom high‐resolution NM MRI (T1‐w with magnetization transfer; 0.3×0.3×0.75mm3) and standard T1‐w MRI (1×1×1mm3) were available. The LC were manually segmented in 30 randomly selected participants on NM MRI, and the standard T1‐w MRI, NM MRI and bilateral segmentations were fed into the ASHS training pipeline to generate an atlas. This new atlas was applied to the 72 remaining subjects to segment the LC and we assessed the effects of age, sex and education on both i) LC intensity (normalized by the intensity of the pons) and ii) LC volume (normalized by the total intracranial volume).ResultFive‐fold cross‐validation experiments revealed high accuracy of the automatic segmentation relative to manual segmentation (Dice coefficient = 0,83 ± 0,04). LC intensity was significantly higher in women than in men (F = 13.61,p<0.001) while no associations with age (ß = ‐0.0002,p = 0.86) or education (ß = 0.002,p = 0.16) were found. In contrast, LC volume was not different between men and women (F = 0.21, p = 0.65) but tended to be negatively associated with age (ß = ‐0.15,p = 0.06) and education (ß = ‐0.19,p = 0.06).ConclusionOverall, this new method allows to automatically and accurately segment the LC, and offers the opportunity to measure its integrity both in terms of intensity and volume. This is of importance since these two metrics might provide complementary information about the integrity of the LC.
First GPR39‐imaging radiotracer to track zinc homeostasis in a rodent model of Alzheimer’s disease
Authors: Gollepalli Krishna Kumar , Bhoopal Bhuvanachandra , Damuka Naresh , Krizan Ivan , Miller Mack , Kumar JV Shanmukha , Bashetti Nagaraju , Whitlow Christopher T , Lockhart Samuel N. , Jadiya Pooja , Sai Kiran K. Solingapuram 
Published: January 2025

AbstractBackgroundThe G protein‐coupled receptor GPR39 is heavily associated with the pathogenesis of neurologic disorders, including Alzheimer’s disease (AD) and related dementia (ADRD). Its dysregulation of zinc 2+ (Zn2+) processes triggers metallic dyshomeostasis, oxidative stress, neuroinflammation, microtubule destabilization, synaptic dysfunction, and tau phosphorylation—all hallmarks of neurodegeneration. Hence, pharmacologic modulation of GPR39 could offer an effective treatment against AD and ADRD. With the right radiotracer, PET could be used to quantify GPR39 in brains in vivo and track distribution, target engagement, and dose occupancy of novel GPR39‐based agonistic drugs to regulate Zn2+ (dys)homeostasis function. In this abstract we report the development and validation of the first PET radiotracer, [11C]TMN‐1324 to image GPR39 in rodent models of AD.MethodGPR39 agonist TM‐N1324, was selected as the lead compound for its brain penetration and high GPR39 affinity—acts with and without Zn2+ to both human and rodent GPR39s. To validate [11C]TM‐N1324 imaging potential, we performed 0‐60 min dynamic PET imaging and post‐PET biodistribution with [11C]TM‐N1324 in (a) normal C57BL/J mice (4 mo, n = 4) and (b) male Aß‐overexpressing APP/PS1 transgenic (TG) mice and age‐matched wild‐type (WT) mice (12 mo, n = 4/group). Brain autoradiography investigated regional uptake in the same cohort. TM‐N1324 blocking studies (n = 4) confirmed in vivo GPR39 specificity of the radioligandResultRadiochemistry was fully optimized for high radiochemical purity (>98%) and molar activity (>48635 MBq/µmol) decay corrected to end‐of‐synthesis. PET imaging of rodents showed brain penetration and ∼65±4% blocking with TM‐N1324 pretreatment. It demonstrated ∼22±3% lower brain uptake in APP/PS1 TG mice compared to WT littermates (Fig 1). Autoradiography showed significant uptake in cortical regions (high GPR39‐expressing regions). Biodistribution showed ∼33±1% lower brain uptake in TG mice than WTs.ConclusionOur pilot study here with the first GPR39‐imaging PET radiotracer, [11C]TM‐N1324 demonstrated brain penetration, differential uptake in mouse model of AD, and regional specificity. By validating our highly specific GPR39 PET radiotracer for studying Zn2+‐based dyshomeostasis, we will elucidate GPR39 PET imaging strategies to monitor target responses to potential novel therapeutics.