bluuebunny/crossref_metadata_2025_split huggingface dataset:
Solving the pervasive problem of protocol non‐compliance in neuroimaging using an open‐source tool mrQA
Authors: Sinha Harsh , Raamana Pradeep Reddy 
Published: December 2023

AbstractBackgroundLarge‐scale datasets are becoming the norm in estimating the brain‐behavior relationships, which are acquired via engagement with participants over several years often across multiple sites and scanners. However, maintenance of imaging protocols in MRI centers is still an ad‐hoc process. Acquisition parameters, including but not limited to flip angle (FA), repetition time (TR), and echo time (TE), are routinely improvised at individual sites to accommodate changes in software/hardware and to suit the needs of the patient. Non‐compliance in acquisition protocol can lead incompatible MR images hindering downstream analysis. For example, co‐registration with the structural counterpart becomes difficult if EPI is non‐compliant with the field map.MethodWe present an open‐source tool mrQA to automatically identify variations in acquisition parameters. A dataset is parsed to extract the parameters for each run. and compared against a reference protocol. If unavailable, reference protocol is inferred based on the most frequent value for each parameter. We recommend using mrQA for datasets in DICOM format (even though mrQA supports NIfTI) to prevent any non‐compliant parameters at the MRI scanner itself because other formats such as JSON sidecar (for NIfTI) lack standardization and hence, are often incongruous with across datasets.ResultTo assess the prevalence of protocol compliance, we evaluate over 20 public datasets on OpenNeuro (BIDS) and the ABCD dataset (FastTrack ‐ DICOM). The exploration is not meant to be a finger‐pointing exercise but to discover common pitfalls in MR acquisition that can confound the research we do. Table 1 and Table 2 summarize the results for OpenNeuro and ABCD datasets, respectively. The results are reported separately for each vendor as even the same parameters differ in the unit of measurement across vendors.ConclusionWe demonstrate the pervasive problem of protocol non‐compliance based on the analyses of many open datasets from OpenNeuro and the ABCD dataset. Our tool, mrQA can summarize acquisition parameters from a MR dataset, in order to discover any issues of non‐compliance. Even though, the effect of non‐compliance on signal intensity will depend on the specific tissue in context, explicit characterization should precede any analyses in case there is considerable non‐compliance in acquisition parameters.
Two novel cerebrospinal fluid markers for vascular injury are associated with CSF markers of AD, neurodegeneration, and gliosis
Authors: Van Hulle Carol A. , Ince Selvi , Jonaitis Erin M. , Betthauser Tobey J , Kollmorgen Gwendlyn , Wild Norbert , Bendlin Barbara B , Love Seth , Asthana Sanjay , Johnson Sterling C , Carlsson Cynthia M , Blennow Kaj , Zetterberg Henrik , Miners James Scott 
Published: December 2023

AbstractBackgroundVascular dysfunction often occurs concurrently with Alzheimer’s disease (AD). Breakdown of the blood–brain barrier (BBB) and vascular injury may be related to amyloid and tau pathology. In preliminary analyses, we examined the relationship between cerebrospinal fluid (CSF) biomarkers of AD, neurodegeneration, and glial activation, and two novel CSF markers of vascular dysfunction: soluble platelet‐derived growth factor receptor beta (sPDGFRβ) a marker of BBB integrity, and angiopoietin‐2 (Ang2), a marker of vascular injury.MethodCSF samples from participants enrolled in the Wisconsin Registry for Alzheimer’s Prevention (WRAP) or the Wisconsin Alzheimer’s Disease Research Center (WADRC) studies were assayed for markers of AD, neurodegeneration, and gliosis, using Roche NeuroToolKit® immunoassays (Roche Diagnostics International Ltd, Switzerland). A subset of serially sampled participants (N = 209, Nob

s = 531) who spanned the AD clinical spectrum (cognitively unimpaired, MCI, dementia) underwent sPDGFRβ measurement (ELISA); a sample of N = 121 (Nobs
= 276) was also assayed for Ang2 (ELISA) (Table 1). Pearson correlations were calculated for all CSF biomarkers. Linear mixed‐effects models with random intercepts, age‐at‐lumbar‐puncture as the measure of time, and CSF vascular biomarker as the outcome were used to test associations with tau positivity (>24.8 pg/mL), and cognitive status.ResultsPDGFRβ correlated with all CSF biomarkers (rs range .18 to .45, ps<.001, Figure 1A) except AB42/40. Ang2 correlated with all CSF biomarkers (rs range .21 to .45 ps <.001, Figure 1B) except AB42/40, and S100B. sPDGFRβ and Ang2 correlated most strongly with Aβ40 and biomarkers of synaptic function (neurogranin and α‐synuclein). Tau positivity was associated with sPDGFRβ in the whole sample (estimate = 64.5, p<.001) and excluding participants with MCI/dementia (estimate = 77.7, p<.001). Tau positivity was associated with Ang2 (estimate = 18.1, p = .007), however the association was not significant after excluding participants with MCI/dementia. There was no difference in sPDGFRβ across the AD clinical spectrum. Ang2 was higher among participants with MCI than cognitively unimpaired participants (estimate = 21.0, p = .037, Figure 2).ConclusionCSF markers of vascular injury were elevated in MCI and were moderately related to tau pathology and markers of neuronal injury and neuroinflammation, but not amyloid pathology, providing insight into the association of of vascular injury to AD related disease
Late‐life hypertension acts together with amyloid‐β pathology to promote early cognitive decline
Authors: Da Ros Lucas Uglione , Ferrari‐Souza João Pedro , Bastiani Marco Antônio De , Hauschild Lucas Augusto , Lussier Firoza Z , Chamoun Mira , Bezgin Gleb , Benedet Andrea Lessa ,   Alzheimer’s Disease Neuroimaging Initiative (ADNI), Pascoal Tharick A. , Rosa‐Neto Pedro 
Published: December 2023

AbstractBackgroundMidlife hypertension (HTN) is a known risk factor for Alzheimer’s Disease (AD) development. However, whether the same effect is observed in older individuals, at risk for AD, remains to be elucidated. Here, we aimed to assess whether late‐life HTN and the presence of amyloid‐β pathology (Aβ) interact to promote longitudinal cognitive decline in cognitively unimpaired (CU) individuals, and if systolic blood pressure (SBP) levels moderate this interaction. Interactive effect of disease pathophysiology is crucial for dementia prevention strategies.MethodWe used two independent cohorts. We evaluated 475 CU individuals over 65 years of age from the ADNI cohort, with available baseline medical data and CSF Elecsys biomarkers (Aβ1‐42 and p‐tau181), as well as longitudinal clinical assessments with neuropsychological testing (up to 6 years); the individuals were classified as (A)+ or (A)‐ based on a previously proposed cut‐off of CSF p‐tau181/Aβ1‐42 lower than 0.025. We also evaluated 162 CU individuals over 65 years of age from the TRIAD cohort with baseline clinical data and Aβ‐PET, as well as longitudinal clinical assessments with neuropsychological testing (up to 3 years). The individuals were classified as (A)+ or (A)‐ based on Aβ‐PET positivity. All individuals were classified as positive or negative for hypertension based on medical history. For the ADNI cohort, we could also evaluate the SBP levels as a continuous variable.ResultLinear mixed‐effects (LME) models showed that HTN and Aβ acted together to promote longitudinal cognitive decline (ADNI: HTN X Aβ X Time, β = ‐0.44, p = 0.001, figure 1, TRIAD: HTN X Aβ X Time, β = ‐0.64, p < 0.001, figure 2). Also, we could see that higher SBP levels acted together with Aβ to promote further cognitive decline (SBP values X Aβ X Time, β = ‐0.011, p = 0.03, figure 3).ConclusionOur results support a framework in which late‐life HTN is a modifiable risk factor for cognitive decline in CU individuals at increased risk for AD. This supports further investigation in determining the best target of SBP levels for individuals at risk for AD, in the context of offering precision medicine for this population.
The Neuropathological Correlates of White Matter Hyperintensities in Cerebral Amyloid Angiopathy
Authors: Makkinejad Nazanin , Zotin Maria Clara Zanon , Brink Hilde , Auger Corinne A. , Iglesias Juan Eugenio , Greenberg Steven M. , Perosa Valentina , Veluw Susanne J 
Published: December 2023

AbstractBackgroundCerebral amyloid angiopathy (CAA) is a common cause of intracerebral hemorrhage and cognitive impairment in older individuals. Hallmark manifestations of CAA on MRI include cortical hemorrhages, as well as perivascular spaces (PVS) in the white matter centrum semiovale and white matter hyperintensities (WMH) in a subcortical multi‐spot pattern. We performed an ex vivo MRI‐neuropathological study to: 1) determine the relationship between WMH volume and CAA severity, and 2) assess the histopathological substrate of confluent WMH, WMH in a multi‐spot pattern (WM_MS), and normal‐appearing white matter (NAWM).MethodNineteen autopsy cases with pathologically confirmed CAA (age 75±8y; 7F) and five non‐CAA controls (age 88±5y; 3F) were included. Formalin‐fixed hemispheres underwent 3T MRI, including a T2‐weighted (500µm isotropic resolution, to obtain manual WMH segmentations) and a T2*‐weighted sequence (1mm isotropic resolution, to automatically segment hemisphere volume using SynthSeg). After scanning, five pre‐defined standard areas were sampled from each brain, then processed to obtain manually assessed arteriolosclerosis scores and AI‐derived cortical and leptomeningeal CAA area measurements. In the CAA cases, specific areas with ex vivo MRI‐observed WM_MS (n = 7), confluent WMH (n = 9), and NAWM (n = 9) were sampled. Sections were stained with LH&E (to determine WM rarefaction, % PVS area, and degree of arteriolosclerosis), and CD68 (a marker of activated microglia, to assess density of CD68‐positive cells).ResultTotal normalized WMH volume did not differ between CAA cases (0.037±0.024) and non‐CAA controls (0.027±0.026) (Mann‐Whitney U test 36, p = 0.31). Within the CAA cases, a multivariable regression model corrected for age at death revealed that normalized WMH volume was associated with cortical CAA area (p = 0.010) and arteriolosclerosis (p = 0.066), but not leptomeningeal CAA area (p = 0.94). Targeted neuropathological assessment revealed that WM rarefaction, arteriolosclerosis score, and density of CD68‐positive cells were higher in areas with WMH compared to WM_MS and NAWM. In contrast, % PVS area was higher in WM_MS compared to WMH and NAWM.ConclusionThe observed differences in neuropathological correlates between WMH in a multi‐spot pattern and confluent WMH in CAA suggest different pathophysiological mechanisms. Future studies are needed to determine these mechanisms as well as the causal relationship between cortical CAA severity and WMH burden.
Pupillometry as a marker of arousal and in relation to cognition and cortical dynamics in Alzheimer’s disease
Authors: David Michael CB , Mallas Emma‐Jane , Karakoc Hanim , Tsoi Chris ML , Hoang Karen , Scott Gregory PT , Sharp David J , Malhotra Paresh A 
Published: December 2023

AbstractBackgroundPupil dilation is an established measure of noradrenergic activity. Cortical EEG alpha power, a measure of attentional engagement, can be recorded simultaneously with pupillometry. Dysfunction in the noradrenergic system in Alzheimer’s disease (AD), contributes to the attentional deficits seen in patients. We investigated whether pupillometry recorded at rest can be used to show reduced noradrenergic activity in AD and how this relates to cortical dynamics.MethodWe recorded simultaneous EEG and pupillometry during 5min of eyes‐open resting‐state in 28 AD patients and 22 age‐matched controls (HC). Pupil dilations – peaks of both pupil diameter and velocity – were identified (Fig. 1A/B). Average pupil diameter and velocity were calculated across all dilations, and compared between groups (Fig. 1 C/D). We plotted EEG power spectra for the 2s pupil dilation‐centred epochs (Fig. 2A). The frequency at which there was the greatest power within the alpha band – the peak alpha frequency (PAF) – was calculated for each individual and compared across groups (Fig. 2B). We then measured the alpha power during the pupil‐dilation epochs and looked at the relationship with the pupils (Fig. 3).ResultIn HCs, the mean pupil dilations – peaks in diameter and peaks in velocity – were greater than in AD; t = ‐2.62 p = 0.01 and t = ‐2.26 p = 0.03, respectively (Fig. 1C/D). Power spectra for the 2s pupil dilation‐centred epochs showed patients’ PAF was significantly lower than HC’s; t = 2.92 p<0.01 (Fig. 2). There was a corresponding peak in alpha power associated with the pupil dilations, in both groups. Regarding peaks in pupil diameter, the alpha power peaked approximately 0.5sec earlier (Fig. 3A). Regarding peaks in pupil velocity, the alpha power peaked simultaneously with the pupils (Fig. 3B).ConclusionThere is a reduction in size and velocity of spontaneous pupil dilations in AD. EEG alpha is shifted to lower frequencies in AD. There is a preserved relationship between pupil dilations and alpha peaks in AD. Pupillometry offers a means of measuring noradrenergic dysfunction in AD that relates to altered cortical dynamics.
A Vocal Assessment Method (VAM) to Evaluate the Effectiveness of Interactive Drawing Therapy for Patients with Dementia (PwD) (A Prospective Paper)
Authors: Parsapoor Mahboobeh , Parsapour Sepideh 
Published: December 2023

AbstractBackgroundIt is crucial to develop non‐pharmacological interventions to help people with dementia. Among different types of non‐pharmaceutical interventions for dementia, art therapy interventions have been shown helpful for improving patients’ physiological and mental states, in particular their cognitive performances, cognitive functionalities, including emotional states, verbal fluency, and behavioral reactions. We use Interactive Drawing Therapy (IDT), proposed by Russell Withers, as an art therapeutic method for people with dementia and to explore the method’s effectiveness, we suggest developing a vocal assessment method.MethodWe will recruit participants with mild AD and individuals without dementia and divide them into two groups, an experimental group that will attend the IDT sessions and a control group that won’t be offered the IDT sessions. All participants will attend two picture description sessions while they describe the cookie theft picture or the picnic scene. For the experimental group, we will offer attending two IDT sessions between two picture description sessions. During the first IDT session, the art therapist helps participants draw their thoughts about what he is doing during the day and describe their feelings. During the second IDT session, the art therapist shows one of the pictures, “Man changing the bulb” or “The Cat in the Tree,” and asks them to describe the picture with drawing and writing words. We collect speeches of participants during picture description and IDT sessions. The cognitive status of each participant will be measured using the Mini‐mental state examination (MMSE) test.ResultWe will aim to develop a binary classifier to distinguish patients with improved verbal fluency from patients without any enhancements in verbal fluency. It can be a part of a vocal assessment method to assess improvements in verbal fluency of patients attending IDT sessions which will be designed by combing the picture description. We also expect that such IDT sessions can enhance the verbal fluency of patients with dementia.ConclusionThis study will promise to develop a vocal system to discover the effectiveness of IDT for peoplewith dementia. As a part of this study we aim to identify linguistic and acoustic features that might change during the IDT sessions.
AD and ADRD Differences in Luminex and Lumipulse ATN Categories
Authors: Jain Lavanya , Khrestian Maria , Formica Shane , Tuason Elizabeth D. , Pillai Jagan A. , Rao Stephen M. , Leverenz James B , Bekris Lynn M. 
Published: December 2023

AbstractBackgroundCerebrospinal fluid (CSF) biomarkers for amyloid (A), tau (T), and neurodegeneration (N) can be utilized to define pre‐mortem pathological status (ATN research framework). However, potential differences across methods present challenges when comparing studies. Our objective was to determine the ATN status in an AD/ADRD cohort using two different methods for measuring CSF AD‐related biomarkers; Fujirebio Lumipulse G1200 and the Luminex 200. The hypothesis was that the proportion of individuals in a given ATN category would differ between these two methods.MethodParticipants were recruited from the Cleveland Alzheimer’s Disease Research Center (CADRC), and Cleveland Clinic Lou Ruvo Center for Brain Health (CBH) and included cognitively normal (CN), mild cognitive impairment (MCI), AD, dementia with Lewy Bodies (DLB), and PD patient groups. Aβ42/40 (A), p‐Tau181 (T) and t‐Tau (N) were quantitated using both Lumipulse and Luminex systems. Receiver Operating Characteristic (ROC) curve was utilized to identify optimal cutpoints for the three biomarkers (A, T, and N) based on the CN and AD cohorts. Youden index was calculated to identify the strength of these biomarkers.ResultCorrelation analyses between the two platforms, indicated that there was a significant correlation for Aβ42/40 (A), p‐Tau181 (T) and t‐Tau (N) among most patient groups, especially for Aβ42/40. The cut‐points were 0.0562 (A), 65 pg/mL (T) and 345 pg/mL (N) for Lumipulse, and 0.1600 (A), 106.77 pg/mL (T) and 399.41 pg/mL (N) for Luminex. Out of the overall cohort of 283 individuals, over half had identical ATN status for both Lumipulse and Luminex.ConclusionThere was a strong correlation for CSF AD‐related biomarkers between the two platforms. However, there was a lack of complete ATN category overlap between platforms suggesting that across study comparisons using ATN categories derived from different platforms (e.g. Luminex and Lumipulse) should be approached with caution. In light of different techniques that are available, it is important to understand the difference between them to inform standardization and data harmonization efforts. A definite and effective method to quantitate AD related biomarkers holds the promise of better differential diagnosis in individuals with AD and ADRD.
Bilingual neurocognitive resiliency, vulnerability, and Alzheimer’s disease biomarkers in Latino older adults enrolled in the Health and Aging Brain Study‐Health Disparities (HABS‐HD)
Authors: Grasso Stephanie M , Clark Alexandra L , Petersen Melissa , O'Bryant Sid E. 
Published: December 2023

AbstractBackgroundAlthough bilingualism has been associated with cognitive reserve and a later age of dementia onset (e.g., Alladi et al., 2013, 2017; Bialystok et al., 2007, 2010; de Leon et al., 2020), the effects of bilingualism on neuropsychological test performance in bilinguals with and without cognitive impairment have not yet been thoroughly investigated (e.g., Briceño et al., 2021; Cherner et al., 2021; Padilla et al., 2016).MethodThe present study explored patterns of cognitive performance and impairment across a large sample of bilingual and monolingual Latino older adults from the Health and Aging Brain: Health Disparities cohort (O’Bryant et al., 2021). In addition to examining differences between bilinguals and monolinguals, the associations between specific bilingual factors (i.e., dominance and age of acquisition) and cognitive performance were examined in order to elucidate which components of the bilingual experience explain such associations.ResultBilingual speakers demonstrated a pattern of cognitive resiliency in the form of better performance on attention/processing speed that can be observed across the cognitively unimpaired (Trails A, p = .001; Trails B, p = .02; Digit Substitution p = .004, and Logical Memory I p = .04) and mild cognitive impairment (Trails A, p < .001 and Digit Substitution, p < .02) diagnostic spectrum. In contrast, bilingual speakers demonstrated a pattern of cognitive vulnerability in the form of poorer performance and higher rates of impairment on a language measure that is only evident in the MCI phase (letter fluency, p = .001). Follow‐up analyses revealed bilinguals that 1) had a later age of language acquisition or 2) unbalanced language dominance performed more poorly on cognitive testing (Table 1) and had higher rates of impairment (Table 2). Exploratory analyses revealed that bilinguals with impaired language scores demonstrated lower levels of plasma Ab 42/40 relative (indicative of greater AD pathology) to unimpaired bilinguals (p = .02; Figure 1).ConclusionResults suggest that patterns of cognitive performance and impairment differ as a function of bilingualism. Bilingual factors must be considered in clinical and research investigations centered on evaluating cognitive outcomes of Latino older adults.
Multivariate white matter differences links to cognition in individuals with family history of Alzheimer’s disease and APOE4 genetic risk
Authors: Tremblay Stefanie A , Spreng R. Nathan , Alasmar Zaki , Pirhadi Amir , Tardif Christine L , Chakravarty M. Mallar , Villeneuve Sylvia , Leppert Ilana R , Carbonell Felix , Medina Yasser Iturria , Steele Christopher J , Gauthier Claudine J ,   The PREVENT‐AD Research Group
Published: December 2023

AbstractBackgroundGrowing evidence suggests Alzheimer’s disease (AD) develops from a complex cascade of events that vary between individuals. Multivariate approaches have the potential to capture the complexity and heterogeneity of pathologies underlying AD in a more holistic manner compared to univariate approaches.MethodThe MRI data of 105 older adults with a family history of AD from the PREVENT‐AD dataset were analysed. Forty six of these individuals had the APOE4‐3 genotype (greater risk of developing AD), while 59 subjects had the APOE3‐3 genotype (normal risk). Diffusion‐weighted imaging and multi‐echo magnetization transfer, proton density and T1‐weighted data were used to compute several WM metrics (Fig1 b‐c). We computed the voxel‐wise Mahalanobis distance (D2) in WM between APOE4‐3 individuals and a reference group (APOE3‐3) (Fig1). D2 is a multivariate measure that combines several MRI metrics, accounting for their covariance, and yielding a score indicative of the degree of abnormality at each WM voxel (Fig2). Associations between WM D2 and cognitive performance were then investigated (Fig3). Independent component analysis (ICA) was performed on spatial dimensions and linear regression analyses were conducted between D2 in ICA components and scores on items of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). We then extracted the contribution of each MRI feature to D2 in the regions where significant associations were found.ResultA significant negative association (R = ‐0.36, p = 0.014) was found between D2 in a component corresponding to the splenium of the corpus callosum (CC) and scores on RBANS‐immediate memory (Fig3), indicating a link between a greater degree of WM abnormality and poorer performance. Proton density (MPM_PD) and longitudinal relaxation rate (MPM_R1), potentially indicative of WM loss, contributed most to D2 in this region.ConclusionOur findings suggest that microstructural alterations in the posterior part of the CC may play a role in memory deficit in older adults who are at greater risk of developing AD. This is in line with other studies that showed a link between CC degeneration and memory impairments in early AD stages.1
1. Qiu et al. (2016). Inter‐hemispheric dysconnectivity in AD and aMCI. Sci.Rep.