bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of COVID‐19 outbreak on individuals with Alzheimer’s disease: Information released through online news
Authors: Park Eunsun , Kollia Betty , Basch Corey 
Published: February 2022

AbstractBackgroundTotal confirmed cases for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) have been increased quickly worldwide after the emergence of COVID‐19 in Wuhan, China, in December 2019. As of January 21, 2021, the total confirmed coronavirus cases are 97,736,758 worldwide with 25,124,602 in the United States (Worldometer). Prior to the COVID‐19 pandemic, the incidence of neurodegenerative diseases including Alzheimer’s disease (AD) and Parkinson’s disease (PD) had been growing rapidly rendering them major threats to human health. COVID‐19 impacted health care for persons with neurodegenerative diseases. This study reviews current research findings and their online news coverage related to the impact of COVID‐19 outbreak on persons with Alzheimer’s Disease (PWAD) in the 10 months from April 2020 to January 2021 and available resources for caregivers and PWAD.MethodWe searched “COVID‐19 Alzheimer’s Disease” in Google News and obtained the URLs of all online news reports from April 1st 2020 to January 15, 2021 for data analysis. The news stories were: a. in English language, b. non‐duplicate, and c. applicable to Alzheimer’s disease occurrence or symptoms related to COVID‐19 positive cases. The content of the selected new stories is being analyzed for references to: 1. Upload date of news report; 2. Country in which the patients in the report are located; 3. Hospital or University names/studies; 4. Journal or source of the information that is being reported; 5. Alzheimer’s disease signs / symptoms; 6. Physical/ medical comorbidities; 7. Comorbidities / associated neuropsychiatric problems mentioned; 8. Alzheimer’s disease management issues; 9. Age of patients.ResultThe study is in progress. We are currently collecting news stories and are analyzing the data.ConclusionThis study will provide information how the COVID‐19 pandemic influences the course of AD and emerging self‐management strategies for PWAD.
Memory advocate peers: Piloting a sustainable, replicable, volunteer peer mentor program to support individuals newly diagnosed with dementia and their care partners
Authors: Walter Sarah , Cisek Edward , Taylor James , Taylor Geri , Tornatore‐Mikesh Eleonora C , Levine Jed 
Published: February 2022

AbstractBackgroundAlzheimer’s disease and related dementias (ADRD) have an enormous impact on persons living with dementia and their care partners. Care partners of people with dementia are more likely to have depression, anxiety, and be isolated, heightened by events like the COVID‐19 pandemic. Connecting individuals to research has been challenging, especially in diverse populations who are disproportionately impacted by ADRD and health and socioeconomic inequities. The Memory Advocate Peers (MAP) Program aims to address these challenges by building and piloting a sustainable, replicable, volunteer peer mentor program to support individuals newly diagnosed with dementia and their care partners, and help to connect them to services.MethodThe MAP program has been developed and is led by people living with dementia, care partners, community‐based experts in dementia care, and healthcare leaders. The program will give people with dementia and care partners the opportunity to share experiences with a volunteer advocate who has lived experience with dementia, obtain valuable education about how to live well with dementia, connect to community services, and access clinical trials or other research opportunities. Partnerships have been established with New York University‐affiliated neurologists to identify and refer newly diagnosed patients to the program, and with the leading local research programs.ResultMAP will recruit and train up to 25 advocates to provide twelve months of post‐diagnostic support to 50 clients and care partners (where applicable), with a focus on under‐represented communities. A research study is embedded within the program to evaluate feasibility, as well as participant quality of life, health resource use, impact on psychological wellbeing, and value of research participation.ConclusionThis pilot will be critical in understanding the impact peer‐to‐peer mentorship can have for both the individual with ADRD and the care partner. It will also be critical to develop best practices to recruit, train and support volunteers serving as these peer advocates. Results from the pilot will be used to improve the program prior to expansion to other regions.
Polypharmacy is associated with functional decline in Alzheimer’s disease and Lewy body dementia
Authors: Borda Miguel German , Tovar Diego , Sonnesyn Hogne , Osterhus Ragnhild , Aarsland Dag 
Published: February 2022

AbstractBackgroundWe aim to study the effects of the number of medications consumed over a five‐year period after diagnosis on functional decline trajectories in older adults living with AD (Alzheimer’s disease) and LBD (Lewy body dementia).MethodsThis is a longitudinal analysis of a Norwegian cohort study entitled “The Dementia Study of Western Norway” (DemVest). We included 196 patients newly diagnosed with AD (n=111) and LBD (n=85), followed annually for 5 years. A linear mixed‐effects model was conducted to analyze the effect of numer of medications on functional decline measured by the Rapid Disability Rating Scale – 2(RDRS).ResultsThe mean of medications consumed at baseline was 4.18 ∓ 2.60, for AD 3.92 ∓ 2.51 and LBD 4.52 ∓ 2.70. The number of medications used increased during the follow‐up; at year five the mean for AD was 7.28 ∓ 4.42 and for LBD 8.11 ∓ 5.16. Comorbidity and Neurophysichiatric symtoms scores were significantly higher in the LBD group compared to AD, meanwhile no differences in MMSE. The use of more medications was associated with faster functional decline in AD ( Est 0.04, SE 0.01, p‐value 0.003 ) and LBD ( Est 0.08, SE 0.03, p‐value 0.008 ) after adjusting by age, sex, comorbidity, Neurophysichiatric symtoms and cognition. For each medication added during the follow‐up function decreased by 1% for AD and 2% for LBD.ConclusionsThe more medications used, the greater is the functional decline in AD and LBD. Medications in older adults with dementia should be used cautiously
Associations between amygdala volume and trajectories of neuropsychiatric symptoms in Alzheimer’s disease and dementia with Lewy Bodies
Authors: Jaramillo‐Jimenez Alberto , Giil Lasse Melvær , Tovar Diego , Borda Miguel German , Ferreira Daniel , Brønnick Kolbjørn , Oppedal Ketil , Aarsland Dag 
Published: February 2022

AbstractBackgroundThe potential role of the amygdala for neuropsychiatric symptoms (NPS) in dementia is not well known, especially in dementia with Lewy bodies (DLB). Cross‐sectional studies have proposed the associations between amygdala volume and NPS in Alzheimer’s Disease (AD). However, less is known about the association between amygdala volume and longitudinal trajectories of NPS. We aimed to analyze the association between amygdala volume and the longitudinal trajectories of NPS in AD and DLB.Method89 patients with mild dementia were included (AD = 55; DLB =34) in this secondary analysis of a longitudinal cohort study. Baseline amygdala volume was segmented from structural magnetic resonance images (sMRI) using a semi‐automatic method (Freesurfer 6.0). NPS were assessed annually over five years with the Neuropsychiatric Inventory (NPI) frequency × severity item‐scores. NPI item‐scores ≥ 4 were considered clinically relevant symptoms. Mixed‐effects logistic regression models were conducted in the whole sample and then in AD and DLB separately. Amygdala volume was included as a predictor of each NPS (i.e. NPI item‐score ≥ 4) over time. The models were adjusted for key demographic variables and diagnostic, as well as for center of sMRI acquisition and cognition.ResultThe cohort characteristics are shown in Table 1. Intracranial volume‐normalized amygdala volumes were comparable between AD and DLB patients. After correcting adjusted models for multiple testing, a lower odds of apathy scores ≥ 4 over time was found in patients with larger amygdala volume at baseline (OR:0.36; 95% CI: 0.21 – 0.64; p < 0.001; FDR = 0.002), with no significant effects of diagnostic (OR: 1.11; 95%CI: 0.56 – 2.17; p = 0.769; FDR = 0.846), Figure 1. The subgroup analyses showed significant results for apathy in both DLB and AD: (DLB (OR: 0.37; 95% CI: 0.16 – 0.87; p = 0.023) and AD (OR: 0.35; 95% CI: 0.15 – 0.79; p = 0.012).ConclusionSmaller amygdala volumes in people with mild dementia were associated with a higher risk of clinically relevant apathy, in both AD and DLB patients, during the 5 years study period. This association between apathy and amygdala might reflect damage in circuits underlying behavioral and cognitive avoidance.
A proposition for analyses and reporting standards for structural and functional magnetic resonance imaging of the noradrenergic locus coeruleus
Authors: Yi Yeo‐Jin , Lüsebrink Falk , Maass Anne , Betts Matthew , Ziegler Gabriel , Yakupov Renat , Kreißl Michael , Speck Oliver , Düzel Emrah , Hammerer Dorothea 
Published: February 2022

AbstractBackgroundThe noradrenergic locus coeruleus (LC) in the brainstem shows earliest signs of protein pathologies in neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Its small size (about 3‐4mm in width and 15 mm in length) makes it less suitable for Positron Emission Tomography (PET) investigations, so the past decade has seen a steep rise in structural and functional Magnetic Resonance (MR) studies aiming to characterise the LC's changes in ageing and neurodegeneration. However, given its position in the brainstem and small volume, great care has to be taken to yield methodologically reliable MR results as imprecisions in spatial transformations of functional data in the range of 2‐3mm might make LC activations at the group level effectively disappear (Figure 1B). Here, we suggest a post‐processing pipeline and set of quality control protocols which will allow LC researchers to reach the spatial precision necessary for investigating this small but potentially impactful brain structure.MethodUsing a combination of available toolboxes (SPM, ANTs, FSL, FreeSurfer), individual 3T scans for structural and functional LC characterisation are transformed into MNI space via a study‐specific template (Figure 1A). Concatenation of independently optimised transformation steps minimises interpolation applied to the data. Following this, spatial misalignment in individual MNI‐transformed are assessed using Euclidean distance (ED) measures using slice‐specific centres of structural LC masks and distance to landmarks defined based on salient anatomical features of mean functional LC images, respectively.ResultMedian Euclidean Distance of all landmarks on the transformed functional as well as structural LC imaging data were below 2 mm, thereby falling below the typical LC width of 2.5 mm shown in post‐mortem data (Fernandes et al., 2012), or half of the maximum width of the standard‐space LC mask of 4 mm (Keren et al. 2009).ConclusionWith the set of spatial post‐processing steps outlined in the poster and available for download soon, we hope to have taken a first step towards establishing reporting standards of LC imaging data and to give readers interested in LC imaging a starting point for more reliable analyses of structural and functional MR data of the LC.
Neuroimaging‐derived phenotypes in the European Prevention of Alzheimer Dementia (EPAD) Cohort Study
Authors: Lorenzini Luigi , Ingala Silvia , Wink Alle Meije , Kuijer Joost , Wottschel Viktor , Sudre Carole H. , Haller Sven , Molinuevo Jose , Gispert Juan Domingo , Cash David M. , Thomas David L. , Vos Sjoerd , Carrasco Ferran Prados , Petr Jan , Wolz Robin , Palombit Alessandro , Schwarz Adam J. , Chetelat Gaël , Payoux Pierre , Di Perri Carol , Pernet Cyril , Frisoni Giovanni B. , Fox Nick C. , Ritchie Craig W. , Wardlaw Joanna M. , Waldman Adam , Barkhof Frederik , Mutsaerts Henk‐Jan 
Published: February 2022

AbstractBackgroundNeuroimaging biomarkers in large‐scale multimodal studies have proven effective for early diagnosis. Image‐derived phenotypes (IDPs) are summary features derived from modalities such as magnetic resonance imaging (MRI). We provide an overview of the IDPs computed from the European Prevention of Alzheimer Dementia (EPAD) cohort study, a multi‐center European study including multimodal brain MRI.MethodBaseline data from the first 1500 participants of the EPAD LCS were included. The imaging protocol consists of core (3D‐T1w, 3D‐FLAIR, 2D‐T2w, 2D‐T2*), and advanced (resting‐state fMRI, SWI, diffusion MRI, and ASL) sequences. 3D‐T1w IDPs consisted of regional volumes derived from FreeSurfer v6.0 and the Learn Embeddings for Atlas Propagation (LEAP) segmentation pipelines and 3D‐FLAIR IDPs were white matter hyperintensity (WMH) volumes measured by Bayesian Model Selection (BaMoS). Mean functional connectivity of rs‐fMRI networks was extracted with FSL MELODIC and dual‐regression analyses. For diffusion‐weighted imaging, we used FSL TBSS to quantify 48 regional fractional anisotropy (FA) values according to the JHU atlas of white matter tracts. ExploreASL was used to calculate mean Cerebral blood flow (CBF) and spatial coefficient‐of‐variation (sCoV) from ASL images. To evaluate the biological relevance of IDPs, we assessed their relationship with non‐imaging phenotypes.ResultA total of 358 core and 119 advanced IDPs were derived. GM volume was inversely correlated with age, with stronger effects in medio‐temporal areas (Figure 1). Regional WMH volumetrics showed mostly frontal and parietal WM lesions that were associated with aging (Figure 2). Heterogeneous changes in within‐network functional connectivity were observed with older age, with mild differences between CDR 0 and 0.5 contrasts, mostly related to the default‐mode and frontoparietal networks (Figure 3). Age was also associated inversely with skeletonised FA values. Stronger reductions appeared in amyloid positive participants (Figure 4).ConclusionWe show the relevance of IDPs from the EPAD neuroimaging dataset. The observed relationships with non‐imaging phenotypes confirm their biological relevance and are in agreement with previous studies. The proposed IDP framework may constitute a valuable resource for researchers using EPAD data, promoting reproducibility of results and easily adaptable for other studies and cohorts.
Abnormal neural oscillations depicting excitatory‐inhibitory imbalance are distinctly associated with amyloid and tau depositions in Alzheimer's disease
Authors: Ranasinghe Kamalini G. , Verma Parul , Cai Chang , Xie Xihe , Kudo Kiwamu , Gao Xiao , Lerner Hannah M. , Mizuiri Danielle , Strom Amelia , Iaccarino Leonardo , La Joie Renaud , Miller Bruce L. , Tempini Maria Luisa Gorno , Rankin Katherine P. , Jagust William J. , Vossel Keith A. , Rabinovici Gil D. , Raj Ashish , Nagarajan Srikantan S. 
Published: February 2022

AbstractBackgroundExcitation‐to‐inhibition (E/I) imbalance is believed to be a key contributor of synaptic and network degeneration in Alzheimer’s disease (AD)(Frere and Slutsky, 2018). Extensive preclinical research on transgenic animal models of AD have demonstrated neuronal and circuit level E/I imbalance mediated by amyloid‐beta (Aβ) and abnormally phosphorylated tau proteins (Harris et al., 2020; Palop and Mucke, 2016). However, the mechanisms of E/I imbalance leading to disrupted networks and their relationships to Aβ and tau in humans remain poorly understood.MethodIn this multimodal imaging study in patients with AD (n=20 AD patients; n=35 age‐matched controls; Table‐1), we first examined the spectral changes in oscillatory brain rhythms using magnetoencephalography and their relationships to tau and amyloid‐beta (Aβ) accumulation in PET imaging (flortaucipir and 11C‐PiB, for tau and Aβ, respectively). Next, we estimated parameters of a linear neural mass model (Raj et al., 2020) that best fit the observed spectra, and examined the relationships between model parameters for excitatory and inhibitory neural sub‐populations, and tau and Aβ accumulations.ResultWe found that neuronal hypoactivity was associated with tau while hyperactivity was associated with Aβ (Figure 1). We also demonstrated E/I imbalance in patients with AD, depicted as abnormal excitatory and inhibitory neuronal parameters in a linear neural mass model that reproduced the empirical macroscopic power spectra (Figure 2). The abnormal excitatory and inhibitory neuronal parameters showed distinct associations with tau and Aβ—higher tau correlated with a longer excitatory time‐constant, whereas higher Aβ correlated with a longer inhibitory time‐constant (Figure 3).ConclusionThe unique contribution of the collective finding in the current study is to demonstrate how abnormalities in the oscillatory power spectrum in AD is mechanistically linked to impaired function of excitatory and inhibitory neuronal populations that are in turn associated with tau and Aβ accumulations. Neural oscillations are modulators of rate and timing of neuronal spiking and have a key role in governing the neuronal excitability (Siegel et al., 2012). The multimodal neuroimaging in AD patients in the current study demonstrate how different frequency oscillations are distinctly affected by Aβ and tau, and offer new perspectives for network stabilizing therapies.
Advanced diffusion‐MRI models reveals sex‐specific differences in white matter organization in patients with mild cognitive impairment
Authors: Mishra Virendra R. , Ritter Aaron , Caldwell Jessica Z.K. 
Published: February 2022

AbstractBackgroundRecent literature suggests that free‐water corrected (fiso) diffusion MRI (dMRI) measures provide higher sensitivity as compared to conventional single‐tensor (ST) dMRI measures to understand white‐matter (WM) changes due to neurodegeneration. However, fiso‐corrected dMRI measures are still biased at crossing‐fiber regions (CFR) of WM which are shown to be around 90% of the total WM voxels with conventional dMRI data acquisition. In this study, we systematically compared dMRI measures from ST‐dMRI, fiso‐corrected ST‐dMRI measures, and measures from advanced dMRI models such as Diffusion Kurtosis Imaging (DKI) and Neurite Orientation Distribution and Density Imaging (NODDI) which are sensitive to CFRs. We hypothesize that these advanced dMRI models will be sensitive in understanding sex‐specific WM organizational changes at regional level in patients with Alzheimer’s disease (AD)‐related mild cognitive impairment (MCI).Method40 healthy controls [HC; 21 Females (F), 19 Males (M)] and 38 MCI participants [13F, 25 M] were recruited at our center. MCI diagnoses were based on expert consensus between a neurologist (AR) and a neuropsychologist (JC) using results of a neuropsychological test battery and the Clinical Dementia Rating (CDR) interview. Isotropic 1.5mm3 multi‐shell dMRI (b‐values=500s/mm2, 1000s/mm2, and 2500s/mm2) each with identical 71 diffusion‐encoding directions was acquired on a 3T Siemens Skyra scanner for every participant using the CMRR sequence. 8 uniformly interspersed non‐diffusion‐weighted (b0) images were also acquired in the same run. ST, fiso‐corrected, DKI, and NODDI dMRI measures were estimated for every brain voxel in‐house using the standard analytic tools. WM was skeletonized using FSL tools and statistical comparisons were done non‐parametrically using PALM tools. GLM was utilized to test for sex‐specific group effect. Significance was established at family‐wise error correction (FWE) pcorr<0.05.ResultThalamocortical tracts of males in both HC and MCI showed a significantly higher axonal kurtosis (AK) and orientation density (ODI) derived from DKI and NODDI when compared to within‐group females. DKI also revealed presence of higher axonal water fraction (AWF) along the entire WM‐tracts between HC‐female and HC‐male, and lower mean kurtosis (MK) along the thalamic‐cortical tracts in HC‐females as compared to MCI‐females.ConclusionAdvanced dMRI‐models are sensitive to understand sex‐specific WM disorganization due to healthy ageing and MCI.
Cortical reinstatement in the visual associative memory network is compromised by early tau in normal older adults
Authors: Mormino Elizabeth C. , Trelle Alexandra N. , Hunt Madison , Tran Tammy , Carr Valerie A. , Toueg Tyler , Deutsch Gayle , Harrison Marc , Sha Sharon , Rutt Brian S. , Kerchner Geoffrey A. , Wagner Anthony D. 
Published: February 2022

AbstractBackgroundThe structure and computations associated with specific hippocampal subfields decline in aging and are also initial sites of Alzheimer’s disease pathology. The degree to which age‐associated changes in hippocampal‐dependent memory are driven by early AD pathology among older normal adults remains unclear.MethodWe enrolled one hundred ninety‐nine clinically unimpaired (CU) older individuals into the Stanford Aging and Memory Study (SAMS, 117 Female, mean age= 68.9±6.2). Participants completed a lumbar puncture to collect cerebrospinal fluid (CSF), high‐resolution fMRI (at 3T) during a visual associative memory paradigm, and ultra high‐resolution structural MRI (at 7T) to assess MTL subregion integrity, as well as extensive cognitive assessment. Data collection is complete, and analysis of fMRI and 7T structural data of the 199 participants is currently underway. To examine neuronal computations underlying hippocampal dependent memory, we focused on fMRI metrics in a subset of 78 participants that quantify cortical reinstatement (the degree to which voxelwise patterns of activation during retrieval match activation patterns during encoding) in two a priori regions known to be important for visual associative memory (ventral temporal cortex, VTC; and angular gyrus, ANG). Additionally, we extracted univariate fMRI signal from the hippocampus during successful retrieval. Finally, hippocampal thickness from CA1 in a subset of 77 participants was manually delineated on 7T scans, and CSF was processed with Lumipulse to measure Ab42:Ab40 ratio and p‐tau181.ResultElevated p‐tau181 was associated with worse performance on the fMRI‐scanned visual associative memory task (Figure A), reduced cortical reinstatement strength in both VTC (r = ‐0.25, p = .027, Figure B) and ANG (r = ‐0.22, p = .048), as well as reduced CA1‐SRLM thickness (r = ‐0.32, p = .004, Figure C). Although Ab42:Ab40 ratios were related to p‐tau181, they were not independently associated with neuronal indices of hippocampal‐dependent memory.ConclusionCU with evidence of early tau abnormalities show worse hippocampal‐dependent memory and differences in fMRI and structural measurements in regions critical for successful associative memory. Initial consequences of AD pathology target specific hippocampal‐cortical circuits, and this is measurable using advanced MRI techniques.