bluuebunny/crossref_metadata_2025_split huggingface dataset:
Augmenting cognitive assessment with instruction‐less Eye‐tracking tests: A machine learning approach for detecting abnormal oculomotor biomarkers
Authors: Mengoudi Kyriaki , Ravi Daniele , Yong Keir X.X. , Primativo Silvia , Pavisic Ivanna M. , Brotherhood Emilie V. , Lu Kirsty , Schott Jonathan M , Crutch Sebastian J. , Alexander Daniel C. 
Published: December 2020

AbstractBackgroundEye‐tracking technology is an innovative tool that holds promise for enhanced dementia screening, offering the potential of brief and quantitative assessment of cognitive functions. Critically, instruction‐less eye‐tracking tests may ameliorate some of the issues with complex test instructions and linguistic variations associated with traditional cognitive tests, and capture additional sensitive metrics of task performance. However, the extraction of relevant biomarkers from large, complex eye‐tracking datasets is non‐trivial. In this work, we introduce a novel automated way of extracting abnormal oculomotor biomarkers using machine learning from raw eye‐tracking data acquired during an instruction‐less cognitive test.MethodA free‐viewing instruction‐less cognitive battery (5 minutes) was administered to healthy controls (N=553) and patients with a range of dementias (N = 30) [Figure 1]. Our method is based on self‐supervised representation learning: a deep neural network is initially trained to solve a pretext task that has well‐defined available labels. Here the pretext task is to identify distinct tasks ‐ scene perception, reading, episodic memory for scenes ‐ in healthy individuals from eye‐tracking patterns. Figure 2 visualises some features of eye‐tracking patterns that correspond to particular tasks. Once trained, this network encodes high‐level semantic information which is useful for solving other problems of interests (e.g. dementia classification) [Figure 3]. The extent to which eye‐tracking features of patients with dementia deviate from healthy behaviour is then explored, followed by a comparison between self‐supervised and handcrafted representations on discriminating between controls and patients.ResultBased on the results of the handcrafted features, patients with dementia had significantly lower scanpath lengths than controls (z = ‐276.56, SE = 97.09, p =0.00439), consistent with less extensive and efficient scanning of the presented stimuli. The self‐supervised learning features showed higher performance in discriminating dementia patients from controls (F1 score (95% CI: [0.78, 0.82]) vs standard handcrafted features [0.62, 0.67]).ConclusionThese results suggest that instruction‐less eye‐tracking tests can detect dementia status, even in the absence of explicit task instructions. We reveal novel self‐supervised learning features that are more sensitive than handcrafted features in detecting performance differences between participants with and without dementia across a variety of eye‐tracking‐based cognitive tasks.
Neuroimaging of amyloid pathology in a non‐human primate model of sporadic CAA
Authors: Genovese Thomas S , Ramadane Dina , Kingsley Charles , Nehete Pramod N , Nehete Bharti P , Patel Akash G , Rusinek Henry , Williams Lawrence E , Zaim‐Wadghiri Youssef , Wisniewski Thomas , Scholtzova Henrieta 
Published: December 2020

AbstractBackgroundThere has been a growing interest in developing MRI technologies to visualize Aβ plaques in animals, using approaches that may eventually be applied to humans. A non‐human primate model, squirrel monkey (SQM), was utilized in the present study due to their unique property of naturally developing age‐dependent cerebral amyloid angiopathy (CAA) identical to that seen in humans. It has been demonstrated that the transverse relaxation rate (R2*) has a linear correlation with iron content, a component of amyloid deposits and microhemorrhages. Here we proposed to evaluate whether the region of interest (ROI)‐based quantitative R2* assessment is able to detect age related differences in SQM neuropathology. An additional focus was to validate the ability of our novel MRI methodology using bi‐functional nanoparticles (USPIO‐PEG‐Aβ) to detect amyloid deposits.MethodMulti‐gradient echo MR images were acquired in three different SQM age cohorts (ages 5, 16, 21) at various stages of Aβ pathology development. The R2* map of pre‐ and post‐Aβ nanoprobe injection MRI scans were generated (Firevoxel parametric map tool) from each subject to enable (ROI)‐based quantitative R2* analyses. 6E10 immunohistochemistry was used to confirm the presence of CAA and parenchymal plaques to correlate with the R2*.ResultMGE imaging was effective in differentiating between the MRI brains of a 5 year old SQM with no Aβ deposits and aged SQMs with established Aβ pathology. Absolute quantitation of R2* values, defined by ROI circumventing the cortex, revealed significant differences between the young and old subjects, with the highest R2* counts detected in the 21 year old monkey. Further increase in R2* values was observed 36 hrs post‐contrast injection scans in specific brain regions in our oldest cohort, indicative of plaque labeling with our contrast agent. No toxicity was observed during the scans, demonstrating the safety of our Aβ nanoprobe. The degree of correspondence between amyloid deposits detected by MRI and 6E10 immunohistochemistry was confirmed via matched histological sections.
ConclusionThe present findings validate the utility of our MRI methodologies to monitor age dependent accumulation of Aβ deposits, opening the possibility of longitudinally evaluating novel therapeutic interventions targeting amyloid pathology.
Psychoeducation at our Belgian geriatric day hospital
Authors: Higuet Sandra , Willems Vanessa , Geurts Marie‐Noëlle , Zuinen Tatiana , Institute Global Brain Health 
Published: December 2020

AbstractBackgroundWith the rising dementia population, more and more programs have been developed to help caregivers. Being a caregiver for people with dementia is associated with psychological stress and physical ill‐health. Benefits in terms of mental health and depression were generally found for caregiver coping strategies involving problem focus, acceptance and social‐emotional support. These programs, call Psychoeducation have been consistently found to be effective in reducing caregiver distress and are suited for delivery in group format. Support groups, multicomponent interventions and joint engagements by both caregivers and people with dementia were generally found to be beneficial.MethodThis is an observational study concerning simultaneous care of dyads (patient with cognitive impairment and caregiver): the family will benefit from Psychoeducation sessions (4 classes of 3 hours during a year) with a psychologist and neuropsychologist in order to learn to modify their interactions with patients via a better understanding of illnesses and thus prevent family exhaustion. At the same time the patient will be supported by an occupational therapist for activities in order to preserve the maintenance at home as long as possible. Measures (Zarit Caregiver Burden Scale, Neuropsychiatric Inventory Questionnaire(NPI‐Q), Beck Depression Inventory (BDI), Scale of Caregiver’s Quality of life (QoL), Scale of Caregivers’ Precariousness, Hospital Anxiety and Depression Scale (HAD) and Lawton Scale) were collected at baseline and post intervention at 12‐months follow‐up.ResultsThe results are ongoing; the preliminary results concerning the caregivers (n=10) and the patients aged from 72 to 88 years old (n=5). We observe a trend decreasing in the caregiver’s emotional charge and a psychic well‐being. Patient assessment is more difficult given the actually small sample size and the advanced degree of dementia.ConclusionThis project made it possible to test the effect of psychoeducation on the helping‐helped dyad allowing on the one hand to make the caregiver expert and on the other hand to try to make the patient as independent as possible in the long term and keeping them in a continuous and transversal link.
Chronic intermittent hypoxia enhances tau seeding and propagation and exacerbates Alzheimer’s‐like memory and synaptic plasticity deficits and molecular signatures
Authors: Kazim Syed Faraz , Sharma Abhijeet , Larson Chloe S. , Ramakrishnan Aarthi , Blitzer Robert , Shen Li , Pena Catherine , Crary John F. , Shimoda Larissa , Nestler Eric , Pereira Ana C. 
Published: December 2020

AbstractBackgroundObstructive sleep apnea (OSA), characterized by sleep fragmentation and chronic intermittent hypoxia (CIH), is a risk factor for Alzheimer’s disease (AD) development and progression. Recent epidemiological studies point to CIH as the best predictor of developing cognitive decline and AD in elderly with OSA. However, the precise underlying mechanism(s) remain unknown. Tau pathology, a major neuropathological hallmark of the disease, is known to be correlated with cognitive impairment in AD. Further, increase in tau pathology has been linked to CIH suggesting that CIH may mediate AD risk through tau pathology. The present study was undertaken to evaluate the effect of CIH on human tau seeding and propagation, and to further investigate the effects of CIH on cognition, synaptic plasticity, neuronal network excitability, and gene expression profiles in a human mutant tau mouse model of AD and related tauopathies (P301S mice).MethodWe exposed 4‐4.5‐month‐old, male, mutant human tau P301S/WT mice to an 8‐week CIH protocol simulating human OSA (6 m cycle: 21% O2 to 8% O2 to 21% O2, 80 cycles per 8 h during daytime), and assessed its effect on tau seeding and spread and on various AD‐related phenotypic and molecular signatures. Age‐ and gender‐ matched P301S/WT mice were reared in normoxia (21% O2) as experimental controls.ResultExperimentally induced CIH significantly enhanced human tau seeding and spread across connected neuroanatomical circuitry in the brains of a P301S mutant human tau model of AD; also, it increased phospho‐tau load in P301S mice. CIH also exacerbated memory deficit and synaptic plasticity impairment and increased disinhibition‐like behavior in P301S mice. However, CIH had no effect on seizure susceptibility and network hyperexcitability in these mice. Finally, CIH exacerbated AD‐related pathogenic molecular signaling in P301S mice.ConclusionIn a comprehensive panel of immunohistochemical, behavioral, biochemical, electrophysiological, and transcriptomic analyses, we found that CIH enhances human tau seeding and spread, and exacerbates tau pathology, cognitive deficit, disinhibition‐like behavior, short‐ and long‐term synaptic plasticity impairment, and AD‐related molecular signaling in P301S mouse model of AD and related tauopathies. These data provide a mechanistic basis of a role for CIH and OSA in AD pathogenesis.
Increased APOE‐e4 expression is associated with reactive A1 astrocytes and may confer the difference in Alzheimer disease risk from different ancestral backgrounds
Authors: Celis Katrina , Griswold Anthony J. , Bussies Parker , Rajabli Farid , Whitehead Patrice L. , Hamilton‐Nelson Kara L. , Beecham Gary W. , Dykxhoorn Derek M. , Nuytemans Karen , Wang Liyong , Gardner Olivia K. , Dorfsman Daniel , Bigio Eileen H , Mesulam Marsel , Weintraub Sandra , Geula Changiz , Gearing Marla , Dalgard Clifton , Mcgrath‐Martinez Elisa , Scott William K. , Haines Jonathan L. , Pericak‐Vance Margaret A. , Young Juan , Vance Jeffery M. 
Published: December 2020

AbstractBackground
APOEε4 is the strongest genetic risk factor for Alzheimer Disease (AD) in European populations. African local genomic ancestry (LA) surrounding the APOEε4 allele has been associated with a decreased risk for AD in African‐American (AA) carriers relative to European LA in Non‐Hispanic Whites (NHW) (Rajalbi et al 2018). Identifying the cause of this protective effect in AA could lead to therapeutic intervention lowering AD risk for European carriers of APOEε4.MethodTo identify potential gene expression variations in the LA region contributing to this differential risk Single Nucleus RNA sequencing (snRNA‐seq) was performed on frozen frontal cortex from four APOEε4 homozygote AA AD patients with only African LA and four APOEε4 homozygote NHW AD patients with only European LA. SnRNA‐seq (10X Chromium platform) was analyzed using Seurat for potential differences in expression between the samples.Result47,113 total nuclei were sequenced at a median depth of ∼131,000 reads per cell. We detected on average ∼1800 genes per nucleus. European LA carriers had significantly more APOEε4 expressed (p < 1.8E−313) than AA patients in 17 of the 42 snRNA‐seq clusters. Cluster 21 was unique, as it was highly enriched for APOEε4 expression and contained proportionately 12‐fold more NHW nuclei than AA. Examination of the transcriptional signature of cluster 21 revealed a strong enrichment for known astrocyte‐specific markers, with significantly higher levels of GFAP, VIM, LGALS1, FGF2, and HSBP1 compared to other astrocyte clusters.ConclusionThese findings suggest that the increased risk for AD seen in NHW versus AA carriers of APOEε4 is likely due to increased APOEε4 expression in carriers with the European LA. This increased APOEε4 expression is strongly associated with a large increase in potentially reactive A1 astrocytes, supporting this as a possible mechanism for the increased risk for AD conferred by the APOEε4 allele.
Yoga training impacts physical function 12 months post intervention for care partners of those with mild cognitive impairment
Authors: Chandler Melanie , Locke Dona E , Thomas Colleen S , Crook Julia E , Graff‐Radford Michelle , Lucas Pauline H , Phatak Vaishali S , Smith Glenn E 
Published: December 2020

AbstractBackgroundThe American Academy of Neurology Practice Guidelines recommends physical exercise to help maintain cognition in people with Mild Cognitive Impairment (pwMCI). We previously demonstrated yoga’s benefit in maintenance of memory related activities of daily living at one year follow‐up in pwMCI (Chandler et al., 2019), and yoga may be beneficial in offsetting a sense of burden in care partners at 12 months (Amofa et al., submitted). In this analysis, we sought to examine the impact of yoga training on physical performance in pwMCI and their care partners.MethodIn this multisite, randomized clinical trial, we enrolled 272 patients meeting National Institute on Aging–Alzheimer’s Association criteria for MCI and a care partner. The intervention program was modeled on the 10 day Mayo Clinic HABIT Healthy Action to Benefit Independence and Thinking® program. Of 5 possible interventions (memory compensation training, computerized cognitive training, yoga, patient and partner support groups, and wellness education), 1 of 5 interventions was randomly selected to be withheld for each intervention group, thus allowing us to examine comparative effectiveness. Participants and their partners had 1‐day booster sessions at 6 and 12 months after intervention. The Short Physical Performance Battery (SPPB), a measure of balance, gait speed, and repeated chair stands was used to assess physical function outcomes.ResultThere was a general pattern of physical decline on the SPPB over the year in pwMCI, regardless of yoga training (d=‐0.04, p=0.78) (Figure 1, Panel A). Among care partners, those randomized to the no yoga group had a worse decline in physical function compared to those receiving yoga (d=‐0.31, p=0.034) (Figure 1, Panel B). While not reaching statistical significance in subgroup comparisons, yoga training tended to have a greater effect on SPPB than computerized cognitive training (d = 0.35, p = .06) or wellness education (d = 0.32, p =.09) (Table 1).ConclusionParticipation in yoga had a positive impact on physical performance outcomes at one year for care partners, but did not counteract general physical decline in pwMCI.
Microglial activation evaluated using flutriciclamide (11F‐GE180) in subjects with cognitive impairment
Authors: Calsolaro Valeria , Hinz Rainer , Femminella Grazia Daniela , Pasqualetti Giuseppe , Buckley Chris J , Gentleman Steve , Brooks David J , Edison Paul 
Published: December 2020

AbstractBackgroundMicroglial activation plays a significant role, and could be quantified using PET tracers targeting TSPO. We evaluated the use of Flutriciclamide PET tracer in a cohort of subject diagnosed with Alzheimer’s Disease (AD) or Mild Cognitive Impairment (MCI), using spectral analysisMethodTwenty‐three subjects with AD, fourteen with MCI and eleven healthy controls (HC) underwent 3T MRI and Flutriciclamide PET with arterial input. Spectral analysis was used to create parametric maps, and IRF at 90 minutes was sampled for region of interest analysis. IRF90 parametric maps were also used for voxel‐wise SPM group analysis.ResultMean ages were 70.65±6.2‐ for AD, 70.3±6‐ for MCI and 63.4±1.4‐ for HCs. MCI and AD were age‐matched. Significant difference was found in the MMSE scores between AD and MCI (mean and SD respectively 21.8±3.7‐ and 26.8±3‐, p<0.001) and between AD and HC (mean and SD of HC 28.9±1.4‐, p<0.001). Significant difference was found in the hippocampal volumes between AD and MCI (mean 2711±477 on the left and 2750±455 on the right for AD, and 3942±284 and 4048±394 for MCI, p<0.01) and between AD and HC (mean 3942±284 on the left and 4048±394 on the right for HC, p<0.001).Significant difference was also found between MCI and HC (p=0.01 for left hippocampus, p=0.02 for the right one). When evaluating the IRF90 flutriciclamide uptake, significantly higher uptake was found in the AD group compared to HC in temporal (p<0.01), parietal (p=0.012), occipital (p=0.03) lobes and composite brain (p=0.01). In the AD group, IRF90 was higher in temporal lobe when compared with MCI group (p=0.04). SPM group wise analysis showed significantly higher uptake in part of temporal, parietal and occipital regions in AD compared to HCs, and a smaller cluster including part of temporal and occipital lobes when comparing AD and MCI.ConclusionOur study, conducted in a population with a clinical diagnosis of AD or MCI demonstrated higher widespread flutriciclamide uptake in the AD group compared with HC, and more limited difference between AD and MCI, and can be used quantify neuroinflammation.
Gender differences in the association of childhood socioeconomic status and late‐life cognition among African Americans: Findings from the STAR study
Authors: Barnes Lisa L , Peterson Rachel , George Kristen M , Gilsanz Paola , Mungas Dan M , Glymour M Maria , Mayeda Elizabeth Rose , Whitmer Rachel A 
Published: December 2020

AbstractBackgroundLow socioeconomic status in childhood has been linked with poor cognitive function in old age. But few studies have focused on African Americans or evaluated gender differences. We examined cross‐sectional associations of childhood socioeconomic factors with late‐life cognition and effect modification by gender.MethodsStudy of Healthy Aging in African Americans (STAR) participants were 722 African Americans (69% women; mean age = 68.4 and education: 60% <High school) community‐residing long‐term members of Kaiser Permanente Northern California. Summary scores in 3 cognitive domains (executive function, semantic memory, verbal memory) and a global cognition composite were based on the Spanish and English Neuropsychological Assessment Scales (SENAS). Participants rated frequency of experiencing hunger as a child (sometimes/often vs. rarely/never), their family’s financial status (average/high vs. poor), and parental education (>= high school vs. < high school), as indicators of childhood SES. Linear regression models adjusted for age were used to examine childhood SES and late‐life cognition, and effect modification by gender.ResultsThere were no gender differences in experiencing childhood hunger (p=.08), having poor family finances (p=0.30), or parental education (p=0.17). In the pooled model with women and men, higher frequency of childhood hunger was associated with worse cognition overall (β=‐0.36, 95% CI=‐0.66, ‐0.06) and in all domains (executive: β=‐0.32, 95% CI=‐0.63, ‐0.01; semantic: β=‐0.38, 95% CI=‐0.53, ‐0.23; verbal: β=‐0.42, 95% CI=‐0.73, ‐0.12). Low parental education was only associated with lower global cognition β=‐0.18, 95% CI=‐0.33, ‐0.02 and semantic memory (β=‐0.40, 95% CI=‐0.57, ‐0.23). Childhood family financial status was not associated with late‐life cognition. In gender‐stratified models, women who reported greater frequency of childhood hunger had worse cognition in every domain except semantic memory (overall: β=‐0.53, 95% CI=‐0.94, ‐0.13; executive: β=‐0.61, 95% CI=‐1.01, ‐0.20; semantic: β=‐0.21 95% CI=‐0.64, 0.21; verbal: β=‐0.46, 95% CI=‐0.87, ‐0.06). In contrast, childhood hunger was not associated with cognition in men (overall: β=‐0.14, 95% CI=‐0.59, 0.32; executive: β=0.11, 95% CI=‐0.35, 0.58; semantic: β=‐0.05 95% CI=‐0.57, 0.48; verbal: β=‐0.40, 95% CI=‐0.88, 0.08), but low parental education was associated with semantic memory (β=‐0.43, 95% CI=‐0.73, ‐0.14).ConclusionChildhood hunger is associated with worse cognition in old age, particularly among women.
MRI visualization of activated monocytes accumulation in the CNS of P301S tau mice by targeted nanoparticle technology: An approach to MRI molecular imaging of neuroinflammation
Authors: Tanifum Eric , Chintakunta Praveen , Badachhape Andrew , Admane Prasad , Srivastava Mayank , Stupin Igor , Devkota Laxman , Annapragada Ananth 
Published: December 2020

AbstractBackgroundChronic neuroinflammation plays a critical role in the pathophysiology of Alzheimer’s disease (AD) and related dementias. The CNS is immune privileged with restricted peripheral leukocyte traffic under normal physiological conditions. Neuroinflammation in disease brains is often accompanied by BBB compromise and increase CNS infiltration by activated peripheral monocytes/macrophages. Part of the inflammatory response in these cells is upregulation of the integrin, very late antigen‐4 (VLA‐4) and present a valuable target for detection and treatment of neuroinflammation.MethodIn vivo MRI scans were performed on 9 to 12 months old P301S mice on a 1 Tesla small animal MR scanner using a 2D fast spin echo inversion recovery (FSE‐IR) scan protocol that approximates a fluid‐attenuated inversion recovery (FLAIR) sequence (scan parameters: TR = 6500 ms, TE = 80 ms, TI = 2000 ms, slice thickness = 2.4 mm, matrix = 192x192, FOV = 30 mm, slices = 6, NEX = 6). Mice were pre‐scanned to obtain a baseline image and then injected with Rhodamine‐labeled VLA‐4 targeted nanoparticles bearing a T1 MR relaxive payload. Four days post‐contrast injections, they were rescanned and then euthanized and brain tissue harvested for ex‐vivo immunohistochemical analysis by confocal microscopy. Test animals included transgenic mice injected with the targeted agent (n = 6). Controls included transgenic mice injected with a non‐targeted agent (n = 6) and wild‐type age‐matched litter mates injected with the targeted agent (n = 6).ResultMR images 4 days post contrast administration showed on average, higher accumulation of the contrast agent in the brains of the test mice compared to moderate to low levels of accumulation in the control mice. The in vivo MR data is validated by ex‐vivo histology results which also showed higher Rhodamine signal intensity in brain disuse sections from the test mice compared to controls. The high accumulation in the test mice is attributed to both active and active particle uptake mechanisms while only passive mechanisms are possible in the controls.ConclusionVLA‐4 targeted MRI sensitive nanoparticles label activated monocytes/macrophages in P301S mice CNS, enabling noninvasive detection of neuroinflammatory activity and highlighting a potentially novel approach to imaging neuroinflammation in AD.