bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detecting mild cognitive impairment by quantifying oculometric features during variable cognitive workload: The novel rapid Oculo‐Cognitive Addition Test
Authors: Hagen Kate , Pradhan Gaurav , Cevette Michael , Stepanek Jan 
Published: December 2020

AbstractBackgroundThe need exists for a device that can rapidly and accurately assess mild cognitive impairment (MCI). Because the link between oculometrics and cognition is well‐documented, the Oculo‐Cognitive Addition Test (OCAT) was developed which tracks users’ eye movements as they complete a simple mental addition test.MethodOCAT consisted of 12 trials of summing three consecutive single‐digit numbers, shown separately on three consecutive screens (Figure 1). The first, second, and third screen in each trial corresponded to low, medium, and high cognitive workload. Using an infinity‐loop pattern of 24 symmetrical positions, eye movements were captured systematically in horizontal, vertical, and diagonal directions (Figure 2).MCI was simulated by exposing subjects to 5 minutes of hypoxic gas mixture (8% O2 + balance N2). 20 subjects completed OCAT in baseline (i.e. normal room air), hypoxic, and post‐baseline (i.e. 20 minutes of room air) conditions. Raw scan‐paths were collected with an eye‐tracking device. Oculometrics pertaining to fixations and saccades were extracted. Statistical significance was assessed using repeated measures ANOVA. Effect size and clinical significance was evaluated using computed Cohen’s d.ResultOCAT completion time significantly increased from baseline to hypoxia, which corresponded to a significant decrease in cerebral oxygenation from baseline to hypoxia (Figure 3). From baseline to hypoxia, saccadic latency significantly increased while saccadic velocity significantly decreased in the diagonal direction, however, results in the horizontal and vertical directions were not significant (Figure 4). Fixation time significantly increased from baseline to hypoxia in medium and high cognitive workload, but did not significantly change in low cognitive workload (Figure 5). From baseline to hypoxia, fixation size did not significantly change in any cognitive workload, however, the fluctuation in fixation size significantly increased in medium cognitive workload. From baseline to hypoxia, fixation area significantly increased in low and high cognitive workload, but did not significantly change in medium cognitive workload.ConclusionOCAT can detect subtle changes in oculometrics that correlate with MCI. This study provides rationale for providing varying degrees of cognitive load to elucidate subtle changes in oculometrics that may otherwise go undetected in neurocognitive tests that do not increase cognitive load.
FDG‐PET subtypes of Alzheimer’s disease and their association with distinct biomarker profiles and clinical trajectories
Authors: Levin Fedor , Ferreira Daniel , Lange Catharina , Dyrba Martin , Westman Eric , Buchert Ralph , Teipel Stefan J. , Grothe Michel J. 
Published: December 2020

AbstractBackgroundPET with the glucose analog FDG is a sensitive marker of neuronal dysfunction/degeneration. The aim of this study was to identify distinct metabolic subtypes in prodromal and dementia stages of AD by a data‐driven exploration of FDG‐PET and to compare the subtypes with respect to molecular biomarkers and clinical trajectory.MethodFirst, we used hierarchical clustering of voxel‐wise FDG‐PET from 177 biomarker‐confirmed AD dementia patients from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort to identify distinct subtypes of hypometabolism in AD. The AD subtypes were then characterized with respect to clinical and molecular biomarker characteristics. Subsequently, we classified FDG‐PET scans of 217 amyloid‐positive MCI patients (‘prodromal AD’) according to the subtypes identified in AD patients, and examined their prognostic value for predicting domain‐specific cognitive decline and conversion to dementia over a follow‐up interval of up to 72 months.ResultFour main AD subtypes characterized by differential hypometabolism patterns were identified (Fig. 1): (i) “AD‐typical” (48.6%), showing a classic posterior temporo‐parietal hypometabolic pattern with intermediate cognitive decline and biomarker characteristics, (ii) “minimal limbic” (24.9%), showing least impaired cognitive performance but comparable amyloid and tau biomarker profiles, (iii) “limbic‐frontal” (19.8%), characterized by old age and most severe hippocampal atrophy, and (iv) a “frontal” subtype (6.8%), characterized by younger age, more severe executive dysfunction, and least severe hippocampal atrophy. The subtypes observed in the prodromal AD sample demonstrated similar characteristics as in the AD dementia sample, and further showed differential courses of cognitive decline and progression to dementia. Specifically, the “AD‐typical” and the “limbic‐frontal” subtypes demonstrated a higher risk of progressing to AD dementia, as well as a faster decline of memory and executive function performance compared to the “minimal limbic” subtype.ConclusionData‐driven clustering of FDG‐PET identified distinct hypometabolic subtypes in AD that were readily detectable at prodromal disease stages and associated with differential clinical courses and biomarker characteristics. The convergence of these hypometabolic subtypes with previously described MRI‐derived atrophy subtypes remains to be determined.
Impact of modulating gut bacteria using antibiotic, probiotic, and prebiotic interventions in the APPNL‐G‐F mouse model of Alzheimer disease
Authors: Kaur Harpreet , Nagamoto‐Combs Kumi , Combs Colin K. 
Published: December 2020

AbstractBackgroundAlzheimer's disease (AD) is a multifactorial, neurodegenerative disorder and several factors are known to contribute to its etiology. Evidence suggests that AD may be associated with a dysbiosis of the intestinal microbiota but whether is it is a cause, or an effect is yet to be understood.MethodIn order to understand the effect of gut bacteria on the pathophysiology of AD, we used two approaches to manipulate gut bacteria in mice; probiotic and antibiotic therapies. Female wild type control C57BL/6 mice were compared to a mouse line that has the human Aβ sequence knocked into the mouse APP gene along with three disease causing mutations (AppNL‐G‐F
). The animals at 2.5 months of age were randomly divided into five groups and three groups were treated with a cocktail of non‐absorbable antibiotics (ABX) in drinking water and two groups were given water only for 10 days. Following ABX treatment, animals were either given normal diet, a probiotic (VSL#3) containing diet, or a diet containing both probiotic and prebiotic for 2 months. Upon completion, learning and memory was assessed along with brain Aβ and cytokines levels. GFAP and Iba‐1 immunohistochemistry was performed on brain sections.Result
AppNL‐G‐F
mice showed a significant deficit in memory performance compared to controls. An increase in pro‐inflammatory cytokines and Aβ along with increased GFAP and Iba‐1 immunoreactivity was observed in AppNL‐G‐F
brains. No change was observed in intestinal permeability across all groups. Two months of probiotic supplementation improved memory and decreased plaque load in AppNL‐G‐F
mice. Consistent with this, probiotic feeding attenuated GFAP and Iba‐1 immunoreactivity in AppNL‐G‐F
brains. On other hand, antibiotic treatment alone or in combination with probiotic/prebiotics appeared to increase microgliosis and astrogliosis in AppNL‐G‐F
brains.ConclusionThese results demonstrate that transiently depleting gut bacteria with antibiotic treatment has a long‐term effect on worsening AD‐associated parameters in AppNL‐G‐F
brains. On the other hand, modulating gut bacteria using probiotic feeding decreases plaque load and gliosis. This data suggests that gut microbiota modulate host brains and probiotics might be useful as supplementary therapy in AD.
Assessing functional disability in individuals with MCI and dementia
Authors: Umucu Emre , Wyman Mary F , Lee Beatrice , Zuelsdorff Megan , Lambrou Nickolas H , Johnson Adrienne L , Bouges Shenikqua , James Taryn T , Salazar Hector , Simó Carola A Ferrer , Carter Fabu P , Asthana Sanjay , Gleason Carey E 
Published: December 2020

AbstractBackgroundMild cognitive impairment (MCI) and dementia are among the most disabling conditions. Patients with MCI and dementia may experience difficulties in executing instrumental activities of daily living (IADL), resulting in distress for patients and families. Measuring and understanding abilities to execute IADL is important to understand how MCI and dementia impacts patients’ functioning. We explored the factor structure of the Functional Activities Questionnaire as a measure of functional disability in a sample with MCI and dementia.MethodsParticipants were 198 enrollees in the Wisconsin ADRC who had MCI, and dementia. Not applicable responses were counted as missing data, resulting in 98 participants in main analyses. The majority of participants were male (61.1%) and Caucasian (88.4%). Average age at baseline was 73.76 (SD=8.90). We conducted the following analysis: exploratory factor analysis (EFA), reliability analysis, correlation analysis, and Mann‐Whitney U test.ResultsThe Kaiser–Meyer–Olkin (KMO) measure of sampling adequacy was .89, and the Barlett’s test of sphericity was significant, χ
2(45,N=98)=717.24, p<.001, indicating suitability for factor analysis. Kaiser–Guttman’s criterion and Cattell’s scree test both indicated a single‐factor measurement structure, accounting for 64% of the total variance. The Cronbach’s alpha was found to be .94 for the FAQ. Functional disability was positively correlated with neuropsychiatric symptoms (r=.43, p<.001), CDR global score (r=.79, p<.001), and lack of independence (r=.66, p<.001). A Mann‐Whitney U test showed that individuals with dementia had significantly higher levels of functional disability than those with MCI (U=214.00, p<.001).ConclusionThe FAQ was found to be a unidimensional, reliable, and valid measure of functional disability. Participants with higher scores on the FAQ endorsed greater levels of neuropsychiatric symptoms, symptoms of cognitive impairment, and dependence to others. As expected, those with dementia had higher levels of functional disability/limitations. Future research may examine whether functional disability/limitations predicts incident MCI or dementia in cognitively normal individuals.
An analysis of driving characteristics and awareness by older adult mild cognitive impairment drivers
Authors: Suzuki Mio 
Published: December 2020

AbstractBackgroundIn Japan, the Traffic Act was revised that Alzheimer drivers prohibited to drive. However, there is no clear relationship between dementia and driving skills. So in this study, we conducted a driving experiment for dementia, mild cognitive impairment, and normal drivers over 65 years old, and compared their driving skills and their awareness.MethodI observed driving characteristics on a training course, a car driving school. At first, I analyzed the relationship among scores of screening tests, their driving customs and driving behavior. Secondly, I also observed 7 MCI drivers’ driving behavior on open roads with driving recorders, and compared the driving behavior between at the driving school and the open roads.ResultDriving behavior of intersections or parking were not different significantly, but the one of lane change and obstacle avoidance on midblocks was different between MCI and normal drivers significantly. On the other hand, the almost all older adult drivers couldn’t behave safely at intersections. Moreover, the surrounding environment, for example, families or friends, affected to the will to continue driving for MCI drivers.ConclusionBoth of MCI or non‐MCI drivers are needed to check their driving skill. And support system should be developed for communication on driving (turn signals, etc.).
Assessment of a novel tau propagation pathway from layer II medial entorhinal cortical neurons to CA1 pyramidal neurons as an early BRAAK stage mouse model
Authors: Delpech Jean Christophe , Pathak Dhruba , Kalava Srinidhi V. , Iwahara Naotoshi , Varghese Merina , Hof Patrick R. , Medalla Maria , Ikezu Seiko , Luebke Jennfier , Ikezu Tsuneya 
Published: December 2020

AbstractBackgroundTau pathology correlates with cognitive impairment and is thought to propagate along neuroanatomical pathways. Tau accumulation is first observed in layer II of the entorhinal cortex (ECII), and then in CA1/2 of the hippocampus. The mechanism and nature of this propagation remains unclear and at present, no animal model recapitulates predominant tau propagation from ECII to CA1. Wolframin‐1‐immunoreactive (Wfs1+) neurons in the mouse ECII project to CA1 pyramidal neurons directly, or indirectly via interneurons in the S. lacunosum‐moleculare. We hypothesized that ECII Wfs1+ neurons mediate tau propagation to the CA1 pyramidal cells, making our model relevant for mimicking early stages of tau pathology in Alzheimer’s disease (AD).MethodTo specifically express mutant tau in Wfs1+ neurons, Wfs1‐Cre mice at 4‐6 months of age were injected with Cre‐inducible AAV2/6‐Flex‐P301Ltau expressing human P301L tau mutant or AAV2/6‐Flex‐Tdtomato in ECII, and euthanized at 4 weeks post‐injection for immunohistochemistry, electrophysiology and electron microscopy. To label and trace ECII‐CA1 connections, AAV9‐hSyn‐FLEX‐TVA‐P2A‐GFP‐2A‐oG and EnvA‐G‐deleted Rabies‐mCherry were injected into the CA1 pyramidal cells. The functional effects of tau on these connections were assessed by the multielectrode array to evaluate light‐evoked CA1 neuronal firing responses after the optogenetic stimulation of Wfs1+ ECII axons and also by measuring chemogenetic activation of CA1 pyramidal cells.ResultWfs1‐Cre mice injected in ECII with AAV2/6‐Flex‐P301Ltau exhibited significant human tau+ cells in the CA1 but not dentate gyrus at 4 weeks post‐injection. Monosynaptic tracing and electron microscopy revealed a direct synaptic connection between ECII Wfs1+ axons and CA1 pyramidal dendrites, and confirmed the presence of human tau in the pre‐ and post‐synaptic elements. Whole cell patch clamp recordings of CA1 pyramidal cells demonstrated reduction in measures of excitability. Optogenetic stimulation of Wfs1+ axons in the hippocampus coupled with multielectrode array‐recordings revealed a reduction in CA1 neuronal firing to light stimulation after AAV2/6‐Flex‐P301Ltau injection. Chemogenetic activation of CA1 neurons showed a reduction in c‐fos+ cells in CA1 after AAV2/6‐Flex‐P301Ltau injection compared to AAV2/6‐Flex‐Tdtomato controls.ConclusionExpression of P301Ltau in Wfs1+ neurons in the ECII induces the spread of human tau specifically to CA1 pyramidal neurons, which as a consequence exhibit several measures of neurophysiological impairment.
An ethnomusicologist's perspective: A potential experimental model to revive long‐term memories of the Alzheimer's patient through individualized music and the amygdala pathway
Authors: Pillay Jayendran 
Published: December 2020

AbstractBackgroundSince a significant symptom of Alzheimer's is memory loss caused through the aggregation of beta‐amyloid, the ethnomusicologist is in a unique position to potentially recover some long‐term memories by developing the personalized music history one patient at a time. The idea is to bypass the amyloid aggregates, accessing the amygdala, therefore using the patient's emotions to recover their memories through their own music and their associative strengths. A song or a strain of music can transport anybody in the world with the functional hearing ability to a place in time retrieving those memories. Instead of sedating a patient, their own music may be better. My case study involved one individual diagnosed with dementia. Being familiar with the patient for a few decades, I pieced together her music history which I treated as a part of her medical history since the music memory resides in the brain. Her cognition and joy increased significantly over the year, according to her and her family. I videotaped some sessions. More research is needed to establish whether my method of individualized music history and memory recollection increases the quality of life of the patient or not. For further research, I propose inviting an ethnomusicologist to build a music profile of a number of Alzheimer's patients the neurologists are treating at a clinic. The music profile will include a playlist of songs or instrumental music that transports the patient to particular memories. The sound database could also include non‐musical sounds that generate memories e.g. the sounds of a drill, a barking dog, etc.. To access the patients’ memories the ethnomusicologist would need to do extensive interviews with the patients, family members, and friends, and look at their music collections. The process of building a music profile of the Alzheimer’s patient for treatment by a neurologist can, therefore, be done globally where the ethnomusicologist teams up with the medical staff.
Three types of white matter hyperintensities have different effects on depression and cognitive function in patients with CADASIL
Authors: Park Joon Hyuk , Lee Jungseok , Yang Hyun‐Ju , Lee Subin , Kim Ki Woong 
Published: December 2020

AbstractBackgroundWhite matter hyperintensities (WMH) according to the distance to the ventricle have been associated with different clinical, histopathological, and etiological correlates, which may provide the clues for understanding pathophysiology of many geriatric syndromes associated with WMH. The purpose of this study was to investigate the effects of WMH on depression and cognitive function in patients with CADASIL according to the locations of WMH.Method84 subjects with CADASIL, aged 34–86 years, participated in this study. They underwent comprehensive clinical evaluation, including 3T MRI and genotyping of NOTCH3. With new subclassification of WMH (Kim, 2008), WMH were subclassified into juxtaventricular WMH (JVWMH), periventricular WMH (PVWMH), and deep WMH (DWMH) according to the distance to the ventricle. Lesions were segmented by the lesion prediction algorithm (Schmidt, 2017, Chapter 6.1) as implemented in the LST toolbox version 3.0.0 (www.statistical‐modelling.de/lst.html) for SPM. WMH volume was corrected as a ratio of the WMH volume to total intracranial volume.ResultUsing linear regression model after controlling for age, only JVWMH volume was associated with the scores of geriatric depression scale (GDS) (p=0.027) and CES‐D (p=0.041) among 3 types of WMH. There were no association trends between DWMH volume and scores of GDS (p=0.641) and CES‐D (p=0.427). After controlling age, education and sex, JVMMH volume was associated with poor performances in Categorical Verbal Fluency Test (cVFT) (P=0.013), 15‐item Boston Naming Test (sBNT) (P=0.020), Word List Memory Test (WLMT) (P=0.006), Word List Recall Test (WLRT) (P=0.010), Constructional Recall Test (CRT) (P=0.012), and Trail Making Test A and B (TMT‐A and TMT‐B) (p=0.003, p=0.004). PVWMH volume was associated with poor performances with in cVFT (P=0.027) and WLMT (P=0.031). DWMH volume had no associations with the scores of CERAD neuropsychological tests.ConclusionJVWMH are closely associated with depression and various domains of cognitive function. However, DWMH have no association with both depression and cognitive decline. 3 Types of WMH have different effects on depression and cognitive function in patients with CADASIL.
Functional connectome vulnerability to Alzheimer’s disease in alcohol use disorder: A preliminary study
Authors: Joseph Jane E , Flanagan Julianne , Nowling Duncan , Vaughan Brandon , Warner Graham , Lohnes Laura , Ross‐Simmons Shaquanda , Mintzer Jacobo , Dean Brian , Lawson Andrew , Back Sudie , Jensen Jens H. , Benitez Andreana 
Published: December 2020

AbstractBackgroundAlcohol Use Disorder (AUD) is a risk factor for Alzheimer’s Disease (AD) and other dementias. Despite the emerging association between AUD and AD, there is a paucity of data available from mid‐life age ranges (e.g., 45 to 65 years) to assess AUD‐related risk for AD that might be present early in the disease trajectory.MethodFunctional connectome measures (graph‐theory) were calculated from resting state fMRI scans in 118 healthy controls (HC), 25 subjects with AUD (45‐61 years of age), and 51 subjects with amnestic mild cognitive impairment (aMCI) or AD. Following dimension reduction of 282 network nodes into 10 components using principal components analysis, predictive modeling with best subsets was used to isolate network components that predicted age in HC. Network components that significantly predicted age in HC were further examined to determine whether the AUD group exhibited premature brain aging or showed similar pathologic profiles as AD/aMCI.ResultPredictive modeling with eigenvector centrality as a predictor of age yielded significant models (p’s < .0001). A network component including occipital and frontal pole nodes was a significant predictor in all models. In the frontal pole, AUD age trajectories showed a baseline shift relative to age‐matched HC subjects (49‐61 years of age), indicating premature brain aging. However, these age trends were not significantly different when Fisher z‐transformations of age trends were compared with a t‐test (p = .5). Nevertheless, the ANOVA revealed a significant main effect of group (AUD, HC, aMCI; p < .0001): average eigenvector centrality of the frontal pole in AUD was significantly lower than in HC (p = 0.0001) and indistinguishable from that of AD/aMCI subjects (p = 1.0), according to Bonferroni post‐hoc tests.ConclusionPremature brain aging in AUD may reflect vulnerability to AD‐like neurodegenerative processes that are manifest at the level of large‐scale network connectivity. Some data used in preparation of this abstract were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report.