bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel computer vision approach to kinematic analysis of handwriting with implications for assessing neurodegenerative diseases
Authors: Nachum Ron , Jackson Kyle , Duric Zoran , Gerber Naomi Lynn 
Published: December 2021

AbstractBackgroundHandwriting kinematic analysis with digitizing tablets has been established as a biomarker for use in discriminative analysis between patients with Parkinson's disease (PD), Alzheimer's disease (AD), and healthy controls (HC). However, vision‐based systems offer a rapid diagnostic assessment and screening solution for neurodegenerative diseases (ND) in low‐income areas and resource‐poor health systems, while also providing further data about movements to increase assessment accuracy.Method146 handwriting videos were captured from a single subject to demonstrate feasibility of extracting kinematic information from videos. Measured tasks included Archimedean spiral drawing, and tracing of l’s and e’s. To enable statistical comparison, video data was captured by a smartphone camera and simultaneously quantified by a digitizing tablet on which the writing template was overlaid. The developed novel system for fine motor movement analysis using computer vision leveraged recurrent region of interest feature matching to quantify kinematic information from video frames. To assess discriminative value of kinematic data collected with computer vision, the PaHaW dataset, consisting of 38 HCs and 37 PD patients, was down‐sampled to 60 Hz and filtered to simulate vision‐based data. This preprocessed data was then used to derive features describing movement fluidity, which were then tested for statistical significance with t‐tests to select final features for classification. An ensemble classifier consisting of a neural network, support vector machine, and random forest was trained on the final feature set using 10‐fold cross validation to prevent over‐fitting and provide patient diagnostic assessments.ResultUsing the collected dataset of synchronized videos and digitizing tablet data, positional accuracy within 0.5 mm (+/‐ 0.088 mm 95% confidence interval) was achieved in fine motor movement quantification (n=146). Quantified speed and acceleration had mean absolute errors of less 1.1% (+/‐ 0.169 mm/s, +/‐ 0.177 mm/s^2 95% confidence intervals respectively) (n=146). Classification of PD patients was demonstrated with 74% accuracy (n=75), pending further data collection to confirm classification structure's literature‐supported use for AD and mild cognitive impairment diagnostic assessment.ConclusionComputer vision‐based kinematic analysis of handwriting with standard cameras offers an accurate and accessible solution for neurodegenerative disease diagnostic assessment, with potential to improve diagnostic accuracy through additional features and movement data.
Adapted Tango to improve blood inflammatory markers in middle‐aged African‐American female caregivers of persons with Alzheimer's disease: A clinical trial
Authors: Wharton Whitney , Jeong Leanne , Ni Liang , Bay Allison A , Shin Ryan , McCullough Lauren , Silverstein Hayley , Hart Ariel R , Swieboda Dominika , Hu William T , Hackney Madeleine E 
Published: December 2021

AbstractBackgroundAlzheimer’s disease (AD) is a devastating, progressive neurodegenerative disease resulting in memory loss and a severe reduction in ability to perform activities of daily living. Ethnicity‐related genetic factors promoting the development of dementias among African Americans (AA) and increased risk among females for developing AD indicates that AA female with a parent with AD are at great risk for developing dementias.MethodThis phase I study assessed the impact of a 12 week, 20‐lesson adapted Argentine Tango intervention (N=24) vs. a no‐contact control group (N=10) on measures of cognition, motor and psychosocial performance, and plasma inflammatory markers in middle‐aged (45‐65 years) AA females who are at increased risk for AD by virtue of parental history.ResultSome females (n=17) were also caregivers, and thus the impact of the program on caregiving burden was examined in this subset. Preliminary analysis of efficacy was conducted with significance tests on biomarkers and key measures of balance, strength, and cognition, including visuospatial and executive function. After 12 weeks, Tango participants had significantly decreased inflammatory cytokine levels: IL‐7 (p=.003), IFN‐γ (p=.011), and TNFα (p=.011), compared to controls. Participants in Tango improved on the Fullerton Advanced Balance Scale, which measures both dynamic and static balance (p=.023), the 30 second chair stand, which assesses functional lower body strength in older adults (p=.018), and inhibition of the color word interference test, which measures to ability to inhibit cognitive interference (p=0.031). Large effects were noted for the Tango group from pre to postintervention in the Trails B test score, which measures executive control and functioning. Other non‐significant, yet large effects were noted in gait speed, spatial cognition, and executive function. Moderate effects were noted in caregiving burden measures among the subset of caregivers.ConclusionThese data show substantial cognitive and motor improvements and reduction in inflammatory biomarkers through a non‐pharmacologic and affordable intervention among a small cohort of AA females with a parental history of AD.
Unraveling the challenging life experience of persons with mild cognitive impairment: A mixed‐methods study
Authors: Lin Rose S.Y. , Li Polly W.C. , Chau Patsy P.H. , Yu Doris S.F. 
Published: December 2021

AbstractBackgroundPersons with mild cognitive impairment (PwMCI) experience a slight but noticeable decline in everyday functioning. Although more attention is directed to the cognitive manifestation in this preclinical stage, little is known about the co‐existing neuropsychiatric symptoms (NPS). This study aimed at examining the symptom experience of PwMCI, with a particular focus on how neuropsychiatric symptoms manifested in the complex dynamic between the personality, coping, and social support profiles of the PwMCI.MethodA mixed‐method study was conducted from March to October 2020 in two community centers in Hong Kong. A convenience sample of 152 PwMCI (response rate: 75.6%) responded on the Chinese version of Memory Inventory in Chinese, Montreal Cognitive Assessment, Mild behavioral impairment ‐ Checklist, Multidimensional Scale of Perceived Social Support, Simplified Coping Style Questionnaire, and NEO‐Five Factor Inventory. A purposive subsample of 30 participants was invited to have in‐depth interviews on how they lived with the symptom experience associated with MCI.ResultThe mean age of the overall sample was 75.1 (SD=5.90), with a majority (87.5%) were female. They were characterized by their cognitive deficits such as impaired attention and memory and intense emotional responses, including depression, anxiety, agitation, and lack of motivation. Surprisingly, the cognitive deficit was not associated with NPS. Instead, by using hierarchical regression analysis, more severe NPS was associated with neuroticism (β=0.333, p<.001), subjective memory complaints (β=0.617, p<.001), perceived lower social supports (β= ‐0.071, p=.049), and negative coping (β=0.384,
p=.027). As for their lived experience, the content analysis identified four themes: 1) symptom manifestations, 2) coping strategies, 3) anticipated losses, and 4) negative outlooks on future orientation. Living with MCI was a highly challenging experience and was characterized by distressing cognitive and psychological symptoms, role and social dysfunction, and fear of losing functional independence and self‐identity. In facing the progressive deteriorating disease trajectory of dementia, the informants reported strong feelings of uncertainty, powerlessness, and helplessness.ConclusionPwMCI were highly aware of their cognitive manifestations and concomitant functional deterioration, together with maladaptive coping, triggered a cluster of negative emotional responses. Future interventions should safeguard their functional independence, optimize their coping, and strengthen their self‐identity.
State of science in nutrition clinical trials for dementia prevention
Authors: Scarmeas Nikolaos 
Published: December 2021

AbstractBackgroundThere is a number of clinical trials of nutrition interventions in relation to prevention of dementia and cognitive decline that have been done. Nevertheless, not only the overall number of such attempted interventional studies is relatively small, but there is also considerable variability in terms not only of results but also of related methodological approaches.MethodWe will review experience of various methodological aspects of performed high quality nutrition and multidomain clinical trials for prevention of dementia and cognitive decline.ResultPerformed trials have demonstrated considerable variability not only in terms of findings but also in terms many different aspects of methodological design including intensity of intervention, success of adherence to the intervention, degree of appropriateness of primary and secondary outcomes selected, duration of the study etc. Prudent participant selection both in terms of baseline cognitive and nutritional status but also in terms of representativeness and disparity dimensions has also been a major issue in most completed trials. All the above and additional methodological strengths and challenges have been also quite prominent in nutritional supplement trials.ConclusionExperience of shortcomings and lessons learned from up‐to‐date conduct of nutrition trials point to areas of specific methodological improvements that we need to consider in the future.
Designing future nutrition clinical trials for dementia prevention
Authors: Schneider Lon S 
Published: December 2021

AbstractBackgroundPast clinical trials for dementia prevention through nutrition enhancement have been wanting; and taken together have been uninformative, and generally yielded uncertain outcomes.MethodA study group of researchers reviewed past experiences and examples of prevention trials involving nutritional interventions, including design, execution, specific treatments, practical problems in execution, and suggested improvements.ResultPast trials show substantial variations in design, types of interventions, timing of treatments, outcomes, duration, and differing views of life course or at‐risk models. We identified, first, an overall lack of effectiveness demonstrated in these prevention trials; and, second, numerous methodologic limitations, including high risks for bias, limited external validity or generalizability that considerably limit the inferences that can be made about outcomes. Further, we identified considerable practical challenges in designing and successfully implementing these long‐term trials. Specific issues involve identifying, defining, and recruiting appropriate research subjects, the nature and conceptualization of the interventions, e.g., single molecule or multidomain, compliance and length of these long‐term trials, and appropriate intermediate and final outcomes that track efficacy. The effectiveness of a given nutritional intervention may depend as well on when in the life course it is implemented.ConclusionInformed by previous trials, we conclude with recommendations for a range of approaches to designing nutritional trials for the prevention of dementia that address nutritional interventions, minimize risk of bias, and that are more likely to be seen as ecologically valid.
The combined influence of beta‐amyloid and vascular risk on prospective brain atrophy in clinically normal individuals
Authors: Rabin Jennifer S , Pruzin Jeremy J , Schultz Aaron P , Scott Matthew R , Hampton Olivia L , Hsieh Stephanie , Yang Hyun‐Sik , Yau Wai‐Ying , Hedden Trey , Rentz Dorene M , Johnson Keith A , Sperling Reisa A , Chhatwal Jasmeer P 
Published: December 2021

AbstractBackgroundAmyloid‐beta (Aβ) and vascular risk factors are commonly observed together among cognitively unimpaired adults. Here, we examined the interactive associations of Aβ burden and systemic vascular risk with respect to longitudinal patterns of neurodegeneration. Secondarily, we assessed whether systemic vascular risk associations with brain atrophy were modified after adjusting for imaging based markers of white matter integrity (white matter hyperintensities (WMH) and diffusion‐derived fractional anisotropy).MethodsParticipants were 197 adults (age=73.5±6.1 years) from the Harvard Aging Brain Study with at least two MRI scans over a median of 4.5 years. Baseline Aβ burden was measured with Pittsburgh Compound‐B PET. Vascular risk was quantified with the Framingham Heart Study general cardiovascular disease risk score. Altered white matter microstructure was measured via diffusion‐derived fractional anisotropy and WMH burden was quantified using FLAIR images. Brain atrophy was assessed longitudinally with serial structural MRI. Aβ burden and vascular risk were examined as interactive and independent predictors of brain atrophy in separate linear mixed models, adjusting for age, sex, education, APOE ε4 status, and intracranial volume (where appropriate).ResultWe found a significant interaction between elevated Aβ burden and higher vascular risk in relation to faster atrophy within frontal (t=‐2.95, p=0.003) and anterior temporal lobes (t =‐2.32, p=0.021), thalamus (t=‐2.61, p=0.010) and striatum (t =‐2.17, p=0.031). Higher Aβ burden, but not vascular risk, was associated with faster atrophy in the parietal lobes (Aβ: t=‐4.14, p<0.001; vascular risk: t=‐1.54, p=0.124), occipital lobes (Aβ: t=‐2.95, p=0.003; vascular risk: t=‐0.63, p=0.526), and hippocampus (Aβ: t=‐2.72, p=0.007; vascular risk: t=0.207, p=0.836). These effects remained very similar after adjusting for WMH and fractional anisotropy measures.ConclusionElevated vascular risk was associated with accelerated Aβ‐related atrophy in frontal and anterior temporal regions. However, higher Aβ burden alone was correlated with greater atrophy in regions often associated with a canonical AD pattern of neurodegeneration, including the hippocampus and parietal regions. These findings highlight interactions between vascular and Aβ‐related pathways with respect to brain atrophy, and the potential benefit of managing vascular risk factors as a possible intervention to slow regional neurodegeneration in preclinical Alzheimer’s disease.
Examining misdiagnosis of mild cognitive impairment among Black/African American older adults
Authors: Kiselica Andrew M , Johnson Ellen , Lewis Kaleea , Trout Kate 
Published: December 2021

AbstractBackgroundBlack/African Americans are less likely to receive an accurate diagnosis of mild cognitive impairment (MCI) than their White counterparts. We examined rates of low cognitive test scores by race among older adults diagnosed with MCI to illuminate possible biases in the diagnostic process.MethodWe compared number of low scores (i.e., <9th percentile) on cognitive tests between Black (n = 545) and White (n = 3,542) participants diagnosed with MCI based on the Clinical Dementia Rating. Participants were drawn from the National Alzheimer’s Coordinating Center Uniform Data Set. Chi‐square tests were used to examine racial differences in rates of low scores for each cognitive test, and t‐tests were used to compare the number of low scores across groups.ResultCompared to Black participants, White individuals demonstrated significantly higher rates of low scores on tests of memory, attention, and verbal fluency. White participants with MCI also evidenced a higher number of low scores overall (M = 3.67, SD = 2.46) than Black participants (M = 2.46, SD = 2.15), d = .48.ConclusionResults suggest there may be bias in MCI classification based on clinical interview, leading to overdiagnosis among Black individuals and/or underdiagnosis among White individuals.
Embedding dementia research in clinical practice: Progress of the Oxford Brain Health Centre
Authors: O'Donoghue M Clare , Blane Jasmine , Mitchell Robert , Aikin Nicola , Lindsay Karen , Campbell Jon , Semple Juliet , Raymont Vanessa , Martos Lola , Mackay Clare 
Published: December 2021

AbstractBackgroundLaunched in August 2020, the Oxford Brain Health Centre (BHC) is the UK's first psychiatry‐led joint clinical‐research service providing high‐quality assessments and increasing research opportunities for patients with memory problems. By embedding research in the NHS service, the BHC aims to address gaps between clinical practice and research advances into dementia. This abstract describes the first 60 referrals from the BHC pilot.MethodsPatients from Oxford Health NHS Foundation Trust memory clinics were referred to the BHC for assessment prior to their diagnostic appointment. At the BHC, patients completed clinical assessments ‐ MRI scan, cognitive assessment and questionnaires – and could consent to use of clinical data for research, additional research assessments, and recontact about future research. Accompanying relatives completed a clinical informant interview and could consent to recontact about research. Patient/relative feedback was obtained via questionnaires.ResultsBetween August and December 2020, the BHC received 60 referrals. 38% were returned to the memory clinic for reasons relating to the patient (n=9, e.g. patient unable to travel to the centre), the referral (n=3, e.g. patient already seen in clinic), or the MRI scan (n=11, e.g. claustrophobia, MR contraindication). BHC appointments occurred on average 26 days (range: 5‐63) after referral from the memory clinic. Only 3% did not attend. Of the 33 attendees in 2020, 58% were female, average age was 77.5 years (66‐90), and average ACE‐III score was 66.8 (9– 98; max: 100). 97% of patients consented to use of clinical data for research, 88% to additional research assessments, and 69% to recontact about research. 81% of relatives consented to recontact about research. Service‐user feedback was consistently high; 100% of responding patients were satisfied with the BHC service, particularly highlighting positive interactions with staff.ConclusionsSince launching, we have demonstrated the feasibility of an integrated clinical‐research service for people with memory problems and demonstrated extremely high research uptake in this population. Evaluation of referrals, procedures, impact on diagnosis, and health economics at the end of the 6‐month pilot will inform sustainability and scalability of Oxford BHC to provide a model for a specialist service that can be adopted throughout the NHS.
Prediction of Alzheimer disease using plasma RNA sequences from dementia genes
Authors: Ibanez Laura , Bergmann Kristy , Eteleeb Abdallah , Wang Fengxian , Norton Joanne , Gentsch Jen , Harari Oscar , Cruchaga Carlos 
Published: December 2021

AbstractBackgroundAlzheimer’s disease (AD) is inexorable, incurable, and in many cases very difficult to diagnose before symptom onset. Thus, there is a clear need to develop tools to detect the pathological changes that occur before clinical symptoms onset. Historically, proteins have been the preferred biomarker. However, biofluids also contains ribonucleic acid in its free form (cfRNA). The source of cfRNA in plasma is not fully understood, but it is thought to be the result of normal cell death throughout the body, thus providing a mirror of the status of a normal functioning body. Therefore, if some organs are functioning incorrectly, we can detect it by changes in cfRNA. To date, several species of cfRNA have been investigated as biomarkers for cancer, fetal development and AD. The aim of this study was to generate predictive models for AD using plasma cell‐free RNA species at different stages of the disease.MethodWe generated cfRNA‐Sequence data from AD cases at CDR=1 (N=44) and controls (N=45) and applied standard quality control. Gene expression was quantified with Salmon and corrected by library complexity and log transformed prior to analysis. Genes known to be involved in AD and other neurodegenerative diseases (N=25) were used to create a predictive model using step‐wise discriminant analysis in the CDR=1. APOE genotype was included in the model afterwards. The predictive power was tested in early (N=27) and pre‐symptomatic (N=21) stages of the disease.ResultOut of the 25 genes, eight were included in the predictive model after step‐wise discriminant analysis. After inclusion of APOE genotype, the area under the ROC curve was 0.96, 0.99 and 0.82 for CDR=1, CDR=0.5 and pre‐symptomatic stages respectively (Figure 1).ConclusionCell‐free RNA is a promising minimally invasive biomarker for AD with an accuracy comparable to the one obtained using CSF biomarkers. This approach can provide a new screening tool for AD that can be used at population level and to evaluate disease‐modifying therapies that target amyloid beta and tau.
Neuroprotective effect of silymarin against 3‐nitropropionic acid‐induced Huntington’s like symptoms in rats
Authors: Chandolia Priyanka 
Published: December 2021

AbstractBackgroundNeuroprotective effect of silymarin against 3‐nitropropionic acid‐induced Huntington’s like symptoms in rats.MethodHuntington's disease (HD) is a chronic neurodegenerative and hyperkinetic movement disorder characterized by degeneration of GABAergic medium spiny neurons, mainly affecting striatum and cortex. 3‐nitropropionic acid (3‐NP) acts as a suitable animal model to induce HD like symptoms in rats. Therefore, the present study aimed to investigate the neuroprotective effect of silymarin against 3‐NP induced HD like symptoms in rats. Rats were administered 3‐NP (10 mg/kg; i.p) for 21 days, whereas silymarin (50, 100 and 200 mg/kg; p.o) was given once a day, 1 hour before the 3‐NP treatment for 21 days. Body weight and behavioral parameters (rotarod, open field test, and narrow beam walk activities) were assessed on 1st, 7th, 14th, and 21st days. On the 22nd day, the animals were sacrificed, and the rat striatum and cortex were isolated to perform biochemical parameters (lipid peroxidation; glutathione; superoxide dismutase; nitrite and catalase).ResultSystemic 3‐NP treatment significantly reduced body weight, motor‐coordination, and oxidative defense. Pretreatment with silymarin significantly attenuated the 3‐NP induced alterations in body weight, locomotor activities, and oxidative defense.ConclusionOur results revealed that in a 3‐NP model of HD, silymarin could underlie the possible neuroprotective effect, which may provide insight into the therapeutic potential of silymarin for HD.