bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medin amyloid forms age‐associated aggregates in the brain vasculature and may contribute to cerebral β‐amyloidosis
Authors: Wagner Jessica , Degenhardt Karoline , Wild Katleen , Obermüller Ulrike , Haesler Lisa M. , Koppelmann Anna Julia , von Zweydorf Felix , Gloeckner Christian Johannes , Maxwell Rusheka , Rotermund Carola , Skodras Angelos , Madine Jillian , Davies Hannah A. , Del Turco Domenico , Deller Thomas , Kahle Philipp J. , Jucker Mathias , Neher Jonas J. 
Published: December 2020

AbstractBackgroundThe most common human amyloid is probably medin (AMed), which deposits in the aorta of nearly everyone above 50 years of age. Previous studies reported that medin amyloid may co‐aggregate and seed serum amyloid A. Because of this finding and its exceedingly high prevalence in the aging population, we studied whether medin aggregates form in the brain during aging and may interact with other age‐associated amyloids such as Aβ.MethodIn order to study the pathobiology of medin amyloid and its contribution to vascular and parenchymal amyloidosis, we first investigated the occurrence of medin in wildtype mice. Additionally, we used APP transgenic mouse lines and human tissue for immuno‐histochemical and immunoprecipitation experiments to study a potential protein‐protein interaction with Aβ.ResultWe find that medin deposits are prevalent in the human brain vasculature and seem to increase both with age and Aβ pathology. Moreover, co‐immunoprecipitation experiments indicate an interaction of Aβ and medin. Strikingly, we also observe that, similar to the human situation, amyloid‐like deposits of medin are formed in the aorta as well as in the brain vasculature of aging wildtype mice. Further experiments in APP transgenic mice showed that medin does not only co‐localize with Aβ Plaques and CAA, but may also promote cerebral β‐amyloidosis in mouse models of Alzheimer’s pathology.ConclusionOur findings suggest that age‐associated medin deposition occurs both in the mouse and human brain, where it may promote cerebral β‐amyloidosis.
Early diagnosis of Alzheimer's dementia with the artificial intelligence‐based Integrated Cognitive Assessment
Authors: Modarres Mohammad Hadi , Khazaie Vahid Reza , Ghorbani Mohammad , Ghoreyshi Amir Mohammad , AkhavanPour Alireza , Ebrahimpour Reza , Vahabi Zahra , Kalafatis Chris , Razavi Seyed‐Mahdi Khaligh 
Published: December 2020

AbstractBackgroundWe have developed the Integrated Cognitive Assessment (ICA), a 5‐minute, self‐administered, computerised test that is independent of language, cultural background and education and aims at screening for cognitive impairment in a way that can simplify and accelerate the diagnosis of Alzheimer's Dementia (AD) and Mild Cognitive Impairment (MCI). The ICA utilises artificial intelligence to analyse high‐dimensional clinical and demographic data.MethodWe carried out head‐to‐head studies comparing classification performance of the ICA with widely used cognitive assessments (MoCA and ACE) in participants with MCI and mild AD. The ICA test measures patterns of reaction time and categorisation accuracy which are utilised by an AI engine, alongside demographic data, to provide a predictive score about participant’s cognitive status. We also investigated the use of a deep (50 layers) neural network to extract informative features from the ICA test response patterns.ResultOn a population of 200 participants (84 healthy, 68 MCI, 48 mild AD), the ICA achieved an area under the ROC accuracy of 91% in distinguishing between healthy and impaired (MCI and mild AD) participants. In comparison MoCA achieved an AUC of 82%, and ACE 84%. Utilising the deep learning network for automatic feature extraction significantly improved the specificity and sensitivity compared to only using a linear classifier. The ICA Spearman correlation of 0.67 (p‐value <0.0001) with MoCA, and 0.73 (p‐value<0.0001) with ACE establishes convergent validity with these cognitive tests. ICA results were not biased by participants level of education (i.e. no significant correlation), whereas MoCA and ACE had correlations of 0.31 (p<0.0001) and 0.31 (p<0.001) respectively with the level of education in the same set of subjects.ConclusionThe ICA can support clinicians by aiding accurate diagnosis of MCI and AD and is appropriate for large‐scale screening of cognitive impairment. The ICA has advantages over MoCA and ACE because of its shorter duration, automatic scoring and potential for medical record or research database integration. ICA’s AI engine is able to learn from additional data and utilise deep learning, further improving the predictive power of the ICA test.
Association between low gait speed and cognition decline in older nursing home residents
Authors: Li Ying , Yang Xue 
Published: December 2020

AbstractBackgroundThe gait speed represented the core determinant of physical function, which is reported to associated with cognitive decline. This study examined the association between gait speed and cognitive function in elderly nursing home residents.MethodWe conducted a cross‐sectional study in seven nursing homes in Western China. The cognitive states were measured by MMSE. The gait speed was measured via a 4m walking test, and appendicular muscle mass was estimated according to a previously validated anthropometric equation. Handgrip strength was measured with a handheld dynamometer. Dementia was defined as MMSE lower than 23. The cut‐off of the gait speed, appendicular muscle mass, handgrip strength was based on the sex‐specific 20% lowest percentile of the study population.ResultFour hundred and ten participants were included. Two hundred and twenty‐three participants (54.39%) were identified as dementia. Compared with the subjects without dementia, the dementia subjects were more likely to have lower gait speed and grip strength (See Table 1).As indicated in Table 2, compared with the normal gait speed subjects, low gait speed subjects exhibited an increased risk factor of dementia (OR: 3.75, 95% CI: 2.09‐6.72) in the unadjusted model. After adjusting for age, sex, education and other confounder, the low gait speed was an independent risk factor of dementia (OR: 2.71, 95% CI: 1.47‐5.00).ConclusionThis study founded that low gait speed was significantly associated with dementia in older adults in nursing home. Screening for slow gait speed may be useful for identifying older nursing home residents at risk of cognition decline.
Functional hearing loss as a marker for early Alzheimer’s disease and dementia: Exploring the potential for reverse causation
Authors: Brenowitz Willa D , Filshtein Teresa J , Yaffe Kristine , Walter Stefan , Ackley Sarah F , Hoffmann Thomas , Jorgenson Eric , Whitmer Rachel A , Glymour M Maria 
Published: December 2020

AbstractBackgroundAge‐related hearing impairment is associated with elevated Alzheimer’s disease (AD) and dementia risk. The hearing impairment ‐ dementia association may be due to underlying AD‐related neurodegeneration or shared risk factors that influence hearing loss (e.g. reverse causation or confounding). This is difficult to assess in traditional observational studies; we used genetic risk for AD as an analytic tool to explore the extent to which genetic risk also influences functional hearing loss.MethodWe studied 401,084 UK Biobank participants aged 40‐70, with Caucasian genetic ancestry, and enrolled 2007‐2010. Participants responded (yes, no) to the question “Do you have any difficulty with your hearing with background noise?” and a subset underwent a speech‐in‐noise hearing test. Participants were followed until 2018 for AD diagnosis (ICD‐9/10 codes). A genetic risk score for AD (AD‐GRS) was calculated as a weighted sum of 23 single nucleotide polymorphisms previously confirmed to be genome‐wide significant predictors of AD. We evaluated whether the AD‐GRS predicted hearing measures (evidence of reverse causation), using age‐, sex‐, and genetic ancestry‐ adjusted logistic and linear regression models and used the AD‐GRS in an instrumental variable analysis to estimate the effect of incipient AD on hearing impairment.ResultHigher AD‐GRS was associated with difficulty hearing in ages 60+(OR= 1.03; 95%CI:1.00, 1.05) but not in adults <60 years (OR=1.00; 95% CI:0.98,1.03). AD‐GRS associations were also stronger in ages 60+ with poor speech‐in‐noise hearing (OR=1.06; 95%CI:1.00,1.11) and the AD‐GRS strongly predicted subsequent AD diagnosis in participants aged 60+ at enrollment (OR=4.19; 95%CI:3.80, 4.72). Using the AD‐GRS as an instrumental variable for AD diagnosis, we estimated that incipient AD increased probability of difficulty hearing at enrollment by 45% (95%CI: 1%, 93%).ConclusionHigher AD‐GRS was associated with slightly higher odds of difficulty hearing in addition to higher odds of AD diagnosis in later life. These trends were age‐related and analyses suggest that genetics that predispose for AD also influence functional hearing difficulty to some extent. Although these findings do not rule out hearing loss as a cause of dementia, they support the hypothesis that disease process related to AD also influences hearing difficulty before dementia onset.
The effect of APOE ɛ4 in Alzheimer’s disease biomarkers in Down syndrome
Authors: Vilaplana Eduard , Videla Laura , Carmona‐Iragui Maria , Benejam Bessy , Barroeta Isabel , Fernandez Susana , Altuna Miren , Pegueroles Jordi , Montal Victor , Bejanin Alexandre , Iulita M. Florencia , Valldeneu Sílvia , González‐Ortiz Sofía , Muñoz Laia , Camacho Valle , Videla Sebastián , Alcolea Daniel , Blesa Rafael , Lleó Alberto , Clarimon Jordi , Fortea Juan 
Published: December 2020

AbstractBackgroundThe APOE ɛ4 allele is the main genetic risk factor for sporadic Alzheimer’s disease (AD). However, its influence on AD in Down syndrome (DS) has received less attention. Our main objective was to study the effect of the APOE ɛ4 allele in AD biomarkers in a population‐based cohort of adults with DS.MethodCross‐sectional study. We selected adults with DS and euploid healthy controls from Hospital de Sant Pau, Barcelona. We included all participants with known APOE genotype and at least one biomarker measured in: plasma, CSF or neuroimaging (MRI, FDG‐PET or Florbetapir‐PET). DS participants were classified into asymptomatic and symptomatic (prodromal or AD dementia). Aβ1‐42, total‐tau and NfL levels were measured in plasma using SIMOA and in CSF using Lumipulse. We extracted mean FDG‐PET SUVR (Landau), we measured the Centiloid score for Florbetapir‐PET and the adjusted hippocampal volumes from MRI. Subjects were classified into APOE ɛ4 carriers and non‐carriers. We compared age of symptoms onset between APOE ɛ4 carriers vs non‐carriers, and we fitted within‐group local regression models to compare the association of biomarkers with age between groups.ResultWe included 325 individuals with DS (214 asymptomatic and 111 symptomatic) and 239 controls (Table 1). When comparing age at diagnosis, subjects with DS harboring at least an APOE ɛ4 allele were two years younger than non‐carriers (51.1 vs 53.2, p=0.08). We then compared biomarker trajectories between APOE ɛ4 carriers and non‐carriers. As displayed in Figure 1, subjects with DS harboring an APOE ɛ4 allele showed earlier decreases in CSF Aß1‐42 and increases in Florbetapir Centiloid. APOE ɛ4 carriers showed a steeper decline in brain metabolism (FDG‐PET SUVR) in the fifth decade compared to APOE ɛ4 non‐carriers. No differences were found in total‐tau and NfL in CSF or plasma, or in hippocampal volume trajectories.ConclusionAPOE ɛ4 allele may influence the onset of AD‐related symptoms in DS. This effect might be due to earlier amyloid deposition and brain hypometabolism. The presence of APOE ɛ4 does not seem to have an effect on total‐tau, NfL or hippocampal volume. In conclusion, these results provide further insight on the relationship between APOE ɛ4 and AD pathophysiological processes.
Multimodal behavioral analysis for early detection of Alzheimer’s disease: A preliminary result
Authors: Yamada Yasunori , Shinkawa Kaoru , Ishikawa Tatsuya , Nishimura Masafumi , Nemoto Miyuki , Tsukada Eriko , Ota Miho , Nemoto Kiyotaka , Arai Tetsuaki 
Published: December 2020

AbstractBackgroundWith the rapid growth in the elderly population worldwide, early detection of Alzheimer’s disease (AD) has become increasingly important. In this respect, behavioral analysis of sensor data is expected to extend opportunities for assessments and help identify subtle changes resulting from AD at an early stage. Gait, speech, and drawing behaviors have been actively investigated and recognized as behavioral biomarkers that can be used for detecting individuals with AD and mild cognitive impairment (MCI). However, previous studies have mainly investigated single types of behavior. It remains unclear whether combining multimodal behavioral data could improve detection performance.MethodIn this study, we collected multimodal behavioral data related to gait, speech, and drawing from 73 Japanese seniors consisting of 36 healthy controls (HC), 26 MCI, and 11 AD. For gait data, we collected motion capture data during 9‐meter walks at the usual walking pace and extracted gait features related to pace, rhythm, variability, and postural control. Speech data were collected while performing tablet‐based cognitive tasks consisting of verbal fluency, calculation, and picture description, followed by extraction of acoustic, prosodic, and linguistic features. We also collected drawing behaviors with a drawing tablet during five tasks including clock drawing and trail making, and obtained features related to kinematic parameters of drawing trajectories and drawing pressure. We then used these features to build binary classification models for differentiating MCI or AD from HC using a support vector machine model with a feature selection method. The models were then evaluated by ten‐fold cross‐validation.ResultOur models using features of three types of behavior achieved 99.8% accuracy for HC vs. AD and 92.0% accuracy for HC vs. MCI. Compared to models using single modality behavioral data, we found that our model improved detection by up to 9.1% for HC vs. AD and 21.0% for HC vs. MCI.ConclusionWe demonstrated that multiple behavioral data could improve detection accuracy for patients with both MCI and AD by capturing different functional changes resulting from AD. Our approach based on multimodal behavioral analysis shows promise for timely diagnosis at an early stage of AD.
Self‐reported hearing impairment and social isolation are potentially modifiable risk factors for cognitive decline in community‐dwelling older adults
Authors: Tay Laura , Bakar Huda Mukhlis Abu , Ho Jolene , Latib Aisyah , Tay EeLing , Mah Shimin , Chan HiuNam , Ng YeeSien 
Published: December 2020

AbstractBackgroundFrailty is a state of excess vulnerability to stressors, and has been associated with increased risk of late‐life cognitive decline. As a multi‐factorial condition which is potentially reversible, frailty represents a modifiable target for prevention of cognitive impairment. We examine the risk of cognitive decline associated with physical frailty and its contributing factors in community‐dwelling older adults.MethodIn this prospective cohort study, community‐dwelling older adults aged >55 years undergo a rapid geriatric assessment that includes social profiling, cognitive (modified Chinese Mini‐Mental State Examination, CMMSE), psychological (Geriatric Depression Scale, GDS), nutritional (Mini Nutritional Assessment‐Short Form, MNA‐SF), and sensory (self‐reported vision, hearing) assessment at baseline and 1‐year. Sarcopenia was assessed using SARC‐F and participants completed a battery of physical fitness tests for flexibility, grip strength, upper limb dexterity, lower limb strength/ power, balance and endurance at baseline and follow‐up. Physical frailty was defined using modified Fried criteria. Cognitive decline was defined as a loss of >2 points on CMMSE at 1‐year relative to baseline.Result229 participants (mean age 67.3+7.0years) completed 1‐year follow‐up. 28 (12.2%) participants exhibited cognitive decline. Age, gender and education were similar between groups with and without cognitive decline. There was no difference in baseline prevalence of frailty, sarcopenia, depression and malnutrition between groups. Self‐reported hearing impairment at baseline was significantly more prevalent amongst older adults exhibiting cognitive decline (39.3% vs 19.9%, p=0.009), and they were more likely to report having no contact with friends or relatives compared with their counterparts with stable cognition (10.7% vs 1.0%, p=0.001). On physical fitness tests, only poorer upper limb dexterity at baseline was significantly associated with risk for cognitive decline (box‐and‐block test: 50.3+10.3 vs 54.5+9.6, p=0.035). In multiple logistic regression adjusted for age, gender, education and baseline cognitive performance, self‐reported hearing impairment independently increased risk for cognitive decline (OR=3.29, 95% CI 1.36‐7.96), while maintenance of social contact was protective (OR=0.04, 95% CI 0.00‐0.42).ConclusionWhile physical frailty was not associated with cognitive decline over the relatively short follow‐up of 1‐year, hearing impairment and social isolation are potentially modifiable and should be targets of intervention to reduce cognitive decline in community‐dwelling older adults.
A systematic review on the physical and mental health risk factors of mild cognitive impairment and Alzheimer’s disease in military veterans
Authors: Akhanemhe Rebecca A , Stevelink Sharon A.M , Aarsland Dag , Greenberg Neil 
Published: December 2020

AbstractBackgroundThe connection between military service, mild cognitive impairment (MCI) and Alzheimer’s disease (AD) has been previously explored but findings remain inconclusive. With age as the greatest and unmodifiable risk factor for dementia in military veterans, there is a need to further explore specific physical and mental health factors that influence cognition and dementia in military veterans compared to the general population. We will review publications as part of a systematic review to identify if traumatic brain injury, post‐traumatic stress disorder and depression influence the risk of MCI and AD in both military veterans and non‐veterans.MethodWe aim to conduct a meta‐analysis but if we identify limited suitable studies, a systematic review will be an alternative approach. Our systematic search will be carried out using various bibliographic databases including MEDLINE and PubMed. Data will be extracted from comparative and non‐comparative epidemiological and observational studies, published between 1990 to December 2019. The study population will be restricted to adults aged ≥50 years who may or may not have served in the military and assessed the occurrence of MCI/dementia whether formally diagnosed or through self‐report.ResultTo date, we identified 135 articles without duplicates and of this, 83 (61.5%) were excluded based on their titles and a further 27 articles (20%) were excluded after reviewing their abstracts. We are currently working on this review and aim to have the full findings before the conference.ConclusionThe potential implication of the findings could influence how health professionals utilise occupation data to identify dementia. Beyond the scientific community, the findings will raise awareness and promote health among veterans and carers.
Biogeographical factors affecting people with dementia of Alzheimer’s type and mild cognitive impairment
Authors: Rai Pooja , Singh Tara , Singh Indramani L. , Tiwari Trayambak , Joshi Deepika 
Published: December 2020

AbstractBackgroundDementia of Alzheimer’s type has been the most common neurodegenerative condition among elderly. The histopathological studies revealed that the formation of neurofibrillary tangles and amyloid plaque in brain have been the major factors affecting DAT. Other than intrusive protein formation there are other factors which pertains to affect DAT.MethodThe present study has accounted for different variables in with 7 mild, 8 moderate DAT and 7 MCI people.ResultAmong all the biographical variables, 10 variables viz. family size, education, smoking, exercise, alcohol, diabetes, heart problems, cholesterol, thyroid and blood pressure were the most affected biographical variables among all the patients. Further, diabetes, cholesterol, heart problem education were the most predictive among all the variables.ConclusionThe study suggested the significance of bio‐physiological factors in assessing dementia of Alzheimer's type so that an early progression of neurodegeneration could be traced.
Investigating the contribution of an intronic variation at the trim11 locus to pathological and clinical heterogeneity in progressive supranuclear palsy
Authors: Bez Sumi , Fowler Stephanie L. , Jabbari Edwin , Morris Huw R. , Duff Karen E. 
Published: December 2020

AbstractBackgroundProgressive supranuclear palsy (PSP) is a tauopathy that exhibits significant heterogeneity, with the three most prominently presenting subtypes showing differences in clinical symptomatology, disease progression, and tau burden. Recently, an intronic variant in the proteasome‐related gene TRIM11 was identified as a potential modifier of phenotypic diversity in PSP. Due to the role of TRIM11 as a known E3 ligase in the ubiquitin‐proteasome system, the single nucleotide polymorphism (SNP) is hypothesized to alter TRIM11 expression and/or function, thereby impacting pathological tau clearance. The current study will investigate the functional relevance of the TRIM11 intronic variant to mechanisms of pathological tau clearance.MethodUsing both full‐length, and repeat domain tau aggregation reporter assays with overexpressed or silenced TRIM11, we are determining if aggregated tau is a substrate of TRIM11 E3 ligase activity by co‐immunoprecipitation and tau ubiquitination assays. Further, we are monitoring tau inclusion formation and clearance by longitudinal imaging, coupled with the investigation of sarkosyl‐insoluble tau levels, and by cycloheximide chase assays for tau.ResultIf tau is a substrate of TRIM11 E3 ligase activity and TRIM11 is found to mediate the clearance of pathological tau, this finding could reveal the molecular mechanisms contributing to the clinical diversity observed in PSP.ConclusionTaken together, these experiments outline the investigation of one of the first genetic clues to phenotypic diversity in PSP, solidify the involvement of the UPS as a viable target in the processing of pathological tau, and may have wide‐reaching implications for the treatment of many other protein aggregation neuropathies.