bluuebunny/crossref_metadata_2025_split huggingface dataset:
Studying the relation between cognition and frailty: How can frailty be assessed using existing data?
Authors: Boekholt Melanie , Nowossadeck Sonja , Michalowsky Bernhard , Hoffmann Wolfgang , Thyrian Jochen René 
Published: February 2022

AbstractBackgroundFrailty, as a measurement of biological age, opposed to calendrical age, got a lot of recognition in geriatric research over the last 20 years. There is little knowledge about the association between impaired cognition and frailty whether it is correlational, due to similar calendrical age ranges, or causal. There is a need for frailty research with cognitively impaired people. Since establishing evidence with analyses of primary data are time‐consuming and expensive, secondary data might hold promising chances.MethodData of n=485 people with dementia from an intervention study with dementia patients (DelpHi‐MV), conducted in Germany, was used. We tested and analyzed different approaches on measuring frailty.ResultUsing a deficit‐cumulating index as a base, while incorporating the phenotype frailty, we were able to build a feasible index with sufficient internal consistency and inter item correlation. A visual comparison of density distributions with a sample of people with the same frame criteria (age, community dwelling) but without mandatory dementia shows that the statistical distribution of frailty within the samples is similar. There was a slight shift to higher values in our sample of cognitively impaired people and a distinct difference in the density of medium to high values between both samples.ConclusionThe distribution of frailty supports the presumption of a relationship between cognition and frailty. It was in principal similar in both samples, with only slight differences. Based on this now created index we will be able to conduct further research on questions such as: To what extent does an intervention influence frailty in the respective study population? Is frailty a risk factor, a moderating or a mediating factor for the success of an intervention? Is the relationship between cognitive impairments and frailty correlational or causal?
Brain amyloid load and cognitive trajectories in older individuals at risk for dementia
Authors: Hossain Gazi Saadmaan , Hall Anette , Ngandu Tiia , Kemppainen Nina , Rinne Juha O. , Kivipelto Miia , Solomon Alina 
Published: February 2022

AbstractBackgroundMost studies have so far investigated the cognitive performances and amyloid status on brain PET scans in cognitively normal, cognitively impaired, or individuals with dementia. In this study associations between brain amyloid status and changes in cognitive performance over time in an at‐risk older general population without dementia or substantial cognitive impairment were evaluated.MethodForty‐eight individuals from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) main study participated in the 11C‐Pittsburgh compound B (PiB)‐positron emission tomography (PET) exploratory sub‐study. Participants were categorized as amyloid+ or amyloid– after baseline PET scans were assessed visually by two experienced readers. A comprehensive cognitive Neuropsychological Test Battery (NTB) was used to assess cognitive performance at baseline, 12‐ and 24‐month follow‐up. The Prospective and Retrospective Memory Questionnaire was used to measure subjective cognitive complaints (SCCs) during the study. Changes in cognitive functions during the 2‐year study were compared across baseline amyloid groups using mixed effects regression models with maximum likelihood estimation.ResultThe mean age for all participants (n=48) was 71.4 years, and 22 participants (45%) were female. At baseline, 20 participants (42%) had amyloid+ PET scans and amyloid positivity was associated with lower NTB executive function (estimate = ‐0.38, 95% CI= ‐0.70 – ‐0.05, p=0.03). Interaction terms between baseline amyloid+ status and time were significant for NTB total score (estimate=‐0.10, 95% CI= ‐0.20 – ‐0.01, p=0.04) and NTB memory score (estimate = ‐0.18, 95% CI= ‐0.34 – ‐0.03, p=0.02). No significant associations were observed between amyloid positivity and change in NTB executive function score or NTB processing speed score. Furthermore, amyloid status was not significantly related to SCCs.ConclusionResults from this study suggest that positive amyloid status is likely to reduce cognitive abilities over time. Interestingly, in this very early at‐risk stage before the onset of substantial impairment or dementia, amyloid status was related to poorer trajectories in global cognition and memory over time, but not to subjective cognitive complaints. However, future studies with larger sample sizes and longer follow up period will be needed to further investigate the impact of amyloid accumulation.
The association between physical activity and brain integrity is partly mediated by cardiovascular mechanisms
Authors: Felisatti Francesca , Gonneaud Julie , Palix Cassandre , Mézenge Florence , Landeau Brigitte , Chocat Anne , Quillard Anne , Devouge Eglantine Ferrand , Sayette Vincent De , Vivien Denis , Chetelat Gaël , Poisnel Géraldine 
Published: February 2022

AbstractBackgroundPhysical activity (PA) has been associated with decreased risk of dementia, but the mechanisms underlying this association remain to be determined. One hypothesis is that PA might reduce cardiovascular risk factors (CVRFs), which in turn would benefit brain health. Our objective was to assess the role of CVRFs in the association between PA and neuroimaging markers of brain integrity.MethodBaseline data of 134 cognitively unimpaired older adults (mean age: 69) from the Age‐Well cohort were analyzed. They underwent a PA questionnaire, CVRFs collection (systolic blood pressure, body mass index [BMI], current smoker status, HDL‐cholesterol, total cholesterol, and insulin), and multimodal neuroimaging (structural and diffusion MRI, FDG‐ ]and Florbetapir‐PET). A global measure of brain integrity was obtained for each neuroimaging modality by extracting the averaged signal across the whole gray matter (GM), or white matter for diffusion. Correlations were first conducted to assess the association between PA, CVRFs, and each neuroimaging modality. Multiple regression and mediation analyses were then performed to test whether the associations found between PA and neuroimaging were mediated by CVRFs.ResultHigher PA was associated with higher global GM volume and FDG metabolism, but not with amyloid deposition or white matter integrity. Higher PA was also associated with lower insulin levels and BMI, but not with the other CVRFs. Lower insulin and BMI were related to higher GM volume, but not to FDG metabolism. Adjusting for insulin and BMI (separately), the association between PA and FDG metabolism remained unchanged while the association with GM volume did not. When adding insulin and BMI in the same model, BMI was the only significant predictor of GM volume. This was confirmed by a mediation analysis.ConclusionPA is specifically associated with greater brain volume and FDG metabolism in older adults. While the association between PA and FDG metabolism appears to be independent from CVRFs, the link with GM volume is mediated by changes in BMI and insulin, with BMI driving the effects. Our results suggest that maintenance of a healthy BMI through PA could help preventing disturbed insulin metabolism usually observed in aging, thus promoting brain health.
The impact of the COVID‐19 pandemic in exacerbating dementia risk factors in a high‐risk Alzheimer’s disease population: Study of a cohort with Down syndrome
Authors: Idris Mina , Saini Fedal 
Published: February 2022

AbstractBackgroundThe COVID‐19 public health crisis and introduction of strict regulations have presented new challenges for people with Down syndrome (DS) and dementia in the UK. Social and cognitive deprivation together with poor mental health are risk factors for dementia. This study aimed to explore the impact of lockdown on well‐being in a population with DS who are already at high‐risk for developing dementia.Method98 individuals with DS were interviewed over the phone about how COVID‐19 and restrictions have affected their daily life, mental and physical health as well as attitude to participating in research. 50 interviews were conducted for younger adults (YA) aged 18‐35 and 48 with older adults (OA) aged 36+ and basic statistics were calculated.ResultSince the start of the pandemic, two participants have been diagnosed with dementia and three are under investigation for dementia. Five were diagnosed with dementia prior to the pandemic, three of whom have experienced symptoms worsening. A third of the total cohort reported worsening of general health, although not directly caused by a COVID infection. 44% of YA and 32% of OA reported a negative psychological impact, while almost all experienced a significant change in their daily activities with only 47% returning to their physical or social activities at the end of the initial lockdown. Regarding outlook on research participation, over 80% of individuals stated they would still be happy to participate in research in person and 75% would also find research conducted over video call to be a feasible option.ConclusionThe pandemic has had a negative impact on physical and mental health of a large proportion of individuals with DS which in turn may potentially affect dementia risk in this already vulnerable group. Although no causal relationship can be established from this study, the aforementioned worsening in health may have partially resulted from the social isolation, reduced physical and cognitive stimulation recorded in this cohort.
Epidemiological spread models of Parkinson’s disease support the prion‐like role of alpha‐synuclein
Authors: Dagher Alain , Tremblay Christina , Rahayel Shady , Abbasi Nooshin , Abdelgawad Alaa , Zheng Ying‐Qiu , Misic Bratislav , Luk Kelvin C. 
Published: February 2022

AbstractBackgroundParkinson’s disease (PD) is a progressive neurodegenerative condition marked by brain atrophy in multiple cortical and subcortical regions. It is now known to be caused by the prion‐like propagation of misfolded alpha‐synuclein, supporting Braak’s hypothesis. The pattern of neurodegeneration is now thought to be explained by a combination of brain connectivity and local vulnerability.MethodWe used MRI and clinical data from the Parkinson Progression Markers Initiative to map the progression of brain atrophy over one, two and four years and related it to brain functional and structural connectivity, cell type expression and gene ontology enrichment analyses. We use two methods to measure atoprhy: cortical thickness measures and deformation based morphometry. We will compare these results to pathology in wild‐type mice sacrificed at different time‐points after injection of alpha‐synuclein preformed fibrils. In both cases we use a spreading model inspired by infectious‐disease epidemiology to map the propagation of misfolded alpha‐synuclein. This Susceptible‐Infectious‐Recovered (SIR) model assumes that alpha‐synuclein molecules become misfolded, propagate along the connectome, and cause tissue damage when they accumulate.Result1) The pattern of brain atrophy in de novo PD is compatible with a propagating process with an epicenter in the substantia nigra. 2) The SIR model recapitulates the observed atrophy pattern, and supports connectivity‐based propagation. 3) In addition, the SIR model suggests that brain areas with higher alpha‐synuclein concentration appear to be more susceptible to injury but also more likely to act as disease propagators. 4) Progression over four years is also explained by connectivity. 5) Gene ontology analyses suggest that synapses are especially targeted by neurodegeneration. 6) Studies in mice, where the injection site of alpha‐synuclein preformed fibrils is determined by the investigator, also confirm the connectivity by local vulnerability model.ConclusionHuman and animal studies support the Braak hypothesis of a “toxic agent” propagating from the brainstem to the cortex, accounting for the stereotyped progression of PD manifestations. Data from gene expression studies and animal experiments confirm the important role of prion‐like alpha‐synuclein in PD pathogenesis.
New applications of diffusion model based prediction of pathological brain alterations: Introducing amyloid‐tau interactions
Authors: Raj Ashish , Anand Chaitali 
Published: February 2022

AbstractBackgroundAlzheimer’s disease involves widespread and progressive deposition of misfolded protein tau. There is mounting evidence for “prion‐like” trans‐neuronal transmission, whereby proteins misfold, triggering subsequent misfolding of adjacent same‐species proteins, which spread along white matter projections. It is not well understood how tau and amyloid beta interact, and how their subsequent spread lead to stereotypical progression in the Alzheimer brain.MethodHere we present a major advancement of our previously established Network Diffusion Model (Raj et al. Neuron 2012) that includes three key processes: a) Tau monomer seeding and production in the entorhinal cortex, and Ab monomer seeding in metabolically active areas. b) Interaction between Ab and tau, whereby Ab facilitates production of tau, or both facilitate each other. c) Both species then undergo network spread via our prior Network‐Diffusion model, whereby anatomic connections govern the rate at which two distant but connected brain regions can transfer pathologic species. This extended joint Ab‐tau model was thoroughly tested on empirical group‐averaged regional data (MRI‐derived atrophy, AV45‐PET for Ab and AV1451‐PET for tau) from ADNI‐3 (Table 1).ResultThe extended NDM model exhibits all hallmarks of tau and amyloid progression seen in human patients (Figure 1), accurately capturing the spatial distribution of empirical regional atrophy, Ab and tau (Table 2). Figure 1 shows evolution of the joint model with (middle column) and without amyloid‐facilitation of tau (right). Remarkably, the introduction of a 1‐way directed Aβ to tau influence recapitulated the concept of amyloid‐facilitated tauopathy, and was critical to the models’ success. In comparison, the non‐interacting model was significantly worse, while the 2‐way interaction model (bidirectional influence between tau and Ab) was essentially the same (see Table 2).ConclusionThis in silico exposition of the “pas de deux” of co‐evolving proteins supports a key role for an amyloid‐facilitated‐tau rather than the classic amyloid‐cascade or pure‐tau hypotheses, and helps explain known but poorly understood aspects of AD (Figure 2).
Rate‐limiting processes of tau aggregate accumulation in Alzheimer's disease
Authors: Meisl Georg , Zuo Yukun , Allinson Kieren , Rittman Timothy , DeVos Sarah L. , Sanchez Justin S , Xu Catherine K. , Duff Karen E. , Johnson Keith A. , Rowe James B. , Hyman Bradley T. , Knowles Tuomas , Klenerman David 
Published: February 2022

AbstractBackgroundBoth the replication of tau aggregates and their spreading throughout the brain are implicated in the progression of Alzheimer’s disease (AD). However, the rates of these processes are unknown and the identity of the rate‐determining process in humans has therefore remained elusive. Using a mathematical framework based on chemical kinetics, we are able to answer these questions by analysis of experimental data from AD patients.MethodOur minimal mathematical model of aggregate spreading and replication enables us to determine the rates of spreading and replication from measurements of tau seeds and aggregates across brain regions. Simulations based on this model show clearly distinct patterns of tau distributions when the behaviour is limited by either replication or spreading (Fig 1). We analysed several already existing datasets from in vitro seeding experiments, tau pathology in P301S transgenic mice, and histochemical post‐mortem as well as 2‐year longitudinal tau PET data in humans (Fig 2).ResultAcross mice and human data, we found that the overall rate of accumulation of tau in cortical regions is limited not by the rate of tau spreading between brain regions but by the rate of local replication within a brain region. In human post‐mortem data, low levels of tau seeds were present already throughout the cortex at Braak stage 3, where effective replication of those initial seeds rather than inter‐regional spreading was the rate limiting factor for further tau accumulation. The rate of replication determined from these data corresponds to a doubling of the number of seeds only every ∼5 years, which was well in line with the our analysis of tau accumulation from longitudinal tau PET data in AD patients. This rate is orders of magnitude slower than that measured for purified tau in vitro, quantifying the efficiency of innate cellular mechanisms curtailing tau seed replication.ConclusionBased on these findings, we believe that limiting local replication constitutes the most promising strategy to control tau accumulation during AD, after Braak stage 2. Our results provide a framework for the determination of the identity and the rates of the key steps controlling disease‐associated aggregation processes within living organisms.
Knowledge, confidence, attitudes and beliefs of physiotherapists and physiotherapy students working with people with dementia: A mixed‐methods systematic review
Authors: Quick Stephen , Snowdon David A , Lawler Katherine , McGinley Jennifer , Soh Sze Ee , Callisaya Michele L 
Published: February 2022

AbstractBackgroundClinical care for people with dementia as a primary diagnosis, or as a co‐morbidity, can be complex. Physiotherapists play a key role in the care of people living with dementia in multiple settings. The aim of this systematic review is to understand the attitudes, beliefs, knowledge and confidence of physiotherapists and physiotherapy students when working with people with dementia.MethodThis was a mixed‐methods systematic review that included qualitative and quantitative studies. Participants were physiotherapists working in any clinical specialty (e.g. gerontology, orthopaedic, neurological, cardio‐respiratory), and physiotherapy students who had completed at least one clinical placement. If studies investigated physiotherapist and physiotherapy students’ knowledge, confidence, attitudes or beliefs on working with a general population of older adults, they were excluded. The phenomena of interest and context were attitudes, beliefs, knowledge and confidence when working with people with dementia in any setting. Eleven databases were searched. Data synthesis followed a convergent integrated approach according to Joanna Briggs Institute methodology for mixed methods systematic reviews.Result15 studies were eligible for inclusion (9 quantitative and 6 qualitative studies). There were 5 key themes: rehabilitation potential (variable outcomes, poor potential), challenges in dementia care (communication, behaviour, cognition, risk, stress and burnout), education in dementia practice (inadequate training and knowledge, importance of experience), specialised area of practice (complexity of presentation, nuance of care, importance of time, holistic approach) and unsupportive systems (environment, time, risk aversion). One code, lack of desire to provide dementia care, did not contribute to any themes.ConclusionPhysiotherapists and physiotherapy students have low levels of knowledge and confidence in several areas important to working with people with dementia. With higher levels of knowledge and confidence associated with more positive attitudes and beliefs, dementia education needs of physiotherapists at all levels needs to be addressed.
Neuroimaging in neurodegeneration: A global diversity problem
Authors: Adams Hieab H.H. , Vilor‐Tejedor Natalia , van Beek Annemieke , Evans Tavia E. 
Published: February 2022

AbstractBackgroundResearch investigating neuroimaging within neurodegenerative diseases is currently lacking in many ethno‐racial groups. Whilst some racially diverse studies are being carried out within North America many still question its generalizability to global populations. Initiatives are being instigated within South America, and data within Asia is more frequently being involved in larger collaborations, however Africa is falling behind. Often research into neuroimaging of neurodegenerative diseases within under‐represented groups is difficult due to numerous barriers, such as MRI accessibility, funding, infrastructure, misconceptions and lack of geriatric neurologists.MethodTo fully understand the current research investigating neuroimaging within neurodegenerative diseases, a large literature review focusing on structural imaging was conducted. Additionally, a large global initiative has been set up to overcome the lack of diversity within this field‐ the uncovering neurodegenerative insights through ethnic diversity (UNITED) consortium. The UNITED consortium aims to bring together‐ and support‐ groups investigating neuroimaging of neurodegenerative diseases, such as Alzheimer’s disease. A pilot study was undertaken to investigate feasibility of meta‐analysing heterogeneous data‐ often a limitation within neuroimaging. Four samples from the UNITED consortium were included, with over 25,000 individuals from population‐based and case‐control designs, to investigate reproducibility of association studies in imaging biomarkers, and explore under‐represented ethnic groups.ResultThe literature review yielded over 28,000 abstracts which were screened. It was found that the majority of research currently published uses samples from North America and Europe, with a high use of ADNI data, further highlighting the need for such initiatives as the UNITED consortium. The preliminary pilot results displayed that reproducible results were seen from heterogeneous samples, highlighting the feasibility of neuroimaging collaborations. Subgroup meta‐analyses suggest this that large collaboration will aid in teasing out differences and similarities in under‐represented groups that we are currently lacking.ConclusionThere is an urgent need for more diversity and global research within neuroimaging of neurodegeneration. This will further reveal insights into complex neurodegenerative disorders and provide more adequate and personal care to individuals around the globe. Multi‐site collaborations, such as the UNITED consortium, have a lot of potential to produce reliable and more generalizable results pertaining to this.