bluuebunny/crossref_metadata_2025_split huggingface dataset:
Harmonisation of assessments in Australian Memory Clinics: Challenges and opportunities
Authors: Mehrani Inga , Kochan Nicole A. , Crawford John D. , Naismith Sharon L , Sachdev Perminder S. ,   Australian Dementia Network (ADNeT) Collaboration
Published: December 2021

AbstractBackgroundSince the late 1980’s, Memory Clinics have been an integral part of Australia’s dementia assessment and care services. Despite their continuous growth over the past 30 years, little benchmarking data is available and no best practice standards have been established. The Australian Dementia Network‐Memory Clinics initiative (ADNeT‐MC) is committed to initiate change and facilitate the harmonisation of assessment process and national collaboration. The main objective is to provide a state‐of‐the‐art diagnostic assessment to all individuals with cognitive disorders.MethodA survey of Australian Memory Clinics was conducted to evaluate the current situation and determine the most commonly used clinical test instruments. Further a Delphi process to develop national Memory Clinic guidelines will be completed in 2021. Informed by the survey results and national and international dementia care and assessment guidelines, a set of best practice recommendations are being developed. A group of national experts, including researchers, clinicians, patients and careers, rates and assesses each recommendation to arrive at consensual final guidelines.ResultThe ADNeT‐MC national Memory Clinics survey showed a vast heterogeneity in clinical (e.g., assessment protocols used) and structural aspects (e.g., staffing, funding). We identified more than 100 different cognitive assessment instruments currently in use, but with agreement on the screening tool (MMSE) and subset of neuropsychological tests (see Table 1). Geriatricians were the most commonly involved specialists. Few clinics reported allied health professionals or social workers, which likely affects post‐diagnostic care delivery. Indeed, the provision of post‐diagnostic care is often limited to short‐term support, whereas more extensive support (e.g., cognitive intervention) is often not funded. First results of the Delphi process as well as recommendations for a consensus assessment protocol will be presented at this session.ConclusionADNeT‐MC will outline one possible pathway to achieve national harmonisation across Memory Clinics. The development of standards that can be met by all Australian Memory Clinics, independent of their location and funding constraints, has the potential to enhance the quality of diagnostic assessments of all neurocognitive disorders and make post‐diagnostic care an integral part of the service delivery.
Clinic‐based data serving Population Neuroscience: NACC example
Authors: Kukull Walter A. , Ganguli Mary 
Published: December 2021

AbstractBackgroundMemory clinics have historically driven case‐definition, clinical diagnostic criteria, and treatment trials in Alzheimer’s disease and related disorders (ADRD) and investigated neuroimaging and molecular factors leading to the development of ADRD biomarkers. The Uniform Data Set (UDS) of the National Alzheimer’s Coordinating Center (NACC)1 provides one such repository of clinic‐based and neuropathologic data2. (https://naccdata.org) With standardized characterization, long followup with low attrition, and post‐mortem neuropathology, memory clinic studies have high internal validity. However, they are rightly faulted for low external validity (generalizability) of results, with samples not representative of definable segments of the general population3. NACC has advanced several research directions proposed by the emerging field of Population Neuroscience.4
MethodApproximately 35 U.S. Alzheimer’s Disease Research Centers (ADRCs) enroll ADRD participants. Standardized (e.g., UDS) data collection and clinico‐pathologic correlations contribute to expanding phenotypic detail and support molecular biomarker, genomics, and soon, metabolomic analyses. NACC data support behavioral intervention trials and are now being used to characterize inadequately studied groups. NACC collaborates with ADRC consortia to facilitate studies of genomics, metabolomics, biomarkers, behavioral and environmental factors. Consortia datasets are interoperable with NACC1 offering opportunities to link UDS with GWAS and genome sequencing data (through NIAGADS), and soon with prospectively collected, standardized imaging biomarker data (through the SCAN project) with other collaborators.ResultBy December 2020, NACC had data from 43,517 participants including 15,440 with normal cognition, 9453 MCI, and 18,627 dementia; 30,019 have at least two longitudinal visits. 6,416 deceased participants have provided standardized neuropathology data. This NACC “case series” has generated >500 publications; NACC data are freely available to researchers worldwide.ConclusionClinic‐based studies function as laboratories observing potential data patterns and associations as a first step towards validation in more representative populations. NACC continues to make its data more “findable, interoperable, accessible and reusable” for the broader scientific community. Reference: 4. Ganguli M, Albanese E, Seshadri S, et al. Population Neuroscience: Dementia Epidemiology Serving Precision Medicine and Population Health. Alzheimer Dis Assoc Disord. Jan‐Mar 2018;32(1):1‐9.
How lifestyle shapes the brain: Associations between physical activity, sleep, beta‐amyloid and cognitive function in older adults
Authors: Sewell Kelsey R , Rainey‐Smith Stephanie R , Villemagne Victor LL , Peiffer Jeremiah J , Sohrabi Hamid R , Taddei Kevin , Ames David , Maruff Paul T , Laws Simon M , Masters Colin L , Rowe Christopher C , Martins Ralph N , Erickson Kirk I. , Brown Belinda M 
Published: December 2021

AbstractBackgroundLifestyle factors such as sleep and physical activity influence risk of cognitive decline and dementia. Higher habitual physical activity and optimal sleep are associated with better cognitive function and lower levels of Alzheimer’s disease biomarkers, including beta‐amyloid (Aß). There is currently a poor understanding of how physical activity may influence the relationship between sleep and cognition, and whether exercise and sleep interact to influence cognition and Aß. Developing this understanding is crucial for creating effective lifestyle interventions for dementia prevention.MethodData from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study were utilised to determine whether self‐reported physical activity moderates the cross‐sectional relationship between self‐reported sleep parameters (duration, efficiency, latency, disturbance, quality), cognitive function (episodic memory, attention and processing speed, executive function), and brain Aß (quantified by amyloid positron emission tomography, using the Centiloid scale). Analyses were adjusted for age, sex, APOE ε4 carriage, mood, premorbid intelligence, and collection point. Participants were 404 community‐dwelling cognitively normal older adults aged 60 and above (75.3 5.7 years). Data from a subset of participants (n = 220, aged 75.2 5.6 years) were used for analyses with AB as the outcome.ResultPhysical activity moderated the relationship between sleep duration and episodic memory (ß = ‐.09, SE = .03, p = .005), and sleep efficiency and episodic memory (ß = ‐.08, SE = .03, p = .016). Physical activity moderated the relationship between sleep duration and A® (ß = ‐.12, SE = .06, p = .036), and sleep quality and Aß (ß = .12, SE = .06, p = .029).ConclusionPhysical activity may play an important role in the relationship between sleep and cognitive function, and sleep and brain Aß. Future longitudinal and intervention studies in this area are crucial for informing interventions for dementia prevention.
Characterizing extracellular vesicles from cerebrospinal fluid by a novel size exclusion chromatography method
Authors: Hirschberg Yael , Schildermans Karin , van Dam Annemieke , Sterck Karen , Boonen Kurt , Nelissen Inge , Vermeiren Yannick , Mertens Inge 
Published: December 2021

AbstractBackgroundExtracellular vesicles (EVs) have recently been considered as a potential biomarker source for a variety of diseases, including neurodegenerative disorders. EVs are important mediators of intercellular communication due to their capacity to transfer genetic material, lipids and proteins. By means of their communication role, interesting biomarkers are often enriched in EVs compared to total biofluid. In order to isolate EVs from a biofluid, like cerebrospinal fluid (CSF), a variety of isolation methods are available of which each methods shows different results, and, to date, there is no golden standard. Our study evaluates the use of size exclusion chromatography (SEC) by the SmartSEC HT kit for EV isolation from CSF.MethodEVs were obtained from 500µL CSF samples, isolated by SmartSEC HT. SmartSEC traps contaminants, like bulk proteins, into the resin beads and subsequently elutes EVs. To evaluate this isolation method, various characterisation analyses were run. To detect cargo or surface proteïns, analyses on the ExoView R100, Surface Plasmon Resonance imaging (SPRi) and LC‐MS based proteomics analysis were performed. Concentration, and size of the vesicles were evaluated by use of transmission electron microscopy (TEM), and fluorescence nanotracking analysis (Zetaview).ResultBy means of the ExoView, tetraspanins such as CD81 and CD9 were measured on the surface of the EVs. Other EV‐specific proteins, e.g. lactadherin, flotillin‐1, and HSP70, were detected by SPRI. Untargeted protein analysis revealed the cargo proteins. TEM images visualized the presence of EVs. Particle size and concentration was calculated by nanotracking analysis, and more specifically the particles with a lipid membrane, like EVs, with fluorescence nanotracking analysis.ConclusionAs EVs hold a lot of promise in the biomarker field, a standard high‐performance isolation method ‐ regarding purity and yield – is essential. From our data, SmartSEC HT is suggested to be an efficient size exclusion chromatography EV isolation method for low volume CSF samples, especially for high throughput, since samples are loaded on a 96‐well plate.
Associations among clinical characteristics of sleep quality, cognitive performance, and brain architecture in Thai dementia spectrum disorders
Authors: Senanarong Vorapun , Piyaamornpan Nattaporn , Chotinaiwattarakul Wattanachai , Cheiwvit Pipat , Rattanabannakit Chatchawan , Wongkom Natthamon , Dujada Pathitta , Vichianin Yudthaphon 
Published: December 2021

AbstractBackgroundSleep disorders are increased with advancing age. Poor sleep quality is a risk factor for cognitive decline and dementia. We aimed 1) to explore the relationship between sleep quality, sleep architecture and cognition; 2) to investigate the association between brain volume and sleep parameters.MethodA total of 95 participants (70 female, mean age 67.18 ± 10 years) were included in this study. Thirty were those with major cognitive disorder patients, twenty‐five individuals had mild cognitive impairment (MCI), and forty were normal controls. Sleep parameters were measured using wrist actigraphy and subjective sleep questioners. The participants were evaluated with high‐resolution MRI. Three Dimensional sequences on Free‐Surfer morphometric procedure was used as the automated segmentation method to obtain brain volume. Demographic data, medical history, sleep characteristics, neuropsychological and mood evaluation were collected from participants.ResultMCI patients had significantly lower sleep efficiency than cognitive healthy persons, 81.30 + 7 .39 % vs. 85.12 + 5.09 %, p=0.04. 66 % of the participants had poor sleep quality. Prevalence of probable REM sleep behavior disorder (RBD) and restless leg syndrome was high in dementia group. Longer sleep latency was associated with worse performance on global cognition. Total sleep time was associated with entorhinal corex volume and hippocampal volume. Sleep latency was associated with hippocampal volumeConclusionSleep disorders were common in both cognitively healthy persons and dementia spectrum disorders. Lower sleep quality and disturbance of sleep maintenance were associated with the development of cognitive impairment. The causes and the consequences of poor sleep quality in patients with dementia spectrum disorders needed to be explored.
Neurogranin: A novel biomarker of Alzheimer’s disease
Authors: Dulewicz Maciej , Kulczynska‐Przybik Agnieszka , Klimkowicz‐Mrowiec Aleksandra , Pera Joanna , Borawska Renata , Slowik Agnieszka , Mroczko Barbara 
Published: December 2021

AbstractBackgroundAlzheimer’s disease (AD) is a progressive, incurable and fatal neurodegenerative disorder characterized by continuing cognitive decline. Early deficits of memory and other cognitive functions has closely related to synaptic loss in AD. Neurogranin (Ng) is a small protein located in postsynaptic neurons, dendrites and spines in brain structures like the hippocampus. Ng plays an crucial role in synaptic plasticity and long‐term potentiation mediated by calcium and calmodulin signalling pathway, which is essential to memory and learning functions. Considering the above mentioned facts, it seems that Ng can be novel biomarker of synaptic injury. The purposes of our investigation were the quantitive assessment of Ng levels in the CSF of AD patients and comparison with classical biomarkers of AD.MethodThe cerebrospinal fluid (CSF) levels of neurogranin and classical AD biomarkers, such as Aβ‐42, Aβ‐42/Aβ‐40, hTau and pTau181 were assessed by immunoenzyme assays. The study included 15 patients with AD and 15 non‐demented controls.ResultThe significantly higher concentration of Ng in cerebrospinal fluid of AD patients compared to non‐demented controls was observed. The CSF level of neurogranin was positively correlated with hTau and pTau181 and negatively with Aβ‐42/Aβ‐40 ratio.ConclusionThe Ng is a crucial indicator of synaptopathy in the AD.Our results suggest that Ng is a promising biomarker for AD, however, further studies on larger group patients are needed. Acknowledgement: The study was conducted with the use of equipment purchased by the Medical University of Białystok as part of the RPOWP 2007‐2013 funding, Priority I, Axis 1.1, contract No. UDA‐RPPD.01.01.00‐20001/15‐00 dated 26 and project № POWR.03.02.00‐00‐I051/16 from European Union funds, POWER 2014‐2020, grant № 04/IMSD/G/2019
Low‐dose acetylsalicylic use shows protective association with Alzheimer’s disease incidence: Results from two large prospective cohort studies
Authors: Nguyen Thi Ngoc Mai , Schöttker Ben 
Published: December 2021

AbstractBackgroundAcetylsalicylic acid (ASA), through multiple mechanisms, has been assigned a potential protective effect on dementia development. However, observational studies and randomized trials have yielded conflicting results so far.MethodCox regression models, adjusted for a propensity score to model the underlying cardiovascular risk, were used to assess the longitudinal associations of low‐dose ASA use with all‐cause dementia, Alzheimer’s disease (AD) and vascular dementia (VD) incidence in two population‐based cohorts: the ESTHER cohort from Germany with 6,049 participants, and the UK Biobank cohort with a total of 501,392 participants.ResultOver a median of 14.3 years of follow‐up, 481 all‐cause dementia cases, including 158 AD and 183 VD cases were diagnosed in ESTHER. In the UK Biobank, 5,177 were diagnosed with dementia, including 1,885 AD cases and 1,281 VD cases during a follow‐up time of 8.9 years. In the ESTHER study, participants who used low‐dose ASA had a reduced risk of 21% for all‐cause dementia (hazard ratio‐HR [95% confidence interval‐CI]: 0.79 [0.62‐1.02]), of 46% for AD (HR [95%CI]: 0.57 [0.35‐0.92]) but there was no association with VD. Results pointed towards the same direction in UK Biobank cohort, with a reduced risk of 11% (HR [95%CI]: 0.89 [0.82‐0.96]) for all‐cause dementia and 14% (HR [95%CI]: 0.86 [0.76‐0.99]) for AD, while there was a null result for VD.ConclusionIndividuals who used low‐dose ASA had a reduced the risk of total dementia and AD incidence in two independent cohort studies. In patients with pre‐existing cardiovascular conditions, who have an indication for low‐dose ASA use anyway, it should be taken care that they get low‐dose ASA prescribed and are compliant. Moreover, other individuals with known high AD risk (e.g., because of APOE ε4/ε4 positive status or family history of early onset AD) should consider to start low‐dose ASA use already in middle adulthood (at age 40‐50 years) as a preventive measure against AD development at older age.
The Cambridge Behavioural Inventory (revised) detects early behavioural and functional impairment in genetic frontotemporal dementia within the GENFI cohort
Authors: Nelson Annabel , Russell Lucy L , Peakman Georgia , Greaves Caroline V , Convery Rhian S , Rohrer Jonathan D ,   GENFI Consortium
Published: December 2021

AbstractBackgroundBehavioural dysfunction is a key feature of genetic frontotemporal dementia (FTD) but validated clinical scales measuring behaviour are lacking at present.MethodWe assessed behaviour using the revised version of the Cambridge Behavioural Inventory (CBI‐R) in 733 participants from the Genetic FTD Initiative study: 466 mutation carriers (195 C9orf72, 76 MAPT, 195 GRN) and 267 non‐mutation carriers (healthy controls). All mutation carriers were stratified according to their CDR® plus NACC FTLD into three groups: asymptomatic (CDR=0), mildly symptomatic (CDR=0.5) and fully symptomatic (CDR=1+). CBI‐R total scores were compared between mutation carrier groups using a mixed effects model that adjusted for age, education, sex and family clustering, with 95% bootstrapped confidence intervals with 2000 repetitions to adjust for non‐normally distributed data. We used the same mixed effects model to run a within‐group analysis between the 10 CBI‐R domains in CDR 1+ groups. Spearman rank correlations were run to assess the relationship of the CDR® plus NACC FTLD SOB and FRS scale with the CBI‐R total in CDR 1+ mutation carrier groups.ResultCBI‐R total scores were significantly higher in all CDR 1+ mutation carrier groups compared to controls (C9orf72 mean 70.5 (standard deviation 27.8), GRN 56.2 (33.5), MAPT 62.1 (36.9)), as well as their respective CDR 0.5 groups (C9orf72 13.5 (14.4), GRN 13.3 (13.5), MAPT 9.4 (10.4)) and CDR 0 groups (C9orf72 6.0 (7.9), GRN 3.6 (6.0), MAPT 8.5 (13.3)). Both C9orf72 and GRN 0.5 groups scored significantly higher than controls and their respective CDR 0 groups. Motivation and Memory were the highest scoring domains in both C9orf72 and GRN CDR 1+ groups, and in the MAPT group it was Stereotypic Behaviour and Memory. There was a positive correlation between the CBI‐R scores and the CDR® plus NACC FTLD SOB scores in all mutation carrier groups (C9orf72: rho= 0.8, p<0.001, GRN: rho= 0.8, p<0.001, MAPT: rho= 0.6, p<0.001), and a negative correlation between CBI‐R scores and FTD Rating Scale (FRS) scores (C9orf72; rho= ‐0.9, p<0.001, GRN; rho= ‐0.9, p<0.001, MAPT; rho= ‐0.9, p<0.001).ConclusionThe CBI‐R detects early behavioural change in genetic FTD, particularly in those with C9orf72 and GRN mutations.
Midlife subclinical atherosclerosis and cardiovascular risk factors linked to hypometabolism in Alzheimer’s disease relevant regions
Authors: Cortes‐Canteli Marta , Gispert Juan Domingo , Salvadó Gemma , Toribio‐Fernández Raquel , Tristao‐Pereira Catarina , Sanchez‐Gonzalez Javier , Ibañez Borja , Molinuevo Jose Luis , Fuster Valentin ,   The Progression of Early Subclinical Atherosclerosis study
Published: December 2021

AbstractBackgroundAtherosclerosis has been linked to cognitive decline in late life; however, the impact of cardiovascular risk factors (CVRFs) and subclinical atherosclerosis on brain metabolism at earlier stages remains unexplored.MethodThis study, aimed at determining the association between brain metabolism, subclinical atherosclerosis and CVRFs in midlife, included 547 asymptomatic middle‐aged participants (50±4 years, 82% men) from the Progression of Early Subclinical Atherosclerosis study with evidence of subclinical atherosclerosis. Participants underwent 18F‐fluorodeoxyglucose‐positron emission tomography (FDG‐PET). Global brain FDG uptake and voxel‐wise analyses were used to evaluate the associations of cerebral metabolism with CVRFs and atherosclerotic plaque burden in carotids and femorals assessed by 3D‐vascular ultrasound.ResultGlobal FDG uptake showed an inverse correlation with 30‐year Framingham Risk Score (30y‐FRS) (β=‐0.15, p<0.001). This association was mainly driven by the presence of hypertension (d=0.36, p<0.001). Carotid plaque burden was inversely associated with global brain FDG uptake (β=‐0.16, p<0.001), even after adjusting for 30y‐FRS. Voxel‐wise approaches revealed that the brain areas most strongly affected by hypometabolism in association with 30y‐FRS, hypertension, and carotid plaque burden were parietotemporal regions (angular, supramarginal, and inferior/middle temporal gyri) and the cingulate gyrus.ConclusionIn asymptomatic middle‐aged individuals, cardiovascular risk is associated with brain hypometabolism, with hypertension being the modifiable CVRF showing the strongest association. Subclinical carotid plaque burden is also linked to reduced brain metabolism independently of CVRFs. Cerebral areas showing hypometabolism include mainly those known to be affected in Alzheimer´s disease. These results suggest that the interplay between cardiovascular disease and altered brain metabolism starts early in life, many years before the clinical manifestation. Understanding the extent to which cardiovascular risk factors influence brain´s vulnerability early in the course of atherosclerosis may help to refine preventive strategies and reduce the incidence of dementia in late life.
From Plan to Impact IV, progress towards the WHO global action plan on dementia
Authors: Lynch Chris 
Published: December 2021

AbstractBackgroundAt the World Health Assembly 2017, the World Health Organization launched the Global action plan on the public health response to dementia 2017‐2025. Alzheimer's Disease International (ADI) monitors progress towards the action areas and targets of the Global plan and in May 20201 will publish "From plan to impact IV", which is especially poignant in the context of Covid‐19.MethodADI continuously gathers information and updates relating to the 7 action areas of the Global action plan through our network of over 100 member associations and federations globally, as well as our contacts and partners in research, science, health and care, people living with dementia and carers. A specific analysis of progress towards the key goal of developing national dementia plans or strategies is a focal point of the research. In addition there will be a focus on the impact and implications of Covid‐19, including disruption to services, diagnosis and research.ResultThere was some encouraging policy developments in 2020 despite the challenges of Covid‐19, with the governments of China, Dominican Republic, Germany and Iceland developing national dementia plans. However, there are still only 35 national plans in existence, increasing urgency, and a need for a new focus and mobilisation to reach the central goal of the Global action plan, of 146 Member States developing a plan by 2025. This equates to the need for over 25 new plans every year.ConclusionProgress is being made across all 7 action areas of the Global action plan on dementia, with hope in the form of potential breakthroughs in disease modifying treatments and diagnostics, but this too is reflected in the need for much better healthcare preparedness. ADI, working with WHO and our partners, will continue to focus attention on governments across the world to take action, to develop robust and well‐funded national plans and to monitor their progress and to fulfil their commitments in adopting the Global action plan on dementia.