bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards a novel set of GPS‐derived metrics to identify the differences between mobility patterns of cognitively intact older adults and older adults with dementia
Authors: Bayat Sayeh , Ye Bing , Stasiulis Elaine , Rapoport Mark J , Naglie Gary , Mihailidis Alex 
Published: December 2020

AbstractBackgroundMaintaining an active lifestyle and participating in social activities are key components of healthy ageing. These components rely on the individuals’ ability to remain mobile out of home. The global positioning system (GPS) is increasingly used to assess outdoor mobility of older adults. However, there is a gap in establishing a framework that recognizes the differences between mobility patterns of cognitively intact older adults and older adults with dementia (OAwD). We propose a set of GPS‐derived metrics to identify these differences, which can be used to evaluate changes in mobility patterns of OAwD over time.MethodWe analyzed the mobility profiles of 15 older adults from the greater Toronto area using GPS technology. Participants were aged between 65 and 90 years (M=74.9, SD=7.05) and were either cognitively healthy (n = 8) or diagnosed with dementia (n = 7). First, we created GPS‐based features representing different dimensions of outdoor mobility. These features include (1) the typical distance covered by individuals, (2) randomness of the travel patterns, (3) the spatial variation of the GPS locations, (4) the number of distinct stops visited per day, (5) the number of daily trips away from home, (6) the score of three levels of outdoor life‐space, and (7) the maximum distance travelled from home. Then, we used Recursive Feature Elimination (RFE) with Random Forest (RF) to select the most important mobility features with respect to cognitive status.ResultA total of 55,580 GPS points were collected by the 15 unique participants over a period of 4 to 8 weeks. The RFE method indicated that features (1), (2), (3), and (5) had the strongest association with cognitive status. Our results suggested that OAwD displayed more predictability (i.e. smaller randomness) in travel patterns compared to the controls (OAwD: M=4.82, SD=0.57 vs. CTL: M=5.62, SD=0.71). Furthermore, the OAwD made fewer daily out‐of‐home trips compared to the controls (OAwD: M=1.06, SD=0.79 vs. CTL: M=1.65, SD=0.45), and covered smaller distances compared to the controls (OAwD: M=12.27, SD=11.73 km vs. CTL: M=15.78, SD=24.31 km).ConclusionThe proposed set of GPS‐based features identified the differences between mobility patterns of cognitively intact older adults and OAwD.
A consensus proteomic analysis of Alzheimer’s disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation
Authors: Johnson Erik C.B. , Dammer Eric B. , Duong Duc , Ping Lingyan , Zhou Maotian , Yin Luming , Higginbotham Lenora A. , Guajardo Andrew , White Bartholomew , Troncoso Juan C. , Thambisetty Madhav , Montine Thomas J. , Lee Eddie B. , Trojanowski John Q. , Beach Thomas G. , Reiman Eric M. , Haroutunian Vahram , Wang Minghui , Schadt Eric , Zhang Bin , Dickson Dennis W. , Ertekin‐Taner Nilufer , Golde Todd E. , Petyuk Vladislav A. , Jager Philip L. , Bennett David A. , Wingo Thomas S. , Rangaraju Srikant , Hajjar Ihab , Shulman Joshua M. , Lah James J. , Levey Allan I. , Seyfried Nicholas T. 
Published: December 2020

AbstractBackgroundOur understanding of the biological changes in the brain associated with Alzheimer’s disease (AD) pathology and cognitive impairment remains incomplete. Unbiased discovery proteomic analysis of AD brain can help to increase our understanding of these changes.MethodWe analyzed dorsolateral prefrontal cortex, precuneus, and temporal cortex of control, asymptomatic AD, and AD brains from multiple different centers by label‐free quantitative mass spectrometry and weighted protein co‐expression analysis to obtain a consensus protein co‐expression network of AD brain. We also analyzed cerebrospinal fluid to investigate potential biomarkers related to this network.ResultThe network consisted of 13 protein co‐expression modules. Six of these modules correlated with amyloid‐β plaque burden, tau neurofibrillary tangle burden, cognitive function, and clinical functional status, and were altered in asymptomatic AD, AD, or in both disease states. These six modules reflected synaptic, mitochondrial, sugar metabolism, extracellular matrix, cytoskeletal, and RNA binding/splicing biological functions. The identified protein network modules were preserved in a community‐based cohort analyzed by a different quantitative mass spectrometry approach. They were also preserved in temporal lobe and precuneus brain regions. Some of the modules were influenced by aging, and showed changes in other neurodegenerative diseases such as frontotemporal dementia and corticobasal degeneration. The module most strongly associated with AD pathology and cognitive impairment was the sugar metabolism module. This module was enriched in AD genetic risk factors, and was also highly enriched in microglia and astrocyte protein markers associated with an anti‐inflammatory state, suggesting that the biological functions it represents may serve a protective role in AD. Proteins from the sugar metabolism module were increased in cerebrospinal fluid from asymptomatic AD and AD cases, highlighting their potential as biomarkers of the altered brain network.ConclusionIn this study of >2000 brains and nearly 400 cerebrospinal fluid samples by quantitative proteomics, we identify proteins and biological processes in AD brain that may serve as therapeutic targets and fluid biomarkers for the disease.
Alzheimer’s disease biomarker roadmap 2020: Second‐generation tau PET tracers
Authors: Bischof Gerard N. , Dodich Alessandra , Ashton Nicholas J , Boccardi Marina , Barthel Henryk , Carrillo Maria C. , Chiotis Konstantinos , Corre Julie , Démonet Jean‐François , Gietl Anton F. , Johnson Keith A. , Hansson Oskar , Leuzy Antoine , Lorenzi Marco , Nordberg Agneta K , Ossenkoppele Rik , Rabinovici Gil D. , Ratib Osman , Sabri Osama , Treyer Valerie , Unschuld Paul G. , Villemagne Victor L.L. , Wolters Emma E. , Winblad Bengt , Frisoni Giovanni B. , Garibotto Valentina , Drzezga Alexander 
Published: December 2020

AbstractBackgroundSelective positron emission tomography (PET) tracers to target neurofibrillary tangles of the second generation have indicated to overcome some of the methodological issues observed with the tau‐tracers of the first generation. How these second‐generation tau tracers may be better suitable for clinical practice was assessed in the context of the Geneva Biomarker Roadmap Initiative during and prior to a two‐day workshop (Geneva, November 2019).MethodGuided by a framework for systematic validation of oncological diagnostic biomarkers adapted for the implementation of biomarker quantifying the pathological hallmarks of Alzheimer’s Disease (AD), we evaluated the performance of the tau‐selective tracers of the second generation. Subsequently we defined research priorities focusing on the advancement of the framework, with the goal for implementation of these PET tracers in clinical practice.ResultAll tracers identified as second generation, have provided evidence for in vitro binding to tau tangles in tissue samples of patients with and without Alzheimer’s disease. Additionally, in vivo pharmacokinetic modeling has been successfully achieved for some (e.g., 18F‐MK‐6240, 18F‐PI‐2620) but not all second‐generation tau tracers (e.g., GTP‐1, 18F‐JNJ‐067). Overall, observational cross‐sectional studies have provided preliminary evidence on the diminished extent of off‐target binding, high discriminatory ability between healthy and diseased populations and sensitivity in clinically diverse samples (e.g., 18F‐RO‐948, 18F‐MK‐6240, 18F‐PI‐2620).ConclusionA readily implementation of the tau tracer of the second‐generation in clinical practice is limited by the scarcity of comprehensive data analysis with bigger samples sizes and by the overall lack of end‐of‐life studies. However, the goal of the second‐generation tau tracers to overcome some of the methodological issues raised by the first generation tau tracers is partially achieved. Finally, the adaptation of the oncological diagnostic framework to the clinical validity of biomarkers measuring AD pathology has proven most useful in formulating new practical research goals to advance the clinical utility of the second generation tau tracer.
Proteomic, transcriptomic and functional characterization of human astrocyte‐derived extracellular vesicles upon inflammatory activation
Authors: You Yang , Borgmann Kathleen , Edara VenkataViswa , Stacy Satomi , Ghorpade Anuja , Ikezu Tsuneya 
Published: December 2020

AbstractBackgroundAstrocytes in the central nervous system provide supportive neural functions and mediate inflammatory responses from microglia. Increasing evidence supports their critical roles in regulating brain homeostasis in response to pro‐inflammatory factors such as cytokines and pathogen/damage‐associated molecular pattern molecules in infectious and neurodegenerative diseases. However, the underlying mechanisms of the trans‐cellular communication is still unclear. Extracellular vesicles (EVs) can transfer a large diversity of molecules such as lipids, nucleic acids and proteins for cellular communications. The purpose of this study is to characterize the EVs cargo proteins derived from human primary astrocytes (AstrEVs) under both physiological and pathophysiological conditions.MethodsWe performed a quantitative proteomic and transcriptomic analysis of exosomes purified from human primary astrocytes with or without interleukin 1‐β (IL1‐β) stimulation in vitro. Exosome‐enriched fractions were purified by size‐exclusion columns. The total proteins isolated from the EVs were run on 1D SDS‐PAGE and mass spectrometry. miRNA was isolated from EVs and subjected to Affymetrix miRNA 4. 0 Array. The data are subjected to bioinformatic analysis and validation for select molecules. Human astrocyte‐derived EVs were tested for their effect on neuronal differentiation and maturation by live confocal imaging and multi‐electrode array.ResultsLabel‐free quantitative proteomic profiling revealed a notable up‐regulation of proteins including actin‐associated molecules, integrins and major histocompatibility complex in IL‐1β‐AstrEVs compared to CTL‐AstrEVs, which were involved in cellular metabolism and organization, cellular communication and inflammatory response. They were also significantly associated with the increased signaling of pathogenic molecules such as APP and tau. IL‐1β‐AstrEVs show increased uptake by primary murine cortical neurons compared to CTL‐AstrEVs, which was partially suppressed by RGD peptide, a pan‐integrin inhibitor. Additionally, treatment of neurons with IL‐1β‐AstrEVs also reduced neurite outgrowth, branching and neuronal firing.ConclusionsThese findings provide insight for the molecular mechanism of the AstrEVs’ effects on neural uptake, neural differentiation and maturation, and its alteration in inflammatory conditions, which may be relevant to neuroinflammation‐mediated Alzheimer’s disease progression.
The influence of cerebrovascular disease in dementia with Lewy bodies and Parkinson’s disease dementia
Authors: Hijazi Zina , Yassi Nawaf , Watson Rosie 
Published: December 2020

AbstractBackgroundLewy body dementia (LBD), which includes dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD), is a common form of neurodegenerative dementia. The frequency and influence of cerebrovascular disease in LBD is not well understood but may be an important contributor to symptoms and outcome.MethodA comprehensive literature search was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) guidelines using the electronic databases Medline and Embase. Studies included assessed the presence and/or location of cerebrovascular lesions using either MRI or neuropathological examination of DLB or PDD. Specific lesions considered included white matter hyperintensities (WMH), cerebral amyloid angiopathy (CAA), cerebral microbleeds (CMB), macroscopic infarcts, microinfarcts and intracerebral haemorrhage.ResultOf the search results (N=3923 articles), 53 were relevant, including 25 studies on WMH (DLB n=438, PDD n=532), 15 on CMB (DLB n=253 PDD n=197) and 12 examining microinfarcts (DLB n=186, PDD n=18). Most studies on WMH reported an increased severity of WMH in DLB compared to PDD, PD and healthy controls, and in PDD compared to PD using visual rating scales. In PD, WMH were associated with progression to PDD in longitudinal studies. CMB were more prevalent in DLB (17‐45%) compared to PDD and healthy controls, and in PDD compared to PD. There was an increased prevalence of microinfarcts in DLB (15‐80%) compared with controls. LBD did not appear to affect the prevalence of gross or lacunar infarcts or intracerebral haemorrhage. Some studies reported that WMH and CMB were associated with lower scores on neuropsychological testing in DLB.ConclusionDiffering cerebrovascular lesion types and detection methods in the studies limit conclusions, with some conflicting results. There was an increased prevalence of certain cerebrovascular lesions in DLB compared to PDD, PD and controls, and in PDD compared to PD and control participants. The influence of cerebrovascular disease on the risk of LBD, disease progression and interaction with other co‐pathologies (e.g. Aβ, tau) is an important area for future research.
Comparison of peer mentoring versus peer support in a 6‐month home‐based physical activity program for inactive older adults at risk of Alzheimer’s disease: Experiences from the INDIGO trial
Authors: Cox Kay L , Ellis Kathryn A , Clare Linda , Cyarto Elizabeth V , Etherton‐Beer Christopher , Ames David , Flicker Leon , Almeida Osvaldo P , LoGiudice Dina , Liew Danny , Southam Jennifer , Lautenschlager Nicola T 
Published: December 2020

AbstractBackgroundThe INDIGO RCT compared the effects of a mentor‐supported individual goal‐setting approach versus peer‐contact only on adherence to a 6‐month home‐based physical activity (PA) program for inactive individuals aged 60‐80 years with mild cognitive impairment (MCI) or subjective cognitive decline (SCD). We report on the mentoring‐peer support experiences from INDIGO.MethodPhysically active volunteers aged 50‐85 years (n = 32) recruited from the community completed demographic, attitudes to ageing, exercise self‐efficacy and mentoring self‐efficacy (self‐rating of % confidence to mentor in a PA program) questionnaires at baseline. They were randomised to mentoring utilising a motivational interviewing style of support (intervention group), or to provide basic peer contact only (Physical Activity Liaisons, PALS). Training was provided for both arms and mentors and PALS met their peer participant during a workshop. Programs were delivered via 6 scripted telephone calls during the intervention. Some mentors/PALS repeated this support for subsequent waves. Baseline measurements were repeated after 6 and 12 months of mentoring.ResultSeven of 32 (21.9%) withdrew after randomisation and before being assigned a participant. Twenty‐five started the intervention, 20 (80%) completed 6‐months of support and 19 (76%) completed 12 months. Mean age (± SD) (n = 25) was 65.80 (6.25) years, 15 (60%) were female. Self‐efficacy for mentoring was rated similarly between groups 93.8 (15.5)% versus 95.0 (7.9)% for mentors and PALS. Adherence to the support calls was high and similar for both groups 73.7 (30.3)% for mentors and 79.6 (29.5)% for PALS. As expected average call time was significantly higher for the mentors than for the PALS 23.4 (8.9) minutes versus 9.3 (3.6) minutes for PALS (p<0.001).There was no significant difference in mentoring self‐efficacy at 6 months but after 12 months it was significantly lower in mentors 88.7 (24.7)% than PALS 97.5 (4.6)% when adjusted for baseline mentoring self‐efficacy and attitudes to ageing (p<0.05). Participation did not result in any changes in peer volunteers own PA self‐efficacy or behaviour.ConclusionThese findings suggest that participation for longer in a more intensive mentoring program in a PA research program may impact on mentoring self‐efficacy in age‐matched volunteers.
A framework of healthy ageing for the Torres Strait: A grassroots approach to dementia risk reduction
Authors: Quigley Rachel , Russell Sarah G , Sagigi Betty , Miller Gavin , Strivens Edward 
Published: December 2020

AbstractBackgroundOlder Aboriginal and Torres Strait Islander Australians play a crucial role in the health of their communities, holding the cultural rights and responsibilities for maintaining connections to Country, caring for extended family members, and providing leadership and support in their families and within communities. Maintaining the health of older adults is crucial not only for their quality of life but also the cohesiveness of the community they live in. Dementia is a key health priority in Indigenous communities given their increased risk of dementia compared to the general population. At present, there is a lack of evidence around what healthy ageing means in the Torres Strait or how older adults can be supported through the health care system to remain in their communities. In this paper, a study protocol will be presented for review. The aim of the study is to develop a culturally appropriate framework of Healthy Ageing for Torres Strait Communities that will include dementia risk reduction strategies to enable older persons to remain living within their communities for as long, and as healthily, as possible.MethodThis project will use Participatory Action Research to enable Torres Strait communities to identify environmental, cultural, spiritual and other priorities to achieve a fulfilling and positive approach to living well as they age. Using a Continuous Quality Improvement framework, primary health care centres will develop quality improvements based on priorities identified by the community.ResultsPrimary health care centres will implement best practice screening, culturally appropriate assessments, and targeted interventions to support their people to age well and remain on country and implement dementia risk reduction strategies.ConclusionResults will inform a culturally appropriate framework of Healthy Ageing for Torres Strait Communities to enable older persons to remain living well at home, and on Country for as long as possible with reduced dementia risk.
Vascular and neurodegenerative imaging markers are associated with increased interstitial fluid diffusion in memory clinic patients
Authors: van der Thiel Merel M. , Freeze Whitney M. , Verheggen Inge C.M. , Wong Sau May , de Jong Joost J. , Postma Linda A. , Verhey Frans R.J. , Ramakers Inez H.G.B. , Backes Walter H. , Jansen Jacobus F.A. 
Published: December 2020

AbstractBackgroundDiffusion measurements in brain tissue may reveal various diffusion regimes reflecting different microstructural topologies, ranging from fast blood circulation, intermediate diffusion in wider interstitial spaces, to highly restricted inter‐ and intra‐cellular diffusion. Intravoxel incoherent motion MRI can detect an intermediate diffusion component, which is thought to be a proxy of brain tissue damage. This intermediate component might be relevant for studying amyloid clearance pathways, but currently remains incompletely understood. This study aims to increase our understanding of this intermediate component by studying associations with vascular (i.e. white matter hyperintensity (WMH) volume) and neurodegenerative (i.e. hippocampal atrophy) imaging markers in a sample of memory clinic patients, who display a wide range of cognitive abilities and variation in neurovascular and neurodegenerative pathology.MethodForty patients (Alzheimer’s disease dementia (AD, n=15), mild cognitive impairment (n=16), vascular cognitive impairment (VCI, n=9)) and 34 healthy controls underwent a 3T MRI protocol. The intermediate diffusion component was identified with spectral analysis using non‐negative least squares (Figure 1), and the contribution of the intermediate component to the signal in each voxel was determined by quantifying its volume fraction fint. The median of fint was determined for the following regions of interest (ROIs): cortical gray matter (GM), subcortical GM, WMH and normal appearing white matter (NAWM). A multivariate linear regression model incorporating age and gender was conducted to investigate group differences. Multiple linear regression was employed to investigate the association of fint per ROI with the vascular and neurodegenerative markers, additionally adjusting for total intracranial volume.ResultAD and VCI patients showed increased f
int in GM and NAWM relative to controls (Figure 2). The fint was found to be associated to WMH and/or hippocampal volume, dependent on the brain region (Table 1).ConclusionThe intermediate component is associated with both vascular and degenerative markers, but this effect is region dependent. The group differences indicate a relation between fint and clinical phenotype. Brain regions where fint is affected by both vascular and degenerative markers show abnormally high fint in AD, which emphasizes the complexity to separate vascular and degenerative influences on AD pathology.
Cantonese adaptation of melodic intonation therapy (MIT) for dementia patients
Authors: Law Tammy Sheung Ting , Fung Andrea Pui Ting , Fong Manson Cheuk‐Man , Cheung Daphne Sze Ki , Wang William Shiyuan 
Published: December 2020

AbstractBackgroundReceptive and expressive speech problems in dementia (e.g., difficulty in understanding complex concepts, incoherent speech) have been well‐documented. Melodic Intonation Therapy (MIT) is a neurologic music therapy technique that was first developed to assist speech recovery in patients with post‐stroke aphasia. While this combination of music and language has been reported to be effective for aphasics, the possible effects of an adapted MIT for the dementia population has not yet been investigated.MethodsNine literate, native Cantonese‐speaking participants with dementia (mean age = 80 ± 7.09 years, 3 male, mean MMSE = 16.89 ± 3.69) and with reported expressive speech problems by caregivers were recruited from an elderly day care centre of the Hong Kong Alzheimer’s Disease Association. Participants completed a 3‐week group‐based MIT program (30 minutes per session, twice a week) designed to improve the speech functions of dementia patients. Over the whole program, two children songs with melody familiar to elderly but newly rewritten lyrics were taught and practiced. The subtests of spontaneous speech and auditory comprehension in Cantonese Aphasia Battery were conducted pre‐ and post‐intervention to assess the changes in expressive and receptive speech of participants.ResultsRates of consent and retention were both 100%, with an attendance rate of 89%. Pre‐post analyses using Wilcoxon signed rank test showed significant improvement in the sub aphasia quotient of spontaneous speech after intervention (Z = 2.54, p < .05). Further analyses revealed that this improvement was contributed solely from the fluency score (Z = 2.69, p < .01), but not from information (Z = ‐0.27, p > .78). Only a trend of improvement was observed for the sub AQ of auditory comprehension (Z = 1.68, p = .093). Qualitative analyses suggested possible improvements in different language domains (e.g., specificity of item description, syntactic complexity of sentence structure).ConclusionThis study is the first to evaluate the feasibility and preliminary effects of the Cantonese adaptation of MIT for dementia. Our results demonstrated positive effects in the fluency of spontaneous speech (significant) and auditory comprehension (trending), showing the potentials of this music therapy in enhancing speech performance of dementia patients.