bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amyloid‐ß aggregation, APOE‐e genotype, and the trajectory of cognitive decline in persons without dementia
Authors: Janssen Olin , Jansen Willemijn J. , Oomens Julie Elisabeth , Tijms Betty M. , Maserejian Nancy Nairi , Ossenkoppele Rik , Vos Stephanie J. B. , Visser Pieter Jelle ,   the Amyloid Biomarker Study group
Published: December 2022

AbstractBackgroundThe association of amyloid abnormality with cognitive decline in persons with normal cognition (NC) and mild cognitive impairment (MCI) is important to guide AD trial design and understand prognoses. We examined the relation between amyloid abnormality and decline over time in several cognitive domains, and tested whether apolipoprotein (APOE)‐e genotype modified this association.MethodWe included 3,820 persons (2,599 NC, 1,221 all‐cause MCI) from 22 Amyloid Biomarker Study cohorts, with baseline PET (n = 846) or CSF (n = 2,974) amyloid measurements available. Amyloid abnormality on PET was based on visual read or cohort‐specific cutoffs, and for CSF on cohort‐specific or data‐driven cutoffs. Global cognition was assessed by Mini‐Mental State Examination (MMSE), functional performance by Clinical Dementia Rating global scale (CDR), and memory immediate and delayed recall by verbal learning tests. We examined baseline amyloid abnormality associations with cognitive performance over time and potential modification by APOE‐e (up to 3‐way interactions) using random‐slope/random‐intercept linear mixed‐models corrected for age, sex, education with random cohort effects.ResultMean follow‐up duration was 2.1 (range 0.5‐8) years. Baseline MMSE was worse in persons with abnormal‐amyloid compared with normal‐amyloid (NC mean difference = 0.2, p = 0.04, MCI mean difference = 2.4, p<0.001). In NC, amyloid abnormality was not associated with decline in any domain (Table 1), nor was the association influenced by APOE‐e4. In MCI, amyloid abnormality was associated with lower baseline performance and steeper decline on all domains (Table 1). In APOE‐e4‐carriers with MCI, MMSE decline was steeper than in non‐carriers (p<0.001, 1.5x steeper in amyloid‐abnormal, 3x steeper in amyloid‐normal). The rate of decline on immediate/delayed recall in MCI was higher in APOE‐e4‐carriers than non‐carriers, independent of amyloid status (p<0.001). For both NC and MCI, decline was steepest in persons with e4e4, followed by e3e4, e3e3, e2e4, and e2e3 (p = 0.001, Figure 1), independent of amyloid status.ConclusionAmyloid abnormality was not associated with cognitive decline in persons with NC after a short‐term follow‐up. In MCI, amyloid abnormality was closely associated with cognitive decline in several domains, with an additive effect of APOE‐e on decline. These results may be relevant for future trial recruitment strategies. Future studies should examine long‐term outcomes in NC.
Individual movement patterns in real‐world navigation as a digital marker of cognitive health in the elderly
Authors: Marquardt Jonas , Mohan Priyanka , Spiliopoulou Myra , Glanz Wenzel , Butryn Michaela , Kuehn Esther , Schreiber Stefanie , Maass Anne , Diersch Nadine 
Published: December 2022

AbstractBackgroundDuring normal aging and, particularly, during pathological aging, people often show problems in spatial navigation (SN), rendering it a promising marker of cognitive health in the elderly. However, SN is rarely investigated in people experiencing subjective cognitive decline (SCD), which is considered a very early stage of Alzheimer’s disease. Impaired performance of SCD patients was observed in a computerized navigation task. However, it remains unclear, how this translates to their everyday navigation behavior. Capitalizing on recent advancements in digital technologies, we measured the performance of healthy younger (HYA), healthy older adults (HOA), and SCD patients, when they solve a smartphone‐based navigation task in the real‐world.MethodWe developed a novel smartphone‐based application “Explore” to track GPS data in 67 individuals (HYA, n = 24, HOA, n = 25, SCD, n = 18, still in progress), while they were asked to find five points of interest on the medical campus in Magdeburg. Dynamic time warping was applied to investigate similarities between the raw trajectories. Also, aggregated measures of navigation performance were extracted (e.g., wayfinding distance, wayfinding duration, orientation stops, help usage). Mixed effect models were used to evaluate the effect of group membership on these summary measures. In addition, within‐group heterogeneity in navigation performance was investigated using clustering algorithms.ResultMixed effect models (Figure 1) show that HYA outperform HOA and SCD on all aggregated measures (all p ≤ .018). Between HOA and SCD, no significant differences were found for wayfinding distance and duration (p ≥ .102). However, a trend was detected for amount of help usage (p = .071) and number of orientation stops (p = .057), indicating that SCDs perform slightly worse compared to HOA. The cluster analysis of the movement trajectories revealed that our sample is best described by four navigation patterns (Figure 2).ConclusionWe provide first evidence that movement trajectories from a real‐world navigation task can be clustered into different groups, that could be indicative of age and cognitive health in the elderly. Our preliminary data indicate that certain measures of real‐world navigation behavior might differ between SCD and HOA, which needs to be confirmed in the full sample when data acquisition is complete.
Using technology to assist creative arts activities in dementia care
Authors: Christensen Justin , MacRitchie Jennifer , Floridou Georgia , Timmers Renee , De Witte Luc 
Published: December 2022

AbstractBackgroundAlongside a growing use of creative arts within community and residential settings to support the health and wellbeing of older adults living with dementia, is an increasing availability of technology, although development for this context has up till now been limited. To examine how technology might be used to meet the leisure, health, and wellbeing needs of people living with dementia, we conducted a scoping review to assess the current state of development of creative assistive technologies across various art‐forms.MethodOur research questions asked i) what are the arts‐based activities being delivered through technology for older adults living with dementia or mild cognitive impairment, and ii) what are the characteristics of technologies being used to enhance these arts‐based activities? A comprehensive search was conducted using PubMed, PsychINFO, Web of Science, Scopus and ACM Digital Library databases. Two raters independently screened titles and abstracts, rating whether articles fit our inclusion criteria. A total of 3762 records were retrieved, of which 51 articles were included after full‐text screening.ResultMusic (29), visual art (7), storytelling (6) and film‐making (2) were delivered through technology to older adults living with dementia. Other activities included dance (1), interactive light and sound (1), and incorporating arts activities into multi‐sensory objects (3). Two applications specifically allowed a choice between multiple creative arts (2). Single papers focused on Technologies were mainly custom‐made devices rather than applications using everyday devices such as smartphones or computers. Devices were often oriented towards individual use, supported by carers rather than groups of individuals at once, with fewer flexible in use alternate between solo/group. Outcomes measured were predominantly in terms of validating feasibility of the device and/or arts activity reported.ConclusionCurrent research concerning technology‐assisted creative arts activities for people living with dementia mainly demonstrates feasibility of new devices, indicating that the field in general is predominantly in the prototyping stage. Future research should consider device development past prototyping, and consider comparing devices across different art‐forms i.e, applications having a varied range of artforms which allow for individual needs and interests to be accommodated.
Sex differences in CSF biomarkers profile of accelerated biological aging individuals at risk of Alzheimer’s disease
Authors: Rodríguez‐Fernández Blanca , Suárez‐Calvet Marc , Arenaza‐Urquijo Eider M , Milà‐Alomà Marta , Minguillón Carolina , Molinuevo Jose Luis , Suridjan Ivonne , Kollmorgen Gwendlyn , Wild Norbert , Navarro Arcadi , Fauria Karine , DeVivo Immaculata , Zetterberg Henrik , Blennow Kaj , Gispert Juan Domingo , Sala‐Vila Aleix , Vilor‐Tejedor Natalia , Crous‐Bou Marta ,   for the ALFA study
Published: December 2022

AbstractBackgroundPrevalence of Alzheimer’s disease (AD) is higher in women than in men; however, underlying biological mechanisms remain unknown. Being aging the major risk factor for AD, sex dimorphism in biological aging could explain sex‐specific patterns of disease manifestation across the Alzheimer’s continuum. This study aimed to explore whether there are sex‐specific differences in specific biological pathways among individuals at accelerated or decelerated biological aging.MethodsThis study included 370 middle‐aged cognitively unimpaired participants at risk of AD from the Alzheimer’s and Families (ALFA) cohort (61.9% women). Telomere length (TL) was determined by qPCR from DNA extracted from peripheral blood leukocytes [Figure 1A]. TL values were normalized by computing z‐scores. Delta‐age was calculated as the residuals from regressing TL z‐scores on chronological age separately in women and men. Accelerated and decelerated aging groups were defined as those individuals in the 10th and 90th percentiles of delta‐age, respectively [Figure 1B]. Aβ42, Aβ40, CCL2, p‐tau, t‐tau, NfL, neurogranin, SNAP25, GAP43, synaptotagmin1, sTREM2, YKL40, GFAP, S100B, IL6, sVCAM1, sICAM1, and α‐synuclein were measured in CSF. Biomarker measurements were performed using immunoassays (colorimetric ELISA, MSD, Elecsys®, Simoa and the exploratory Roche NeuroToolKit robust prototype assays) and mass spectrometry. Differences on CSF biomarkers levels were assessed using non‐parametric tests for equality of means. P‐values <0.05 were considered significant. Multiple comparisons corrections were performed.ResultsLevels of CSF t‐tau, p‐tau, GAP43 and α‐synuclein were significantly higher in accelerated aging females compared to males (q‐values = 0.030, 0.031, 0.022, 0.041, respectively) [Figure 1C]. These differences were not observed when comparing the whole sample of women and men. Intra sex‐specific differences showed that the cytokine CCL2 was significantly higher in men at accelerated aging compared to men at decelerated aging (p‐value = 0.028) [Figure 1D].ConclusionsAccelerated aging women present higher levels of CSF biomarkers for tau‐pathology and synaptic dysfunction compared to their male counterparts. Accelerated biological aging could be associated with neuroinflammatory processes in cognitively unimpaired men at risk of AD. Biological aging based on TL determination could provide useful insights in tracking sex‐specific patterns of disease progression across the AD continuum.
Design and implementation of the participatory German network for translational dementia care research (TaNDem) – A Qualitative Study on the Perspectives of Stakeholders and Healthcare Providers in Dementia Care Research
Authors: Scharf Annelie , Raedke Anika , Köhler Stefanie , Heppner Marie Marleen , Purwins Daniel , Roes Martina , Teipel Stefan , Hoffmann Wolfgang , Michalowsky Bernhard 
Published: December 2022

AbstractBackgroundCurrently, there is a lack of sustainable, translational structures in dementia care research that enable a nationally guided participatory interaction between research, care practice, and those affected by dementia. A close cooperation between research and care practice with a simultaneous inclusion of those affected by dementia is essential to translate scientific evidence into practice and address routine care needs in healthcare research. Within the project TaNDem we aim to close the gap between research and practice by establishing a translational dementia care research network with participatory elements. We interviewed healthcare providers to identify their expectations for the design and implementation of this network.MethodsWe interviewed n = 87 stakeholders in healthcare practice and healthcare research within focus group interviews. We followed a structured interview guide including, questions about (i) the main objectives and areas of such network, (ii) the preferred way of coordination, collaboration, and interaction, (iii) and barriers and facilitators of implementation. The recorded interviews were transcribed and analyzed using qualitative content analysis according to Mayring.ResultsInterviewees expressed the desire for an understandable translation of research results for practitioners, for a strengthening of networking, and for interaction between research and practice. Stakeholders would like to see evaluations of healthcare situations in specific geographic regions and the involvement of people affected by dementia in research. Furthermore, they preferred better communication between researchers and practitioners, support in identifying suitable cooperation partners, and a unified approach towards health policy. According to collaboration, regional and national meetings as well as communication channels could be implemented via online platforms, databases, or local advisory hubs. Obstacles mentioned include limitations in terms of staff, budget and time of stakeholders, as well as regional differences and duplicate structures. To successfully implement the TaNDem network, there should be local contact persons. Furthermore, the cooperation should be based on trust and jointly defined objectives that add value to the individual’s work of each member of the research network.ConclusionThe results show that stakeholders in healthcare practice and healthcare research have similar expectations related to a participatory collaboration that provides an added value to all participants.
Underlying cerebrovascular pathology in Subjective Cognitive Decline: A systematic review and meta‐analysis
Authors: Gonzalez‐Burgos Lissett , Pitti Helda , Diaz‐Galvan Patricia , Barroso Jose , Badji Atef , Westman Eric , Ferreira Daniel , Cedres Nira 
Published: December 2022

AbstractBackgroundSubjective cognitive decline (SCD) implies self‐reported cognitive complaints in absence of objective cognitive impairment. SCD has been postulated as an early marker of Alzheimer’s Disease (AD). However, longitudinal studies have linked SCD to future vascular dementia. Thus, we conducted a systematic review and meta‐analysis aiming to synthesise and analyse the available data on the association between SCD and the presence of underlying cerebrovascular pathology measured by MRI.MethodOur study was performed following the PRISMA statement. The search strategy included terms for “subjective cognitive decline” and “white matter signal abnormalities”. It was conducted in 3 databases (PubMed, Scopus and Web of Science) from origin by December 8th, 2021. Two authors screened the studies in a 2‐stepwise approach. Primary studies including cognitively unimpaired adults with subjective cognitive complaints meeting the SCD‐I criteria for SCD that evaluated cerebrovascular pathology based on white matter signal abnormalities (WMSA) on MR images were selected. Study quality was assessed using the FLC 3.0 tool. Meta‐analysis comparing case‐control mean difference of WMSA was performed.ResultOf 240 articles identified, 16 research articles were selected. Of those, 8 case‐control studies were selected for the meta‐analysis. The sample size of the SCD group across the studies ranged from 8 to 906 participants, with age ranged from 40 to 84 years. All eight studies comprised a total of 2.637 SCD individuals. Study quality was deemed moderate (n=6) to high (n=10). The meta‐analysis showed a significant overall effect‐size between the mean WMSA burden of SCD and the controls, that was not significantly heterogeneous (Q(gl=7)=14.20; p=0,04; I2=42,5%). SCD was significantly associated with higher CVP burden based on neuroimaging measures.ConclusionThis is the first study to synthesise and analyse the current evidence on the association between SCD and WMSA. Our findings show the usefulness of SCD as a marker of underlying cerebrovascular pathology. Thus, the potential role of SCD as a preclinical stage of vascular cognitive impairment needs further investigation. Changes in lifestyle (e.g. exercise, diet, smoking cessation), cognitive stimulation or pharmacotherapy may be key to avoid an evolution towards cognitive deterioration in SCD.
Odor identification and discrimination as markers of early Alzheimer’s disease
Authors: Audronytė Eglė , Kaubrys Gintaras 
Published: December 2022

AbstractBackgroundReliable markers are essential in order to achieve accurate diagnosis in the early stages of Alzheimer’s disease (AD). Olfactory impairment has been identified as a possible non‐invasive biomarker of AD. Odor identification tasks are most commonly used for measuring olfactory abilities. However, odor identification is associated to verbal abilities and cultural context. The aim of this study was to determine whether odor discrimination could be a valid marker of early AD.Method65 participants were enrolled in the study. 26 patients with mild cognitive impairment due to AD (MCI‐AD), 26 patients with mild dementia due to AD (MD‐AD) and 13 cognitively normal elderly subjects (CN). All participants underwent cognitive examination (MMSE, CDR, ADAS‐Cog 13, fluency tests) and olfactory function assessment (Burghart Sniffin’ Sticks odor identification and odor discrimination tests).ResultMD‐AD and MCI‐AD subjects performed significantly worse than CN subjects in both odor identification (mean correct responses ± SD was 6.77±1.91; 9.08±2.30; 13.31±1.55 respectively; p<0.001) and odor discrimination (mean correct responses ± SD was 6.27±1.66; 8.19±1.65; 12.92±1.71 respectively; p<0.001) tests. MD‐AD subjects performed significantly worse than MCI‐AD subjects in both odor identification (p<0.05) and odor discrimination (p<0.001) tests.Both odor identification and odor discrimination tests had AUC>0.9 on ROC analysis for differentiating MCI‐AD subjects from CN subjects (AUC 0.938 and 0.982) and for differentiating MD‐AD subjects from CN subjects (AUC 0.99 for both). Neither odor identification, nor odor discrimination test reached AUC>0.8 on ROC analysis for differentiating MCI‐AD from MD‐AD subjects (AUC 0.777 and 0.793).Odor identification differentiated MCI‐AD from CN subjects with sensitivity of 69% and specificity of 100% at cut‐off score of ≤10 correct responses. Odor discrimination differentiated MCI‐AD from CN subjects with sensitivity of 77% and specificity of 100% at cut‐off score of ≤9 correct responses.ConclusionThe study confirmed that tests for olfactory dysfunction can reliably differentiate patients with mild cognitive impairment due to AD from cognitively normal subjects. Both odor identification and discrimination are reliable markers for identification of patients with early Alzheimer’s disease.
Testing causality in the association between amyloid‐β and tau in genetically identical twins
Authors: Coomans Emma M , Tomassen Jori , Ossenkoppele Rik , Konijnenberg Elles , Rikken Roos M. , Collij Lyduine E. , Golla Sandeep SV , Windhorst Albert D. , Tijms Betty M. , Barkhof Frederik , Scheltens Philip , de Geus Eco J.C. , Visser Pieter Jelle , van Berckel Bart NM , den Braber Anouk 
Published: December 2022

AbstractBackgroundThe amyloid‐cascade hypothesis of Alzheimer’s disease posits that there is a causal relationship between amyloid‐β (Aβ) and tau pathology. However, the mechanism through which Aβ would cause tau remains unclear. We cannot exclude the possibility of an additional underlying factor influencing Aβ at one time‐point and tau at a later time‐point. One such potential underlying factor can be genetic variation among individuals. This study aimed to examine the relationship between Aβ and tau, taking potential genetic confounding into account using a genetically identical twin design.MethodsWe included 70 identical twins (35 pairs) from the EMIF‐AD PreclinAD study with normal baseline cognition. We extracted baseline global [18F]flutemetamol (Aβ)‐PET binding potential (BPND) and 4‐year follow‐up [18F]flortaucipir (tau)‐PET BPND in a temporal meta‐region‐of‐interest. If Aβ is causally related to tau, the twin with more Aβ should also have more tau compared to the co‐twin. We tested this using regional and voxel‐wise within‐pair difference models, in which the within‐pair difference in Aβ is regressed on the within‐pair difference in tau. The resulting effect represents an association that is free of confounding due to factors that are shared between twins of the same pair, which includes genetic factors (twins are genetically identical), but also shared demographic (e.g. sex, age) and shared environmental (e.g. raised in the same family) factors.ResultsParticipant characteristics are shown in Table 1. Total group analysis showed that global Aβ‐PET BPND was associated with temporal tau‐PET BPND (β=0.49, p<0.001) (Fig‐1A). The twin‐difference model replicated this. We observed a highly comparable effect size for the association between within‐pair differences in global Aβ‐PET and within‐pair differences in temporal tau‐PET (β=0.56, p<0.001) (Fig‐1B). Compared to the total group voxel‐wise analysis, we observed an overlapping (and more widespread) pattern when regressing within‐pair differences in global Aβ‐PET on within‐pair differences in voxel‐wise tau‐PET, except for effects on tau in the medial temporal lobe (Fig‐2).ConclusionOur within‐pair difference results show that the association between Aβ and tau is minimally affected by confounding by genetic variation. Our voxel‐wise results support a causal association between global Aβ and tau outside of the medial temporal lobe.