| 1. |
- Aad, G, et al.
(author)
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- 2015
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swepub:Mat__t
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| 2. |
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| 3. |
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- 2017
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In: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
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Journal article (peer-reviewed)
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| 4. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 5. |
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| 6. |
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| 7. |
- Obers, Niels A., et al.
(author)
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Quantum gravity phenomenology at the dawn of the multi-messenger era—A review
- 2022
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In: Progress in Particle and Nuclear Physics. - : Elsevier BV. - 0146-6410 .- 1873-2224. ; 125
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Research review (peer-reviewed)abstract
- The exploration of the universe has recently entered a new era thanks to the multi-messenger paradigm, characterized by a continuous increase in the quantity and quality of experimental data that is obtained by the detection of the various cosmic messengers (photons, neutrinos, cosmic rays and gravitational waves) from numerous origins. They give us information about their sources in the universe and the properties of the intergalactic medium. Moreover, multi-messenger astronomy opens up the possibility to search for phenomenological signatures of quantum gravity. On the one hand, the most energetic events allow us to test our physical theories at energy regimes which are not directly accessible in accelerators; on the other hand, tiny effects in the propagation of very high energy particles could be amplified by cosmological distances. After decades of merely theoretical investigations, the possibility of obtaining phenomenological indications of Planck-scale effects is a revolutionary step in the quest for a quantum theory of gravity, but it requires cooperation between different communities of physicists (both theoretical and experimental). This review, prepared within the COST Action CA18108 “Quantum gravity phenomenology in the multi-messenger approach”, is aimed at promoting this cooperation by giving a state-of-the art account of the interdisciplinary expertise that is needed in the effective search of quantum gravity footprints in the production, propagation and detection of cosmic messengers.
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| 8. |
- Librado, P., et al.
(author)
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The origins and spread of domestic horses from the Western Eurasian steppes
- 2021
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 598, s. 634-640
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Journal article (peer-reviewed)abstract
- Analysis of 273 ancient horse genomes reveals that modern domestic horses originated in the Western Eurasian steppes, especially the lower Volga-Don region. Domestication of horses fundamentally transformed long-range mobility and warfare(1). However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling(2-4) at Botai, Central Asia around 3500 bc(3). Other longstanding candidate regions for horse domestication, such as Iberia(5) and Anatolia(6), have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 bc, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association(7) between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 bc(8,9) driving the spread of Indo-European languages(10). This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium bc Sintashta culture(11,12).
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| 9. |
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| 10. |
- Vermunt, L., et al.
(author)
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Duration of preclinical, prodromal, and dementia stages of Alzheimer's disease in relation to age, sex, and APOE genotype
- 2019
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In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:7, s. 888-898
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Journal article (peer-reviewed)abstract
- Introduction: We estimated the age-specific duration of the preclinical, prodromal, and dementia stages of Alzheimer's disease (AD) and the influence of sex, setting, apolipoprotein E (APOE) genotype, and cerebrospinal fluid tau on disease duration. Methods: We performed multistate modeling in a combined sample of 6 cohorts (n = 3268) with death as the end stage and estimated the preclinical, prodromal, and dementia stage duration. Results: The overall AD duration varied between 24 years (age 60) and 15 years (age 80). For individuals presenting with preclinical AD, age 70, the estimated preclinical AD duration was 10 years, prodromal AD 4 years, and dementia 6 years. Male sex, clinical setting, APOE epsilon 4 allele carriership, and abnormal cerebrospinal fluid tau were associated with a shorter duration, and these effects depended on disease stage. Discussion: Estimates of AD disease duration become more accurate if age, sex, setting, APOE, and cerebrospinal fluid tau are taken into account. This will be relevant for clinical practice and trial design. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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| 11. |
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| 12. |
- Hamilton, B. R., et al.
(author)
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Integrating Transwomen and Female Athletes with Differences of Sex Development (DSD) into Elite Competition: The FIMS 2021 Consensus Statement
- 2021
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In: Sports Medicine. - : Springer Science and Business Media LLC. - 0112-1642 .- 1179-2035. ; 51:7, s. 1401-1415
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Journal article (peer-reviewed)abstract
- Sport is historically designated by the binary categorization of male and female that conflicts with modern society. Sport's governing bodies should consider reviewing rules determining the eligibility of athletes in the female category as there may be lasting advantages of previously high testosterone concentrations for transwomen athletes and currently high testosterone concentrations in differences in sex development (DSD) athletes. The use of serum testosterone concentrations to regulate the inclusion of such athletes into the elite female category is currently the objective biomarker that is supported by most available scientific literature, but it has limitations due to the lack of sports performance data before, during or after testosterone suppression. Innovative research studies are needed to identify other biomarkers of testosterone sensitivity/responsiveness, including molecular tools to determine the functional status of androgen receptors. The scientific community also needs to conduct longitudinal studies with specific control groups to generate the biological and sports performance data for individual sports to inform the fair inclusion or exclusion of these athletes. Eligibility of each athlete to a sport-specific policy needs to be based on peer-reviewed scientific evidence made available to policymakers from all scientific communities. However, even the most evidence-based regulations are unlikely to eliminate all differences in performance between cisgender women with and without DSD and transwomen athletes. Any remaining advantage held by transwomen or DSD women could be considered as part of the athlete's unique makeup.
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| 13. |
- Vermunt, L., et al.
(author)
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Prescreening for European Prevention of Alzheimer Dementia (EPAD) trial-ready cohort: impact of AD risk factors and recruitment settings
- 2020
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In: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12:1
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Journal article (peer-reviewed)abstract
- Background Recruitment is often a bottleneck in secondary prevention trials in Alzheimer disease (AD). Furthermore, screen-failure rates in these trials are typically high due to relatively low prevalence of AD pathology in individuals without dementia, especially among cognitively unimpaired. Prescreening on AD risk factors may facilitate recruitment, but the efficiency will depend on how these factors link to participation rates and AD pathology. We investigated whether common AD-related factors predict trial-ready cohort participation and amyloid status across different prescreen settings. Methods We monitored the prescreening in four cohorts linked to the European Prevention of Alzheimer Dementia (EPAD) Registry (n = 16,877; mean +/- SD age = 64 +/- 8 years). These included a clinical cohort, a research in-person cohort, a research online cohort, and a population-based cohort. Individuals were asked to participate in the EPAD longitudinal cohort study (EPAD-LCS), which serves as a trial-ready cohort for secondary prevention trials. Amyloid positivity was measured in cerebrospinal fluid as part of the EPAD-LCS assessment. We calculated participation rates and numbers needed to prescreen (NNPS) per participant that was amyloid-positive. We tested if age, sex, education level, APOE status, family history for dementia, memory complaints or memory scores, previously collected in these cohorts, could predict participation and amyloid status. Results A total of 2595 participants were contacted for participation in the EPAD-LCS. Participation rates varied by setting between 3 and 59%. The NNPS were 6.9 (clinical cohort), 7.5 (research in-person cohort), 8.4 (research online cohort), and 88.5 (population-based cohort). Participation in the EPAD-LCS (n = 413 (16%)) was associated with lower age (odds ratio (OR) age = 0.97 [0.95-0.99]), high education (OR = 1.64 [1.23-2.17]), male sex (OR = 1.56 [1.19-2.04]), and positive family history of dementia (OR = 1.66 [1.19-2.31]). Among participants in the EPAD-LCS, amyloid positivity (33%) was associated with higher age (OR = 1.06 [1.02-1.10]) and APOE e4 allele carriership (OR = 2.99 [1.81-4.94]). These results were similar across prescreen settings. Conclusions Numbers needed to prescreen varied greatly between settings. Understanding how common AD risk factors link to study participation and amyloid positivity is informative for recruitment strategy of studies on secondary prevention of AD.
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| 14. |
- Ash, G. I., et al.
(author)
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Establishing a Global Standard for Wearable Devices in Sport and Exercise Medicine: Perspectives from Academic and Industry Stakeholders
- 2021
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In: Sports Medicine. - : Springer Science and Business Media LLC. - 0112-1642 .- 1179-2035. ; 51, s. 2237-2250
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Journal article (peer-reviewed)abstract
- Millions of consumer sport and fitness wearables (CSFWs) are used worldwide, and millions of datapoints are generated by each device. Moreover, these numbers are rapidly growing, and they contain a heterogeneity of devices, data types, and contexts for data collection. Companies and consumers would benefit from guiding standards on device quality and data formats. To address this growing need, we convened a virtual panel of industry and academic stakeholders, and this manuscript summarizes the outcomes of the discussion. Our objectives were to identify (1) key facilitators of and barriers to participation by CSFW manufacturers in guiding standards and (2) stakeholder priorities. The venues were the Yale Center for Biomedical Data Science Digital Health Monthly Seminar Series (62 participants) and the New England Chapter of the American College of Sports Medicine Annual Meeting (59 participants). In the discussion, stakeholders outlined both facilitators of (e.g., commercial return on investment in device quality, lucrative research partnerships, and transparent and multilevel evaluation of device quality) and barriers (e.g., competitive advantage conflict, lack of flexibility in previously developed devices) to participation in guiding standards. There was general agreement to adopt Keadle et al.'s standard pathway for testing devices (i.e., benchtop, laboratory, field-based, implementation) without consensus on the prioritization of these steps. Overall, there was enthusiasm not to add prescriptive or regulatory steps, but instead create a networking hub that connects companies to consumers and researchers for flexible guidance navigating the heterogeneity, multi-tiered development, dynamicity, and nebulousness of the CSFW field.
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| 15. |
- Bach, Lennart T, et al.
(author)
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Influence of Ocean Acidification on a Natural Winter-to-Summer Plankton Succession: First Insights from a Long-Term Mesocosm Study Draw Attention to Periods of Low Nutrient Concentrations
- 2016
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:8
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Journal article (peer-reviewed)abstract
- Every year, the oceans absorb about 30% of anthropogenic carbon dioxide (CO2) leading to a re-equilibration of the marine carbonate system and decreasing seawater pH. Today, there is increasing awareness that these changes-summarized by the term ocean acidification (OA)-could differentially affect the competitive ability of marine organisms, thereby provoking a restructuring of marine ecosystems and biogeochemical element cycles. In winter 2013, we deployed ten pelagic mesocosms in the Gullmar Fjord at the Swedish west coast in order to study the effect of OA on plankton ecology and biogeochemistry under close to natural conditions. Five of the ten mesocosms were left unperturbed and served as controls (similar to 380 mu atm pCO(2)), whereas the others were enriched with CO2-saturated water to simulate realistic end-of-the-century carbonate chemistry conditions (mu 760 mu atm pCO(2)). We ran the experiment for 113 days which allowed us to study the influence of high CO2 on an entire winter-to-summer plankton succession and to investigate the potential of some plankton organisms for evolutionary adaptation to OA in their natural environment. This paper is the first in a PLOS collection and provides a detailed overview on the experimental design, important events, and the key complexities of such a "long-term mesocosm" approach. Furthermore, we analyzed whether simulated end-of-the-century carbonate chemistry conditions could lead to a significant restructuring of the plankton community in the course of the succession. At the level of detail analyzed in this overview paper we found that CO2-induced differences in plankton community composition were non-detectable during most of the succession except for a period where a phytoplankton bloom was fueled by remineralized nutrients. These results indicate: (1) Long-term studies with pelagic ecosystems are necessary to uncover OA-sensitive stages of succession. (2) Plankton communities fueled by regenerated nutrients may be more responsive to changing carbonate chemistry than those having access to high inorganic nutrient concentrations and may deserve particular attention in future studies.
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| 16. |
- Graham, E. K., et al.
(author)
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Personality predicts mortality risk: An integrative data analysis of 15 international longitudinal studies
- 2017
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In: Journal of Research in Personality. - : Elsevier BV. - 0092-6566. ; 70, s. 174-186
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Journal article (peer-reviewed)abstract
- This study examined the Big Five personality traits as predictors of mortality risk, and smoking as a mediator of that association. Replication was built into the fabric of our design: we used a Coordinated Analysis with 15 international datasets, representing 44,094 participants. We found that high neuroticism and low conscientiousness, extraversion, and agreeableness were consistent predictors of mortality across studies. Smoking had a small mediating effect for neuroticism. Country and baseline age explained variation in effects: studies with older baseline age showed a pattern of protective effects (HR<1.00) for openness, and U.S. studies showed a pattern of protective effects for extraversion. This study demonstrated coordinated analysis as a powerful approach to enhance replicability and reproducibility, especially for aging-related longitudinal research. © 2017 Elsevier Inc.
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| 17. |
- Jensen, S. B., et al.
(author)
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A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact
- 2010
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In: SUPPORTIVE CARE IN CANCER. - 0941-4355. ; 18:8, s. 1061-1079
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Journal article (peer-reviewed)abstract
- Purpose This systematic review aimed to assess the literature for management strategies and economic impact of salivary gland hypofunction and xerostomia induced by cancer therapies and to determine the quality of evidence-based management recommendations. Methods The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. For each article, two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results, and conclusions. Results Seventy-two interventional studies met the inclusion criteria. In addition, 49 intensity-modulated radiation therapy (IMRT) studies were included as a management strategy aiming for less salivary gland damage. Management guideline recommendations were drawn up for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Conclusions There is evidence that salivary gland hypofunction and xerostomia induced by cancer therapies can be prevented or symptoms be minimized to some degree, depending on the type of cancer treatment. Management guideline recommendations are provided for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Fields of sparse literature identified included effects of gustatory and masticatory stimulation, specific oral mucosal lubricant formulas, submandibular gland transfer, acupuncture, hyperbaric oxygen treatment, management strategies in pediatric cancer populations, and the economic consequences of salivary gland hypofunction and xerostomia.
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| 18. |
- Keller, P. S., et al.
(author)
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Global CO2 emissions from dry inland waters share common drivers across ecosystems
- 2020
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In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- Many inland waters exhibit complete or partial desiccation, or have vanished due to global change, exposing sediments to the atmosphere. Yet, data on carbon dioxide (CO2) emissions from these sediments are too scarce to upscale emissions for global estimates or to understand their fundamental drivers. Here, we present the results of a global survey covering 196 dry inland waters across diverse ecosystem types and climate zones. We show that their CO2 emissions share fundamental drivers and constitute a substantial fraction of the carbon cycled by inland waters. CO2 emissions were consistent across ecosystem types and climate zones, with local characteristics explaining much of the variability. Accounting for such emissions increases global estimates of carbon emissions from inland waters by 6% (~0.12 Pg C y−1). Our results indicate that emissions from dry inland waters represent a significant and likely increasing component of the inland waters carbon cycle.
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Álvarez-Muñiz, Jaime, et al.
(author)
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The Giant Radio Array for Neutrino Detection (GRAND) : Science and design
- 2020
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In: Science China Physics, Mechanics & Astronomy. - : Springer Science and Business Media LLC. - 1674-7348 .- 1869-1927. ; 63:1
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Research review (peer-reviewed)abstract
- The Giant Radio Array for Neutrino Detection (GRAND) is a planned large-scale observatory of ultra-high-energy (UHE) cosmic particles, with energies exceeding 108 GeV. Its goal is to solve the long-standing mystery of the origin of UHE cosmic rays. To do this, GRAND will detect an unprecedented number of UHE cosmic rays and search for the undiscovered UHE neutrinos and gamma rays associated to them with unmatched sensitivity. GRAND will use large arrays of antennas to detect the radio emission coming from extensive air showers initiated by UHE particles in the atmosphere. Its design is modular: 20 separate, independent sub-arrays, each of 10000 radio antennas deployed over 10000 km(2). A staged construction plan will validate key detection techniques while achieving important science goals early. Here we present the science goals, detection strategy, preliminary design, performance goals, and construction plans for GRAND.
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| 23. |
- Bendayan, R., et al.
(author)
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Decline in memory, visuospatial ability, and crystalized cognitive abilities in older adults: normative aging or terminal decline?
- 2017
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In: Journal of Aging Research. - : Hindawi Limited. - 2090-2204 .- 2090-2212. ; 2017
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Journal article (peer-reviewed)abstract
- The aim of this study is to explore the pattern of change in multiple measures of cognitive abilities in a sample of oldest-old adults, comparing two different time metrics (chronological age and time to death) and therefore examining both underlying conceptual assumptions (age-related change and terminal decline). Moreover, the association with individual characteristics as sex, education, and dementia diagnosis was also examined. Measures of cognitive status (Mini-Mental State Examination and the Swedish Clock Test) and tests of crystallized (knowledge and synonyms), memory (verbal memory, nonverbal long-term memory, recognition and correspondence, and short-term memory), and visuospatial ability were included. The sample consisted of 671 older Swedish adult participants of the OCTO Twin Study. Linear mixed models with random coefficients were used to analyse change patterns and BIC indexes were used to compare models. Results showed that the time to death model was the best option in analyses of change in all the cognitive measures considered (except for the Information Test). A significant cognitive decline over time was found for all variables. Individuals diagnosed with dementia had lower scores at the study entrance and a faster decline. More educated individuals performed better in all the measures of cognition at study entry than those with poorer education, but no differences were found in the rate of change. Differences were found in age, sex, or time to death at baseline across the different measures. These results support the terminal decline hypothesis when compared to models assuming that cognitive changes are driven by normative aging processes. © 2017 R. Bendayan et al.
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| 24. |
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| 25. |
- Boxhammer, Tim, et al.
(author)
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Enhanced transfer of organic matter to higher trophic levels caused by ocean acidification and its implications for export production: A mass balance approach
- 2018
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:5
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Journal article (peer-reviewed)abstract
- Ongoing acidification of the ocean through uptake of anthropogenic CO 2 is known to affect marine biota and ecosystems with largely unknown consequences for marine food webs. Changes in food web structure have the potential to alter trophic transfer, partitioning, and biogeochemical cycling of elements in the ocean. Here we investigated the impact of realistic end-of-the-century CO 2 concentrations on the development and partitioning of the carbon, nitrogen, phosphorus, and silica pools in a coastal pelagic ecosystem (Gullmar Fjord, Sweden). We covered the entire winter-to-summer plankton succession (100 days) in two sets of five pelagic mesocosms, with one set being CO 2 enriched (~760 μatm pCO 2 ) and the other one left at ambient CO 2 concentrations. Elemental mass balances were calculated and we highlight important challenges and uncertainties we have faced in the closed mesocosm system. Our key observations under high CO 2 were: (1) A significantly amplified transfer of carbon, nitrogen, and phosphorus from primary producers to higher trophic levels, during times of regenerated primary production. (2) A prolonged retention of all three elements in the pelagic food web that significantly reduced nitrogen and phosphorus sedimentation by about 11 and 9%, respectively. (3) A positive trend in carbon fixation (relative to nitrogen) that appeared in the particulate matter pool as well as the downward particle flux. This excess carbon counteracted a potential reduction in carbon sedimentation that could have been expected from patterns of nitrogen and phosphorus fluxes. Our findings highlight the potential for ocean acidification to alter partitioning and cycling of carbon and nutrients in the surface ocean but also show that impacts are temporarily variable and likely depending upon the structure of the plankton food web.
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| 26. |
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| 27. |
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| 28. |
- Cadar, D., et al.
(author)
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Education, occupational class, and cognitive decline in preclinical dementia
- 2016
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In: GeroPsych: The Journal of Gerontopsychology and Geriatric Psychiatry. - : Hogrefe Publishing Group. - 1662-9647 .- 1662-971X. ; 29:1, s. 5-15
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Journal article (peer-reviewed)abstract
- We investigated education and occupational influences as markers of cognitive reserve in relation to cognitive performance and decline on multiple fluid and crystallized abilities in preclinical dementia. From the total sample of 702 participants stemming from the OCTO-Twin Study (Sweden), aged 80+ at baseline in 1992-1993, only those who developed dementia during the study period (N = 127) were included in these analyses. Random effects models were used to examine the level of performance at the time of dementia diagnosis and the rates of decline prior to diagnosis. The results demonstrated that both fluid and crystallized abilities decline in preclinical stages, and that education and occupational class have independent moderating roles on the cognitive performance at the time of diagnosis, but not on the rates of decline. © 2016 Hogrefe.
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| 29. |
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| 30. |
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| 31. |
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| 32. |
- Garcia, P, et al.
(author)
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Hippo-YAP1 Is a Prognosis Marker and Potentially Targetable Pathway in Advanced Gallbladder Cancer
- 2020
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In: Cancers. - : MDPI AG. - 2072-6694. ; 12:4
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Journal article (peer-reviewed)abstract
- Gallbladder cancer is an aggressive disease with late diagnosis and no efficacious treatment. The Hippo-Yes-associated protein 1 (YAP1) signaling pathway has emerged as a target for the development of new therapeutic interventions in cancers. However, the role of the Hippo-targeted therapy has not been addressed in advanced gallbladder cancer (GBC). This study aimed to evaluate the expression of the major Hippo pathway components mammalian Ste20-like protein kinase 1 (MST1), YAP1 and transcriptional coactivator with PDZ-binding motif (TAZ) and examined the effects of Verteporfin (VP), a small molecular inhibitor of YAP1-TEA domain transcription factor (TEAD) protein interaction, in metastatic GBC cell lines and patient-derived organoids (PDOs). Immunohistochemical analysis revealed that advanced GBC patients had high nuclear expression of YAP1. High nuclear expression of YAP1 was associated with poor survival in GBC patients with subserosal invasion (pT2). Additionally, advanced GBC cases showed reduced expression of MST1 compared to chronic cholecystitis. Both VP treatment and YAP1 siRNA inhibited the migration ability in GBC cell lines. Interestingly, gemcitabine resistant PDOs with high nuclear expression of YAP1 were sensitive to VP treatment. Taken together, our results suggest that key components of the Hippo-YAP1 signaling pathway are dysregulated in advanced gallbladder cancer and reveal that the inhibition YAP1 may be a candidate for targeted therapy.
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| 33. |
- Gregory, S., et al.
(author)
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Self-reported diabetes is associated with allocentric spatial processing in the European Prevention of Alzheimer's Dementia Longitudinal Cohort Study
- 2022
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In: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 56:10, s. 5917-5930
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Journal article (peer-reviewed)abstract
- Type 2 diabetes is a robust predictor of cognitive impairment. Impairment in allocentric processing may help identify those at increased risk for Alzheimer's disease dementia. The objective of this study was to investigate the performance of participants with and without diabetes on a task of allocentric spatial processing. This was a cross-sectional secondary data analysis study using baseline data from the European Prevention of Alzheimer's Dementia Longitudinal Cohort Study (EPAD LCS). Participants were aged 50 years and above and were free of dementia at baseline. Participants with no missing data on the variables of interest were included in this study. Our exposure variable was diabetes reported in the medical history. Our primary outcome was the Four Mountains Test (4MT), a novel task of allocentric processing. Covariates included demographics (age, sex, family history of dementia and years of education), APOE epsilon 4 carrier status, cognitive status (Clinical Dementia Rating scale), cerebrospinal fluid phosphorylated tau and amyloid-beta 1-42. Of 1324 participants (mean age = 65.95 (+/- 7.45)), 90 had diabetes. Participants with diabetes scored 8.32 (+/- 2.32) on the 4MT compared with 9.24 (+/- 2.60) for participants without diabetes. In a univariate model, diabetes was significantly associated with worse 4MT total scores (beta = -.92, p = .001), remaining significant in a fully adjusted model (beta = -.64, p = .01). Cerebrospinal fluid phosphorylated tau was significantly higher in participants with diabetes compared with those without. Novel cognitive tests, such as the 4MT, may be appropriate to identify early cognitive changes in this high-risk group. Identifying those at greatest risk for future neurodegeneration is key to prevention efforts.
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| 34. |
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| 35. |
- Mann, Frank D., et al.
(author)
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A novel approach to model cumulative stress: Area under the s-factor curve
- 2024
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In: Social Science and Medicine. - : Elsevier. - 0277-9536 .- 1873-5347. ; 348
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Journal article (peer-reviewed)abstract
- Objective: Using a large longitudinal sample of adults from the Midlife in the United States (MIDUS) study, the present study extended a recently developed hierarchical model to determine how best to model the accumulation of stressors, and to determine whether the rate of change in stressors or traditional composite scores of stressors are stronger predictors of health outcomes. Method: We used factor analysis to estimate a stress-factor score and then, to operationalize the accumulation of stressors we examined five approaches to aggregating information about repeated exposures to multiple stressors. The predictive validity of these approaches was then assessed in relation to different health outcomes. Results: The prediction of chronic conditions, body mass index, difficulty with activities of daily living, executive function, and episodic memory later in life was strongest when the accumulation of stressors was modeled using total area under the curve (AUC) of estimated factor scores, compared to composite scores that have traditionally been used in studies of cumulative stress, as well as linear rates of change. Conclusions: Like endogenous, biological markers of stress reactivity, AUC for individual trajectories of self-reported stressors shows promise as a data reduction technique to model the accumulation of stressors in longitudinal studies. Overall, our results indicate that considering different quantitative models is critical to understanding the sequelae and predictive power of psychosocial stressors from midlife to late adulthood.
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| 36. |
- Muñiz, Luis, et al.
(author)
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ACAULIS5 controls Arabidopsis xylem specification through the prevention of premature cell death
- 2008
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In: Development. - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 135:15, s. 2573-2582
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Journal article (peer-reviewed)abstract
- Cell size and secondary cell wall patterning are crucial for the proper functioning of xylem vessel elements in the vascular tissues of plants. Through detailed anatomical characterization of Arabidopsis thaliana hypocotyls, we observed that mutations in the putative spermine biosynthetic gene ACL5 severely affected xylem specification: the xylem vessel elements of the acl5 mutant were small and mainly of the spiral type, and the normally predominant pitted vessels as well as the xylem fibers were completely missing. The cell-specific expression of ACL5 in the early developing vessel elements, as detected by in situ hybridization and reporter gene analyses, suggested that the observed xylem vessel defects were caused directly by the acl5 mutation. Exogenous spermine prolonged xylem element differentiation and stimulated cell expansion and cell wall elaboration in xylogenic cell cultures of Zinnia elegans, suggesting that ACL5 prevents premature death of the developing vessel elements to allow complete expansion and secondary cell wall patterning. This was further supported by our observations that the vessel elements of acl5 seemed to initiate the cell death program too early and that the xylem defects associated with acl5 could be largely phenocopied by induction of premature, diphtheria toxin-mediated cell death in the ACL5-expressing vessel elements. We therefore provide, for the first time, mechanistic evidence for the function of ACL5 in xylem specification through its action on the duration of xylem element differentiation.
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| 37. |
- Muniz-Terrera, G., et al.
(author)
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Do I lose cognitive function as fast as my twin partner? Analyses based on classes of MMSE trajectories of twins aged 80 and older
- 2021
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In: Age and ageing. - : Oxford University Press (OUP). - 1468-2834 .- 0002-0729. ; 50:3, s. 847-853
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Journal article (peer-reviewed)abstract
- BACKGROUND: Aging is associated with an increasing risk of decline in cognitive abilities. The decline is, however, not a homogeneous process. There are substantial differences across individuals although previous investigations have identified individuals with distinct cognitive trajectories. Evidence is accumulating that lifestyle contributes significantly to the classification of individuals into various clusters. How and whether genetically related individuals, like twins, change in a more similar manner is yet not fully understood. METHODS: In this study, we fitted growth mixture models to Mini Mental State Exam (MMSE) scores from participants of the Swedish OCTO twin study of oldest-old monozygotic and same-sex dizygotic twins with the purpose of investigating whether twin pairs can be assigned to the same class of cognitive change. RESULTS: We identified four distinct groups (latent classes) whose MMSE trajectories followed different patterns of change over time: two classes of high performing individuals who remained stable and declined slowly, respectively, a group of mildly impaired individuals with a fast decline and a small group of impaired individuals who declined more rapidly. Notably, our analyses show no association between zygosity and class assignment. CONCLUSIONS: Our study provides evidence for a more substantial impact of environmental, rather than genetic, influences on cognitive change trajectories in later life. © The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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| 38. |
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| 39. |
- Piccinin, A. M., et al.
(author)
-
Coordinated analysis of age, sex, and education effects on change in MMSE scores
- 2013
-
In: The journals of gerontology. Series B, Psychological sciences and social sciences. - : Oxford University Press (OUP). - 1079-5014 .- 1758-5368. ; 68:3, s. 374-390
-
Journal article (peer-reviewed)abstract
- We describe and compare the expected performance trajectories of older adults on the Mini-Mental Status Examination (MMSE) across six independent studies from four countries in the context of a collaborative network of longitudinal studies of aging. A coordinated analysis approach is used to compare patterns of change conditional on sample composition differences related to age, sex, and education. Such coordination accelerates evaluation of particular hypotheses. In particular, we focus on the effect of educational attainment on cognitive decline. Regular and Tobit mixed models were fit to MMSE scores from each study separately. The effects of age, sex, and education were examined based on more than one centering point. Findings were relatively consistent across studies. On average, MMSE scores were lower for older individuals and declined over time. Education predicted MMSE score, but, with two exceptions, was not associated with decline in MMSE over time. A straightforward association between educational attainment and rate of cognitive decline was not supported. Thoughtful consideration is needed when synthesizing evidence across studies, as methodologies adopted and sample characteristics, such as educational attainment, invariably differ.
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| 40. |
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| 41. |
- Ramanathan, A., et al.
(author)
-
Superflow in a toroidal bose-einstein condensate : an atom circuit with a tunable weak link
- 2011
-
In: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 106:13
-
Journal article (peer-reviewed)abstract
- We have created a long-lived (∼40s) persistent current in a toroidal Bose-Einstein condensate held in an all-optical trap. A repulsive optical barrier across one side of the torus creates a tunable weak link in the condensate circuit, which can affect the current around the loop. Superflow stops abruptly at a barrier strength such that the local flow velocity at the barrier exceeds a critical velocity. The measured critical velocity is consistent with dissipation due to the creation of vortex-antivortex pairs. This system is the first realization of an elementary closed-loop atom circuit.
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| 42. |
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| 43. |
- Ritchie, CW, et al.
(author)
-
The European Prevention of Alzheimer's Dementia (EPAD) Longitudinal Cohort Study: Baseline Data Release V500.0
- 2020
-
In: The journal of prevention of Alzheimer's disease. - : SERDI. - 2426-0266 .- 2274-5807. ; 7:1, s. 8-13
-
Journal article (peer-reviewed)abstract
- Background: The European Prevention of Alzheimer’s Dementia (EPAD) Programme is a pan-European project whose objective is to deliver a platform, adaptive, Phase 2 proof of concept (PoC) trial for the secondary prevention of Alzheimer’s dementia. A component of this platform is the Longitudinal Cohort Study (LCS) which acts as a readiness cohort for the PoC Trial as well as generating data for disease modelling work in the preclinical and prodromal phases of Alzheimer’s dementia. Objectives: The first data wave has been collected, quality checked, released and now available for analysis to answer numerous research questions. Here we describe the results from key variables in the EPAD LCS with the objective of using these results to compliment analyses of these data in the future. Design: EPAD LCS is a cohort study whose primary objective is as a readiness cohort for the EPAD PoC Trial. As such recruitment is not capped at any particular number but will continue to facilitate delivery of the EPAD PoC Trial. Research Participants are seen annually (with an additional 6 month visit in the first year). Setting: The EPAD Trial Delivery Network comprises currently 21 centres across Europe. Participants: Research participants are included if they are over 50 years old and do not have a diagnosis of dementia. Measurements: All research participants undergo multiple assessments to fully characterise the biology of Alzheimer’s disease and relate this to risk factors (both fixed and modifiable) and biomarker expression of disease through brain imaging, fluid samples (CSF, blood, urine and saliva), cognitive performance, functional abilities and neuropsychiatric symptomatology. Results: V500.0 represents the first 500 research participants baselined into EPAD LCS. The mean age was 66.4 (SD=6.7) and 47.8% were male. The data was split for presentation into 4 groups: [1] CDR=0 and Amyloid + (preclinical AD), [2] CDR=0 and Amyloid –, [3] CDR=0.5 and Amyloid + (prodromal AD) and [4] CDR=0.5 and Amyloid -. Conclusions: The EPAD LCS is achieving its primary objective of trial readiness and the structured approach to data release as manifest by this first data release of V500.0 will assist researchers to describe and compare their findings as well as in systematic reviews and meta-analyses. It is anticipated given current recruitment rates that V1500.0 data release will take place in Autumn 2019. V500.1 (when the 1 year follow up is completed on the V500.0 (sub)cohort will be in Autumn 2019 also.
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| 44. |
- Robitaille, A, et al.
(author)
-
Physical activity and cognitive functioning in the oldest old: Within- and between-person cognitive and psychosocial mediators
- 2014
-
In: European Journal of Ageing. - : Springer Science and Business Media LLC. - 1613-9372 .- 1613-9380. ; 11:4
-
Journal article (peer-reviewed)abstract
- The current study examines the role of social contact intensity, cognitive activity, and depressive symptoms as within- and between-person mediators for the relationships between physical activity and cognitive functioning. All three types of mediators were considered simultaneously using multilevel structural equations modeling with longitudinal data. The sample consisted of 470 adults ranging from 79.37 to 97.92 years of age (M = 83.4; SD = 3.2) at the first occasion. Between-person differences in cognitive activity mediated the relationship between physical activity and cognitive functioning, such that individuals who participated in more physical activities, on average, engaged in more cognitive activities and, in turn, showed better cognitive functioning. Mediation of between-person associations between physical activity and memory through social contact intensity was also significant. At the within-person level, only cognitive activity mediated the relationship between physical activity and change in cognition; however, the indirect effect was small. Depressive symptomatology was not found to significantly mediate within- or between-person effects on cognitive change. Our findings highlight the implications of physical activity participation for the prevention of cognitive decline and the importance of meditational processes at the between-person level. Physical activity can provide older adults with an avenue to make new friendships and engage in more cognitive activities which, in turn, attenuates cognitive decline.
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| 45. |
- Saunders, T. S., et al.
(author)
-
Association between Longitudinal Cerebrospinal Fluid Alzheimer's Biomarkers and the Lifestyle for Brain Health (LIBRA) Index: Findings from the European Prevention of Alzheimer's Dementia Cohort Study (EPAD LCS)
- 2023
-
In: Jpad-Journal of Prevention of Alzheimers Disease. - : SERDI. - 2274-5807 .- 2426-0266. ; 10:3, s. 543-550
-
Journal article (peer-reviewed)abstract
- BackgroundIn the absence of preventative pharmacological interventions for Alzheimer's Disease dementia, there is a growing interest in modifiable risk factors associated with AD. Such risk factors are thought to contribute up to 40% of the risk of dementia. The Lifestyle for Brain Health (LIBRA) index, a dementia risk score which focuses exclusively on modifiable factors, has been found to be associated with increased risk of dementia and cognitive decline. It is currently unclear how the LIBRA index relates to cerebrospinal fluid (CSF) biomarkers of Alzheimer's Disease.ObjectivesTo examine the association between LIBRA index scores and trajectories of phospho-tau 181 and total tau in the European Prevention of Alzheimer's Dementia Longitudinal Cohort Study (EPAD LCS), and to examine whether these trajectories differ between participants with high and low CSF amyloid-beta 1-42 (A beta 42).DesignAnalysis of CSF biomarker and LIBRA index scores from the European Prevention of Alzheimer's Dementia Longitudinal Cohort Study.SettingThe European Prevention of Alzheimer's Dementia Longitudinal Cohort Study is a multi-centre, pan-European study.MeasurementsCerebrospinal fluid samples were taken by lumbar puncture and analysed using electrochemiluminescence. LIBRA index scores were calculated from self-reported variables, questionnaires, and physiological measurements.ResultIn the total sample (n = 1715; mean age = 66.0, 56.4% female), there were no significant associations between LIBRA scores (mean = 0.73 points) and rate of change in cerebrospinal fluid biomarkers. In participants with high A beta, reflecting less deposition in the brain, (n = 1134), LIBRA scores were significantly associated with the rate of change in total tau, where higher LIBRA scores (denoting higher dementia risk) were associated with increases in t-tau. There were no significant associations between LIBRA scores and change in cerebrospinal biomarkers in participants with low A beta.ConclusionWe found an association between modifiable risk factors and total tau accumulation in participants without dementia and without A beta accumulation. This suggests that increasing levels of total tau may be driven by factors other than A beta accumulation and highlights the need for developing and examining tau-targeting drugs in Alzheimer's Disease development.
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| 46. |
- Saunders, T. S., et al.
(author)
-
Interactions between apolipoprotein E, sex, and amyloid-beta on cerebrospinal fluid p-tau levels in the European prevention of Alzheimer's dementia longitudinal cohort study (EPAD LCS)
- 2022
-
In: eBioMedicine. - : Elsevier BV. - 2352-3964. ; 83
-
Journal article (peer-reviewed)abstract
- Background Alzheimer's Disease, the leading cause of dementia, is over-represented in females. The apolipoprotein E (APOE) e4 allele is the strongest genetic risk factor for late-onset AD and is associated with aberrant cerebrospinal fluid levels (CSF) of total tau (t-tau), phosphorylated tau (p-tau), and amyloid-l3 (Al3). There is some evidence that sex may mediate the relationship between APOE status and CSF tau, however, evidence is mixed. Methods We aimed to examine the interaction between sex, APOE s4 status, CSF Al3 on t-tau and p-tau in 1599 mid-to-late life individuals without a diagnosis of dementia in the European Prevention of Alzheimer's Dementia (EPAD) longitudinal cohort study. Findings We found a significant interaction between APOE status, sex, and CSF Al3 on CSF p-tau levels (l3 = 0.18, p = 0.04). Specifically, there was a stronger association between APOE status and CSF Al342 on CSF p-tau in males compared to females. Further, in females with high Al3 levels (reflecting less cortical deposition), e4 carriers had sig-nificantly elevated p-tau levels relative to non-carriers (W = 39663, p = 0.01). However, there were no significant dif-ferences in p-tau between male s4 carriers and non-carriers with high Al3 (W = 23523, p = 0.64). Interpretation An interaction between sex and cerebrospinal fluid Al3 may mediate the relationship between APOE status and CSF p-tau. These data suggest tau accumulation may be independent of Al3 in females, but not males.Copyright (c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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| 47. |
- Saunders, T. S., et al.
(author)
-
Predictive blood biomarkers and brain changes associated with age-related cognitive decline
- 2023
-
In: Brain Communications. ; 5:3
-
Journal article (peer-reviewed)abstract
- Growing evidence supports the use of plasma levels of tau phosphorylated at threonine 181, amyloid-beta, neurofilament light and glial fibrillary acidic protein as promising biomarkers for Alzheimer's disease. While these blood biomarkers are promising for distinguishing people with Alzheimer's disease from healthy controls, their predictive validity for age-related cognitive decline without dementia remains unclear. Further, while tau phosphorylated at threonine 181 is a promising biomarker, the distribution of this phospho-epitope of tau in the brain is unknown. Here, we tested whether plasma levels of tau phosphorylated at threonine 181, amyloid-beta, neurofilament light and fibrillary acidic protein predict cognitive decline between ages 72 and 82 in 195 participants in the Lothian birth cohorts 1936 study of cognitive ageing. We further examined post-mortem brain samples from temporal cortex to determine the distribution of tau phosphorylated at threonine 181 in the brain. Several forms of tau phosphorylated at threonine 181 have been shown to contribute to synapse degeneration in Alzheimer's disease, which correlates closely with cognitive decline in this form of dementia, but to date, there have not been investigations of whether tau phosphorylated at threonine 181 is found in synapses in Alzheimer's disease or healthy ageing brain. It was also previously unclear whether tau phosphorylated at threonine 181 accumulated in dystrophic neurites around plaques, which could contribute to tau leakage to the periphery due to impaired membrane integrity in dystrophies. Brain homogenate and biochemically enriched synaptic fractions were examined with western blot to examine tau phosphorylated at threonine 181 levels between groups (n = 10-12 per group), and synaptic and astrocytic localization of tau phosphorylated at threonine 181 were examined using array tomography (n = 6-15 per group), and localization of tau phosphorylated at threonine 181 in plaque-associated dystrophic neurites with associated gliosis were examined with standard immunofluorescence (n = 8-9 per group). Elevated baseline plasma tau phosphorylated at threonine 181, neurofilament light and fibrillary acidic protein predicted steeper general cognitive decline during ageing. Further, increasing tau phosphorylated at threonine 181 over time predicted general cognitive decline in females only. Change in plasma tau phosphorylated at threonine 181 remained a significant predictor of g factor decline when taking into account Alzheimer's disease polygenic risk score, indicating that the increase of blood tau phosphorylated at threonine 181 in this cohort was not only due to incipient Alzheimer's disease. Tau phosphorylated at threonine 181 was observed in synapses and astrocytes in both healthy ageing and Alzheimer's disease brain. We observed that a significantly higher proportion of synapses contain tau phosphorylated at threonine 181 in Alzheimer's disease relative to aged controls. Aged controls with pre-morbid lifetime cognitive resilience had significantly more tau phosphorylated at threonine 181 in fibrillary acidic protein-positive astrocytes than those with premorbid lifetime cognitive decline. Further, tau phosphorylated at threonine 181 was found in dystrophic neurites around plaques and in some neurofibrillary tangles. The presence of tau phosphorylated at threonine 181 in plaque-associated dystrophies may be a source of leakage of tau out of neurons that eventually enters the blood. Together, these data indicate that plasma tau phosphorylated at threonine 181, neurofilament light and fibrillary acidic protein may be useful biomarkers of age-related cognitive decline, and that efficient clearance of tau phosphorylated at threonine 181 by astrocytes may promote cognitive resilience.
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| 48. |
- Taucher, Jan, et al.
(author)
-
Influence of ocean acidification and deep water upwelling on oligotrophic plankton communities in the subtropical North Atlantic : insights from an in situ mesocosm study
- 2017
-
In: Frontiers in Marine Science. - : Frontiers Media S.A.. - 2296-7745. ; 4
-
Journal article (peer-reviewed)abstract
- Oceanic uptake of anthropogenic carbon dioxide (CO2) causes pronounced shifts in marine carbonate chemistry and a decrease in seawater pH. Increasing evidence indicates that these changes—summarized by the term ocean acidification (OA)—can significantly affect marine food webs and biogeochemical cycles. However, current scientific knowledge is largely based on laboratory experiments with single species and artificial boundary conditions, whereas studies of natural plankton communities are still relatively rare. Moreover, the few existing community-level studies were mostly conducted in rather eutrophic environments, while less attention has been paid to oligotrophic systems such as the subtropical ocean gyres. Here we report from a recent in situ mesocosm experiment off the coast of Gran Canaria in the eastern subtropical North Atlantic, where we investigated the influence of OA on the ecology and biogeochemistry of plankton communities in oligotrophic waters under close-to-natural conditions. This paper is the first in this Research Topic of Frontiers in Marine Biogeochemistry and provides (1) a detailed overview of the experimental design and important events during our mesocosm campaign, and (2) first insights into the ecological responses of plankton communities to simulated OA over the course of the 62-day experiment. One particular scientific objective of our mesocosm experiment was to investigate how OA impacts might differ between oligotrophic conditions and phases of high biological productivity, which regularly occur in response to upwelling of nutrient-rich deep water in the study region. Therefore, we specifically developed a deep water collection system that allowed us to obtain ~85 m3 of seawater from ~650 m depth. Thereby, we replaced ~20% of each mesocosm's volume with deep water and successfully simulated a deep water upwelling event that induced a pronounced plankton bloom. Our study revealed significant effects of OA on the entire food web, leading to a restructuring of plankton communities that emerged during the oligotrophic phase, and was further amplified during the bloom that developed in response to deep water addition. Such CO2-related shifts in plankton community composition could have consequences for ecosystem productivity, biomass transfer to higher trophic levels, and biogeochemical element cycling of oligotrophic ocean regions.
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| 49. |
- Tikhonoff, V., et al.
(author)
-
Symptoms of anxiety and depression across adulthood and blood pressure in late middle age: the 1946 British birth cohort
- 2014
-
In: Journal of Hypertension. - : Ovid Technologies (Wolters Kluwer Health). - 0263-6352. ; 32:8, s. 1590-1599
-
Journal article (peer-reviewed)abstract
- Objective: Previous studies testing the hypothesis that symptoms of anxiety and depression increase blood pressure (BP) levels show inconsistent and limited findings. We examined the association between those symptoms across adult life and BP in late middle age. Methods: Using data from 1683 participants from the MRC NSHD, we investigated associations between affective symptoms at ages 36, 43, 53 and 60-64 years and SBP and DBP at age 60-64. Multivariable linear regression was used to examine the effect on BP of affective symptoms at each age separately and as a categorical cumulative score based on the number of times an individual was classified as a 'case'. Models were adjusted for sex, BMI, educational attainment, socioeconomic position, heart rate, lifestyle factors and antihypertensive treatment. Results: In fully adjusted models, we observed lower SBP in study members with case-level symptoms at one to two time-points [-1.83mmHg; 95% confidence interval (CI) -3.74 to 0.01] and at three to four time-points (-3.93 mmHg; 95% CI -7.19 to -0.68) compared with those never meeting case criteria suggesting a cumulative inverse impact of affective symptoms on SBP across adulthood (P value for trend 0.022). Sex and BMI had a large impact on the estimates while not other confounders. Potential mediators such as heart rate and lifestyle behaviours had a little impact on the association. SBP at age 36 and behavioural changes across adulthood, as additional covariates, had a little impact on the association. A similar but weaker trend was observed for DBP. Conclusion: A cumulative effect of symptoms of anxiety and depression across adulthood results in lower SBP in late middle age that is not explained by lifestyle factors and antihypertensive treatment. Mechanisms by which mood may impact BP should be investigated.
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| 50. |
- Watermeyer, T., et al.
(author)
-
Cognitive dispersion and ApoEe4 genotype predict dementia diagnosis in 8-year follow-up of the oldest-old
- 2021
-
In: Age and ageing. - : Oxford University Press (OUP). - 1468-2834 .- 0002-0729. ; 50:3, s. 868-874
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Cognitive dispersion, or inconsistencies in performance across cognitive domains, has been posited as a cost-effective tool to predict conversion to dementia in older adults. However, there is a dearth of studies exploring cognitive dispersion in the oldest-old (>80years) and its relationship to dementia incidence. OBJECTIVE: The main aim of this study was to examine whether higher cognitive dispersion at baseline was associated with dementia incidence within an 8-year follow-up of very old adults, while controlling for established risk factors and suggested protective factors for dementia. METHODS: Participants (n=468) were from the Origins of Variance in the Old-Old: Octogenarian Twins study, based on the Swedish Twin Registry. Cox regression analyses were performed to assess the association between baseline cognitive dispersion scores and dementia incidence, while controlling for sociodemographic variables, ApoEe4 carrier status, co-morbidities, zygosity and lifestyle engagement scores. An additional model included a composite of average cognitive performance. RESULTS: Cognitive dispersion and ApoEe4 were significantly associated with dementia diagnosis. These variables remained statistically significant when global cognitive performance was entered into the model. Likelihood ratio tests revealed that cognitive dispersion and cognitive composite scores entered together in the same model was superior to either predictor alone in the full model. CONCLUSIONS: The study underscores the usefulness of cognitive dispersion metrics for dementia prediction in the oldest-old and highlights the influence of ApoEe4 on cognition in very late age. Our findings concur with others suggesting that health and lifestyle factors pose little impact upon cognition in very advanced age. © The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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