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- Farnsworth von Cederwald, Bryn, et al.
(författare)
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Association of cardiovascular risk trajectory with cognitive decline and incident dementia
- 2022
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Ingår i: Neurology. - : Wolters Kluwer. - 0028-3878 .- 1526-632X. ; 98:20, s. e2013-e2022
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: Cardiovascular risk factors have a recently established association with cognitive decline and dementia, yet most studies examine this association through cross-sectional data, precluding an understanding of the longitudinal dynamics of such risk. The current study aims to explore how the ongoing trajectory of cardiovascular risk affects subsequent dementia and memory decline risk. We hypothesize that an accelerated, long-term accumulation of cardiovascular risk, as determined by the Framingham Risk Score (FRS), will be more detrimental to cognitive and dementia state outcomes than a stable cardiovascular risk.Methods: We assessed an initially healthy, community-dwelling sample recruited from the prospective cohort Betula study. Cardiovascular disease risk, as assessed by the FRS, episodic memory performance, and dementia status were measured at each 5-year time point (T) across 20 to 25 years. Analysis was performed with bayesian additive regression tree, a semiparametric machine-learning method, applied herein as a multistate survival analysis method.Results: Of the 1,244 participants, cardiovascular risk increased moderately over time in 60% of sample, with observations of an accelerated increase in 18% of individuals and minimal change in 22% of individuals. An accelerated, as opposed to a stable, cardiovascular risk trajectory predicted an increased risk of developing Alzheimer disease dementia (average risk ratio [RR] 3.3–5.7, 95% CI 2.6–17.5 at T2, 1.9–6.7 at T5) or vascular dementia (average RR 3.3–4.1, 95% CI 1.1–16.6 at T2, 1.5–7.6 at T5) and was associated with an increased risk of memory decline (average RR 1.4–1.2, 95% CI 1–1.9 at T2, 1–1.5 at T5). A stable cardiovascular risk trajectory appeared to partially mitigate Alzheimer disease dementia risk for APOE ε4 carriers.Discussion: The findings of the current study show that the longitudinal, cumulative trajectory of cardiovascular risk is predictive of dementia risk and associated with the emergence of memory decline. As a result, clinical practice may benefit from directing interventions at individuals with accelerating cardiovascular risk.
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| 4. |
- Jensen, Tommy Nöhr
(författare)
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Översättningar av konkurrens i ekonomiska laboratorier : Om ekonomiska teoriers förenkling, komplexitet och fördunkling i hälso- och sjukvården
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- FRAGMENTERAD SAMMANFATTNINGAktörerna i Stockholms läns landsting simulerar marknad och konkurrens och är väl medvetna om att de gör detta (Den Stora Upphandlingen; en inre marknad inom ramen för en förvaltningsstyrd struktur). Det är inte det denna alternativa berättelse om konkurrens avslöjar. Aktörerna vet precis vad de försöker göra när de försöker organisera hälso- och sjukvården i Stockholms läns landsting genom att låta sig influeras av andra ”världar”. En särskilt relevant ”annan värld” är ekonomen och ekonomisk teori. Men i den till synes medvetna processen händer något, det uppstår komplexitet; det uppträder många olika världar som cirkulerar i Stockholms läns landsting. Men översättningsprocessen av konkurrens stannar inte här. Aktörerna intensifierar sina ansträngningar för att komma tillrätta med det som blivit komplicerat. Nya förslag på hur hälso- och sjukvården ska organiseras konstrueras, där var och en för fram Det Bästa Sättet för att komma till rätta med de observerade problemen. Situationen och tillvaron blir fördunklad och ekonomisk teori har nu översatts så många gånger, av så många olika aktörer, att det cirkulerar otaliga kopior av den. Det är processen av förenkling, komplexitet och fördunkling som är essensen i min re-presentation och i mina anspråk på att försöka förstå konkurrensprocesser. En essens som jag fångar och illustrerar med hur aktörer i aktörsnätverk översätter (associerar, enrollerar och etiketterar) den neoklassiska marknaden.Men annat står också på spel. Aktörer översätter såväl människor som ting samtidigt som ting i sin tur influerar mänskliga föreställningar och ageranden. Men tings förmåga att konstruera människor är begränsat eftersom ting agerar utifrån givna koder, en given Ordning, (som givetvis kan bryta samman och ta oanade vägar, till exempel dataprogram), men som i sig är fyllda av mänskliga avsikter och intentioner. Vissa ”sociotekniska” ting är designade att centrera ”världar”, exempelvis Stockholms läns landsting uttryckt i siffror i en årsredovisning. Likafullt är det bara människor som, i processerna av förenkling, komplexitet och fördunkling, kan träda fram och konstruera och centrera heterogent materiella världar, men genom att centrera mängder av heterogena material (såväl människor som ting) förmår ting visa epistemologiska möjligheter för mänskligt agerande. Människor kan med andra ord färdas långt ut i världen med hjälp av ting. En empirisk observation är att ju längre aktörerna, i hälso- och sjukvården i Stockholms läns landsting, reser i de centrerade heterogent materiella världarna desto mer närsynta blir de samtidigt som potentialen att orsaka allvarliga sidoeffekter blir större och större. En annan empirisk observation i studien är att sidoeffekter hanteras på samma sätt i den nationalekonomiska neoklassiska teorin som i hälso- och sjukvårdens praktik, där internaliserade och väl avgränsade ekonomiska transaktioner antas utgöra normen och sidoeffekter undantagen på marknaden. Istället förhåller sig det precis tvärtom: Sidoeffekter är normen och internaliserade och väl avgränsade ekonomiska transaktioner utgör undantagen.
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| 5. |
- Karalija, Nina, 1984-, et al.
(författare)
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C957T-mediated Variation in Ligand Affinity Affects the Association between C-11-raclopride Binding Potential and Cognition
- 2019
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Ingår i: Journal of cognitive neuroscience. - : MIT Press. - 0898-929X .- 1530-8898. ; 31:2, s. 314-325
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Tidskriftsartikel (refereegranskat)abstract
- The dopamine (DA) system plays an important role in cognition. Accordingly, normal variation in DA genes has been found to predict individual differences in cognitive performance. However, little is known of the impact of genetic differences on the link between empirical indicators of the DA system and cognition in humans. The present work used PET with C-11-raclopride to assess DA D2-receptor binding potential (BP) and links to episodic memory, working memory, and perceptual speed in 179 healthy adults aged 64-68 years. Previously, the T-allele of a DA D2-receptor single-nucleotide polymorphism, C957T, was associated with increased apparent affinity of C-11-raclopride, giving rise to higher BP values despite similar receptor density values between allelic groups. Consequently, we hypothesized that C-11-raclopride BP measures inflated by affinity rather than D2-receptor density in T-allele carriers would not be predictive of DA integrity and therefore prevent finding an association between C-11-raclopride BP and cognitive performance. In accordance with previous findings, we show that C-11-raclopride BP was increased in T-homozygotes. Importantly, C-11-raclopride BP was only associated with cognitive performance in groups with low or average ligand affinity (C-allele carriers of C957T, n = 124), but not in the high-affinity group (T-homozygotes, n = 55). The strongest C-11-raclopride BP-cognition associations and the highest level of performance were found in C-homozygotes. These findings show that genetic differences modulate the link between BP and cognition and thus have important implications for the interpretation of DA assessments with PET and C-11-raclopride in multiple disciplines ranging from cognitive neuroscience to psychiatry and neurology.
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| 6. |
- Karalija, Nina, 1984-, et al.
(författare)
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Longitudinal Dopamine D2 Receptor Changes and Cerebrovascular Health in Aging
- 2022
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Ingår i: Neurology. - 1526-632X .- 0028-3878. ; 99, s. e1278-e1289
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Cross-sectional studies suggest marked dopamine (DA) decline in aging, but longitudinal evidence is lacking. The aim of this study was to estimate within-person decline rates for DA D2-like receptors (DRD2) in aging and examine factors that may contribute to individual differences in DRD2 decline rates. METHODS: We investigated 5-year within-person changes in DRD2 availability in a sample of older adults. At both occasions, PET with 11C-raclopride and MRI were used to measure DRD2 availability in conjunction with structural and vascular brain integrity. RESULTS: Longitudinal analyses of the sample (baseline: n = 181, ages: 64-68 years, 100 men and 81 women; 5-year follow-up: n = 129, 69 men and 60 women) revealed aging-related striatal and extrastriatal DRD2 decline, along with marked individual differences in rates of change. Notably, the magnitude of striatal DRD2 decline was ∼50% of past cross-sectional estimates, suggesting that the DRD2 decline rate has been overestimated in past cross-sectional studies. Significant DRD2 reductions were also observed in select extrastriatal regions, including hippocampus, orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC). Distinct profiles of correlated DRD2 changes were found across several associative regions (ACC, dorsal striatum, and hippocampus) and in the reward circuit (nucleus accumbens and OFC). DRD2 losses in associative regions were associated with white matter lesion progression, whereas DRD2 losses in limbic regions were related to reduced cortical perfusion. DISCUSSION: These findings provide the first longitudinal evidence for individual and region-specific differences of DRD2 decline in older age and support the hypothesis that cerebrovascular factors are linked to age-related dopaminergic decline.
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| 7. |
- Wåhlin, Anders, et al.
(författare)
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At the Heart of Cognitive Functioning in Aging
- 2019
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Ingår i: Trends in cognitive sciences. - : Elsevier. - 1364-6613 .- 1879-307X. ; 23:9, s. 717-720
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Several neural and non-neural factors contribute to individual differences in cognitive performance. Here we outline a sequence of vascular events where excessive transfer of arterial-pressure pulsatility damages hippocampal capillaries. We argue that the vascular alterations decrease the ability to sustain neural activity and thereby contribute to episodic-memory impairment in aging.
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| 8. |
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| 9. |
- Nyberg, Lars, 1966-, et al.
(författare)
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Longitudinal stability in working memory and frontal activity in relation to general brain maintenance
- 2022
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive functions are well-preserved for some older individuals, but the underlying brain mechanisms remain disputed. Here, 5-year longitudinal 3-back in-scanner and offline data classified individuals in a healthy older sample (baseline age = 64–68 years) into having stable or declining working-memory (WM). Consistent with a vital role of the prefrontal cortex (PFC), WM stability or decline was related to maintained or reduced longitudinal PFC functional responses. Subsequent analyses of imaging markers of general brain maintenance revealed higher levels in the stable WM group on measures of neurotransmission and vascular health. Also, categorical and continuous analyses showed that rate of WM decline was related to global (ventricles) and local (hippocampus) measures of neuronal integrity. Thus, our findings support a role of the PFC as well as general brain maintenance in explaining heterogeneity in longitudinal WM trajectories in aging.
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| 10. |
- Zackariasson, Peter, 1972-
(författare)
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World Builders : A Study on the Development of a Massively Multiplayer Online Role-Playing Game
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation is a study of the development of a video game called Anarchy Online. This game was developed by the Funcom company between 1995 and 2001, and is a so-called Massively Multiplayer Online Role-Playing Game (MMORPG). This genre of video games differs from traditional games in that it offers a persistent virtual world that gamers can access at all hours of the night or day. It is also a world where gamers make avatars that play with or against each other. All in all, it is as much a social sphere as a game. The popularity of MMORGPGs has continued to increase, and today there are several million gamers worldwide who participate in these virtual worlds. Because virtual worlds are places where many people socialize, play, and spend a great deal of time, there is a need to form an understanding of them. In this thesis, I am studying how Anarchy Online was produced in order to understand the assumptions behind the rules governing the interaction in this specific virtual world were selected and organized. In doing so, I am using material from two sources: the developers and the game itself. This material was gathered through interviews, documents, and virtual ethnographic observations.Ultimately, games consist of codes; but in order to program the code, they need to be specified by a game content. The analysis shows that the content of the game is defined by the developers’ view of a good society – the belief in a human being’s need for self-actualization and social interaction. The thesis thus concludes with the observation that the need to select the discourses and/or philosophies for content and possible gamers’ actions requires the development of games and virtual worlds such as Anarchy Online to be more than the creation of an entertaining product. Rather, discourses were recreated from the physical world in which the developers live. In the end, gamers are locked into a discoursive prison created by the developers.
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