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| 2. |
- Gorcenco, Sorina, et al.
(författare)
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Ataxia-pancytopenia syndrome with SAMD9L mutations
- 2017
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Ingår i: Neurology: Genetics. - 2376-7839. ; 3:5
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We describe the neurologic, neuroradiologic, and ophthalmologic phenotype of 1 Swedish and 1 Finnish family with autosomal dominant ataxia-pancytopenia (ATXPC) syndrome and SAMD9L mutations.METHODS: Members of these families with germline SAMD9L c.2956C>T, p.Arg986Cys, or c.2672T>C, p.Ile891Thr mutations underwent structured interviews and neurologic and ophthalmologic examinations. Neuroimaging was performed, and medical records were reviewed. Previous publications on SAMD9L-ATXPC were reviewed.RESULTS: Twelve individuals in both families were affected clinically. All mutation carriers examined had balance impairment, although severity was very variable. All but 1 had nystagmus, and all but 1 had pyramidal tract signs. Neurologic features were generally present from childhood on and progressed slowly. Two adult patients, who experienced increasing clumsiness, glare, and difficulties with gaze fixation, had paracentral retinal dysfunction verified by multifocal electroretinography. Brain MRI showed early, marked cerebellar atrophy in most carriers and variable cerebral periventricular white matter T2 hyperintensities. Two children were treated with hematopoietic stem cell transplantation for hematologic malignancies, and the neurologic symptoms of one of these worsened after treatment. Three affected individuals had attention deficit hyperactivity disorder or cognitive problems. Retinal dysfunction was not previously reported in individuals with ATXPC.CONCLUSIONS: The neurologic phenotype of this syndrome is defined by balance or gait impairment, nystagmus, hyperreflexia in the lower limbs and, frequently, marked cerebellar atrophy. Paracentral retinal dysfunction may contribute to glare, reading problems, and clumsiness. Timely diagnosis of ATXPC is important to address the risk for severe hemorrhage, infection, and hematologic malignancies inherent in this syndrome; regular hematologic follow-up might be beneficial.
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| 3. |
- Tesi, Bianca, et al.
(författare)
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Gain-of-function SAMD9L mutations cause a syndrome of cytopenia, immunodeficiency, MDS, and neurological symptoms
- 2017
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Ingår i: Blood. - : AMER SOC HEMATOLOGY. - 0006-4971 .- 1528-0020. ; 129:16, s. 2266-2279
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Tidskriftsartikel (refereegranskat)abstract
- Several monogenic causes of familial myelodysplastic syndrome (MDS) have recently been identified. We studied 2 families with cytopenia, predisposition to MDS with chromosome 7 aberrations, immunodeficiency, and progressive cerebellar dysfunction. Genetic studies uncovered heterozygous missense mutations in SAMD9L, a tumor suppressor gene located on chromosome arm 7q. Consistent with a gain-of-function effect, ectopic expression of the 2 identified SAMD9L mutants decreased cell proliferation relative to wild-type protein. Of the 10 individuals identified who were heterozygous for either SAMD9L mutation, 3 developed MDS upon loss of the mutated SAMD9L allele following intracellular infections associated with myeloid, B-, and natural killer (NK)-cell deficiency. Five other individuals, 3 with spontaneously resolved cytopenic episodes in infancy, harbored hematopoietic revertant mosaicism by uniparental disomy of 7q, with loss of the mutated allele or additional in cis SAMD9L truncating mutations. Examination of 1 individual indicated that somatic reversions were postnatally selected. Somatic mutations were tracked to CD34 1 hematopoietic progenitor cell populations, being further enriched in B and NK cells. Stimulation of these cell types with interferon (IFN)-alpha or IFN-gamma induced SAMD9L expression. Clinically, revertant mosaicism was associated with milder disease, yet neurological manifestations persisted in 3 individuals. Two carriers also harbored a rare, in trans germ line SAMD9L missense loss-of-function variant, potentially counteracting the SAMD9L mutation. Our results demonstrate that gain-of-function mutations in the tumor suppressor SAMD9L cause cytopenia, immunodeficiency, variable neurological presentation, and predisposition to MDS with 27/del(7q), whereas hematopoietic revertant mosaicism commonly ameliorated clinical manifestations. The findings suggest a role for SAMD9L in regulating IFN-driven, demand-adapted hematopoiesis.
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| 5. |
- Berggren, Rasmus, et al.
(författare)
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Education Does Not Affect Cognitive Decline in Aging : A Bayesian Assessment of the Association Between Education and Change in Cognitive Performance.
- 2018
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Ingår i: Frontiers in psychology. - : Frontiers Media SA. - 1664-1078. ; 9, s. 1138-
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Tidskriftsartikel (refereegranskat)abstract
- Education is positively associated with level of cognitive function but the association between education and rate of cognitive decline remains unresolved, partly for methodological reasons. In this article, we address this issue using linear mixed models and Bayesian hypothesis testing, using data from the Betula cohort-sequential longitudinal study. Our results support the null hypothesis that education does not alter the rate of cognitive decline for visuospatial ability, semantic knowledge, and episodic memory. We propose that education is only a relevant variable for understanding cognitive performance in older age because of the association between performance and education that is formed in early development.
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| 6. |
- Berggren, Rasmus, et al.
(författare)
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Foreign language learning in older age does not improve memory or intelligence : Evidence from a randomized controlled study.
- 2020
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Ingår i: Psychology and Aging. - : American Psychological Association (APA). - 0882-7974 .- 1939-1498. ; 35:2, s. 212-219
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Tidskriftsartikel (refereegranskat)abstract
- Foreign language learning in older age has been proposed as a promising avenue for combatting age-related cognitive decline. We tested this hypothesis in a randomized controlled study in a sample of 160 healthy older participants (aged 65-75 years) who were randomized to 11 weeks of either language learning or relaxation training. Participants in the language learning condition obtained some basic knowledge in the new language (Italian), but between-groups differences in improvements on latent factors of verbal intelligence, spatial intelligence, working memory, item memory, or associative memory were negligible. We argue that this is not due to either poor measurement, low course intensity, or low statistical power, but that basic studies in foreign languages in older age are likely to have no or trivially small effects on cognitive abilities. We place this in the context of the cognitive training and engagement literature and conclude that while foreign language learning may expand the behavioral repertoire, it does little to improve cognitive processing abilities. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
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| 7. |
- Bergman, Annika, et al.
(författare)
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Genome-wide linkage scan for breast cancer susceptibility loci in Swedish hereditary non-BRCA1/2 families : Suggestive linkage to 10q23.32-q25.3
- 2007
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Ingår i: Genes, Chromosomes and Cancer. - : John Wiley & Sons. - 1045-2257 .- 1098-2264. ; 46:3, s. 302-309
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Tidskriftsartikel (refereegranskat)abstract
- The two breast cancer genes BRCA1 and BRCA2 were identified more than 10 years ago and, depending on population, mutations in these genes are responsible for a varying percentage of familial breast cancer. In more than half the families, the increased risk of breast cancer cannot be explained by mutations in these genes, and the goal of this study was to locate novel susceptibility genes. One of the main difficulties in identifying the cause of hereditary non-BRCA1/BRCA2 breast cancer is genetic heterogeneity, possibly due to multiple, incompletely penetrant susceptibility genes, along with ethnic and geographic differences. In this study, one large family and 13 small to medium-sized families with multiple cases of breast cancer were analyzed by genome-wide linkage analysis. The genome scan was performed by genotype analysis of 10,000 SNP markers on microarrays. The strongest evidence of linkage (HLOD 2.34) was obtained on chromosome region 10q23.32-q25.3. A further two regions were identified, with LOD scores above 2.10 on 12q14-q21 and 19p13.3-q12. In a subset of families of western Swedish origin, two regions generated LOD scores exceeding 1.8: 10q23.32-q25.3 and 19q13.12-q13.32. The large family in the study exceeded LOD 1.5 in three regions: 10q23.32-q25.3, 19q13.12-q13.32, and 17p13. Our results indicate that one or more of the suggested regions may harbor genes that are involved in the development of breast cancer.
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| 9. |
- Bojsen-Møller, Emil, 1989-
(författare)
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Movement Behaviors and Cognitive Health for Office Workers
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The lifetime trajectories of movement behavior and cognitive functioning depend on complex interactions between genetic and environmental factors. There is substantial evidence suggesting that physical activity benefits cognitive functions. However, how sedentary behavior and the composition of movement behaviors (i.e., sleep, physical activity, and sedentary behavior) influences cognitive functions remains to be elucidated. Observational studies suggest that sedentary time is unfavorably related to cognitive functions in older adults, but the majority of evidence comes from self-reported estimates of movement behavior, which are rather weakly related to device-based measures. Furthermore, while evidence suggests that structured exercise can have protective effects on cognition in inactive older adults, much less is known about how midlife movement behavior is related to cognitive functions. Thus, knowledge of how midlife movement behavior relates to and possibly affects cognitive functions and its underlying mechanisms is much needed. This thesis is part of a larger research project investigating how movement behaviors relate to and influence cognitive function, mental health, and neurophysiological mechanisms underpinning these. The project specifically targets healthy office workers and is co-produced with employers of office workers and health-promoting companies. This thesis aimed to investigate how movement behaviors relate to and influence cognitive functions and neuroplasticity among office workers.The first study investigated cross-sectional relationships between device-measured movement behavior and cognitive functions among 334 office workers. The results revealed no association between total time spent in moderate to vigorous physical activity or sedentary behavior and cognitive functions, suggesting that this association may not be as robust as previously suggested in older populations or as inferred from self-report. The second study investigated the extent to which corticospinal excitability is influenced by different movement behaviors. Sixteen sedentary office workers participated in a cross-over randomized controlled trial. We contrasted 3 hours of prolonged sitting with 3 hours of interrupted sitting and 2.5 hours sitting followed by a 25-minute bout of exercise. Acute changes in corticospinal excitability and long-term potentiation-like neuroplasticity were investigated using transcranial magnetic stimulation and paired associative stimulation. Changes in corticospinal excitability over time did not differ between conditions, suggesting that in inactive middle-aged office workers, a physical activity bout or frequently breaking up prolonged sitting does not induce immediate changes in corticospinal excitability or long-term potentiation-like neuroplasticity. The third and fourth studies are based on a 6-month cluster-randomized intervention conducted in 263 healthy office workers. An ecological model for behavior change was used to design two interventions aiming at reducing sedentary behavior or increasing physical activity relative to a passive control group, with the ultimate aim of improving cognitive functions and mental health. The third study investigated how effective each intervention was at changing the 24-hour movement behavior, and the fourth study examined intervention effects on cognitive functions. The results showed that the interventions were ineffective in reducing sedentary behavior and increasing physical activity, respectively, with no detected beneficial effects on cardiorespiratory fitness or cognitive functions relative to the control group. Changes in cognition from baseline to follow-up were not associated with changes in the composition of movement behaviors or cardiorespiratory fitness, but some associations between changes in movement behaviors and cognition were moderated by sex, age, and cardiorespiratory fitness. Thus, the third and fourth studies of the thesis have highlighted the challenges involved in successfully achieving movement behavior change to address the possible effects on cognitive improvements in an ecological setting.In summary, the results presented in this thesis did not provide support for an association between movement behaviors and cognitive functions in healthy physically active office workers, demonstrated no acute effect of a single session of physical activity or breaking up prolonged sitting on corticospinal excitability in sedentary office workers, and revealed no evidence for successful movement behavior change or benefits for cognition in an ecological cluster-randomized intervention in healthy physically active office workers. The findings suggest that among physically active office workers, sedentary behavior may not be as detrimental for cognition and neuroplasticity as previously suggested and shows that changing movement behavior in office workers at the workplace represents a challenging endeavor. Still, these findings do not exclude the possibility that changes in movement behaviors might benefit cognitive functions in physically inactive office workers at higher cardiovascular risk, with lower cardiorespiratory fitness and/or lower daily cognitive stimulation.
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| 10. |
- Bojsen-Møller, Emil, 1989-, et al.
(författare)
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The effect of two multi-component behavior change interventions on cognitive functions.
- 2022
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Ingår i: BMC Public Health. - : BioMed Central (BMC). - 1471-2458. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We previously reported the effects of two cluster-randomized 6-month multi-component workplace interventions, targeting reducing sedentary behavior or increasing physical activity among office workers, on movement behaviors and cardiorespiratory fitness. The primary aim of this study was to investigate the effects of these interventions on cognitive functions compared to a wait-list control group. The secondary aims were to examine if changes in cognition were related to change in cardiorespiratory fitness or movement behaviors and if age, sex, or cardiorespiratory fitness moderated these associations.METHODS: Both interventions encompassed multi-components acting on the individual, environmental, and organizational levels and aimed to change physical activity patterns to improve mental health and cognitive function. Out of 263 included participants, 139 (mean age 43 years, 76% females) completed a neuropsychological test battery and wore accelerometers at baseline and 6-month follow-up. The intervention effect (aim 1) on cognitive composite scores (i.e., Executive Functions, Episodic Memory, Processing Speed, and Global Cognition) was investigated. Additionally, associations between changes in movement behaviors and cardiorespiratory fitness, and changes in cognition were examined (aim 2). Moreover, age, sex, and cardiorespiratory fitness level were investigated as possible moderators of change associations (aim 3).RESULTS: Overall, cognitive performance improved from baseline to follow-up, but the change did not differ between the intervention groups and the control group. Changes in cardiorespiratory fitness or any movement behavior category did not predict changes in cognitive functions. The association between changes in time in bed and changes in both Executive Function and Global Cognition were moderated by age, such that a more positive relation was seen with increasing age. A less positive association was seen between changes in sedentary behavior and Processing Speed for men vs. women, whereas higher cardiorespiratory fitness was related to a more positive association between changes in moderate-intensity physical activity and Global Cognition.CONCLUSION: The lack of an intervention effect on cognitive functions was expected since the intervention did not change movement behavior or fitness. Age, sex, and cardiorespiratory fitness level might moderate the relationships between movement behaviors and cognitive functions changes.TRIAL REGISTRATION: ISRCTN92968402 . Registered 09/04/2018.
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