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1.
  • Wikgren, Mikael, 1981-, et al. (författare)
  • APOE ε4 is associated with longer telomeres, and longer telomeres among ε4 carriers predicts worse episodic memory
  • 2012
  • Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 33:2, s. 335-344
  • Tidskriftsartikel (refereegranskat)abstract
    • Both leukocyte telomere length and the apolipoprotein ε4 allele have been associated with mortality, cardiovascular disease, cognition, and dementia. The authors investigated whether leukocyte telomere length was associated with APOE genotype or cognitive abilities in the context of APOE genotype. The setting for this cross-sectional study was 427 nondemented individuals aged 41–81 yr. The authors found that ε4 carriers overall exhibited significantly longer telomeres compared with non-carriers (difference of 268 bp, p = 0.001). This difference was greatest at the lower limit of the age span and nonsignificant at the upper limit, which translated into a significantly higher telomere attrition rate (p = 0.049) among ε4 carriers (37 bp/years) compared with non-carriers (21 bp/year). Further, longer telomeres among ε4 carriers significantly predicted worse performance on episodic memory tasks. No significant associations were found on tasks tapping semantic and visuospatial ability, or among ε3/ε3 carriers. In conclusion, APOE ε4 carriers had longer telomeres compared with non-carriers, but higher rate of attrition. Among them, longer telomeres predicted worse performance on episodic memory tasks. These observations suggest that the ε4 allele is associated with abnormal cell turnover of functional and possibly clinical significance.
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2.
  • Wikgren, Mikael, et al. (författare)
  • Longer Leukocyte Telomere Length Is Associated with Smaller Hippocampal Volume among Non-Demented APOE epsilon 3/epsilon 3 Subjects
  • 2012
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 7:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Telomere length shortens with cellular division, and leukocyte telomere length is used as a marker for systemic telomere length. The hippocampus hosts adult neurogenesis and is an important structure for episodic memory, and carriers of the apolipoprotein E epsilon 4 allele exhibit higher hippocampal atrophy rates and differing telomere dynamics compared with non-carriers. The authors investigated whether leukocyte telomere length was associated with hippocampal volume in 57 cognitively intact subjects (29 epsilon 3/epsilon 3 carriers; 28 epsilon 4 carriers) aged 49-79 yr. Leukocyte telomere length correlated inversely with left (r(s) = -0.465; p = 0.011), right (r(s) = -0.414; p = 0.025), and total hippocampus volume (r(s) = -0.519; p = 0.004) among APOE epsilon 3/epsilon 3 carriers, but not among epsilon 4 carriers. However, the epsilon 4 carriers fit with the general correlation pattern exhibited by the epsilon 3/epsilon 3 carriers, as epsilon 4 carriers on average had longer telomeres and smaller hippocampi compared with epsilon 3/epsilon 3 carriers. The relationship observed can be interpreted as long telomeres representing a history of relatively low cellular proliferation, reflected in smaller hippocampal volumes. The results support the potential of leukocyte telomere length being used as a biomarker for tapping functional and structural processes of the aging brain.
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3.
  • Ekström, Magnus Pär, et al. (författare)
  • The association of body mass index, weight gain and central obesity with activity-related breathlessness : the Swedish Cardiopulmonary Bioimage Study
  • 2019
  • Ingår i: Thorax. - : BMJ Publishing Group Ltd. - 0040-6376 .- 1468-3296. ; 74:10, s. 958-964
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Breathlessness is common in the population, especially in women and associated with adverse health outcomes. Obesity (body mass index (BMI) >30 kg/m(2)) is rapidly increasing globally and its impact on breathlessness is unclear.Methods: This population-based study aimed primarily to evaluate the association of current BMI and self-reported change in BMI since age 20 with breathlessness (modified Research Council score >= 1) in the middle-aged population. Secondary aims were to evaluate factors that contribute to breathlessness in obesity, including the interaction with spirometric lung volume and sex.Results: We included 13 437 individuals; mean age 57.5 years; 52.5% women; mean BMI 26.8 (SD 4.3); mean BMI increase since age 20 was 5.0 kg/m(2); and 1283 (9.6%) reported breathlessness. Obesity was strongly associated with increased breathlessness, OR 3.54 (95% CI, 3.03 to 4.13) independent of age, sex, smoking, airflow obstruction, exercise level and the presence of comorbidities. The association between BMI and breathlessness was modified by lung volume; the increase in breathlessness prevalence with higher BMI was steeper for individuals with lower forced vital capacity (FVC). The higher breathlessness prevalence in obese women than men (27.4% vs 12.5%; p<0.001) was related to their lower FVC. Irrespective of current BMI and confounders, individuals who had increased in BMI since age 20 had more breathlessness.Conclusion: Breathlessness is independently associated with obesity and with weight gain in adult life, and the association is stronger for individuals with lower lung volumes.
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4.
  • Wikgren, Mikael, 1981-, et al. (författare)
  • Short Telomeres in Depression and the General Population Are Associated with a Hypocortisolemic State
  • 2012
  • Ingår i: Biological Psychiatry. - New York : Elsevier. - 0006-3223 .- 1873-2402. ; 71:4, s. 294-300
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The hypothalamic-pituitary-adrenal (HPA) axis plays a central role in stress regulation, and leukocyte telomere length (TL) has been suggested to represent a cumulative measure of stress. Depression is intimately related with stress and frequently exhibits a dysregulated HPA axis. We aimed to study the relationships between TL and biological and psychological facets of stress in recurrent major depressive disorder and controls. Methods Leukocyte TL was measured in 91 subjects with recurrent major depressive disorder and 451 control subjects. Stress was assessed from both a biological perspective, by assessing HPA axis function with a weight-adjusted very-low-dose dexamethasone suppression test (DST), and a psychological perspective, with self-report questionnaires. Results TL was shorter among patients compared with control subjects (277 base pairs, p = .001). Overall, short TL was associated with a hypocortisolemic state (low post-DST cortisol and high percentage of cortisol reduction after the DST) among both patients and control subjects but more pronounced among patients. This state, which was overrepresented among patients, was characterized by high familial loading of affective disorders among patients (p = .001) and high C-reactive protein levels among control subjects (p = .040). TL was also inversely associated with stress measured with the Perceived Stress Questionnaire (rs = −.258, p = .003). Conclusions Short TL is associated with depression and hypocortisolism. Because hypocortisolism has been shown to develop from chronic stress exposure, our findings corroborate the concept of TL as a cumulative measure of stress and provide novel insights into the detrimental role of stress in depressive illness and the general population.
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5.
  • Wikgren, Mikael, 1981-, et al. (författare)
  • Shorter telomere length is linked to brain atrophy and white matter hyperintensities
  • 2014
  • Ingår i: Age and Ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 43:2, s. 212-217
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: leukocyte telomere length (TL) is considered a marker of biological aging. Several studies have investigated the link between leukocyte TL and aging-associated functional attributes of the brain, but no prior study has investigated whether TL can be linked to brain atrophy and white matter hyperintensities (WMHs); two prominent structural manifestations of brain aging. Methods: we investigated whether leukocyte TL was related to brain atrophy and WMHs in a sample of 102 non-demented individuals aged 64-75 years. Results: shorter TL was related to greater degree of subcortical atrophy (beta = -0.217, P = 0.034), but not to cortical atrophy. Furthermore, TL was 371 bp shorter (P = 0.041) in participants exhibiting subcortical WMHs, and 552 bp shorter (P = 0.009) in older participants exhibiting periventricular WMHs. Conclusion: this study provides the first evidence of leukocyte TL being associated with cerebral subcortical atrophy and WMHs, lending further support to the concept of TL as a marker of biological aging, and in particular that of the aging brain.
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6.
  • Brändström, Sven, 1952-, et al. (författare)
  • Swedish normative data on personality using the Temperament and Character Inventory
  • 1998
  • Ingår i: Comprehensive Psychiatry. - 0010-440X .- 1532-8384. ; 39:3, s. 122-128
  • Tidskriftsartikel (refereegranskat)abstract
    • The Temperament and Character Inventory (TCI) is a self-report personality questionnaire based on Cloninger's psychobiological model of personality, which accounts for both normal and abnormal variation in the two major components of personality, temperament and character. Normative data for the Swedish TCI based on a representative Swedish sample of 1,300 adults are presented, and the psychometric properties of the questionnaire are discussed. The structure of the Swedish version replicates the American version well for the means, distribution of scores, and relationships within the between scales and subscales. Further, the Swedish inventory had a reliable factor structure and test-retest performance. The results of this study confirm the theory of temperament and character as a seven-factor model of personality.
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7.
  • Engström, Gunnar, et al. (författare)
  • Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications
  • 2024
  • Ingår i: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49
  • Tidskriftsartikel (refereegranskat)abstract
    • Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
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8.
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9.
  • Levén, Anna, 1976-, et al. (författare)
  • Prospective memory and intellectual disability
  • 2017
  • Ingår i: Abstracts of the 20thConference of the European Society for Cognitive Psychology, Potsdam, Germany, 3-6 September 2017. - Potsdam : University of Potsdam. ; , s. 157-157
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Persons with intellectual disability often omit acting on intentions in the future, e.g., to take medicine at lunch. Despite research in different clinical groups, prospective memory has received little attention in relation to intellectual disability. A prospective part (when to act/timing) and a retrospective part of prospective memory (what to do/plan)are identified. Retrospective memory and vigilance are important for execution in prospective memory in persons with intellectual disability.Method: A group with intellectual disability (IQ < 70, n=58) was defined together with a control group matched on age, sex, level of education and years of education (n=116)in the Swedish Betula database.Results: Prospective memory performance was lower in the intellectual disability than the control group. About half of the participants with intellectual disability remembered the retrospective part of the prospective memory task if the experimenter provided a cue. Persons with intellectual disability were able to perform on the prospective memory task, despite performance at floor level for verbal prospective memory tasks in previous studies. Episodic memory was related to recognition, recall and semantic memory in both groups. Contrary to previous results, prospective memory correlated with episodic memory, semantic memory, short-term memory, recall, recognition, and knowledge only int he control group.Discussion: Persons with intellectual disability remembered the retrospective aspect of the prospective memory task despite lower performance than the control group on other memory tasks. The intellectual disability group performed lower than the control group although performance preceded the ongoing task. Finishing all tasks may have formed a context to associate with prospective memory performance in particular for the control group with a higher memory capacity to engage in memory processing compared to the intellectual disability group. We suggest matching on education as a reason for this result.
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10.
  • Levén, Anna, 1976-, et al. (författare)
  • Prospective memory and intellectual disability
  • 2017
  • Konferensbidrag (refereegranskat)abstract
    • Previous studies have shown prospective memory errors in persons with intellectual disability (adults, Levén et al., 2007, 2008, 2011, 2013, adolescents, Meilan et al., 2009). As prospective memory failures are one of the most common memory errors (Crovitz and Daniel, 1984), this may explain part of the difficulties in handling demands in everyday life for persons with intellectual disability. Prospective memory refers to memory focused on realising intentions in the future. The ongoing task is performed as the intention is stored in long-term memory. Despite research in different clinical groups (brain injuries, Mioni et al., 2013; Aging, Kvavilashvili et al, 2013; schizophrenia, Raskin et al, 2013; ADHD,  Brandimonte et al., 2011, Kliegel, 2013, etc.) this aspect of memory has received little attention in relation to intellectual disability (adults, Levén et al., 2007, 2008, 2011, 2013, adolescents, Meilan et al., 2009).Meilan et al. (2009) got results supporting the multi-process view on prospective memory (McDaniel & Einstein, 1990). The multiprocess view on PM (Einstein & McDaniel, 1990) predicts that the prospective part will be noticed more automatic in specific circumstances, specifically, if the PM cue is either; (a) strongly associated with the planned action, (b) associated with the ongoing task, (c) salient, or (d) has relevant features that come into focus of attention as a result of processing associated with the ongoing task (M. A. McDaniel & Einstein, 2000; M. A. McDaniel, Guynn, Einstein, & Breneiser, 2004).Intellectual disability and prospective memory.Research on prospective memory has increased dramatically in recent years, although persons with intellectual disability have not been thoroughly investigated. Recent studies have studied prospective memory in persons with traumatic brain injury. Persons with intellectual disability may have suffered a brain injury in childhood, but there are also genetic and foremost unknown (about 50%) reasons for intellectual disability.Keeping appointments (Rivermead Behavioural Memory Test) have been found to be a difficult subtest for persons with intellectual disability (Martin et al., 2000; Meilan et al., 2009). The child version of the test has been used in adult persons with Down's syndrome (Aldrich et al., 1991; Wilson 1995). Performance was low also on the borrowed item subtest of the River Mead Behavioural Memory Test. In this task the experimenter borrows an item and the participant is to ask for it later on in the experiment. Prospective memory performance is strongly related to retrospective memory performance in persons with intellectual disability similar as in children. This has been attributed to a general weakness in memory processes such as episodic memory, and/or attention (Levén et al, 2008).Method.Population. The participants in the present study were a subsample drawn from the prospective Betula cohort study testing wave 2. There were 2840 people between 35 and 90 years of age. People with genetic syndromes (e.g. Down syndrome) were excluded in Betula, which gave a mixed or non-specific intellectual disabilities sample. In the Betula database, a group with intellectual disability (IQ < 70, n=58) was defined, using a verbal and a nonverbal IQ test, together with a control group matched on age, sex, level of education and years of education (n=116). Note that these groups were old (mean age = 73 years) compared to most other studies on ID.Tasks: At the beginning of all of the memory tests each day, the test leader asked the subject to remind him/her that they should sign a paper at the end of the day after all the tests were finished. Subjects were not told that this was a memory test. Together with this task on prospective memory, several tasks of episodic memory (recall, recognition), semantic memory (knowledge, fluency) and short-term memory was used.The task was scored as follows:4, recall no cue: Subjects remembered this without any aid3, after cue: Test leader: Was there not something else we should do?2, after reminding: Test leader: Were you not supposed to remind me of something?1, failed completely: Failed to remember despite of cues givenResults.See Table 1 for frequencies for the different prospective memory answers. The controls perform better than persons with intellectual disability on the prospective memory task, F(1,173) = 10.8, p<.001. However, almost all participants with ID managed to perform the task with reminders.Table 1. Frequencies for the prospective memory answers in percent in the two groups.Prospective memory answerIDControls1, failed completely14 %8 %2, recall after reminding53 %25 %3, recall after cue14 %37 %4, recall without cue19 %30 % In the control group, prospective memory correlated significantly with episodic memory (.19), semantic memory (.32) and short-term memory (.22), whereas in the intellectual disability group none of the correlations were significant (episodic memory .16, semantic memory .08, and short-term memory .18). The memory measures were also more intercorrelated in the control group compared to the intellectual disability group. This is contrary to previous results (Levén et al., 2008, 2011, 2013) where the ID group had higher intercorrelations.Discussion.Low prospective memory performance was found in the intellectual disability group as in previous studies. Prospective memory correlated with other memory functions only in the control group. One possibility is that prospective memory loads on executive functions, or vigilance not measured in this study.Persons with intellectual disability have not been able to perform verbal prospective memory tasks at all in previous studies. In this study, on the contrary, persons with intellectual disability performed a verbal prospective memory task. About half of the participants with intellectual disability remembered the prospective memory task if the experimenter asked what they should remind them of. That is, they managed the task with a cue that reduced the load on long-term memory. Previous studies have used a less explicit cue which did not improve performance significantly in the intellectual disability group.Selected ReferencesBrandimonte, M. A., Filippello, P., Coluccia, E., Altgassen, M., & Kliegel, M. (2011). To do or not to do? Prospective memory versus response inhibition in autism spectrum disorder and attention-deficit/hyperactivity disorder. Memory, 19(1), 56-66. doi:10.1080/09658211.2010.535657Einstein, G. O., & McDaniel, M. A. (1990). Normal aging and prospective memory. Journal of Experimental Psychology. Learning, Memory, and Cognition, (4), 717-726.Levén, A., Lyxell, B., Andersson, J., Danielsson, H., & Rönnberg, J. (2011). The relationship between prospective memory, working memory and self-rated memory performance in individuals with intellectual disability. Scandinavian Journal of Disability Research. 1-17.                                           Levén, A., Lyxell, B., Andersson, J., Danielsson, H. & Rönnberg, J. (2008). Prospective memory, working memory, retrospective memory and self-rated memory performance in persons with intellectual disability. Scandinavian Journal of Disability Research. , 10(3), 147-165.Levén, A., Lyxell, B., Andersson, J. & Danielsson, H. (2013). Pictures as cues or as support to verbal cues at encoding and execution of prospective memories in individuals with intellectual disability. Scandinavian Journal of Disability Research.Meilán, J. G., Pérez, E., Arana, J. M., & Carro, J. (2009). Neuropsychological and cognitive factors in event-based prospective memory performance in adolescents and young people with an intellectual disability. British Journal Of Developmental Disabilities, 55(108,Pt1), 61-75. doi:10.1179/096979509799103179Mioni, G., Rendell, P. G., Henry, J. D., Cantagallo, A., & Stablum, F. (2013). An investigation of prospective memory functions in people with traumatic brain injury using Virtual Week. Journal Of Clinical And Experimental Neuropsychology, 35(6), 617-630. doi:10.1080/13803395.2013.804036Wilson, B. A. and Ivani-Chalian, R. (1995), Performance of adults with Down's syndrome on the Children's Version of the Rivermead Behavioural Memory Test: A brief report. British Journal of Clinical Psychology, 34: 85–88. doi: 10.1111/j.2044-8260.1995.tb01440.x
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