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  • 1.
    Degerman, Sofie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Josefsson, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Nordin Adolfsson, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Wennstedt, Sigrid
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Landfors, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Haider, Zahra
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Pudas, Sara
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Maintained memory in aging is associated with young epigenetic age2017Ingår i: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 55, s. 167-171Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Epigenetic alterations during aging have been proposed to contribute to decline in physical and cognitive functions, and accelerated epigenetic aging has been associated with disease and all-cause mortality later in life. In this study, we estimated epigenetic age dynamics in groups with different memory trajectories (maintained high performance, average decline, and accelerated decline) over a 15-year period. Epigenetic (DNA-methylation [DNAm]) age was assessed, and delta age (DNAm age - chronological age) was calculated in blood samples at baseline (age: 55-65 years) and 15 years later in 52 age- and gender-matched individuals from the Betula study in Sweden. A lower delta DNAm age was observed for those with maintained memory functions compared with those with average (p = 0.035) or accelerated decline (p = 0.037). Moreover, separate analyses revealed that DNAm age at follow-up, but not chronologic age, was a significant predictor of dementia (p = 0.019). Our findings suggest that young epigenetic age contributes to maintained memory in aging.

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  • 2. Ekström, Ingrid
    et al.
    Josefsson, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Larsson, Maria
    Rönnlund, Michael
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Nordin, Steven
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Olofsson, Jonas K.
    Subjective olfactory loss in older adults concurs with long-term odor identification decline2019Ingår i: Chemical Senses, ISSN 0379-864X, E-ISSN 1464-3553, Vol. 44, nr 2, s. 105-112Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Olfactory impairments may provide early indications of future health outcomes in older adults. Thus, an important question concerns whether these impairments can be self-assessed. Previous findings of cross-sectional studies indicate low correlations between self-reported olfactory function and objective olfactory performance. On the other hand, subjective olfactory impairments predict future dementia and mortality in longitudinal settings. No previous study has assessed the relationship between subjectively and objectively measured decline in olfaction over time. Based on data for 903 older adults derived from the Betula Study, a Swedish population-based prospective study, we tested whether rate-of-change in odor identification could be predicted from subjective olfactory decline over a time span of 10 years during which subjective and objective odor functions were assessed on 2 or 3 test occasions. Indeed, we found that participants who experienced subjective olfactory decline over the study period also had significantly steeper rates of decline in odor identification, even after adjusting for demographic, cognitive, and genetic factors that previously have been associated with performance in odor identification. This association was, however, not present in a subsample with baseline cognitive impairment. We interpret these results as evidence that when asked about whether they have an olfactory impairment or not, older persons are assessing intraindividual olfactory changes, rather than interindividual differences. Our results indicate that subjective olfactory loss reflects objective olfactory decline in cognitively intact older adults. This association might be harnessed to predict health outcomes and highlights the need to develop effective olfactory self-assessments.

  • 3.
    Eriksson Sörman, Daniel
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Josefsson, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Marsh, John Everett
    Hansson, Patrik
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Ljungberg, Jessica K.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Longitudinal effects of bilingualism on dual-tasking2017Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 12, artikel-id e0189299Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    An ongoing debate surrounds whether bilinguals outperform monolinguals in tests of executive processing. The aim of this study was to investigate if there are long-term (10 year) bilingual advantages in executive processing, as indexed by dual-task performance, in a sample that were 40-65 years at baseline. The bilingual (n = 24) and monolingual (n = 24) participants were matched on age, sex, education, fluid intelligence, and study sample. Participants performed free-recall for a 12-item list in three dual-task settings wherein they sorted cards either during encoding, retrieval, or during both encoding and retrieval of the word-list. Free recall without card sorting was used as a reference to compute dual-task costs. The results showed that bilinguals significantly outperformed monolinguals when they performed card-sorting during both encoding and retrieval of the word-list, the condition that presumably placed the highest demands on executive functioning. However, dual-task costs increased over time for bilinguals relative to monolinguals, a finding that is possibly influenced by retirement age and limited use of second language in the bilingual group.

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  • 4.
    Gorbach, Tetiana
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Pudas, Sara
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Lundquist, Anders
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Orädd, Greger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Josefsson, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Salami, Alireza
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
    de Luna, Xavier
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Longitudinal association between hippocampus atrophy and episodic-memory decline2017Ingår i: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 51, s. 167-176Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is marked variability in both onset and rate of episodic-memory decline in aging. Structural magnetic resonance imaging studies have revealed that the extent of age-related brain changes varies markedly across individuals. Past studies of whether regional atrophy accounts for episodic-memory decline in aging have yielded inconclusive findings. Here we related 15-year changes in episodic memory to 4-year changes in cortical and subcortical gray matter volume and in white-matter connectivity and lesions. In addition, changes in word fluency, fluid IQ (Block Design), and processing speed were estimated and related to structural brain changes. Significant negative change over time was observed for all cognitive and brain measures. A robust brain-cognition change-change association was observed for episodic-memory decline and atrophy in the hippocampus. This association was significant for older (65-80 years) but not middle-aged (55-60 years) participants and not sensitive to the assumption of ignorable attrition. Thus, these longitudinal findings highlight medial-temporal lobe system integrity as particularly crucial for maintaining episodic-memory functioning in older age. 

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  • 5.
    Josefsson, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Attrition in Studies of Cognitive Aging2013Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Longitudinal studies of cognition are preferred to cross-sectional stud- ies, since they offer a direct assessment of age-related cognitive change (within-person change). Statistical methods for analyzing age-related change are widely available. There are, however, a number of challenges accompanying such analyzes, including cohort differences, ceiling- and floor effects, and attrition. These difficulties challenge the analyst and puts stringent requirements on the statistical method being used.

    The objective of Paper I is to develop a classifying method to study discrepancies in age-related cognitive change. The method needs to take into account the complex issues accompanying studies of cognitive aging, and specifically work out issues related to attrition. In a second step, we aim to identify predictors explaining stability or decline in cognitive performance in relation to demographic, life-style, health-related, and genetic factors.

    In the second paper, which is a continuation of Paper I, we investigate brain characteristics, structural and functional, that differ between suc- cessful aging elderly and elderly with an average cognitive performance over 15-20 years.

    In Paper III we develop a Bayesian model to estimate the causal effect of living arrangement (living alone versus living with someone) on cog- nitive decline. The model must balance confounding variables between the two living arrangement groups as well as account for non-ignorable attrition. This is achieved by combining propensity score matching with a pattern mixture model for longitudinal data.

    In paper IV, the objective is to adapt and implement available impu- tation methods to longitudinal fMRI data, where some subjects are lost to follow-up. We apply these missing data methods to a real dataset, and evaluate these methods in a simulation study.

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    Attrition in studies of cognitive aging
  • 6.
    Josefsson, Maria
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    de Luna, Xavier
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Daniels, Michael
    University of Texas at Austin.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Causal inference with longitudinal outcomes and non-ignorable drop-out: Estimating the effect of living alone on cognitive decline2016Ingår i: Journal of the Royal Statistic Society, Series C: Applied Statistics, ISSN 0035-9254, E-ISSN 1467-9876, Vol. 65, nr 1, s. 131-144Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We develop a model to estimate the causal effect of living arrangement (living alone versus living with someone) on cognitive decline based on a 15-year prospective cohort study, where episodic memory function is measured every 5 years. One key feature of the model is the combination of propensity score matching to balance confounding variables between the two living arrangement groups—to reduce bias due to unbalanced covariates at baseline, with a pattern–mixture model for longitudinal data—to deal with non-ignorable dropout. A fully Bayesian approach allows us to convey the uncertainty in the estimation of the propensity score and subsequent matching in the inference of the causal effect of interest. The analysis conducted adds to previous studies in the literature concerning the protective effect of living with someone, by proposing a modelling approach treating living arrangement as an exposure.

  • 7.
    Josefsson, Maria
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    de Luna, Xavier
    Umeå universitet, Samhällsvetenskapliga fakulteten, Statistiska institutionen.
    Pudas, Sara
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nilsson, Lars-Göran
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Samhällsvetenskapliga fakulteten, Centrum för befolkningsstudier (CBS). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Genetic and lifestyle predictors of 15-Year longitudinal change in episodic memory2012Ingår i: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 60, nr 12, s. 2308-2312Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To reveal distinct longitudinal trajectories in episodic memory over 15 years and to identify demographic, lifestyle, health-related, and genetic predictors of stability or decline. DESIGN: Prospective cohort study. SETTING: The Betula Project, Umeå, Sweden. PARTICIPANTS: One thousand nine hundred fifty-four healthy participants aged 35 to 85 at baseline. MEASUREMENTS: Memory was assessed according to validated episodic memory tasks in participants from a large population-based sample. Data were analyzed using a random-effects pattern-mixture model that considered the effect of attrition over two to four longitudinal sessions. Logistic regression was used to determine significant predictors of stability or decline relative to average change in episodic memory. RESULTS: Of 1,558 participants with two or more test sessions, 18% were classified as maintainers and 13% as decliners, and 68% showed age-typical average change. More educated and more physically active participants, women, and those living with someone were more likely to be classified as maintainers, as were carriers of the met allele of the catechol-O-methyltransferase gene. Less educated participants, those not active in the labor force, and men were more likely to be classified as decliners, and the apolipoprotein E ɛ4 allele was more frequent in decliners. CONCLUSION: Quantitative, attrition-corrected assessment of longitudinal changes in memory can reveal substantial heterogeneity in aging trajectories, and genetic and lifestyle factors predict such heterogeneity.

  • 8.
    Josefsson, Maria
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Larsson, Maria
    Nordin, Steven
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Olofsson, Jonas
    APOE-ɛ4 effects on longitudinal decline in olfactory and non-olfactory cognitive abilities in middle-aged and old adults2017Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikel-id 1286Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Characterizing aging-related decline trajectories in mental abilities, and relationships of the ɛ4 allele of the Apolipoprotein gene, helps to identify individuals at high risk for dementia. However, longitudinal changes in olfactory and non-olfactory cognitive abilities have not been investigated in relation to the ɛ4 allele. In the present study, participants from a large population-based study (657 middle-aged and 556 old) were tested over 10 years on their performance on an odor identification task and three non-olfactory cognitive tasks; MMSE, episodic memory, and semantic memory. Our key finding is that in middle-aged participants, odor identification declined twice as fast for ɛ4/4 homozygotes, compared to non-carriers. However, in old participants, the ɛ4/4 homozygotes showed an impaired odor identification ability, but they declined at a similar rate as the non-carriers. Furthermore, in old participants all assessments displayed aging-related declines, but exaggerated declines in ɛ4-carriers were found only in MMSE and episodic memory assessments. In sum, we present evidence that odor identification ability starts to decline already in middle-aged, and that carriers of ɛ4/4, who are at highest risk of developing dementia, decline twice as fast. Our results may have implications for use of odor identification assessment in detection of early-stage dementia.

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  • 9.
    Josefsson, Maria
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Lundquist, Anders
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Imputation of missing longitudinal fMRI dataManuskript (preprint) (Övrigt vetenskapligt)
  • 10.
    Josefsson, Maria
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR). Demographic Data Base.
    Sundström, Anna
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Pudas, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nordin Adolfsson, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Memory profiles predict dementia over 23–28 years in normal but not successful aging2019Ingår i: International psychogeriatrics, ISSN 1041-6102, E-ISSN 1741-203XArtikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Prospective studies suggest that memory deficits are detectable decades before clinical symptoms of dementia emerge. However, individual differences in long-term memory trajectories prior to diagnosis need to be further elucidated. The aim of the current study was to investigate long-term dementia and mortality risk for individuals with different memory trajectory profiles in a well-characterized population-based sample.

    Methods: 1062 adults (aged 45–80 years) who were non-demented at baseline were followed over 23–28 years. Dementia and mortality risk were studied for three previously classified episodic memory trajectory groups: maintained high performance (Maintainers; 26%), average decline (Averages; 64%), and accelerated decline (Decliners; 12%), using multistate modeling to characterize individuals’ transitions from an initial non-demented state, possibly to a state of dementia and/or death.

    Results: The memory groups showed considerable intergroup variability in memory profiles, starting 10–15 years prior to dementia diagnosis, and prior to death. A strong relationship between memory trajectory group and dementia risk was found. Specifically, Decliners had more than a fourfold risk of developing dementia compared to Averages. In contrast, Maintainers had a 2.6 times decreased dementia risk compared to Averages, and in addition showed no detectable memory decline prior to dementia diagnosis. A similar pattern of association was found for the memory groups and mortality risk, although only among non-demented.

    Conclusion: There was a strong relationship between accelerated memory decline and dementia, further supporting the prognostic value of memory decline. The intergroup differences, however, suggest that mechanisms involved in successful memory aging may delay symptom onset.

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  • 11.
    Ljungberg, Jessica K.
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. School of Psychology, Cardiff University, Cardiff, United Kingdom.
    Hansson, Patrik
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Andrés, Pilar
    Department of Psychology, University of the Balearic Islands, Palma, Spain.
    Josefsson, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University, Stockholm, Sweden.
    A Longitudinal Study of Memory Advantages in Bilinguals2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 9, s. e73029-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Typically, studies of cognitive advantages in bilinguals have been conducted previously by using executive and inhibitory tasks (e.g. Simon task) and applying cross-sectional designs. This study longitudinally investigated bilingual advantages on episodic memory recall, verbal letter and categorical fluency during the trajectory of life. Monolingual and bilingual participants (n=178) between 35–70 years at baseline were drawn from the Betula Prospective Cohort Study of aging, memory, and health. Results showed that bilinguals outperformed monolinguals at the first testing session and across time both in episodic memory recall and in letter fluency. No interaction with age was found indicating that the rate of change across ages was similar for bilinguals and monolinguals. As predicted and in line with studies applying cross-sectional designs, no advantages associated with bilingualism were found in the categorical fluency task. The results are discussed in the light of successful aging.

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  • 12.
    Lopatko Lindman, Karin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Weidung, Bodil
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Uppsala, Sweden.
    Olsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Josefsson, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Kok, Eloise
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Eriksson, Sture
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Lövheim, Hugo
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    A genetic signature including apolipoprotein Eε4 potentiates the risk of herpes simplex-associated Alzheimer's disease2019Ingår i: Alzheimer's & dementia, ISSN 1552-5279, Vol. 5, s. 697-704Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Herpes simplex virus type 1 (HSV1) in combination with genetic susceptibility has previously been implicated in Alzheimer's disease (AD) pathogenesis.

    Methods: Plasma from 360 AD cases, obtained on average 9.6 years before diagnosis, and their age- and sex-matched controls, were analyzed for anti-HSV1 immunoglobulin (Ig) G with enzyme-linked immunosorbent assays (ELISAs). APOE genotype and nine other selected risk genes for AD were extracted from a genome-wide association study analysis by deCODE genetics, Reykjavik, Iceland.

    Results: The interaction between APOEε4 heterozygosity (APOEε24 or ε3/ε4) and anti-HSV1 IgG carriage increased the risk of AD (OR 4.55, P = .02). A genetic risk score based on the nine AD risk genes also interacted with anti-HSV1 IgG for the risk of developing AD (OR 2.35, P = .01).

    Discussion: The present findings suggest that the APOEε4 allele and other AD genetic risk factors might potentiate the risk of HSV1-associated AD.

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  • 13.
    Lövheim, Hugo
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Norman, Tove
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Weidung, Bodil
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Sweden.
    Olsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Josefsson, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Herpes Simplex Virus, APOE ɛ4, and Cognitive Decline in Old Age: Results from the Betula Cohort Study2019Ingår i: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 67, nr 1, s. 211-220Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Herpes simplex virus (HSV) has been suggested to play a role in Alzheimer’s disease (AD) development.

    Objective: The aim of the present study was to investigate the early AD-related symptom episodic memory decline in relation to HSV and carriage of allele 4 of the apolipoprotein E gene (APOE ɛ4) in a large population-based cohort with a long follow-up time.

    Methods: The study included 3,413 persons, with longitudinal data available for 1,293 persons with a mean follow-up time of 11.6 years. The associations between HSV carriage, APOE ɛ4 carriage, and episodic memory was investigated at baseline, as well as in longitudinal analyses where individuals with and without HSV antibodies (HSV1/2 non-specific) were matched and episodic memory decline compared.

    Results: Cross-sectional analyses revealed an age-dependent association of HSV carriage with lower episodic memory function, particularly among APOE ɛ4 carriers (p = 0.008). Longitudinal analyses showed an increased risk of episodic memory decline in HSV carriers (≥65 years: p < 0.001, all ages: non-significant), and a significant interaction between HSV and APOE ɛ4 for episodic memory decline (p < 0.001).

    Conclusion: In this large population-based cohort study, both cross-sectional and longitudinal results support an association between HSV carriage and declining episodic memory function, especially among APOE ɛ4 carriers. The results strengthen the hypothesis that HSV is associated with AD development.

  • 14.
    Malmberg Gavelin, Hanna
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Eskilsson, Therese
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi.
    Boraxbekk, Carl-Johan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR). Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark..
    Josefsson, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Stigsdotter Neely, Anna
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Department of Social and Psychological Studies, Karlstad University, Karlstad, Sweden..
    Slunga Järvholm, Lisbeth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Rehabilitation for improved cognition in patients with stress-related exhaustion disorder: RECO – a randomized clinical trial2018Ingår i: Stress, ISSN 1025-3890, E-ISSN 1607-8888, Vol. 21, nr 4, s. 279-291Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Stress-related exhaustion has been associated with selective and enduring cognitive impairments. However, little is known about how to address cognitive deficits in stress rehabilitation and how this influences stress recovery over time. The aim of this open-label, parallel randomized controlled trial (ClinicalTrials.gov: NCT03073772) was to investigate the long-term effects of 12 weeks cognitive or aerobic training on cognitive function, psychological health and work ability for patients diagnosed with exhaustion disorder (ED). One-hundred-and-thirty-two patients (111 women) participating in multimodal stress rehabilitation were randomized to receive additional cognitive training (n = 44), additional aerobic training (n = 47) or no additional training (n = 41). Treatment effects were assessed before, immediately after and one-year post intervention. The primary outcome was global cognitive function. Secondary outcomes included domain-specific cognition, self-reported burnout, depression, anxiety, fatigue and work ability, aerobic capacity and sick-leave levels. Intention-to-treat analysis revealed a small but lasting improvement in global cognitive functioning for the cognitive training group, paralleled by a large improvement on a trained updating task. The aerobic training group showed improvements in aerobic capacity and episodic memory immediately after training, but no long-term benefits. General improvements in psychological health and work ability were observed, with no difference between interventional groups. Our findings suggest that cognitive training may be a viable method to address cognitive impairments for patients with ED, whereas the effects of aerobic exercise on cognition may be more limited when performed during a restricted time period. The implications for clinical practice in supporting patients with ED to adhere to treatment are discussed.

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  • 15. Olofsson, Jonas K
    et al.
    Josefsson, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Ekström, Ingrid
    Wilson, Donald
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Nordin, Steven
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Nordin Adolfsson, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nilsson, Lars-Göran
    Larsson, Maria
    Long-term episodic memory decline is associated with olfactory deficits only in carriers of ApoE-є42016Ingår i: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 85, s. 1-9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The ɛ4 allele of the Apolipoprotein E gene is a genetic risk factor for late-onset dementia of the Alzheimers' type (DAT), which is characterized by loss of both episodic memory and olfactory functions. Little is known about the possible role of ɛ4 in the association between ongoing episodic memory decline and olfactory deficits in the general population, but such information is relevant in determining the relevance of olfaction as a marker of DAT risk. The present study was based on a large, population-based sample (n=1087, aged 45-90 years, of which 324 were ɛ4-carriers). Episodic memory change rates were established using data collected every 5 years for a 10-20 year interval leading up to an olfactory assessment using the Scandinavian Odor Identification Test at the last wave of data collection. Participants were classified according to whether or not their episodic memory ability declined more rapidly than the age-typical norm (by > 1SD). Our main result is that only in ɛ4-carriers was episodic memory decline associated with odor identification impairment. In individuals without ɛ4, odor identification was unrelated to episodic memory decline status. Follow-up analyses indicated that this moderation by ɛ4 was due to the olfactory nature of the identification test, and that the effect was not caused by 63 individuals with dementia. Our results suggest that the ɛ4 determines the functional association between ongoing episodic memory decline and olfaction. These findings are consistent with the notion that ɛ4-carriers with DAT, compared to non-carriers, display a cortical atrophy pattern that is more focused on mediotemporal lobe regions supporting olfactory and episodic memory functions. Olfactory and memory assessments might provide complementary information on mediotemporal atrophy prior to clinical dementia onset, but the ɛ4 should be considered when using olfactory assessment as an early-stage indicator.

  • 16. Olofsson, Jonas K.
    et al.
    Josefsson, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Stanciu, Ingrid
    Wilson, Donald
    Nordin, Steven
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Nilsson, Lars-Goran
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Larsson, Maria
    ApoE-e4 Mediates the Association Between Episodic Memory Decline and Olfactory Identification Deficit2015Ingår i: Chemical Senses, ISSN 0379-864X, E-ISSN 1464-3553, Vol. 40, nr 7, s. 667-667Artikel i tidskrift (Övrigt vetenskapligt)
  • 17.
    Pudas, Sara
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Josefsson, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Rieckmann, Anna
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Longitudinal evidence for increased functional response in frontal cortex for older adults with hippocampal atrophy and memory decline2018Ingår i: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 28, nr 3, s. 936-948Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The functional organization of the frontal cortex is dynamic. Age-related increases in frontal functional responses have been shown during various cognitive tasks, but the cross-sectional nature of most past studies makes it unclear whether these increases reflect reorganization or stable individual differences. Here, we followed 130 older individuals' cognitive trajectories over 20-25 years with repeated neuropsychological assessments every 5th year, and identified individuals with stable or declining episodic memory. Both groups displayed significant gray matter atrophy over 2 successive magnetic resonance imaging sessions 4 years apart, but the decline group also had a smaller volume of the right hippocampus. Only individuals with declining memory demonstrated increased prefrontal functional responses during memory encoding and retrieval over the 4-year interval. Regions with increased functional recruitment were located outside, or on the borders of core task-related networks, indicating an expansion of these over time. These longitudinal findings offer novel insight into the mechanisms behind age-associated memory loss, and are consistent with a theoretical model in which hippocampus atrophy, past a critical threshold, induces episodic-memory decline and altered prefrontal functional organization.

  • 18.
    Pudas, Sara
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Persson, Jonas
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Josefsson, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    de Luna, Xavier
    Umeå universitet, Samhällsvetenskapliga fakulteten, Statistiska institutionen.
    Nilsson, Lars-Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Brain Characteristics of Individuals Resisting Age-Related Cognitive Decline over Two Decades2013Ingår i: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 33, nr 20, s. 8668-8677Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Some elderly appear to resist age-related decline in cognitive functions, but the neural correlates of successful cognitive aging are not well known. Here, older human participants from a longitudinal study were classified as successful or average relative to the mean attrition-corrected cognitive development across 15-20 years in a population-based sample (n = 1561). Fifty-one successful elderly and 51 age-matched average elderly (mean age: 68.8 years) underwent functional magnetic resonance imaging while performing an episodic memory face-name paired-associates task. Successful older participants had higher BOLD signal during encoding than average participants, notably in the bilateral PFC and the left hippocampus (HC). The HC activation of the average, but not the successful, older group was lower than that of a young reference group (n = 45, mean age: 35.3 years). HC activation was correlated with task performance, thus likely contributing to the superior memory performance of successful older participants. The frontal BOLD response pattern might reflect individual differences present from young age. Additional analyses confirmed that both the initial cognitive level and the slope of cognitive change across the longitudinal measurement period contributed to the observed group differences in BOLD signal. Further, the differences between the older groups could not be accounted for by differences in brain structure. The current results suggest that one mechanism behind successful cognitive aging might be preservation of HC function combined with a high frontal responsivity. These findings highlight sources for heterogeneity in cognitive aging and may hold useful information for cognitive intervention studies.

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