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  • 1.
    Andersson, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University Hospital.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Stiernman, Lars J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Rieckmann, Anna
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Center for the Economics of Aging, Max Planck Institute for Social Law and Social Policy, Germany.
    Cognitive decline in Parkinson’s disease: a subgroup of extreme decliners revealed by a data-driven analysis of longitudinal progression2021In: Frontiers in Psychology, E-ISSN 1664-1078, Vol. 12, article id 729755Article in journal (Refereed)
    Abstract [en]

    Cognitive impairment is an important symptom of Parkinson’s disease (PD) and predicting future cognitive decline is crucial for clinical practice. Here, we aim to identify latent sub-groups of longitudinal trajectories of cognitive change in PD patients, and explore predictors of differences in cognitive change. Longitudinal cognitive performance data from 349 newly diagnosed PD patients and 145 healthy controls from the Parkinson Progression Marker Initiative were modeled using a multivariate latent class linear mixed model. Resultant latent classes were compared on a number of baseline demographics, and clinical variables, as well as cerebrospinal fluid (CSF) biomarkers and striatal dopamine transporter (DAT) density markers of neuropathology. Trajectories of cognitive change in PD were best described by two latent classes. A large subgroup (90%), which showed a subtle impairment in cognitive performance compared to controls but remained stable over the course of the study, and a small subgroup (10%) which rapidly declined in all cognitive performance measures. Rapid decliners did not differ significantly from the larger group in terms of disease duration, severity or motor symptoms at baseline. However, rapid decliners had lower CSF amyloidß42 levels, a higher prevalence of sleep disorder and pronounced loss of caudate DAT density at baseline. These data suggest the existence of a distinct minority sub-type of PD in which rapid cognitive change in PD can occur uncoupled from motor symptoms or disease severity, likely reflecting early pathological change that extends from motor areas of the striatum into associative compartments and cortex.

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  • 2.
    Degerman, Sofie
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Nordin Adolfsson, Annelie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Wennstedt, Sigrid
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Landfors, Mattias
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Haider, Zahra
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Pudas, Sara
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Hultdin, Magnus
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Maintained memory in aging is associated with young epigenetic age2017In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 55, p. 167-171Article in journal (Refereed)
    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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  • 3.
    Domellöf, Magdalena Eriksson
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Walton, Lois
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark; Institute of Sports Medicine Copenhagen (ISMC), Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark.
    Bäckström, David
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Stigsdotter Neely, Anna
    Evaluating a frontostriatal working-memory updating-training paradigm in Parkinson's disease: the iPARK trial, a double-blinded randomized controlled trial2020In: BMC Neurology, E-ISSN 1471-2377, Vol. 20, no 1, article id 337Article in journal (Refereed)
    Abstract [en]

    Background: Cognitive decline and dementia are common in Parkinson's disease (PD). Cognitive deficits have been linked to the depletion of dopamine in the nigrostriatal pathway, but pharmacological treatments for PD have little evidence of improving or delaying cognitive decline. Therefore, exploring non-pharmacological treatment options is important. There have been some promising results of cognitive training interventions in PD, especially for improvements in working memory and executive functions. Yet, existing studies are often underpowered, lacking appropriate control condition, long term follow-up, a thorough description of the intervention and characteristics of the participants. Working memory updating training has previously shown to increase striatal activation in healthy young and old participants as well as dopaminergic neurotransmission in healthy young participants. In the light of dopamine dysfunction in PD, with negative effects on both motor and cognitive functions it is of interest to study if an impaired striatal system can be responsive to a non-invasive, non-pharmacological intervention.

    Methods and design: The iPARK trial is a double-blinded, randomized controlled trial with a parallel-group design that aims to recruit 80 patients with PD (during the period 02/2017–02/2023). Included patients need to have PD, Hoehn and Yahr staging I-III, be between 45 to 75 years of age and not have a diagnosis of dementia. All patients will undergo 30 sessions (6–8 weeks) of web-based cognitive training performed from home. The target intervention is a process-based training program targeting working memory updating. The placebo program is a low dose short-term memory program. A battery of neuropsychological tests and questionnaires will be performed before training, directly after training, and 16 weeks after training.

    Discussion: We expect that the iPARK trial will provide novel and clinically useful information on whether updating training is an effective cognitive training paradigm in PD. Further, it will hopefully contribute to a better understanding of cognitive function in PD and provide answers regarding cognitive plasticity as well as determining critical factors for a responsive striatal system.

    Trial registration: Clinicaltrials.gov registry number: NCT03680170, registry name: "Cognitive Training in Parkinson's Disease: the iPARK study", retrospectively registered on the 21st of September 2018. The inclusion of the first participant was the 1st of February 2017.

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  • 4. Ekström, Ingrid
    et al.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Larsson, Maria
    Rönnlund, Michael
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Nordin, Steven
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Olofsson, Jonas K.
    Subjective olfactory loss in older adults concurs with long-term odor identification decline2019In: Chemical Senses, ISSN 0379-864X, E-ISSN 1464-3553, Vol. 44, no 2, p. 105-112Article in journal (Refereed)
    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.

  • 5.
    Eriksson Sörman, Daniel
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Marsh, John Everett
    Hansson, Patrik
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Ljungberg, Jessica K.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Longitudinal effects of bilingualism on dual-tasking2017In: PLOS ONE, E-ISSN 1932-6203, Vol. 12, no 12, article id e0189299Article in journal (Refereed)
    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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  • 6.
    Farnsworth von Cederwald, Bryn
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Karalija, Nina
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Association of cardiovascular risk trajectory with cognitive decline and incident dementia2022In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 98, no 20, p. e2013-e2022Article in journal (Refereed)
    Abstract [en]

    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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  • 7.
    Fors Connolly, Filip
    et al.
    Umeå University, Faculty of Social Sciences, Department of Sociology.
    Olofsson, Jenny
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Do reductions of daily activities mediate the relationship between COVID-19 restrictions and mental ill-health among older persons in Europe?2024In: Aging & Mental Health, ISSN 1360-7863, E-ISSN 1364-6915Article in journal (Refereed)
    Abstract [en]

    Objective: Previous research has shown that daily activities are crucial for mental health among older people, and that such activities declined during the COVID-19 pandemic. While previous studies have confirmed a link between stringent restrictions and an increase in mental ill-health, the role of daily activities as a mediator in this relationship remains underexplored. We analyzed whether reductions in daily activities mediated the impact of these COVID-19 restrictions on mental ill-health during the pandemic’s initial phase.

    Methods: We used data from Wave 8 SHARE Corona Survey covering 41,409 respondents from 25 European countries and Israel as well as data on COVID-19 restrictions from the Oxford Government Response  Tracker  (OxCGRT).  Multilevel  regression  and  multilevel-mediation  analysis  were  used  to  examine the relationships between restrictions, daily activities and mental ill-health.

    Results: Reductions in walking and shopping showed a notably stronger association with increases in mental ill-health compared to social activities. Furthermore, declines in walking could account for about  a  quarter  of  the  relationship  between  restrictions  and  increased  mental  ill-health,  but  the  mediating effects of the other activates were negligible.

    Conclusions: The study highlights the essential role of maintaining daily activities, particularly walking, to  mitigate  the  negative  psychological  effects  of  pandemic-related  restrictions  among  older  populations in Europe.

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  • 8.
    Gorbach, Tetiana
    et al.
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Pudas, Sara
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lundquist, Anders
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Orädd, Greger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Salami, Alireza
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
    de Luna, Xavier
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Longitudinal association between hippocampus atrophy and episodic-memory decline2017In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 51, p. 167-176Article in journal (Refereed)
    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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  • 9.
    Hemmingsson, Eva-Stina
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Hjelmare, Ellen
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Weidung, Bodil
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Uppsala, Sweden.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Lövheim, Hugo
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Antiviral treatment associated with reduced risk of clinical Alzheimer's disease: A nested case-control study2021In: Alzheimer’s & Dementia: Translational Research & Clinical Interventions, E-ISSN 2352-8737, Vol. 7, no 1, article id e12187Article in journal (Refereed)
    Abstract [en]

    Introduction: In this nested case-control study, we investigated if antiviral treatment given prior to onset of Alzheimer's disease (AD) could influence incident AD.

    Methods: From a large population-based cohort study in northern Sweden, 262 individuals that later developed AD were compared to a non-AD matched control group with respect to prescriptions of herpes antiviral treatment. All included subjects were herpes simplex virus 1 (HSV1) carriers and the matching criteria were age, sex, apolipoprotein E genotype (ε4 allele carriership), and study sample start year.

    Results: Among those who developed AD, 6 prescriptions of antivirals were found, compared to 20 among matched controls. Adjusted for length of follow-up, a conditional logistic regression indicated a difference in the risk for AD development between groups (odds ratio for AD with an antiviral prescription 0.287, P = .018).

    Discussion: Antiviral treatment might possibly reduce the risk for later development of HSV1-associated AD.

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  • 10.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Attrition in Studies of Cognitive Aging2013Doctoral thesis, comprehensive summary (Other academic)
    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
  • 11.
    Josefsson, Maria
    et al.
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE).
    Daniels, Michael J.
    Bayesian semi-parametric G-computation for causal inference in a cohort study with MNAR dropout and death2021In: The Journal of the Royal Statistical Society, Series C: Applied Statistics, ISSN 0035-9254, E-ISSN 1467-9876, Vol. 70, no 2, p. 398-414Article in journal (Refereed)
    Abstract [en]

    Causal inference with observational longitudinal data and time-varying exposures is often complicated by time-dependent confounding and attrition. The G-computation formula is one approach for estimating a causal effect in this setting. The parametric modelling approach typically used in practice relies on strong modelling assumptions for valid inference, and moreover depends on an assumption of missing at random, which is not appropriate when the missingness is missing not at random (MNAR) or due to death. In this work we develop a flexible Bayesian semi-parametric G-computation approach for assessing the causal effect on the subpopulation that would survive irrespective of exposure, in a setting with MNAR dropout. The approach is to specify models for the observed data using Bayesian additive regression trees, and then use assumptions with embedded sensitivity parameters to identify and estimate the causal effect. The proposed approach is motivated by a longitudinal cohort study on cognition, health, and aging and we apply our approach to study the effect of becoming a widow on memory. We also compare our approach to several standard methods.

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  • 12.
    Josefsson, Maria
    et al.
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Daniels, Michael J.
    Department of Statistics, University of Florida, USA.
    Pudas, Sara
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    A Bayesian semiparametric approach for inference on the population partly conditional mean from longitudinal data with dropout2023In: Biostatistics, ISSN 1465-4644, E-ISSN 1468-4357, Vol. 24, no 2, p. 372-387Article in journal (Refereed)
    Abstract [en]

    Studies of memory trajectories using longitudinal data often result in highly non-representative samples due to selective study enrollment and attrition. An additional bias comes from practice effects that result in improved or maintained performance due to familiarity with test content or context. These challenges may bias study findings and severely distort the ability to generalize to the target population. In this study we propose an approach for estimating the finite population mean of a longitudinal outcome conditioning on being alive at a specific time point. We develop a flexible Bayesian semi-parametric predictive estimator for population inference when longitudinal auxiliary information is known for the target population. We evaluate sensitivity of the results to untestable assumptions and further compare our approach to other methods used for population inference in a simulation study. The proposed approach is motivated by 15-year longitudinal data from the Betula longitudinal cohort study. We apply our approach to estimate lifespan trajectories in episodic memory, with the aim to generalize findings to a target population.

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  • 13.
    Josefsson, Maria
    et al.
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    de Luna, Xavier
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Daniels, Michael
    University of Texas at Austin.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Causal inference with longitudinal outcomes and non-ignorable drop-out: Estimating the effect of living alone on cognitive decline2016In: The Journal of the Royal Statistical Society, Series C: Applied Statistics, ISSN 0035-9254, E-ISSN 1467-9876, Vol. 65, no 1, p. 131-144Article in journal (Refereed)
    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.

  • 14.
    Josefsson, Maria
    et al.
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    de Luna, Xavier
    Umeå University, Faculty of Social Sciences, Department of Statistics.
    Pudas, Sara
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nilsson, Lars-Göran
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Centre for Population Studies (CPS). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Genetic and lifestyle predictors of 15-Year longitudinal change in episodic memory2012In: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 60, no 12, p. 2308-2312Article in journal (Refereed)
    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.

  • 15.
    Josefsson, Maria
    et al.
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Larsson, Maria
    Nordin, Steven
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Olofsson, Jonas
    APOE-ɛ4 effects on longitudinal decline in olfactory and non-olfactory cognitive abilities in middle-aged and old adults2017In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, article id 1286Article in journal (Refereed)
    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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  • 16.
    Josefsson, Maria
    et al.
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Lundquist, Anders
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Imputation of missing longitudinal fMRI dataManuscript (preprint) (Other academic)
  • 17.
    Josefsson, Maria
    et al.
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Demographic Data Base.
    Sundström, Anna
    Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Pudas, Sara
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nordin Adolfsson, Annelie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Memory profiles predict dementia over 23–28 years in normal but not successful aging2023In: International psychogeriatrics, ISSN 1041-6102, E-ISSN 1741-203X, Vol. 35, no 7, p. 351-359Article in journal (Refereed)
    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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  • 18.
    Körning-Ljungberg, Jessica
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology. School of Psychology, Cardiff University, Cardiff, United Kingdom.
    Hansson, Patrik
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Andrés, Pilar
    Department of Psychology, University of the Balearic Islands, Palma, Spain.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University, Stockholm, Sweden.
    A Longitudinal Study of Memory Advantages in Bilinguals2013In: PLOS ONE, E-ISSN 1932-6203, Vol. 8, no 9, article id e73029Article in journal (Refereed)
    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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  • 19.
    Lopatko Lindman, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Hemmingsson, Eva-Stina
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Weidung, Bodil
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Uppsala, Sweden.
    Brännström, Jon
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Lövheim, Hugo
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Herpesvirus infections, antiviral treatment, and the risk ofdementia: a registry-based cohort study in Sweden2021In: Alzheimer’s & Dementia: Translational Research & Clinical Interventions, E-ISSN 2352-8737, Vol. 7, no 1, article id e12119Article in journal (Refereed)
    Abstract [en]

    Introduction: Herpesviruses, including Herpes simplex virus type 1 (HSV1) and varicella zoster‐virus (VZV), have been implicated in Alzheimer's disease (AD) development. Likewise, antiviral treatment has been suggested to protect against dementia development in herpes‐infected individuals.

    Methods: The study enrolled 265,172 subjects aged ≥ 50 years, with diagnoses of VZV or HSV, or prescribed antiviral drugs between 31 December 2005 and 31 December 2017. Controls were matched in a 1:1 ratio by sex and birth year.

    Results: Antiviral treatment was associated with decreased risk of dementia (adjusted hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.86 to 0.92), while herpes infection without antiviral drugs increased the risk of dementia (adjusted HR 1.50, 95% CI 1.29 to 1.74).

    Discussion: Antiviral treatment was associated with a reduced long‐term risk of dementia among individuals with overt signs of herpes infection. This is consistent with earlier findings indicating that herpesviruses are involved in the pathogenesis of AD.

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  • 20.
    Lopatko Lindman, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Weidung, Bodil
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Uppsala, Sweden.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Eriksson, Sture
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Lövheim, Hugo
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Plasma Amyloid-β in Relation to Antibodies Against Herpes Simplex Virus, Cytomegalovirus, and Chlamydophila pneumoniae2021In: Journal of Alzheimer's Disease Reports, E-ISSN 2542-4823, Vol. 5, no 1, p. 229-235Article in journal (Refereed)
    Abstract [en]

    Background: Amyloid-β (Aβ), the key constituent of Alzheimer’s disease (AD) plaques, has antimicrobial properties.

    Objective: To investigate the association between plasma Aβ and antibodies against the AD-related pathogens herpes simplex virus (HSV), cytomegalovirus (CMV), and C. pneumoniae.

    Methods: Plasma from 339 AD cases, obtained on average 9.4 years (±4.00) before diagnosis, and their matched controls were analyzed for Aβ40 and Aβ42 concentrations with Luminex xMAP technology and INNOBIA plasma Aβ-form assays. Enzyme-linked immunosorbent assays were utilized for analyses of anti-HSV immunoglobulin (Ig) G, anti-HSV1 IgG, anti-HSV2 IgG, anti-CMV IgG, and anti-C. pneumoniae IgG. Follow-up samples were available for 150 of the cases.

    Results: Presence and levels of anti-HSV1 IgG, anti-HSV2 IgG, anti-CMV IgG, and anti-C. pneumoniae IgG did not correlate with concentrations of Aβ42 or Aβ40 in cases or controls.

    Conclusion: Levels of plasma Aβ were not associated with antibodies against different AD-related pathogens.

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  • 21.
    Lopatko Lindman, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Weidung, Bodil
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Uppsala, Sweden.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Kok, Eloise
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Eriksson, Sture
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Lövheim, Hugo
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    A genetic signature including apolipoprotein Eε4 potentiates the risk of herpes simplex-associated Alzheimer's disease2019In: Alzheimer’s & Dementia: Translational Research & Clinical Interventions, E-ISSN 2352-8737, Vol. 5, p. 697-704Article in journal (Refereed)
    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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  • 22.
    Lövheim, Hugo
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Norman, Tove
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Weidung, Bodil
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Sweden.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Herpes Simplex Virus, APOE ɛ4, and Cognitive Decline in Old Age: Results from the Betula Cohort Study2019In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 67, no 1, p. 211-220Article in journal (Refereed)
    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.

  • 23.
    M. Gavelin, Hanna
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Stigsdotter Neely, Anna
    Department of Social Sciences, Technology and Arts, Luleå University of Technology, Sweden; Department of Health, Education and Technology, Luleå University of Technology, Sweden; Department of Social and Psychological studies, Karlstad University, Sweden.
    Aronsson, Ingela
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Andersson, Linus
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Mental fatigue, cognitive performance and autonomic response following sustained mental activity in clinical burnout2023In: Biological Psychology, ISSN 0301-0511, E-ISSN 1873-6246, Vol. 183, article id 108661Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the effects of sustained mental activity on perceptions of mental fatigue, cognitive performance, and autonomic response in patients with clinical burnout as compared to a healthy control group.

    Methods: Patients with clinical burnout (n = 30) and healthy control participants (n = 30) completed a 3-hour test session, in which they were administered a set of cognitive tests before and after an effortful cognitive task with concurrent sound exposure. Perceptions of mental fatigue and task demands (mental effort and concentration difficulties) were assessed repeatedly over the course of the test session. Heart rate variability was recorded to index autonomic response.

    Results: In comparison with controls, perceived mental fatigue increased earlier in the session for the clinical burnout group and did not recover following a short rest period. Throughout the session, patients rated the tasks as more demanding and showed less improvement on measures of attention and processing speed, inhibition and working memory. While autonomic responses were initially comparable, there was a unique decrease in high-frequency heart rate variability in the clinical burnout group after extended testing and exposure.

    Conclusion: Patients with clinical burnout are affected differently than healthy controls by sustained mental activity, as reflected by ratings of perceived mental fatigue, aspects of cognitive performance and autonomic response. Further investigation into the role of autonomic regulation in relation to cognitive symptoms in clinical burnout is warranted.

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  • 24.
    Malmberg Gavelin, Hanna
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Eskilsson, Therese
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark..
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Stigsdotter Neely, Anna
    Umeå University, Faculty of Social Sciences, Department of Psychology. Department of Social and Psychological Studies, Karlstad University, Karlstad, Sweden..
    Slunga Järvholm, Lisbeth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Rehabilitation for improved cognition in patients with stress-related exhaustion disorder: RECO – a randomized clinical trial2018In: Stress, ISSN 1025-3890, E-ISSN 1607-8888, Vol. 21, no 4, p. 279-291Article in journal (Refereed)
    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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  • 25. Nelson, Andreas
    et al.
    Malmberg Gavelin, Hanna
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Eskilsson, Therese
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Section of Physiotherapy. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Slunga-Järvholm, Lisbeth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Stigsdotter Neely, Anna
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Subjective cognitive complaints and its associations to response inhibition and neural activation in patients with stress-related exhaustion disorder2023In: Stress, ISSN 1025-3890, E-ISSN 1607-8888, Vol. 26, no 1, article id 2188092Article in journal (Refereed)
    Abstract [en]

    Stress-related exhaustion is associated with cognitive deficits, measured subjectively using questionnaires targeting everyday slips and failures or more objectively as performance on cognitive tests. Yet, only weak associations between subjective and objective cognitive measures in this group has been presented, theorized to reflect recruitment of compensational resources during cognitive testing. This explorative study investigated how subjectively reported symptoms of cognitive functioning and burnout levels relate to performance as well as neural activation during a response inhibition task. To this end, 56 patients diagnosed with stress-related exhaustion disorder (ED; ICD-10 code F43.8A) completed functional magnetic resonance imaging (fMRI) using a Flanker paradigm. In order to investigate associations between neural activity and subjective cognitive complaints (SCCs) and burnout, respectively, scores on the Prospective and retrospective memory questionnaire (PRMQ) and the Shirom-Melamed burnout questionnaire (SMBQ) were added as covariates of interest to a general linear model at the whole-brain level. In agreement with previous research, the results showed that SCCs and burnout levels were largely unrelated to task performance. Moreover, we did not see any correlations between these self-report measures and altered neural activity in frontal brain regions. Instead, we observed an association between the PRMQ and increased neural activity in an occipitally situated cluster. We propose that this finding may reflect compensational processes at the level of basic visual attention which may go unnoticed in cognitive testing but are reflected in the experience of deficits in everyday cognitive functioning.

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  • 26. Nelson, Andreas
    et al.
    Malmberg Gavelin, Hanna
    Umeå University, Faculty of Social Sciences, Department of Psychology. Academic Unit for Psychiatry of Old Age, University of Melbourne, Australia.
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Institute of Sports Medicine Copenhagen (ISMC), Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark; Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Amager and Hvidovre, Denmark.
    Eskilsson, Therese
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Section of Physiotherapy. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Slunga Järvholm, Lisbeth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Neely, Anna Stigsdotter
    Subjective cognitive complaints in patients with stress-related exhaustion disorder: a cross sectional study2021In: BMC Psychology, E-ISSN 2050-7283, Vol. 9, no 1, article id 84Article in journal (Refereed)
    Abstract [en]

    Background: Stress-related exhaustion is associated with cognitive impairment as measured by both subjective cognitive complaints (SCCs) and objective cognitive test performance. This study aimed to examine how patients diagnosed with exhaustion disorder differ from healthy control participants in regard to levels and type of SCCs, and if SCCs are associated with cognitive test performance and psychological distress.

    Methods: We compared a group of patients with stress-related exhaustion disorder (n = 103, female = 88) with matched healthy controls (n = 58, female = 47) cross-sectionally, concerning the type and magnitude of self-reported SCCs. We furthermore explored the association between SCCs and cognitive test performance as well as with self-reported depression, anxiety and burnout levels, in the patient and the control group, respectively.

    Results: Patients reported considerably more cognitive failures and were more likely than controls to express memory failures in situations providing few external cues and reminders in the environment. In both groups, SCCs were associated with demographic and psychological factors, and not with cognitive test performance.

    Conclusion: Our findings underline the high burden of cognitive problems experienced by patients with exhaustion disorder, particularly in executively demanding tasks without external cognitive support. From a clinical perspective, SCCs and objective cognitive test performance may measure different aspects of cognitive functioning, and external cognitive aids could be of value in stress rehabilitation.

    Trial registration: Participants were recruited as part of the Rehabilitation for Improved Cognition (RECO) study (ClinicalTrials.gov: NCT03073772). Date of registration: 8 March 2017

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  • 27.
    Olofsson, Jenny
    et al.
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Fors Connolly, Filip
    Umeå University, Faculty of Social Sciences, Department of Sociology.
    Malmberg, Gunnar
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Social Sciences, Department of Geography.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Stattin, Mikael
    Umeå University, Faculty of Social Sciences, Department of Sociology.
    Sociodemographic factors and adjustment of daily activities during the COVID-19 pandemic – findings from the SHARE Corona Survey2023In: Journal of Aging & Social Policy, ISSN 0895-9420, E-ISSN 1545-0821Article in journal (Refereed)
    Abstract [en]

    In the wake of the COVID-19 pandemic in 2020, older people across Europe have adjusted their daily activities as personal risk avoidance and as an amendment to policy recommendations and restrictions. In this study, we use multilevel logistic regressions to examine to what extent sociodemographic factors are associated with activity reduction among the older population (50+) in Europe and whether these associations are moderated by governmental policy responses to COVID-19. By combining data for~35,000 respondents from the SHARE Corona Survey on reported changes in daily activities and stringency of restrictions at the national level, we find that older age, poorer health and being female versus male were (consistently) associated with greater activity reduction across all activities both in countries with weak and in those with strong restrictions. Associations between education, employment and living situation, on the one hand, and activity reduction, on the other, were weaker and less consistent. We conclude that differences between sociodemographic groups are rather similar for countries with weak and those with strong restrictions and hence argue that group-specific policy recommendation are relevant independent of stringency recommendations.

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  • 28. Olofsson, Jonas K
    et al.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Ekström, Ingrid
    Wilson, Donald
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nordin, Steven
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Nordin Adolfsson, Annelie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nilsson, Lars-Göran
    Larsson, Maria
    Long-term episodic memory decline is associated with olfactory deficits only in carriers of ApoE-є42016In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 85, p. 1-9Article in journal (Refereed)
    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.

  • 29. Olofsson, Jonas K.
    et al.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Stanciu, Ingrid
    Wilson, Donald
    Nordin, Steven
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Nilsson, Lars-Goran
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Larsson, Maria
    ApoE-e4 Mediates the Association Between Episodic Memory Decline and Olfactory Identification Deficit2015In: Chemical Senses, ISSN 0379-864X, E-ISSN 1464-3553, Vol. 40, no 7, p. 667-667Article in journal (Other academic)
  • 30.
    Panes Lundmark, Vania
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Rieckmann, Anna
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Institut für Psychologie, Universität der Bundeswehr München, Neubiberg, Germany.
    Predictors of loneliness onset and maintenance in European older adults during the COVID-19 pandemic2023In: Frontiers in Psychology, E-ISSN 1664-1078, Vol. 14, article id 1172552Article in journal (Refereed)
    Abstract [en]

    Objectives: Loneliness is a major public health concern. Duration of loneliness is associated with severity of health outcomes, and further research is needed to direct interventions and social policy. This study aimed to identify predictors of the onset vs. the maintenance of loneliness in older adults before and during the pandemic using longitudinal data from the Survey of Health, Age, and Retirement in Europe (SHARE).

    Methods: Groupings of persistent, situational, and no loneliness were based on self-reports from an ordinary pre-pandemic SHARE wave and a peri-pandemic telephone interview. Predictors were identified and compared in three hierarchical binary regression analyses, with independent variables added in blocks of geographic region, demographics, pre-pandemic social network, pre-pandemic health, pandemic-related individual, and country level variables.

    Results: Self-reported loneliness levels for the persistent, situational, and no loneliness groups were stable and distinct through 7 years preceding the pre-pandemic baseline measure. Shared predictors were chronic diseases, female sex, depression, and no cohabitant partner. Persistent loneliness was uniquely predicted by low network satisfaction (OR: 2.04), functional limitations (OR: 1.40), and a longer country-level isolation period for older adults (OR: 1.24).

    Conclusion: Interventions may target persons with depression, functional limitations, chronic health issues, and no cohabitant partner. The added burden of the length of isolation on those who are already lonely should be taken into account when employing social policies that target older adults. Further research should distinguish between situational and persistent loneliness, and seek to identify predictors of chronic loneliness onset.

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  • 31.
    Pudas, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Nordin Adolfsson, Annelie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Landfors, Mattias
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Kauppi, Karolina
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Veng-Taasti, Line Marie
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Hultdin, Magnus
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Degerman, Sofie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Short leukocyte telomeres, but not telomere attrition rates, predict memory decline in the 20-year longitudinal Betula study2021In: The journals of gerontology. Series A, Biological sciences and medical sciences, ISSN 1079-5006, E-ISSN 1758-535X, Vol. 76, no 6, p. 955-963Article in journal (Refereed)
    Abstract [en]

    Leukocyte telomere length (LTL) is a proposed biomarker for aging-related disorders, including cognitive decline and dementia. Long-term longitudinal studies measuring intra-individual changes in both LTL and cognitive outcomes are scarce, precluding strong conclusions about a potential aging-related relationship between LTL shortening and cognitive decline. This study investigated associations between baseline levels and longitudinal changes in LTL and memory performance across an up to 20-year follow-up in 880 dementia-free participants from a population-based study (mean baseline age: 56.8 years, range: 40–80; 52% female). Shorter baseline LTL significantly predicted subsequent memory decline (r = .34, 95% confidence interval: 0.06, 0.82), controlling for age, sex, and other relevant covariates. No significant associations were however observed between intra-individual changes in LTL and memory, neither concurrently nor with a 5-year time-lag between LTL shortening and memory decline. These results support the notion of short LTL as a predictive factor for aging-related memory decline, but suggest that LTL dynamics in adulthood and older age may be less informative of cognitive outcomes in aging. Furthermore, the results highlight the importance of long-term longitudinal evaluation of outcomes in biomarker research.

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  • 32.
    Pudas, Sara
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Rieckmann, Anna
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Longitudinal evidence for increased functional response in frontal cortex for older adults with hippocampal atrophy and memory decline2018In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 28, no 3, p. 936-948Article in journal (Refereed)
    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.

  • 33.
    Pudas, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Persson, Jonas
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    de Luna, Xavier
    Umeå University, Faculty of Social Sciences, Department of Statistics.
    Nilsson, Lars-Göran
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Brain Characteristics of Individuals Resisting Age-Related Cognitive Decline over Two Decades2013In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 33, no 20, p. 8668-8677Article in journal (Refereed)
    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.

  • 34.
    Schäfer Hackenhaar, Fernanda
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Nordin Adolfsson, Annelie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Landfors, Mattias
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Kauppi, Karolina
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Hultdin, Magnus
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Degerman, Sofie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Pudas, Sara
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Short leukocyte telomeres predict 25-year Alzheimer's disease incidence in non-APOE ε4-carriers2021In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 13, article id 130Article in journal (Refereed)
    Abstract [en]

    Background: Leukocyte telomere length (LTL) has been shown to predict Alzheimer’s disease (AD), albeit inconsistently. Failing to account for the competing risks between AD, other dementia types, and mortality, can be an explanation for the inconsistent findings in previous time-to-event analyses. Furthermore, previous studies indicate that the association between LTL and AD is non-linear and may differ depending on apolipoprotein E (APOE) ε4 allele carriage, the strongest genetic AD predictor.

    Methods: We analyzed whether baseline LTL in interaction with APOE ε4 predicts AD, by following 1306 initially non-demented subjects for 25 years. Gender- and age-residualized LTL (rLTL) was categorized into tertiles of short, medium, and long rLTLs. Two complementary time-to-event models that account for competing risks were used; the Fine-Gray model to estimate the association between the rLTL tertiles and the cumulative incidence of AD, and the cause-specific hazard model to assess whether the cause-specific risk of AD differed between the rLTL groups. Vascular dementia and death were considered competing risk events. Models were adjusted for baseline lifestyle-related risk factors, gender, age, and non-proportional hazards.

    Results: After follow-up, 149 were diagnosed with AD, 96 were diagnosed with vascular dementia, 465 died without dementia, and 596 remained healthy. Baseline rLTL and other covariates were assessed on average 8 years before AD onset (range 1–24). APOE ε4-carriers had significantly increased incidence of AD, as well as increased cause-specific AD risk. A significant rLTL-APOE interaction indicated that short rLTL at baseline was significantly associated with an increased incidence of AD among non-APOE ε4-carriers (subdistribution hazard ratio = 3.24, CI 1.404–7.462, P = 0.005), as well as borderline associated with increased cause-specific risk of AD (cause-specific hazard ratio = 1.67, CI 0.947–2.964, P = 0.07). Among APOE ε4-carriers, short or long rLTLs were not significantly associated with AD incidence, nor with the cause-specific risk of AD.

    Conclusions: Our findings from two complementary competing risk time-to-event models indicate that short rLTL may be a valuable predictor of the AD incidence in non-APOE ε4-carriers, on average 8 years before AD onset. More generally, the findings highlight the importance of accounting for competing risks, as well as the APOE status of participants in AD biomarker research.

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  • 35.
    Schäfer Hackenhaar, Fernanda
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Nordin Adolfsson, Annelie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Landfors, Mattias
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Kauppi, Karolina
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Porter, Tenielle
    Centre for Precision Health, Edith Cowan University, Joondalup, WA, Australia; Collaborative Genomics and Translation Group, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia; Curtin Medical School, Curtin University, Bentley, WA, Australia.
    Milicic, Lidija
    Centre for Precision Health, Edith Cowan University, Joondalup, WA, Australia; Collaborative Genomics and Translation Group, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
    Laws, Simon M.
    Centre for Precision Health, Edith Cowan University, Joondalup, WA, Australia; Collaborative Genomics and Translation Group, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia; Curtin Medical School, Curtin University, Bentley, WA, Australia.
    Hultdin, Magnus
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Degerman, Sofie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Pudas, Sara
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    the Australian Imaging Biomarkers and Lifestyle Study,
    Sixteen-year longitudinal evaluation of blood-based DNA methylation biomarkers for early prediction of Alzheimer’s disease2023In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 94, no 4, p. 1443-1464Article in journal (Refereed)
    Abstract [en]

    Background: DNA methylation (DNAm), an epigenetic mark reflecting both inherited and environmental influences, hasshown promise for Alzheimer’s disease (AD) prediction.Objective: Testing long-term predictive ability (>15 years) of existing DNAm-based epigenetic age acceleration (EAA)measures and identifying novel early blood-based DNAm AD-prediction biomarkers.

    Methods: EAA measures calculated from Illumina EPIC data from blood were tested with linear mixed-effects models(LMMs) in a longitudinal case-control sample (50 late-onset AD cases; 51 matched controls) with prospective data up to 16years before clinical onset, and post-onset follow-up. NovelDNAmbiomarkers were generated with epigenome-wide LMMs,and Sparse Partial Least Squares Discriminant Analysis applied at pre- (10–16 years), and post-AD-onset time-points.

    Results: EAA did not differentiate cases from controls during the follow-up time (p > 0.05). Three new DNA biomarkersshowed in-sample predictive ability on average 8 years pre-onset, after adjustment for age, sex, and white blood cell proportions(p-values: 0.022-<0.00001). Our longitudinally-derived panel replicated nominally (p = 0.012) in an external cohort (n = 146cases, 324 controls). However, its effect size and discriminatory accuracy were limited compared to APOE 4-carriership(OR = 1.38 per 1 SD DNAmscore increase versus OR= 13.58 for 4-allele carriage; AUCs = 77.2% versus 87.0%). Literaturereview showed low overlap (n = 4) across 3275 AD-associated CpGs from 8 published studies, and no overlap with ouridentified CpGs.

    Conclusion: The limited predictive value of EAA for AD extends prior findings by considering a longer follow-up time, andwith appropriate control for age, sex, APOE, and blood-cell proportions. Results also highlight challenges with replicatingdiscriminatory or predictive CpGs across studies.

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  • 36.
    Sundström, Anna
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Rönnlund, Michael
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    A Nationwide Swedish Study of Age at Retirement and Dementia Risk2020In: International Journal of Geriatric Psychiatry, ISSN 0885-6230, E-ISSN 1099-1166, Vol. 35, no 10, p. 1234-1249Article in journal (Refereed)
    Abstract [en]

    Objectives: The aim of this nationwide study was to examine the association between age at retirement and dementia risk, with a follow-up period of up to 24 years.

    Methods/design: This cohort study comprised Swedish citizens born in 1930 who were alive in the year 1990 (n=63,505). The cohort was followed for incidents of dementia through data provided by the Swedish National Patient Register and the Cause of Death Register. Age at retirement and socioeconomic variables were retrieved from Statistics Sweden.

    Results: During the follow-up, 5,181 individuals received a dementia diagnosis. Competing risk regression models, adjusted for sex, education, marital status, occupation, and previous history of cardiovascular diseases, showed that later-than-average retirement age was associated with decreased dementia risk.

    Conclusions: The present results supports the idea that individuals who retired at an older age has a decrease risk of dementia. However, as this was an observation study, unmeasured factors, such as premorbid cognitive level and genetic predisposition, may have influenced our findings and remains to be elucidated in future studies.

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  • 37.
    Vega-Mendoza, Mariana
    et al.
    Luleå University of Technology, Luleå, Sweden.
    Eriksson Sörman, Daniel
    Luleå University of Technology, Luleå, Sweden.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Ljungberg, Jessica K.
    Luleå University of Technology, Luleå, Sweden.
    A longitudinal study of episodic memory recall in multilinguals2024In: International Journal of Bilingualism, ISSN 1367-0069, E-ISSN 1756-6878, Vol. 28, no 1, p. 125-145Article in journal (Refereed)
    Abstract [en]

    Aim: This study investigates the effects of degree of multilingualism on cognitive functions in adulthood, with focus on episodic memory recall and including measures of verbal fluency as well as global cognition.

    Design: We studied a large population-based cohort cross-sectionally, and we also assessed changes over time through longitudinal measurements on four time-points over a 15 year period. Participants were drawn from the Betula prospective cohort study in Umeå, Sweden. The participants included in this study at baseline (n = 894, mean age = 51.44, 59.4% females) were divided according to number of languages into bilinguals (n = 395), trilinguals (n = 284), quadrilinguals (n = 169), and pentalinguals (n = 46). 

    Data and analysis: We analysed performance on tasks of episodic memory recall, verbal fluency (letter and category) and global cognition (Minimental State Examination, MMSE) both cross-sectionally and longitudinally. The control background variables were baseline age, gender, years of education, general fluid ability Gf (Wechsler Block Design Test), and socioeconomic status. We employed a linear mixed modelling approach with entropy balancing weights to assess effects of degree of multilingualism on cognitive functions.

    Findings and conclusions: Using bilinguals as the reference group, our results indicated that all the other multilingual groups exhibited superior performance on episodic memory recall than bilinguals at baseline. The rate of change over time did not differ for trilinguals and pentalinguals compared to bilinguals. While quadrilinguals declined more over time than bilinguals, they still scored significantly higher than bilinguals at the last test wave. For letter fluency, similarly, all language groups scored higher than bilinguals at baseline, and none of the groups differed from bilinguals in rate of change over time. With regard to category fluency, quadrilinguals scored higher than bilinguals at baseline, but trilinguals and pentalinguals did not differ from bilinguals and none of the groups differed in change over time compared to bilinguals. Finally, for global cognition (MMSE), trilinguals and quadrilinguals scored significantly higher than bilinguals at baseline with no differences in change over time for any of the groups relative to bilinguals. Our study contributes to the understanding of multilingual cognition and sheds light into an under-researched cognitive domain known to decline in normal ageing, namely episodic memory recall.

    Significance: Our study emphasizes the importance of researching less explored aspects of multilingualism on cognition, in particular on episodic memory recall, to aid our understanding of factors that could potentially aid cognitive decline in later adulthood.

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  • 38.
    Wallmark, Joakim
    et al.
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Wiberg, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Efficiency analysis of item response theory kernel equating for mixed-format tests2023In: Applied psychological measurement, ISSN 0146-6216, E-ISSN 1552-3497, Vol. 47, no 7-8, p. 496-512Article in journal (Refereed)
    Abstract [en]

    This study aims to evaluate the performance of Item Response Theory (IRT) kernel equating in the context of mixed-format tests by comparing it to IRT observed score equating and kernel equating with log-linear presmoothing. Comparisons were made through both simulations and real data applications, under both equivalent groups (EG) and non-equivalent groups with anchor test (NEAT) sampling designs. To prevent bias towards IRT methods, data were simulated with and without the use of IRT models. The results suggest that the difference between IRT kernel equating and IRT observed score equating is minimal, both in terms of the equated scores and their standard errors. The application of IRT models for presmoothing yielded smaller standard error of equating than the log-linear presmoothing approach. When test data were generated using IRT models, IRT-based methods proved less biased than log-linear kernel equating. However, when data were simulated without IRT models, log-linear kernel equating showed less bias. Overall, IRT kernel equating shows great promise when equating mixed-format tests.

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  • 39.
    Wallmark, Joakim
    et al.
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Wiberg, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Kernel equating presmoothing methods: an empirical study with mixed-format test forms2023In: Quantitative psychology: The 87th annual meeting of the psychometric society, Bologna, Italy, 2022 / [ed] Marie Wiberg; Dylan Molenaar; Jorge González; Jee-Seon Kim; Heungsun Hwang, Springer, 2023, p. 49-59Conference paper (Refereed)
    Abstract [en]

    When equating test forms, it is common to presmooth the test score distributions before conducting the equating. In this study, the log-linear and item response theory (IRT) presmoothing methods were compared when equating mixed-format test forms using kernel equating. Test forms from two different high-stakes tests were equated: The Swedish national test in mathematics, using the equivalent group sampling design, and the verbal part of the Swedish SAT test, using the nonequivalent groups with anchor test sampling design. In both cases, the analytical equating standard errors were lower for high and low performing test takers when using IRT presmoothing compared to log-linear presmoothing. Both presmoothing methods resulted in reasonable equated curves. As no true equating transformation is known in a practical setting, using IRT models for presmoothing appears to be a viable alternative to log-linear models when equating mixed-format tests such as the Swedish SAT.

  • 40.
    Weidung, Bodil
    et al.
    Department of Public Health and Caring Sciences, Section of Clinical Geriatrics, Uppsala University, Uppsala, Sweden.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Lyttkens, Peter
    Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Lind, Lars
    Department of Medical Sciences, Acute and Internal Medicine, Uppsala University, Uppsala, Sweden.
    Kilander, Lena
    Department of Public Health and Caring Sciences, Section of Clinical Geriatrics, Uppsala University, Uppsala, Sweden.
    Lövheim, Hugo
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Longitudinal Effects of Herpesviruses on Multiple Cognitive Outcomes in Healthy Elderly Adults2023In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 94, no 2, p. 751-762Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Herpesviruses have been proposed to be involved in Alzheimer's disease development as potentially modifiable pathology triggers.

    OBJECTIVE: To investigate associations of serum antibodies for herpes simplex virus (HSV)-1 and cytomegalovirus (CMV) and anti-herpesvirus treatment with cognitive outcomes in relation to interactions with APOE ɛ4.

    METHODS: The study included 849 participants in the population-based Prospective Investigation of the Vasculature in Uppsala Seniors study. Cognitive performance at the ages of 75 and 80 years was assessed using the Mini-Mental State Examination (MMSE), trail-making test (TMT) A and B, and 7-minute screening test (7MS).

    RESULTS: Anti- HSV-1 IgG positivity was associated cross-sectionally with worse performance on the MMSE, TMT-A, TMT-B, 7MS, enhanced free recall, and verbal fluency tests (p = 0.016, p = 0.016, p < 0.001, p = 0.001, p = 0.033, and p < 0.001, respectively), but not orientation or clock drawing. Cognitive scores did not decline over time and longitudinal changes did not differ according to HSV-1 positivity. Anti- CMV IgG positivity was not associated cross-sectionally with cognition, but TMT-B scores declined more in anti- CMV IgG carriers. Anti- HSV-1 IgG interacted with APOE ɛ4 in association with worse TMT-A and better enhanced cued recall. Anti- HSV IgM interacted with APOE ɛ4 and anti-herpesvirus treatment in association with worse TMT-A and clock drawing, respectively.

    CONCLUSION: These findings indicate that HSV-1 is linked to poorer cognition in cognitively healthy elderly adults, including impairments in executive function, memory, and expressive language. Cognitive performance did not decline over time, nor was longitudinal decline associated with HSV-1.

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