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Josefsson, Maria
Publications (10 of 16) Show all publications
Lövheim, H., Norman, T., Weidung, B., Olsson, J., Josefsson, M., Adolfsson, R., . . . Elgh, F. (2019). Herpes Simplex Virus, APOE ɛ4, and Cognitive Decline in Old Age: Results from the Betula Cohort Study. Journal of Alzheimer's Disease, 67(1), 211-220
Open this publication in new window or tab >>Herpes Simplex Virus, APOE ɛ4, and Cognitive Decline in Old Age: Results from the Betula Cohort Study
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2019 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 67, no 1, p. 211-220Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
IOS Press, 2019
Keywords
Alzheimer’s disease, APOE ɛ4, apolipoprotein E4, cognitive impairment, cohort study, dementia, epidemiological study, episodic memory, herpes simplex virus
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-162728 (URN)10.3233/JAD-171162 (DOI)000457778000017 ()30636735 (PubMedID)
Available from: 2019-08-27 Created: 2019-08-27 Last updated: 2019-09-10Bibliographically approved
Ekström, I., Josefsson, M., Larsson, M., Rönnlund, M., Nordin, S. & Olofsson, J. K. (2019). Subjective olfactory loss in older adults concurs with long-term odor identification decline. Chemical Senses, 44(2), 105-112
Open this publication in new window or tab >>Subjective olfactory loss in older adults concurs with long-term odor identification decline
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2019 (English)In: Chemical Senses, ISSN 0379-864X, E-ISSN 1464-3553, Vol. 44, no 2, p. 105-112Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Oxford: Oxford University Press, 2019
Keywords
decline, longitudinal studies, odor identification, self-reported olfaction, smell, subjective
National Category
Neurosciences Psychology (excluding Applied Psychology)
Identifiers
urn:nbn:se:umu:diva-157657 (URN)10.1093/chemse/bjy079 (DOI)000461508600004 ()30544138 (PubMedID)
Available from: 2019-03-27 Created: 2019-03-27 Last updated: 2019-04-23Bibliographically approved
Pudas, S., Josefsson, M., Rieckmann, A. & Nyberg, L. (2018). Longitudinal evidence for increased functional response in frontal cortex for older adults with hippocampal atrophy and memory decline. Cerebral Cortex, 28(3), 936-948
Open this publication in new window or tab >>Longitudinal evidence for increased functional response in frontal cortex for older adults with hippocampal atrophy and memory decline
2018 (English)In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 28, no 3, p. 936-948Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Oxford University Press, 2018
Keywords
aging, fMRI, hippocampus, longitudinal study, memory decline, prefrontal cortex
National Category
Neurosciences Psychology (excluding Applied Psychology)
Identifiers
urn:nbn:se:umu:diva-131270 (URN)10.1093/cercor/bhw418 (DOI)000426817600010 ()28119343 (PubMedID)
Available from: 2017-02-10 Created: 2017-02-10 Last updated: 2018-06-09Bibliographically approved
Malmberg Gavelin, H., Eskilsson, T., Boraxbekk, C.-J., Josefsson, M., Stigsdotter Neely, A. & Slunga Järvholm, L. (2018). Rehabilitation for improved cognition in patients with stress-related exhaustion disorder: RECO – a randomized clinical trial. Stress, 21(4), 279-291
Open this publication in new window or tab >>Rehabilitation for improved cognition in patients with stress-related exhaustion disorder: RECO – a randomized clinical trial
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2018 (English)In: Stress, ISSN 1025-3890, E-ISSN 1607-8888, Vol. 21, no 4, p. 279-291Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Taylor & Francis, 2018
Keywords
burnout, stress rehabilitation, cognitive training, aerobic training, exhaustion disorder, randomized controlled trial
National Category
Applied Psychology
Identifiers
urn:nbn:se:umu:diva-147074 (URN)10.1080/10253890.2018.1461833 (DOI)000442694000001 ()29693483 (PubMedID)
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2009-0772Forte, Swedish Research Council for Health, Working Life and Welfare, 2013-2056Swedish Social Insurance Agency, 99368-2009/RS09Västerbotten County Council
Available from: 2018-04-26 Created: 2018-04-26 Last updated: 2019-01-07Bibliographically approved
Josefsson, M., Larsson, M., Nordin, S., Adolfsson, R. & Olofsson, J. (2017). APOE-ɛ4 effects on longitudinal decline in olfactory and non-olfactory cognitive abilities in middle-aged and old adults. Scientific Reports, 7, Article ID 1286.
Open this publication in new window or tab >>APOE-ɛ4 effects on longitudinal decline in olfactory and non-olfactory cognitive abilities in middle-aged and old adults
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 1286Article in journal (Refereed) Published
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.

National Category
Psychology (excluding Applied Psychology)
Identifiers
urn:nbn:se:umu:diva-134716 (URN)10.1038/s41598-017-01508-7 (DOI)000400247600045 ()28455505 (PubMedID)
Available from: 2017-05-23 Created: 2017-05-23 Last updated: 2018-06-09Bibliographically approved
Gorbach, T., Pudas, S., Lundquist, A., Orädd, G., Josefsson, M., Salami, A., . . . Nyberg, L. (2017). Longitudinal association between hippocampus atrophy and episodic-memory decline. Neurobiology of Aging, 51, 167-176
Open this publication in new window or tab >>Longitudinal association between hippocampus atrophy and episodic-memory decline
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2017 (English)In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 51, p. 167-176Article in journal (Refereed) Published
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. 

Keywords
Aging, cognitive decline, episodic memory, hippocampus, longitudinal changes, non-ignorable attrition
National Category
Probability Theory and Statistics Neurosciences
Identifiers
urn:nbn:se:umu:diva-128725 (URN)10.1016/j.neurobiolaging.2016.12.002 (DOI)000397168600018 ()28089351 (PubMedID)
Funder
Swedish Research CouncilKnut and Alice Wallenberg FoundationRagnar Söderbergs stiftelse
Available from: 2016-12-15 Created: 2016-12-13 Last updated: 2019-01-25Bibliographically approved
Eriksson Sörman, D., Josefsson, M., Marsh, J. E., Hansson, P. & Ljungberg, J. K. (2017). Longitudinal effects of bilingualism on dual-tasking. PLoS ONE, 12(12), Article ID e0189299.
Open this publication in new window or tab >>Longitudinal effects of bilingualism on dual-tasking
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 12, article id e0189299Article in journal (Refereed) Published
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.

National Category
Psychology (excluding Applied Psychology)
Identifiers
urn:nbn:se:umu:diva-143465 (URN)10.1371/journal.pone.0189299 (DOI)000419006200021 ()
Funder
Swedish Research Council, 345-2003-3883Swedish Research Council, 315-2004-6977Swedish Research Council, 421-2011-1782
Available from: 2018-01-02 Created: 2018-01-02 Last updated: 2018-06-09Bibliographically approved
Degerman, S., Josefsson, M., Nordin Adolfsson, A., Wennstedt, S., Landfors, M., Haider, Z., . . . Adolfsson, R. (2017). Maintained memory in aging is associated with young epigenetic age. Neurobiology of Aging, 55, 167-171
Open this publication in new window or tab >>Maintained memory in aging is associated with young epigenetic age
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2017 (English)In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 55, p. 167-171Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2017
National Category
Other Basic Medicine
Identifiers
urn:nbn:se:umu:diva-132221 (URN)10.1016/j.neurobiolaging.2017.02.009 (DOI)000405068100018 ()28292535 (PubMedID)
Available from: 2017-03-07 Created: 2017-03-07 Last updated: 2019-05-10Bibliographically approved
Josefsson, M., de Luna, X., Daniels, M. & Nyberg, L. (2016). Causal inference with longitudinal outcomes and non-ignorable drop-out: Estimating the effect of living alone on cognitive decline. Journal of the Royal Statistic Society, Series C: Applied Statistics, 65(1), 131-144
Open this publication in new window or tab >>Causal inference with longitudinal outcomes and non-ignorable drop-out: Estimating the effect of living alone on cognitive decline
2016 (English)In: Journal of the Royal Statistic Society, Series C: Applied Statistics, ISSN 0035-9254, E-ISSN 1467-9876, Vol. 65, no 1, p. 131-144Article in journal (Refereed) Published
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.

Keywords
Aging, Bayesian inference, Episodic memory, Non-ignorable missingness, Pattern–mixture model, Propensity score matching, Sensitivity
National Category
Probability Theory and Statistics Neurosciences
Research subject
Statistics
Identifiers
urn:nbn:se:umu:diva-82511 (URN)10.1111/rssc.12110 (DOI)000367978400007 ()
Projects
Statistiska metoder för studier av kognitiv åldrande: kognitionstester och hjärnavbildning
Funder
Swedish Research Council
Available from: 2013-11-04 Created: 2013-11-04 Last updated: 2018-06-08Bibliographically approved
Olofsson, J. K., Josefsson, M., Ekström, I., Wilson, D., Nyberg, L., Nordin, S., . . . Larsson, M. (2016). Long-term episodic memory decline is associated with olfactory deficits only in carriers of ApoE-є4. Neuropsychologia, 85, 1-9
Open this publication in new window or tab >>Long-term episodic memory decline is associated with olfactory deficits only in carriers of ApoE-є4
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2016 (English)In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 85, p. 1-9Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2016
Keywords
Dementia, Alzheimer disease, Olfactory perception, Memory, Aging, Mild cognitive impairment
National Category
Neurology Applied Psychology
Identifiers
urn:nbn:se:umu:diva-122577 (URN)10.1016/j.neuropsychologia.2016.03.004 (DOI)000376546400001 ()26956928 (PubMedID)
Available from: 2016-06-20 Created: 2016-06-20 Last updated: 2018-06-07Bibliographically approved
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