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  • 1.
    Avelar-Pereira, Bárbara
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
    Backman, Lars
    Wåhlin, Anders
    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).
    Salami, Alireza
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
    Age-Related Differences in Dynamic Interactions Among Default Mode, Frontoparietal Control, and Dorsal Attention Networks during Resting-State and Interference Resolution2017In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 9, article id 152Article in journal (Refereed)
    Abstract [en]

    Resting-state fMRI (rs-fMRI) can identify large-scale brain networks, including the default mode (DMN), frontoparietal control (FPN) and dorsal attention (DAN) networks. Interactions among these networks are critical for supporting complex cognitive functions, yet the way in which they are modulated across states is not well understood. Moreover, it remains unclear whether these interactions are similarly affected in aging regardless of cognitive state. In this study, we investigated age-related differences in functional interactions among the DMN, FPN and DAN during rest and the Multi-Source Interference task (MSIT). Networks were identified using independent component analysis (ICA), and functional connectivity was measured during rest and task. We found that the FPN was more coupled with the DMN during rest and with the DAN during the MSIT. The degree of FPN-DMN connectivity was lower in older compared to younger adults, whereas no age-related differences were observed in FPN-DAN connectivity in either state. This suggests that dynamic interactions of the FPN are stable across cognitive states. The DMN and DAN were anti correlated and age-sensitive during the MSIT only, indicating variation in a task-dependent manner. Increased levels of anticorrelation from rest to task also predicted successful interference resolution. Additional analyses revealed that the degree of DMN-DAN anticorrelation during the MSIT was associated to resting cerebral blood flow (CBF) within the DMN. This suggests that reduced DMN neural activity during rest underlies an impaired ability to achieve higher levels of anticorrelation during a task. Taken together, our results suggest that only parts of age-related differences in connectivity are uncovered at rest and thus, should be studied in the functional connectome across multiple states for a more comprehensive picture.

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  • 2. Ballesteros, Soledad
    et al.
    Mayas, Julia
    Prieto, Antonio
    Toril, Pilar
    Pita, Carmen
    Ponce de Leon, Laura
    Reales, Jose
    Waterworth, John
    Umeå University, Faculty of Social Sciences, Department of Informatics.
    A randomized controlled trial of brain training with non-action video games in older adults: results of the 3-month follow-up2015In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 7, article id UNSP 45Article in journal (Refereed)
    Abstract [en]

    This randomized controlled study (ClinicalTrials.gov NCT02007616)investigated the maintenance of training effects of 20 1-hr non-action video gametraining sessions with selected games from a commercial package on several agedecliningcognitive functions and subjective wellbeing after a 3-month no-contactperiod. Two groups of cognitively normal older adults participated in both the posttraining(posttest) and the present follow-up study, the experimental group who receivedtraining and the control group who attended several meetings with the research teamduring the study but did not receive training. Groups were similar at baseline ondemographics, vocabulary, global cognition, and depression status. Significant improvements in the trained group, and no variation in the control group had been previously found at posttest, in processing speed, attention and visual recognition memory, as well as in two dimensions of subjective wellbeing. In the current study, improvement from baseline to 3 months follow-up was found only in wellbeing (Affection and Assertivity dimensions) in the trained group whereas there was no change in the control group. Previous significant improvements in processing speed, attentionand spatial memory become nonsignificant after the 3-month interval. Training olderadults with non-action video games enhanced aspects of cognition just after training butthis effect disappeared after a 3-month no-contact follow-up period. Cognitive plasticitycan be induced in older adults by training, but to maintain the benefits periodic boosting sessions would be necessary.

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  • 3.
    Ballesteros, Soledad
    et al.
    Studies on Aging and Neurodegenerative Diseases Research Group, Department of Basic Psychology II, Universidad Nacional de Educación a Distancia, Madrid, Spain.
    Prieto, Antonio
    Studies on Aging and Neurodegenerative Diseases Research Group, Department of Basic Psychology II, Universidad Nacional de Educación a Distancia, Madrid, Spain.
    Mayes, Julia
    Studies on Aging and Neurodegenerative Diseases Research Group, Department of Basic Psychology II, Universidad Nacional de Educación a Distancia, Madrid, Spain.
    Toril, Pilar
    Studies on Aging and Neurodegenerative Diseases Research Group, Department of Basic Psychology II, Universidad Nacional de Educación a Distancia, Madrid, Spain.
    Pita, Carmen
    Studies on Aging and Neurodegenerative Diseases Research Group, Department of Basic Psychology II, Universidad Nacional de Educación a Distancia, Madrid, Spain.
    Ponce de León, Laura
    Studies on Aging and Neurodegenerative Diseases Research Group, Department of Basic Psychology II, Universidad Nacional de Educación a Distancia, Madrid, Spain.
    Reales, José
    Studies on Aging and Neurodegenerative Diseases Research Group, Department of Basic Psychology II, Universidad Nacional de Educación a Distancia, Madrid, Spain.
    Waterworth, John
    Umeå University, Faculty of Social Sciences, Department of Informatics.
    Brain training with non-action video games enhances aspects of cognition in older adults: a randomized controlled trial2014In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 6, article id 277Article in journal (Refereed)
    Abstract [en]

    Age-related cognitive and brain declines can result in functional deterioration in many cognitive domains, dependency, and dementia. A major goal of aging research is to investigate methods that help to maintain brain health, cognition, independent living and wellbeing in older adults. This randomized controlled study investigated the effects of 20 1-hr non-action video game training sessions with games selected from a commercially available package (Lumosity) on a series of age-declined cognitive functions and subjective wellbeing. Two groups of healthy older adults participated in the study, the experimental group who received the training and the control group who attended two meetings with the research team along the study. Groups were similar at baseline on demographics, vocabulary, global cognition, and depression status. All participants were assessed individually before and after the intervention, or a similar period of time, using neuropsychological tests and laboratory tasks to investigate possible transfer effects. The results showed significant improvements in the trained group, and no variation in the control group, in processing speed (choice reaction time), attention (reduction of distraction and increase of alertness), immediate and delayed visual recognition memory, as well as a trend to improve in Affection and Assertivity, two dimensions of the Wellbeing Scale. Visuospatial working memory (WM) and executive control (shifting strategy) did not improve. Overall, the current results support the idea that training healthy older adults with non-action video games will enhance some cognitive abilities but not others.

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  • 4. Bjorkli, Christiana
    et al.
    Sandvig, Axel
    Sandvig Group, Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway, Institute of Neuromedicine and Movement Science, Department of Neurology, St. Olavs Hospital, Trondheim, Norway, Department of Pharmacology and Clinical Neurosciences, Division of Neuro, Head, and Neck, University Hospital of Umeå, Umeå, Sweden.
    Sandvig, Ioanna
    Bridging the Gap Between Fluid Biomarkers for Alzheimer's Disease, Model Systems, and Patients2020In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 12, article id 272Article in journal (Refereed)
    Abstract [en]

    Alzheimer's disease (AD) is a debilitating neurodegenerative disease characterized by the accumulation of two proteins in fibrillar form: amyloid-β (Aβ) and tau. Despite decades of intensive research, we cannot yet pinpoint the exact cause of the disease or unequivocally determine the exact mechanism(s) underlying its progression. This confounds early diagnosis and treatment of the disease. Cerebrospinal fluid (CSF) biomarkers, which can reveal ongoing biochemical changes in the brain, can help monitor developing AD pathology prior to clinical diagnosis. Here we review preclinical and clinical investigations of commonly used biomarkers in animals and patients with AD, which can bridge translation from model systems into the clinic. The core AD biomarkers have been found to translate well across species, whereas biomarkers of neuroinflammation translate to a lesser extent. Nevertheless, there is no absolute equivalence between biomarkers in human AD patients and those examined in preclinical models in terms of revealing key pathological hallmarks of the disease. In this review, we provide an overview of current but also novel AD biomarkers and how they relate to key constituents of the pathological cascade, highlighting confounding factors and pitfalls in interpretation, and also provide recommendations for standardized procedures during sample collection to enhance the translational validity of preclinical AD models.

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  • 5.
    Flodin, Pär
    et al.
    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).
    Jonasson, 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 Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Riklund, Katrine
    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, 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).
    Boraxbekk, Carl-Johan
    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). Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark.
    Does Aerobic Exercise Influence Intrinsic Brain Activity? An Aerobic Exercise Intervention among Healthy Old Adults2017In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 9, article id 267Article in journal (Refereed)
    Abstract [en]

    Previous studies have indicated that aerobic exercise could reduce age related decline in cognition and brain functioning. Here we investigated the effects of aerobic exercise on intrinsic brain activity. Sixty sedentary healthy males and females (64–78 years) were randomized into either an aerobic exercise group or an active control group. Both groups recieved supervised training, 3 days a week for 6 months. Multimodal brain imaging data was acquired before and after the intervention, including 10 min of resting state brain functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL). Additionally, a comprehensive battery of cognitive tasks assessing, e.g., executive function and episodic memory was administered. Both the aerobic and the control group improved in aerobic capacity (VO2-peak) over 6 months, but a significant group by time interaction confirmed that the aerobic group improved more. Contrary to our hypothesis, we did not observe any significant group by time interactions with regard to any measure of intrinsic activity. To further probe putative relationships between fitness and brain activity, we performed post hoc analyses disregarding group belongings. At baseline, VO2-peak was negativly related to BOLD-signal fluctuations (BOLDSTD) in mid temporal areas. Over 6 months, improvements in aerobic capacity were associated with decreased connectivity between left hippocampus and contralateral precentral gyrus, and positively to connectivity between right mid-temporal areas and frontal and parietal regions. Independent component analysis identified a VO2-related increase in coupling between the default mode network and left orbitofrontal cortex, as well as a decreased connectivity between the sensorimotor network and thalamus. Extensive exploratory data analyses of global efficiency, connectome wide multivariate pattern analysis (connectome-MVPA), as well as ASL, did not reveal any relationships between aerobic fitness and intrinsic brain activity. Moreover, fitness-predicted changes in functional connectivity did not relate to changes in cognition, which is likely due to absent cross- sectional or longitudinal relationships between VO2-peak and cognition. We conclude that the aerobic exercise intervention had limited influence on patterns of intrinsic brain activity, although post hoc analyses indicated that individual changes in aerobic capacity preferentially influenced mid-temporal brain areas.

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  • 6.
    Giacobbo, B.
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Özalay, Özgun
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Mediavilla, Tomás
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Ericsson, Madelene
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Rieckmann, Anna
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Sultan, Fahad
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Marcellino, Daniel
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    The Aged Striatum: Evidence of Molecular and Structural Changes Using a Longitudinal Multimodal Approach in Mice2022In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 14, article id 795132Article in journal (Refereed)
    Abstract [en]

    To study the aging human brain requires significant resources and time. Thus, mice models of aging can provide insight into changes in brain biological functions at a fraction of the time when compared to humans. This study aims to explore changes in dopamine D1 and D2 receptor availability and of gray matter density in striatum during aging in mice and to evaluate whether longitudinal imaging in mice may serve as a model for normal brain aging to complement cross-sectional research in humans. Mice underwent repeated structural magnetic resonance imaging (sMRI), and [11C]Raclopride and [11C]SCH23390 positron emission tomography (PET) was performed on a subset of aging mice. PET and sMRI data were analyzed by binding potential (BP ND ), voxel- and tensor-based morphometry (VBM and TBM, respectively). Longitudinal PET revealed a significant reduction in striatal BP ND for D2 receptors over time, whereas no significant change was found for D1 receptors. sMRI indicated a significant increase in modulated gray matter density (mGMD) over time in striatum, with limited clusters showing decreased mGMD. Mouse [11C]Raclopride data is compatible with previous reports in human cross-sectional studies, suggesting that a natural loss of dopaminergic D2 receptors in striatum can be assessed in mice, reflecting estimates from humans. No changes in D1 were found, which may be attributed to altered [11C]SCH23390 kinetics in anesthetized mice, suggesting that this tracer is not yet able to replicate human findings. sMRI revealed a significant increase in mGMD. Although contrary to expectations, this increase in modulated GM density may be attributed to an age-related increase in non-neuronal cells.

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  • 7.
    Griffiths, William J.
    et al.
    Swansea University Medical School, ILS1 Building, Swansea, United Kingdom.
    Abdel-Khalik, Jonas
    Swansea University Medical School, ILS1 Building, Swansea, United Kingdom.
    Moore, Sarah F.
    Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom.
    Wijeyekoon, Ruwani S.
    Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom.
    Crick, Peter J.
    Swansea University Medical School, ILS1 Building, Swansea, United Kingdom.
    Yutuc, Eylan
    Swansea University Medical School, ILS1 Building, Swansea, United Kingdom.
    Farrell, Krista
    Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom.
    Breen, David P.
    Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom; Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Edinburgh, United Kingdom; Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom.
    Williams-Gray, Caroline H.
    Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom.
    Theofilopoulos, Spyridon
    Swansea University Medical School, ILS1 Building, Swansea, United Kingdom.
    Arenas, Ernest
    Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
    Trupp, Miles
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Barker, Roger A.
    Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
    Wang, Yuqin
    Swansea University Medical School, ILS1 Building, Swansea, United Kingdom.
    The Cerebrospinal Fluid Profile of Cholesterol Metabolites in Parkinson’s Disease and Their Association With Disease State and Clinical Features2021In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 13, article id 685594Article in journal (Refereed)
    Abstract [en]

    Disordered cholesterol metabolism is linked to neurodegeneration. In this study we investigated the profile of cholesterol metabolites found in the cerebrospinal fluid (CSF) of Parkinson’s disease (PD) patients. When adjustments were made for confounding variables of age and sex, 7α,(25R)26-dihydroxycholesterol and a second oxysterol 7α,x,y-trihydroxycholest-4-en-3-one (7α,x,y-triHCO), whose exact structure is unknown, were found to be significantly elevated in PD CSF. The likely location of the additional hydroxy groups on the second oxysterol are on the sterol side-chain. We found that CSF 7α-hydroxycholesterol levels correlated positively with depression in PD patients, while two presumptively identified cholestenoic acids correlated negatively with depression.

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  • 8.
    Gudberg, Christel
    et al.
    Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield, Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
    Stevelink, Remi
    Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield, Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
    Douaud, Gwenaëlle
    Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield, Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
    Wulff, Katharina
    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). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Nuffield Laboratory of Ophthalmology, Nuffield, Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
    Lazari, Alberto
    Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield, Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
    Fleming, Melanie K.
    Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield, Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
    Johansen-Berg, Heidi
    Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield, Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
    Individual differences in slow wave sleep architecture relate to variation in white matter microstructure across adulthood2022In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 14, article id 745014Article in journal (Refereed)
    Abstract [en]

    Sleep plays a key role in supporting brain function and resilience to brain decline. It is well known that sleep changes substantially with aging and that aging is associated with deterioration of brain structure. In this study, we sought to characterize the relationship between slow wave slope (SWslope)—a key marker of sleep architecture and an indirect proxy of sleep quality—and microstructure of white matter pathways in healthy adults with no sleep complaints. Participants were 12 young (24–27 years) and 12 older (50–79 years) adults. Sleep was assessed with nocturnal electroencephalography (EEG) and the Pittsburgh Sleep Quality Index (PSQI). White matter integrity was assessed using tract-based spatial statistics (TBSS) on tensor-based metrics such as Fractional Anisotropy (FA) and Mean Diffusivity (MD). Global PSQI score did not differ between younger (n = 11) and older (n = 11) adults (U = 50, p = 0.505), but EEG revealed that younger adults had a steeper SWslope at both frontal electrode sites (F3: U = 2, p < 0.001, F4: U = 4, p < 0.001, n = 12 younger, 10 older). There were widespread correlations between various diffusion tensor-based metrics of white matter integrity and sleep SWslope, over and above effects of age (n = 11 younger, 9 older). This was particularly evident for the corpus callosum, corona radiata, superior longitudinal fasciculus, internal and external capsule. This indicates that reduced sleep slow waves may be associated with widespread white matter deterioration. Future studies should investigate whether interventions targeted at improving sleep architecture also impact on decline in white matter microstructure in older adults.

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  • 9.
    Hedner, Margareta
    et al.
    Stockholm University, Stockholm Brain Institute.
    Nilsson, Lars-Göran
    Stockholm University, Stockholm Brain Institute.
    Olofsson, Jonas K
    Stockholm University, Stockholm Brain Institute.
    Bergman, Olle
    Göteborg University.
    Eriksson, Elias
    Göteborg University.
    Nyberg, Lars
    Umeå University, Faculty of Social Sciences, Centre for Population Studies (CPS). Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Larsson, Maria
    Stockholm University, Stockholm Brain Institute.
    Age-related olfactory decline is associated with the BDNF Val66met Polymorphism: Evidence from a population-based study2010In: Frontiers in Aging Neuroscience, E-ISSN 1663-4365, Vol. 2, p. 24-Article in journal (Refereed)
    Abstract [en]

    The present study investigates the effect of the brain-derived neurotrophic factor (BDNF) val66met polymorphism on change in olfactory function in a large scale, longitudinal population-based sample (n = 836). The subjects were tested on a 13 item force-choice odor identification test on two test occasions over a 5-year-interval. Sex, education, health-related factors, and semantic ability were controlled for in the statistical analyses. Results showed an interaction effect of age and BDNF val66met on olfactory change, such that the magnitude of olfactory decline in the older age cohort (70-90 years old at baseline) was larger for the val homozygote carriers than for the met carriers. The older met carriers did not display larger age-related decline in olfactory function compared to the younger group. The BDNF val66met polymorphism did not affect the rate of decline in the younger age cohort (45-65 years). The findings are discussed in the light of the proposed roles of BDNF in neural development and maintenance.

  • 10.
    Jonasson, Lars
    et al.
    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 Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    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), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Kramer, Arthur
    Departments of Psychology and Mechanical and Industrial Engineering, Northeastern University, Boston, MA, USA.
    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).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Boraxbekk, Carl-Johan
    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). Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark.
    Aerobic Exercise Intervention, CognitivePerformance, and Brain Structure: results from the Physical Influences on Brain in Aging (PHIBRA) Study2017In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 8, p. 1-15, article id 336Article in journal (Refereed)
    Abstract [en]

    Studies have shown that aerobic exercise has the potential to improve cognition and reduce brain atrophy in older adults. However, the literature is equivocal with regards to the specificity or generality of these effects. To this end, we report results on cognitive function and brain structure from a 6-month training intervention with 60 sedentary adults (64–78 years) randomized to either aerobic training or stretching and toning control training. Cognitive functions were assessed with a neuropsychological test battery in which cognitive constructs were measured using several different tests. Freesurfer was used to estimate cortical thickness in frontal regions and hippocampus volume. Results showed that aerobic exercisers, compared to controls, exhibited a broad, rather than specific, improvement in cognition as indexed by a higher “Cognitive score,” a composite including episodic memory, processing speed, updating, and executive function tasks (p = 0.01). There were no group differences in cortical thickness, but additional analyses revealed that aerobic fitness at baseline was specifically related to larger thickness in dorsolateral prefrontal cortex (dlPFC), and hippocampus volume was positively associated with increased aerobic fitness over time. Moreover, “Cognitive score” was related to dlPFC thickness at baseline, but changes in “Cognitive score” and dlPFC thickness were associated over time in the aerobic group only. However, aerobic fitness did not predict dlPFC change, despite the improvement in “Cognitive score” in aerobic exercisers. Our interpretation of these observations is that potential exercise-induced changes in thickness are slow, and may be undetectable within 6-months, in contrast to change in hippocampus volume which in fact was predicted by the change in aerobic fitness. To conclude, our results add to a growing literature suggesting that aerobic exercise has a broad influence on cognitive functioning, which may aid in explaining why studies focusing on a narrower range of functions have sometimes reported mixed results.

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  • 11.
    Kremen, William S.
    et al.
    Department of Psychiatry and Center for Behavior Genetics of Aging, University of California San Diego, La Jolla, CA, United States.
    Nation, Daniel A.
    Department of Psychological Science, University of California, Irvine, CA, Irvine, United States.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Editorial: The importance of cognitive practice effects in aging neuroscience2022In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 14, article id 1079021Article in journal (Other academic)
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  • 12.
    Lilja-Lund, Otto
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    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, Diagnostic Radiology. Center for Lifespan Changes in Brain and Cognition, University of Oslo, Oslo, Norway.
    Maripuu, Martin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Laurell, Katarina
    Department of Medical Sciences, Neurology, Uppsala University, Uppsala, Sweden.
    Dual-Task Performance in Older Adults With and Without Idiopathic Normal Pressure Hydrocephalus2022In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 14, article id 904194Article in journal (Refereed)
    Abstract [en]

    Two of the main features of idiopathic normal pressure hydrocephalus (iNPH) are disturbed gait and cognition. These features are typically investigated separately, but here we combined walking with a cognitive task to investigate if older adults with iNPH were more susceptible to dual-task interference on walking than those without iNPH. In total, 95 individuals from the general population participated in our study. Of these, 20 were classified as Possible iNPH (median [interquartile range, IQR] 80 years [75–82.5]) and 75 as Unlikely iNPH (74 years [72–78]). Conversation, 10-m walking, semantic and phonemic verbal fluency were performed either combined or independently. “Stopping walking while talking” was noted. Pairwise comparisons and multiple logistic regression analyses were used. We found that the Possible iNPH group was older, stopped walking more frequently during the conversation, and had a slower single-task pace. The dual-task pace was slower for both groups. Only single-task walking pace could predict Possible iNPH when adjusted for age. We could establish a dual-task cost on gait performance in this sample of older adults from the general population, but the cost was not exclusive for individuals with Possible iNPH. To further assess the value of dual-task testing in iNPH, including observations of stopping walking while talking, a study of a clinical iNPH material with more severe symptoms would be valuable.

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  • 13. Persson, Ninni
    et al.
    Lavebratt, Catharina
    Sundström, Anna
    Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Fischer, Håkan
    Pulse Pressure magnifies the effect of COMTVal158Met on 15 Year Episodic Memory Trajectories2016In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 8, article id 34Article in journal (Refereed)
    Abstract [en]

    We investigated whether a physiological marker of cardiovascular health, pulse pressure (PP), and age magnified the effect of the functional COMT Val(158)Met (rs4680) polymorphism on 15-years cognitive trajectories [episodic memory (EM), visuospatial ability, and semantic memory] using data from 1585 non-demented adults from the Betula study. A multiple-group latent growth curve model was specified to gauge individual differences in change, and average trends therein. The allelic variants showed negligible differences across the cognitive markers in average trends. The older portion of the sample selectively age-magnified the effects of Val(158)Met on EM changes, resulting in greater decline in Val compared to homozygote Met carriers. This effect was attenuated by statistical control for PP Further, PP moderated the effects of COMT on 15-years EM trajectories, resulting in greater decline in Val carriers, even after accounting for the confounding effects of sex, education, cardiovascular diseases (diabetes, stroke, and hypertension), and chronological age, controlled for practice gains. The effect was still present after excluding individuals with a history of cardiovascular diseases. The effects of cognitive change were not moderated by any other covariates. This report underscores the importance of addressing synergistic effects in normal cognitive aging, as the addition thereof may place healthy individuals at greater risk for memory decline.

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  • 14.
    Ronat, Lucas
    et al.
    Umeå University, Faculty of Medicine, Department of Medical and Translational Biology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Centre de Recherche de l’Institut Universitaire de Gériatrie de Montréal, Neuroimaging of Emotions Lab, Montreal, QC; Canada Department of Medicine, Faculty of Medicine, University of Montreal, Montreal, QC, Canada.
    Rönnlund, Michael
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Hanganu, Alexandru
    Centre de Recherche de l’Institut Universitaire de Gériatrie de Montréal, Neuroimaging of Emotions Lab, Montreal, QC, Canada; Department of Psychology, Faculty of Arts and Sciences, University of Montreal, Montreal, QC, Canada.
    Pudas, Sara
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Medical and Translational Biology.
    Revised temperament and character inventory factors predict neuropsychiatric symptoms and aging-related cognitive decline across 25 years2024In: Frontiers in Aging Neuroscience, E-ISSN 1663-4365, Vol. 16, article id 1335336Article in journal (Refereed)
    Abstract [en]

    Introduction: Personality traits and neuropsychiatric symptoms such as neuroticism and depression share genetic overlap and have both been identified as risks factors for development of aging-related neurocognitive decline and Alzheimer’s disease (AD). This study aimed to examine revised personality factors derived from the Temperament and Character Inventory, previously shown to be associated with psychiatric disorders, as predictors of neuropsychiatric, cognitive, and brain trajectories of participants from a population-based aging study.

    Methods: Mixed-effect linear regression analyses were conducted on data for the full sample (Nmax = 1,286), and a healthy subsample not converting to AD-dementia during 25-year follow-up (Nmax = 1,145), complemented with Cox proportional regression models to determine risk factors for conversion to clinical AD.

    Results: Two personality factors, Closeness to Experience (CE: avoidance of new stimuli, high anxiety, pessimistic anticipation, low reward seeking) and Tendence to Liabilities (TL: inability to change, low autonomy, unaware of the value of their existence) were associated with higher levels of depressive symptoms, stress (CE), sleep disturbance (TL), as well as greater decline in memory, vocabulary and verbal fluency in the full sample. Higher CE was additionally associated with greater memory decline across 25 years in the healthy subsample, and faster right hippocampal volume reduction across 8 years in a neuroimaging subsample (N = 216). Most, but not all, personality-cognition associations persisted after controlling for diabetes, hypertension and cardiovascular disease. Concerning risks for conversion to AD, higher age, and APOE-ε4, but none of the personality measures, were significant predictors.

    Conclusion: The results indicate that personality traits associated with psychiatric symptoms predict accelerated age-related neurocognitive declines even in the absence of neurodegenerative disease. The attenuation of some personality effects on cognition after adjustment for health indicators suggests that those effects may be partly mediated by somatic health. Taken together, the results further emphasize the importance of personality traits in neurocognitive aging and underscore the need for an integrative (biopsychosocial) perspective of normal and pathological age-related cognitive decline.

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  • 15. Salmi, Juha
    et al.
    Ritakallio, Liisa
    Fellman, Daniel
    Umeå University, Faculty of Social Sciences, Department of applied educational science.
    Ellfolk, Ulla
    Rinne, Juha O.
    Laine, Matti
    Disentangling the Role of Working Memory in Parkinson's Disease2020In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 12, article id 572037Article in journal (Refereed)
    Abstract [en]

    Working memory (WM) represents a core cognitive function with a major striatal contribution, and thus WM deficits, commonly observed in Parkinson's disease (PD), could also relate to many other problems in PD patients. Our online study aimed to determine the subdomains of WM that are particularly affected in PD and to clarify the links between WM and everyday cognitive deficits, other executive functions, psychiatric and PD symptoms, as well as early cognitive impairment. Fifty-two mild-to-moderate PD patients and 54 healthy controls performed seven WM tasks tapping selective updating, continuous monitoring, or maintenance of currently active information. Self-ratings of everyday cognition, depression, and apathy symptoms, as well as screenings of global cognitive impairment, were also collected. The data were analyzed using structural equation modeling. Of the three WM domains, only selective updating was directly predictive of PD group membership. More widespread WM deficits were observed only in relation to global cognitive impairment in PD patients. Self-rated everyday cognition or psychiatric symptoms were not linked to WM performance but correlated with each other. Our findings suggest that WM has a rather limited role in the clinical manifestation of PD. Nevertheless, due to its elementary link to striatal function, the updating component of WM could be a candidate for a cognitive marker of PD also in patients who are otherwise cognitively well-preserved.

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  • 16.
    Solé-Padullés, Cristina
    et al.
    Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, Barcelona, Spain.
    Macià, Dídac
    Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, Barcelona, Spain; ISGlobal, Hospital Clínic – University of Barcelona, Barcelona, Spain.
    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).
    Stiernstedt, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    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).
    Düzel, Sandra
    Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany; Max Planck, UCL Centre for Computational Psychiatry and Ageing Research, Berlin, Germany.
    Zsoldos, Enikő
    Department of Psychiatry, Wellcome Centre for Integrative Neuroimaging, University of Oxford, Oxford, United Kingdom.
    Ebmeier, Klaus P.
    Department of Psychiatry, Wellcome Centre for Integrative Neuroimaging, University of Oxford, Oxford, United Kingdom.
    Binnewies, Julia
    Department of Psychiatry, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
    Drevon, Christian A.
    Vitas Ltd, Oslo, Norway; Department of Nutrition, Institute of Basic Medical Sciences, Faculty Medicine, University of Oslo, Oslo, Norway.
    Brandmaier, Andreas M.
    Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany; Max Planck, UCL Centre for Computational Psychiatry and Ageing Research, Berlin, Germany.
    Mowinckel, Athanasia M.
    Center for Lifespan Changes in Brain and Cognition, University of Oslo, Oslo, Norway; Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
    Fjell, Anders M.
    Center for Lifespan Changes in Brain and Cognition, University of Oslo, Oslo, Norway; Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
    Madsen, Kathrine Skak
    Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Amager and Hvidovre, Copenhagen, Denmark; Radiography, Department of Technology, University College Copenhagen, Copenhagen, Denmark.
    Baaré, William F. C.
    Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Amager and Hvidovre, Copenhagen, Denmark.
    Lindenberger, Ulman
    Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany; Max Planck, UCL Centre for Computational Psychiatry and Ageing Research, Berlin, Germany.
    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).
    Walhovd, Kristine B.
    Center for Lifespan Changes in Brain and Cognition, University of Oslo, Oslo, Norway; Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
    Bartrés-Faz, David
    Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
    No Association Between Loneliness, Episodic Memory and Hippocampal Volume Change in Young and Healthy Older Adults: A Longitudinal European Multicenter Study2022In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 14, article id 795764Article in journal (Refereed)
    Abstract [en]

    Background: Loneliness is most prevalent during adolescence and late life and has been associated with mental health disorders as well as with cognitive decline during aging. Associations between longitudinal measures of loneliness and verbal episodic memory and brain structure should thus be investigated.

    Methods: We sought to determine associations between loneliness and verbal episodic memory as well as loneliness and hippocampal volume trajectories across three longitudinal cohorts within the Lifebrain Consortium, including children, adolescents (N = 69, age range 10–15 at baseline examination) and older adults (N = 1468 over 60). We also explored putative loneliness correlates of cortical thinning across the entire cortical mantle.

    Results: Loneliness was associated with worsening of verbal episodic memory in one cohort of older adults. Specifically, reporting medium to high levels of loneliness over time was related to significantly increased memory loss at follow-up examinations. The significance of the loneliness-memory change association was lost when eight participants were excluded after having developed dementia in any of the subsequent follow-up assessments. No significant structural brain correlates of loneliness were found, neither hippocampal volume change nor cortical thinning.

    Conclusion: In the present longitudinal European multicenter study, the association between loneliness and episodic memory was mainly driven by individuals exhibiting progressive cognitive decline, which reinforces previous findings associating loneliness with cognitive impairment and dementia.

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  • 17.
    Stomby, Andreas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Jönköping County Hospital, Region Jönköping County, Jönköping, Sweden.
    Otten, Julia
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ryberg, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    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), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Boraxbekk, Carl-Johan
    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). Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark.
    A Paleolithic Diet with and without Combined Aerobic and Resistance Exercise Increases Functional Brain Responses and Hippocampal Volume in Subjects with Type 2 Diabetes2017In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 9, article id 391Article in journal (Refereed)
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  • 18.
    Ågren, Richard
    et al.
    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Awad, Amar
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Fytagoridis, Anders
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Voxel-Based Morphometry of Cerebellar Lobules in Essential Tremor2021In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 13, article id 667854Article in journal (Refereed)
    Abstract [en]

    Background: The extent of neurodegeneration underlying essential tremor (ET) remains a matter of debate. Despite various extents of cerebellar atrophy on structural magnetic resonance imaging (MRI), previous studies have shown substantial heterogeneity and included a limited number of patients. Novel automated pipelines allow detailed segmentation of cerebellar lobules based on structural MRI. Objective: To compare the volumes of cerebellar lobules in ET patients with those in healthy controls (HCs) using an automated segmentation pipeline. Methods: Structural MRI scans of ET patients eligible for deep brain stimulation (n = 55) and of age-matched and gender-matched HCs (n = 55, from the IXI database) were segmented using the automated CEREbellum Segmentation pipeline. Lobule-specific volume differences between the ET and HC groups were evaluated using a general linear model corrected for multiple tests. Results: Total brain tissue volumes did not differ between the ET and HC groups. ET patients demonstrated reduced volumes of lobules I-II, left Crus II, left VIIB, and an increased volume of right X when compared with the HC group. Conclusion: A large cohort of ET patients demonstrated subtle signs of decreased cerebellar lobule volumes. These findings oppose the hypothesis of localized atrophy in cerebellar motor areas in ET, but not the possibility of cerebellar pathophysiology in ET. Prospective investigations using alternative neuroimaging modalities may further elucidate the pathophysiology of ET and provide insights into diagnostic and therapeutic approaches.

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