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Aerobic fitness and healthy brain aging: cognition, brain structure, and dopamine
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).ORCID iD: 0000-0001-6169-5836
2017 (English)Doctoral thesis, comprehensive summary (Other academic)Alternative title
Aerobisk träning och hjärnans hälsosamma åldrande : kognition, hjärnstruktur och dopamin (Swedish)
Abstract [en]

Background: Performing aerobic exercise and maintaining high levels of aerobic fitness may have positive effects on both brain structure and function in older adults. Despite decades of research however, there is still a rather poor understanding of the neurocognitive mechanisms explaining the positive effects of aerobic exercise on cognition. Changes in prefrontal gray matter as well as dopaminergic neurotransmission in striatum are both candidate neurocognitive mechanisms. The main aims of this thesis are: 1. To investigate the effects of aerobic exercise and fitness on cognition and magnetic resonance imaging (MRI) derived gray matter volumes using data from a 6 month physical exercise intervention in older adults (Study I). 2. To simulate the effect of atrophy in longitudinal positron emission tomography (PET) which could pose a challenge to interpreting changes in longitudinal PET imaging (Study II). 3. To study the influence of aerobic exercise and fitness on the dopamine D2-receptor (D2R) system in striatum using [11C]raclopride PET as a potential mechanism for improved cognition (Study III).

Results: In Study I, aerobic exercise was found to improve cognitive performance in a broad, rather than domain-specific sense. Moreover, aerobic fitness was related to prefrontal cortical thickness, and improved aerobic fitness over 6 months was related to increased hippocampal volume. In Study II, we identified areas in the striatum vulnerable to the effect of shrinkage, which should be considered in longitudinal PET imaging. Finally, in Study III, the effect of being aerobically fit, and improving fitness levels was found to impact dopaminergic neurotransmission in the striatum, which in turn mediated fitness-induced improvements in working memory updating performance.

Conclusion: The findings in this thesis provide novel evidence regarding the neurocognitive mechanisms of aerobic exercise-induced improvements in cognition, and impacts the interpretation of longitudinal PET imaging. Performing aerobic exercise and staying aerobically fit at an older age have positive effects on cognition and brain systems important for memory and cognition. Specifically, fitness-induced changes to the dopaminergic system stands out as one novel neurocognitive mechanism explaining the positive effects of aerobic fitness on working-memory performance in healthy older adults.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet , 2017. , p. 81
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1908
Keywords [en]
Aerobic exercise, VO2, working memory, executive function, freesurfer, striatum, dopamine, D2-receptors, [11C]raclopride
National Category
Neurosciences Sport and Fitness Sciences
Identifiers
URN: urn:nbn:se:umu:diva-139056ISBN: 978-91-7601-753-1 (print)OAI: oai:DiVA.org:umu-139056DiVA, id: diva2:1138606
Public defence
2017-09-29, Sal 933, Building 3B, Norrland University Hospital, Umeå, 09:35 (English)
Opponent
Supervisors
Available from: 2017-09-08 Created: 2017-09-06 Last updated: 2018-06-09Bibliographically approved
List of papers
1. Aerobic Exercise Intervention, CognitivePerformance, and Brain Structure: results from the Physical Influences on Brain in Aging (PHIBRA) Study
Open this publication in new window or tab >>Aerobic Exercise Intervention, CognitivePerformance, and Brain Structure: results from the Physical Influences on Brain in Aging (PHIBRA) Study
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2017 (English)In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 8, p. 1-15, article id 336Article in journal (Refereed) Published
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.

Keywords
aerobic exercise, cognition, executive function, plasticity, hippocampus, prefrontal cortex, freesurfer, transfer
National Category
Neurosciences Sport and Fitness Sciences Psychology (excluding Applied Psychology)
Identifiers
urn:nbn:se:umu:diva-130526 (URN)10.3389/fnagi.2016.00336 (DOI)000392049000001 ()
Funder
Swedish Research Council, 2012- 00530
Available from: 2017-01-22 Created: 2017-01-22 Last updated: 2018-06-09Bibliographically approved
2. Simulating effects of brain atrophy in longitudinal PET imaging with an anthropomorphic brain phantom
Open this publication in new window or tab >>Simulating effects of brain atrophy in longitudinal PET imaging with an anthropomorphic brain phantom
2017 (English)In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 62, no 13, p. 5213-5227Article in journal (Refereed) Published
Abstract [en]

In longitudinal positron emission tomography (PET), the presence of volumetric changes over time can lead to an overestimation or underestimation of the true changes in the quantified PET signal due to the partial volume effect (PVE) introduced by the limited spatial resolution of existing PET cameras and reconstruction algorithms. Here, a 3D-printed anthropomorphic brain phantom with attachable striata in three sizes was designed to enable controlled volumetric changes. Using a method to eliminate the non-radioactive plastic wall, and manipulating BP levels by adding different number of events from list-mode acquisitions, we investigated the artificial volume dependence of BP due to PVE, and potential bias arising from varying BP. Comparing multiple reconstruction algorithms we found that a high-resolution ordered- subsets maximization algorithm with spatially variant point-spread function resolution modeling provided the most accurate data. For striatum, the BP changed by 0.08% for every 1% volume change, but for smaller volumes such as the posterior caudate the artificial change in BP was as high as 0.7% per 1% volume change. A simple gross correction for striatal volume is unsatisfactory, as the amplitude of the PVE on the BP differs depending on where in the striatum the change occurred. Therefore, to correctly interpret age-related longitudinal changes in the BP, we must account for volumetric changes also within a structure, rather than across the whole volume. The present 3D-printing technology, combined with the wall removal method, can be implemented to gain knowledge about the predictable bias introduced by the PVE differences in uptake regions of varying shape.

Place, publisher, year, edition, pages
Institute of Physics Publishing (IOPP), 2017
Keywords
longitudinal, PET, partial volume effect, brain phantom, dopamine
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
radiation physics
Identifiers
urn:nbn:se:umu:diva-136030 (URN)10.1088/1361-6560/aa6e1b (DOI)000402879700001 ()28561014 (PubMedID)
Available from: 2017-06-13 Created: 2017-06-13 Last updated: 2018-06-09Bibliographically approved
3. Aerobic fitness influences working memory updating via the striatal dopaminergic system in older adults
Open this publication in new window or tab >>Aerobic fitness influences working memory updating via the striatal dopaminergic system in older adults
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

There is much evidence that dopamine is vital for cognitive functioning in aging. Here we tested the hypothesis that aerobic exercise and fitness influences dopaminergic neurotransmission in the striatum as measured by positron emission tomography (PET) and the non-displacable binding potential (BPND ) of [11C]raclopride, and in turn performance on offline working-memory updating tasks. In a sample of 58 older sedentary adults undergoing a six-months exercise intervention, aerobic exercise compared to stretching, toning, and resistance training did not have a differential effect on BPND . At baseline, higher aerobic fitness levels (VO2peak ) were associated with higher BPND  in the striatum. Following the intervention, for both forms of training, we found reduced BPND , indicating increased dopamine (DA), in a cluster in the anterior striatum in individuals with larger improvements in VO2peak . This reduction in BPND  mediated a positive indirect effect of VO2peak  on working-memory updating performance. Collectively these findings implicate DA as a neurocognitive mechanism explaining the positive effects of staying physically active at an old age for working memory.

National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-139053 (URN)
Projects
PHIBRA
Funder
Västerbotten County CouncilSwedish Research Council, 2012- 00530
Available from: 2017-09-06 Created: 2017-09-06 Last updated: 2018-09-28

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