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      SMART: physical activity and cerebral metabolism in older people: study protocol for a randomised controlled trial

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          Abstract

          Background

          Physical activity exerts a variety of long-term health benefits in older adults. In particular, it is assumed to be a protective factor against cognitive decline and dementia.

          Methods/design

          Randomised controlled assessor blinded 2-armed trial (n = 60) to explore the exercise- induced neuroprotective and metabolic effects on the brain in cognitively healthy older adults. Participants (age ≥ 65), recruited within the setting of assisted living facilities and newspaper advertisements are allocated to a 12-week individualised aerobic exercise programme intervention or a 12-week waiting control group. Total follow-up is 24 weeks. The main outcome is the change in cerebral metabolism as assessed with Magnetic Resonance Spectroscopic Imaging reflecting changes of cerebral N-acetyl-aspartate and of markers of neuronal energy reserve. Imaging also measures changes in cortical grey matter volume. Secondary outcomes include a broad range of psychometric (cognition) and movement-related parameters such as nutrition, history of physical activity, history of pain and functional diagnostics. Participants are allocated to either the intervention or control group using a computer-generated randomisation sequence. The exercise physiologist in charge of training opens sealed and opaque envelopes and informs participants about group allocation. For organisational reasons, he schedules the participants for upcoming assessments and exercise in groups of five. All assessors and study personal other than exercise physiologists are blinded.

          Discussion

          Magnetic Resonance Spectroscopic Imaging gives a deeper insight into mechanisms of exercise-induced changes in brain metabolism. As follow-up lasts for 6 months, this study is able to explore the mid-term cerebral metabolic effects of physical activity assuming that an individually tailored aerobic ergometer training has the potential to counteract brain ageing.

          Trial registration

          NCT02343029 (clinicaltrials.gov; 12 January 2015).

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          Most cited references53

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          Cardiovascular fitness, cortical plasticity, and aging.

          Cardiovascular fitness is thought to offset declines in cognitive performance, but little is known about the cortical mechanisms that underlie these changes in humans. Research using animal models shows that aerobic training increases cortical capillary supplies, the number of synaptic connections, and the development of new neurons. The end result is a brain that is more efficient, plastic, and adaptive, which translates into better performance in aging animals. Here, in two separate experiments, we demonstrate for the first time to our knowledge, in humans that increases in cardiovascular fitness results in increased functioning of key aspects of the attentional network of the brain during a cognitively challenging task. Specifically, highly fit (Study 1) or aerobically trained (Study 2) persons show greater task-related activity in regions of the prefrontal and parietal cortices that are involved in spatial selection and inhibitory functioning, when compared with low-fit (Study 1) or nonaerobic control (Study 2) participants. Additionally, in both studies there exist groupwise differences in activation of the anterior cingulate cortex, which is thought to monitor for conflict in the attentional system, and signal the need for adaptation in the attentional network. These data suggest that increased cardiovascular fitness can affect improvements in the plasticity of the aging human brain, and may serve to reduce both biological and cognitive senescence in humans.
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            Running enhances neurogenesis, learning, and long-term potentiation in mice.

            Running increases neurogenesis in the dentate gyrus of the hippocampus, a brain structure that is important for memory function. Consequently, spatial learning and long-term potentiation (LTP) were tested in groups of mice housed either with a running wheel (runners) or under standard conditions (controls). Mice were injected with bromodeoxyuridine to label dividing cells and trained in the Morris water maze. LTP was studied in the dentate gyrus and area CA1 in hippocampal slices from these mice. Running improved water maze performance, increased bromodeoxyuridine-positive cell numbers, and selectively enhanced dentate gyrus LTP. Our results indicate that physical activity can regulate hippocampal neurogenesis, synaptic plasticity, and learning.
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              Three-dimensional magnetization-prepared rapid gradient-echo imaging (3D MP RAGE).

              A new three-dimensional imaging technique which is applicable for 3D MR imaging throughout the body is introduced. In our preliminary investigations we have acquired high-quality 3D image sets of the abdomen showing minimal respiratory artifacts in just over 7 min (voxel size 2.7 X 2.7 X 2.7 mm3), and 3D image sets of the head showing excellent gray/white contrast in less than 6 min (voxel size 1.0 X 2.0 X 1.4 mm3).
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                Author and article information

                Contributors
                Johannes.fleckenstein@sport.uni-frankfurt.de
                Matura@allgemeinmedizin.uni-frankfurt.de
                engeroff@sport.uni-frankfurt.de
                fuezeki@sport.uni-frankfurt.de
                Tesky@allgemeinmedizin.uni-frankfurt.de
                u.pilatus@em.uni-frankfurt.de
                Elke.Hattingen@kgu.de
                deichmann@med.uni-frankfurt.de
                l.vogt@sport.uni-frankfurt.de
                banzer@sport.uni-frankfurt.de
                Pantel@allgemeinmedizin.uni-frankfurt.de
                Journal
                Trials
                Trials
                Trials
                BioMed Central (London )
                1745-6215
                11 April 2015
                11 April 2015
                2015
                : 16
                : 155
                Affiliations
                [ ]Department of Sports Medicine, Institute of Sports Sciences, Goethe University, Ginnheimer Landstrasse 39, Frankfurt am Main, 60487 Germany
                [ ]Institute of General Practice, Goethe University, Frankfurt/Main, Germany
                [ ]Institute of Neuroradiology, Goethe University Hospital Frankfurt, Frankfurt, Germany
                [ ]Brain Imaging Centre, Frankfurt/Main, Germany
                Article
                662
                10.1186/s13063-015-0662-9
                4403840
                25872789
                d0e232e8-b571-4bfa-bb2c-41cec52129b4
                © Fleckenstein et al.; licensee BioMed Central. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 21 January 2015
                : 18 March 2015
                Categories
                Study Protocol
                Custom metadata
                © The Author(s) 2015

                Medicine
                magnetic resonance spectroscopic imaging,aerobic exercise training,cognitive impairment,older adults,psychometric tests,cognition,dementia,prevention

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