Background
Scientific background
Objectives
Primary objective
Secondary objectives
Secondary objectives | To evaluate the predictive value of a preceding aerobic and coordination training for transfer of cognitive training gains in healthy older adults (HOA) |
To evaluate the predictive value of baseline physical activity on transfer in HOA. Baseline physical activity will be measured by a 1-week actigraphy and the Global Physical Activity Questionnaire (see “Measures” section below). | |
To evaluate the predictive value of brain vascular lesion (as determined by T2-weighted magnetic resonance imaging (MRI), cortical amyloid burden (as determined by positron-emission tomography), higher default mode network activity (as determined by resting state functional MRI (fMRI) for transfer of cognitive training gains in HOA | |
To model and analyze multimodal, high-dimensional datasets with respect to transfer prediction and to build a robust individual index of transfer likelihood |
Methods/design
Study type
Study design
Population
Sample size
Inclusion criteria (for all trial sites)
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Age ≥ 60 years
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Ability of subject to understand character and individual consequences of clinical trial
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Signed and dated informed consent must be available before start of any procedures
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Sufficient mobility and motivation to be able to participate in the examinations
Exclusion criteria (for all trial sites)
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Incapability of giving consent
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Current (or history of) psychiatric illness
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Current (or history of) neurological or cerebrovascular illness, brain lesions
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Current (or history of) cardiovascular disease (i.e., myocardial infarct, peripheral arterial disease)
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Secondary disorders restricting individuals’ physical capacity (i.e., chronic obstructive pulmonary disease, rheumatism, osteoarthritis, bone fractures)
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Current (or history of) cognitive illness
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Diabetes types 1 and 2
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Intake of medications that may influence cognitive performance
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Insufficient German language skills
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Participation in other clinical trials during the present clinical trial or within the last month
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MRI contraindication (pacemaker, metal implants, tattoos, permanent-make-up, chochlear implant, medication pump, acupuncture needles)
Measures
Assessment of inclusion/exclusion criteria
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Telephone screening
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Study information and informed consentGeneral study information and informed consent, MRI information and informed consent, PET information and informed consent, genetics information and informed consent
Neuropsychological examination at baseline (NP I)
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Intelligence
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Memory
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Executive function
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Stimulus interferenceComputerized version of the Stroop Test
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Information processing speed
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Visual constructionRay-Osterrieth Complex Figure Test – copy [66].
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AttentionTest battery for attention performance – subtests: alertness, divided attention
Neuropsychological examination immediately after cognitive training (NP II)
Neuropsychological examination after 3 months (NP III)
Neuropsychological training
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Executive functions, memory, information processing speedCogpack: Cogpack is a computerized cognitive training and testing program. The subtests comparisons, searching, logic, anagrams, complete a logical block, and remembering will be applied
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AlertnessAttention capacities will be trained using the test battery for attention performance, which permits us to assess/train a variety of attentional aspects. The subtests alertness and divided attention will be trained.
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Working memory
Physical activity examination
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ActigraphyObjective physical activity, sleep/wake and energy expenditure measurement solution. The portable wristband (GeneActive, Kimbolton, UK) uses a three-axis accelerometer, a heat flux sensor, a galvanic skin-response sensor, a skin-temperature sensor, and a near-body ambient temperature sensor to capture data for 1 week
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Global Physical Activity QuestionaireThe Global Physical Activity Questionaire covers several components of physical activity typical of an elderly population. The score takes into account self-reported occupational, household and leisure activities items over a 1-week period (World Health Organization (WHO), http://www.who.int/chp/steps/GPAQ/en/)
Fitness examinations
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Cardiovascular fitnessCardiovascular fitness will be assessed using a modified, graded, exercise-testing protocol in the field. Endurance capacity will be estimated on the basis of walking/running speed, the corresponding concentration of blood lactate and the perceived exertion of each participant.Additionally, the maximum oxygen uptake (VO2max) and the peak oxygen uptake (VO2peak) will be estimated using the 6-minute Walking Test.
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Motor fitnessGross motor fitness will be assessed using a test battery comprising the following basic motor skills:
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Static and dynamic balance
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Short Physical Performance Battery
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Feet tapping
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Hand tapping
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Kasten-Bumerang Test
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Movement-Coordination Test
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Agility Test
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Fine motor fitness will be assessed using the following subtests of the Vienna Test System:
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Motor performance series
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Sensomotor coodination
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Spatial orientation
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Reaction time
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Response inhibition
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Time/movement anticipation
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Imaging data acquisition
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Structural MRIDTI, T1-weighted structural MRI, FLAIR, high-resolution T2-weighted structural MRI
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Functional MRIResting-state MRI, task-related fMRI. For task-related fMRI, participants will perform three runs of the Hybrid Response Inhibition task [69]. Using identical visual stimulus material the Hybrid Response Inhibition task assesses three subcomponents of response inhibition: response interference, action withholding, and action cancelation (Fig. 3). Stimuli will be presented in the center of the screen. Participants will be asked to perform a button press according to the pointing direction of an arrow and to refrain from a button press whenever the ellipse surrounding the arrows turns blue (nogo−/stop trials). Event-related fMRI data acquisition will be performed using standard echo planar imaging sequences with whole-brain coverage and isotropic voxels. SPM 12 (http://www.fil.ion.ucl.ac.uk/spm) will be used to conduct all image preprocessing and statistical analyses. In addition to standard general linear model analyses, a BOLD lateralization index [70] will be computed for each subcomponent separately. The lateralization index is hypothesized to mediate transfer capabilities in older adults and to be associated with the structural integrity of the corpus callosum.
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PETThe amyloid tracer [18F]Florbetaben will be applied via a venous cannula. Subjects will be instructed to void their bladder to allow rapid excretion of unbound radioactivity. Subjects will be placed on the scanner approximately 70 min after injection. At 80 min p.i. (post injection) two low-dose computer tomography scans will be acquired for position and attenuation correction. At 90 mins p.i., the PET acquisition will be initiated. PET data will be acquired for 20 min. After the scan the subject will be asked about their well-being and instructed to void their bladder to accelerate excretion of radioactivity. Subjects will be instructed to minimize contact with small children and pregnant women for 12 h after tracer injection. The entire examination, including preparation and scanning procedures, can be finished within 3–3.5 h.
Genetics
Statistics
Sample size
Definition and analysis of primary endpoint
Analysis of secondary endpoints
Data management
Responsibilities
Data collection
Data handling
Assessment of safety
Assessment of adverse events (AEs) by investigator
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Mild: temporary event which is tolerated well by the subject and does not interfere with normal daily activities
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Moderate: event which results in discomfort for the subject and impairs their normal activity
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Severe: event which results in substantial impairment of normal activities of the subject