Effects of Long-Duration Spaceflight on General and Spatial Cognition and Its Neural Basis

Study Overview
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Brief Summary
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This study investigates the effects of extended-duration spaceflight (12-month International Space Station missions) on general cognitive performance (measured with the Cognition test battery), spatial cognition, structural and functional brain changes in general, and hippocampal plasticity more specifically relative to the shorter 6-month and 2-month missions.

Detailed Description
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This is an international proposal consisting of two projects with synergistic aims that will be carried out in a joint effort by the National Aeronautics and Space Administration (NASA) and the German Aerospace Center (DLR) as well as the European Space Agency (ESA). The project targets NASA's particular interest in studying the 'Cognitive-perceptual-visuospatial brain domain changes due to isolation and confinement' as part of the Complement of Integrated Protocols for Human Exploration Research (CIPHER) project on the International Space Station (ISS). The collected data will demonstrate whether prolonging mission duration to one year will have detrimental effects on general cognitive performance (measured with the Cognition test battery), spatial cognition, structural and functional brain changes in general, and hippocampal plasticity more specifically relative to the shorter 6-month and 2-month ISS missions. Using state-of-the-art neuroimaging techniques, investigators will determine the biological basis for any changes in cognitive performance, with a focus on hippocampal plasticity and spatial cognition. Similar data already gathered on the ISS and in several short- and long-duration space analog environments will be used to generate a normative data base for long-duration missions. Finally, investigators will derive dose-response relationships between cognitive-visuospatial brain domain changes and mission duration that will allow predicting vulnerability to adverse cognitive or behavioral impairment and psychiatric disorders on interplanetary expeditions such as a mission to Mars. The two projects will deliver a highly unique and comprehensive set of integrated neuroimaging and neurocognitive tools for the evaluation and ultimately prevention of adverse effects on brain structure and function that lead to behavioral effects associated with exploration-type missions.

Official Title
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Temporal Nature of Cognitive and Visuospatial Brain Domain Changes During Long-Duration Low-Earth Orbit Missions (Spatial Cognition)

Conditions
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Brain Structure, Cognitive Performance

Intervention / Treatment
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* Other: Spaceflight
* Other: Controls


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Astronauts (according to NASA requirements) Normal, healthy volunteers (astronaut surrogates) - Astronaut surrogates will be matched for sex, age and education relative to astronauts Exclusion Criteria: For astronauts and normal, healthy volunteers (astronaut surrogates): Subjects that do not comply with the MRI testing requirements. The following and other conditions may exclude the subject from MRI scanning or require additional examination to assess specific contraindications: Tinnitus; Sensori-neural hearing loss > 30 decibels (dB); Pace-maker or internal defibrillator; metallic implants (e.g. orthopedic plates after bone fractures, joint replacements, surgical staples or clips, artificial heart valves, stents, cava filters); Metallic splinters (e.g. after an accident or due to war injury); Non-removable dental brace; Intrauterine contraceptive devices (IUD) that are not MRI-compatible; Cochlear implant (implanted hearing device); Medication pump; Acupuncture needle; Other foreign bodies/objects which are non-removable; Pregnancy (or its possibility); Previous brain and/or heart surgery. Tattoos and/or permanent make-up in the body (some inks contain metallic particles). Female subjects in this study are either astronauts or will model those in the astronaut population for whom participation in space missions is not allowed during pregnancy.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study will investigate 10 astronauts on 12-month ISS missions, 10 astronauts on 12-month ISS missions, 10 astronauts on 12-month ISS missions and 10 control subjects that are matched to 12-month mission astronauts and investigated at similar time points.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2-Month Arm<br>Astronauts on 2-month International Space Station missions will be exposed to spaceflight for a duration of 2 months. Biometric and cognitive data will routinely be collected. | Other: Spaceflight<br>* Exposure to the spaceflight environment on the International Space Station for 2, 6, or 12 months.<br>|
| Experimental: 6-Month Arm<br>Astronauts on 6-month International Space Station missions will be exposed to spaceflight for a duration of 6 months. Biometric and cognitive data will routinely be collected. | Other: Spaceflight<br>* Exposure to the spaceflight environment on the International Space Station for 2, 6, or 12 months.<br>|
| Experimental: 12-Month Arm<br>Astronauts on 12-month International Space Station missions will be exposed to spaceflight for a duration of 12 months. Biometric and cognitive data will routinely be collected. | Other: Spaceflight<br>* Exposure to the spaceflight environment on the International Space Station for 2, 6, or 12 months.<br>|
| Experimental: No Intervention<br>Subjects matched to 12-month astronauts that stay on Earth and are investigated at similar time points. | Other: Controls<br>* No intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive performance | Cognitive efficiency across domains as determined with the Cognition test battery | Change from pre-flight performance (average of tests performed 180, 120 and 60 days prior to launch) to in-flight performance (average of all tests: 1 month mission = 1 test, 2 months = 2 tests, 6 months = 6 tests, 12 months = 12 tests) | 
| Local task activation Cognition | fMRI local task activation while performing the MRI version of Cognition in the scanner | Change from pre-flight local task activation (investigated 60 days prior to launch) to post-flight local task activation (investigated 5 days and 30 days after return to Earth) | 
| Spatial cognition performance | Accuracy and reaction times for each cognitive task as determined with the Spatial Cognition test batteries | Change from pre-flight performance (average of tests performed 180, 120 and 60 days prior to launch) to in-flight performance (average of all tests: 1 month mission = 1 test, 2 months = 2 tests, 6 months = 4 tests, 12 months = 7 tests) | 
| Structural brain changes | Structural brain changes assessed with MRI | Change from pre-flight local task activation (investigated 60 days prior to launch) to post-flight (investigated 5 days and 30 days after return to Earth) | 
| Local task activation Spatial Cognition | fMRI local task activation while performing visuospatial tasks in the scanner | Change from pre-flight local task activation (investigated 60 days prior to launch) to post-flight local task activation (investigated 5 days and 30 days after return to Earth) | 
| Brain-Derived Neurotropic Factor (BDNF) | Changes in Brain-Derived Neurotropic Factor (BDNF) | Change from pre-flight values (average of blood drawn180 and 60 days prior to launch) to in-flight values (average of all in-flight blood draws: 1 month mission = 1 draw, 2 months = 2 draws, 6 months = 4 draws,12 months = 7 draws) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin-like Growth Factor 1 (IGF-1) | Changes in Insulin-like Growth Factor 1 (IGF-1) | Change from pre-flight values (average of blood drawn180 and 60 days prior to launch) to in-flight values (average of all in-flight blood draws: 1 month mission = 1 draw, 2 months = 2 draws, 6 months = 4 draws,12 months = 7 draws) | 
| Vascular Endothelial Growth Factor (VEGF) | Changes in Vascular Endothelial Growth Factor (VEGF) | Change from pre-flight values (average of blood drawn180 and 60 days prior to launch) to in-flight values (average of all in-flight blood draws: 1 month mission = 1 draw, 2 months = 2 draws, 6 months = 4 draws,12 months = 7 draws) | 
| Oxytocin | Changes in Oxytocin | Change from pre-flight values (average of blood drawn180 and 60 days prior to launch) to in-flight values (average of all in-flight blood draws: 1 month mission = 1 draw, 2 months = 2 draws, 6 months = 4 draws,12 months = 7 draws) | 
| Interleukin (IL)-1 | Changes in Interleukin (IL)-1 | Change from pre-flight values (average of blood drawn180 and 60 days prior to launch) to in-flight values (average of all in-flight blood draws: 1 month mission = 1 draw, 2 months = 2 draws, 6 months = 4 draws,12 months = 7 draws) | 
| Interleukin (IL)-1ra | Changes in Interleukin (IL)-1ra | Change from pre-flight values (average of blood drawn180 and 60 days prior to launch) to in-flight values (average of all in-flight blood draws: 1 month mission = 1 draw, 2 months = 2 draws, 6 months = 4 draws,12 months = 7 draws) | 
| Interleukin (IL)-10 | Changes in Interleukin (IL)-10 | Change from pre-flight values (average of blood drawn180 and 60 days prior to launch) to in-flight values (average of all in-flight blood draws: 1 month mission = 1 draw, 2 months = 2 draws, 6 months = 4 draws,12 months = 7 draws) | 
| Tumor Necrosis Factor a (TNFa) | Changes in Tumor Necrosis Factor a (TNFa) | Change from pre-flight values (average of blood drawn180 and 60 days prior to launch) to in-flight values (average of all in-flight blood draws: 1 month mission = 1 draw, 2 months = 2 draws, 6 months = 4 draws,12 months = 7 draws) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Astronauts, Spaceflight, Cognition, Long Duration Spaceflight