Changes in Cognition During a 24-h Simulated Military Operation
Condition: Cognitive Impairment
MeSH terms: Cognitive Dysfunction
Study type: Interventional

Summary: 
      Sustained military operations (SUSOPs) result in psychological stress and cognitive
      dysfunction, which may be related to the recruitment of classical monocytes into the brain.

      Goals:

        -  To investigate the effect of sustained-release beta-alanine on changes in cognition and
           markers of immune cell recruitment during a 24-hour simulated military operation.

        -  To examine associations between changes cognition and changes in markers mediating
           immune cell recruitment.
    

Detailed description: 
      Sustained military operations (SUSOPs) expose soldiers to a multitude of stressors, including
      sustained physical activity, caloric deficit, and sleep deprivation. Several studies have
      shown that the combination of these factors result in psychological stress, which often leads
      to significant cognitive impairment.

      Psychological stress has been shown to result in activation of neuroendocrine pathways that
      signal into the periphery and relay information from the brain to the immune system. This
      process is generally characterized by elevations of several key pro-inflammatory cytokines,
      chemokines, secondary messengers and reactive oxygen species. Notably, peripheral classical
      monocytes are reported to undergo recruitment to the brain during periods of psychological
      stress following priming by cytokines secreted from activated microglia.

      Carnosine, an endogenous dipeptide consisting of beta-alanine and L-histidine, has been shown
      to inhibit the synthesis of inflammatory and oxidative mediators in microglia in vitro.
      Beta-alanine, which is the rate limiting amino acid in carnosine formation has been shown to
      increase carnosine concentrations in various regions of the brain in rodents which been
      associated with biochemical changes that resulted in favorable improvements in resilience to
      stress exposure. However, data on the effects of beta-alanine supplementation on cognition in
      humans is less clear. Further, the effect of beta-alanine supplementation on systemic and
      cellular mediators of monocyte recruitment has not been examined.

      Goals:

        -  To investigate the effect of sustained-release beta-alanine on changes in psychological
           stress and cognition using Automated Neuropsychological Assessment Metric (ANAM)
           cognitive assessments during a 24-hour simulated military operation.

        -  To examine the effect of sustained-release beta-alanine on monocyte chemoattractant
           protein-1 (MCP-1), interleukin-8, Lymphocyte function-associated antigen-1 (CD11a),
           macrophage-1-antigen (CD11b) expression and C-C chemokine receptor 2 (CCR2) expression
           on neutrophils and classical monocytes during a 24-hour simulated military operation.

        -  To examine associations between MCP-1, interleukin-8, CD11a, CD11b, CCR2 and a composite
           measure of cognition derived from ANAM assessment scores during a 24-hour simulated
           military operation.

      Method:

      Double-blind placebo controlled trial compared the effect of supplementation with sustained
      release beta-alanine (12 grams per day) versus placebo (equivalent amount of rice powder) on
      cognition and monocyte responses during a 24-hour simulated military operation consisting of
      sleep-restriction, caloric restriction, and acute and sustained periods military specific
      physical activity.

      Supplementation occurred over a period of 14 days prior to completion of the simulated
      military operation. ANAM tests were assessed and blood samples taken upon arrival to the lab
      for the 24 hour simulated operation (0 hours) and at 12, 18 and 24 hours during the SUSOP.
    

Intervention name(s): beta-alanine; placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): beta-alanine tablet; rice powder tablet
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Other
Keywords: beta-alanine; immune cells