Enhancing Cognition in Older Adults With Intermittent Hypoxia and Cognitive Training
Condition: Aging
MeSH terms: Hypoxia
Study type: Interventional

Summary: 
      The current study will investigate methods for enhancing cognitive training (CT) effects in
      healthy older adults by employing a combination of interventions facilitating neural
      plasticity and optimizing readiness for learning. Adults over the age of 65 represent the
      fastest growing group in the US population. As such, age-related cognitive decline represents
      a major concern for public health. Recent research suggests that cognitive training in older
      adults can improve cognitive performance, with effects lasting up to 10 years. However, these
      effects are typically limited to the tasks trained, with little transfer to other cognitive
      abilities or everyday skills. A pilot randomized clinical trial will examine the individual
      and combined impact of pairing cognitive training with an intermittent hypoxia (IH)
      intervention. The investigators will compare changes in cognitive and brain function
      resulting from CT combined with active IH versus CT combined with sham IH using a
      comprehensive neurocognitive, clinical, and multimodal neuroimaging assessment of brain
      structure, function, and metabolic state. Functional magnetic resonance imaging (FMRI) will
      be used to assess brain response during speed of processing; the active cognitive abilities
      trained by CT. Magnetic resonance spectroscopy (MRS) will assess cerebral metabolites,
      including ATP and GABA concentrations sensitive to neural plasticity.
    

Detailed description: 
      Age-related cognitive decline has become a major public health concern. As the population
      ages, the number of older adults experiencing cognitive and functional disturbances has
      increased. There is currently a paucity of effective interventions to prevent or treat
      cognitive decline or to enhance brain function in the elderly. The proposed study will
      recruit a cohort from the state with the highest growth of older adults. The study team will
      employ a randomized controlled trial (RCT) to test whether the benefits of cognitive training
      (CT) can be enhanced by a combined adjunctive intervention aimed at increasing neural
      plasticity and optimizing readiness for learning: intermittent hypoxia (IH).

      Current CT approaches have been shown to improve performance on trained tasks, with effects
      lasting up to ten years. However, generalization of effects to other cognitive domains and
      everyday functioning has been a problem in the past. There is now compelling evidence that
      the elderly do experience functional improvements that persist long after initial training,
      though peoples' ability to derive such benefits varies. Combined interventions have rarely
      been examined and methods aimed at increasing neural plasticity and optimizing readiness for
      learning are only now beginning to be explored. The proposed study will test one theoretical
      approach for facilitating and optimizing CT effects on functional outcome. The investigators
      will use an adjunctive physiological method to further stimulate task-related brain regions,
      directly enhancing neural responsivity/plasticity and ultimately learning. While theoretical
      rationales exist for each of these approaches, no studies to date have shown whether
      adjunctive administration can optimize learning and functional status in the elderly.

      A pilot randomized clinical trial will enroll 55 participants, with a target of 20
      participants completing the study, and as many as 30 participants consenting but failing to
      meet inclusion criteria at in person screening, and 5 participants withdrawing prior to
      completion. Cognitively healthy elderly adults, age 65-89 will undergo either a CT
      intervention in combination with IH or sham IH control. The CT intervention will employ the
      Double Decision task from the POSIT Science Brain HQ; a well validated CT method for
      enhancing cognitive functioning in the elderly. Participants will receive IH or sham/placebo
      IH administered during training.

      Participants will be assessed at baseline and after CT (2 weeks). At each time point, a
      comprehensive neurocognitive, clinical and multimodal neuroimaging assessment of brain
      function, metabolic state, and brain structure will be conducted.

      FMRI will be used to assess brain response during working memory, attention and memory
      encoding. Proton magnetic resonance spectroscopy (MRS) will assess cerebral metabolites,
      including gamma-aminobutyric acid (GABA) concentrations, sensitive to neural plasticity in
      task-associated brain regions.
    

Intervention name(s): Acute Intermittent Hypoxia; Computerized Cognitive Training
Intervention type(s): Device; Behavioral
Intervention description(s): Acute intermittent hypoxia is a safe, non-invasive technique. All sessions will be monitored by research study staff trained in delivering acute intermittent hypoxia. Hypoxic intervals will be delivered with a commercially available sports performance hypoxicator. A unit capable of delivering a fraction of inspired oxygen ranging from 21%-9% will be used. Air will be delivered into a mask that will be secured comfortably over the subject's nose and mouth. Intervention sessions will occur for 10 days over a 2 week period.; 60 minutes of Double Decision cognitive training for 10 days over a 2 week period.
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: Intermittent Hypoxia; Cognitive Training