Objectives: Difficulty retrieving the right word to communicate a message is the most common complaint in healthy older adults and individuals with stroke-induced language impairment (i.e., aphasia). Novel word learning paradigms have been used to investigate a variety of behavioral and neuromodulatory approaches to improve word retrieval deficits. Previous novel word learning studies have shown that physical exercise can improve long term recall in healthy young adults and that increased levels of dopamine may be responsible for this effect; however, no studies have investigated the effects of exercise on novel word learning in older adults and individuals with aphasia, and very little is known about the mechanisms that support exercise-enhanced word learning in these populations.
The aims of this SPiRE are to: 1) to identify the novel word learning paradigm that facilitates immediate and long-term word recall; 2a) to investigate how acute, moderate-intensity exercise alters levels of serum brain-derived neurotrophic factor (BDNF) and plasma dopamine; and 2b) to describe and quantify the association between novel word learning and any observed changes in serum BDNF and plasma dopamine. This research will provide a platform for future investigations of immediate exercise effects on word learning, which are essential for achieving our long-term goal of developing exercise-based word retrieval interventions for healthy older veterans and veterans with aphasia. Methods: A within subjects crossover design will be used to address Aims 1, 2a and 2b. Subjects will complete aerobic exercise or stretching (training) before engaging in Study Only or Retrieval Practice (learning). Subjects will be counterbalanced within and across conditions. Twelve healthy older veterans and 12 veterans with aphasia, age 65-89 years, will be recruited. The study will comprise 18 sessions over 12 weeks. In Week 1, subjects will undergo baseline blood draws, a physical assessment, cognitive and language assessments, and a practice word learning task. In Weeks 2-12, subjects will complete the four conditions. Each condition will last two weeks, with a one-week break between conditions. In each condition, training and learning sessions will take place on Monday, Wednesday and Friday. Training: Subjects will engage in 30 minutes of moderate-intensity cycling or gentle upper and lower limb stretching (control) prior to engaging in a novel word learning task. Learning: Familiar objects (e.g., cup) will be paired with nonwords (e.g., flark). In the Study Only paradigm, object/nonword pairs will be presented three times across three days (Monday, Wednesday, Friday). In the Retrieval Practice paradigm, object/nonword pairs will be presented during the first session (Monday). In subsequent sessions (Wednesday, Friday), subjects will be asked to recall the nonword name of presented objects. Corrective feedback will be provided on each trial. Testing: Recognition and recall testing without corrective feedback will be administered immediately after learning (short-term memory), before training in the second and third learning session (overnight consolidation) and one week after learning (long-term memory). Blood Draws: Three blood samples will be taken at baseline (rest, 30 minutes, 60 minutes). In each of the four conditions, blood samples will be taking during the first and third learning session (at rest, after training, and after learning). Whole blood will be collected in plain tubes and in anticoagulant-treated tubes for subsequent serum BDNF and plasma dopamine analysis by ELISA. Samples will be analyzed in triplicate to increase reliability. To address Aim 1, we will use a mixed effects model approach to fit repeated measures ANOVAs to word recall scores at after learning (immediate recall) and one week later (long-term recall). To address Aim 2a, we will use a mixed effects model approach to fit repeated measures ANOVA to serum BDNF and plasma dopamine levels obtained at rest, after 30 minutes and 60 minutes at baseline and during training sessions on Monday and Friday. To address Aim2b, we will use a mixed effects model approach to fit ANCOVA mediator analyses to investigate the association between neurophysiological changes (BDNF, dopamine) on word recall (immediate, long-term).

Public Health Relevance

Our aging veteran population will substantially increase over the next 10 years, as the 24.9% of veterans who are currently between 55-64 years of age join the 38.5% who are already over age 65. The risk of stroke more than doubles each decade after age 55, which places our veterans at an ever-increasing risk of suffering stroke-related language impairment (i.e., aphasia). Difficulty retrieving words, which negatively impacts psychosocial well-being and quality of life, is the most common complaint in healthy aging and aphasia. Word retrieval interventions to maintain or restore communicative function are needed. Studies have shown that physical exercise can improve word learning in young adults. This study will investigate the effects of exercise on word learning in aging and aphasia. The results will help us understand how exercise may be used to optimize word retrieval interventions for our aging veterans.

National Institute of Health (NIH)
Veterans Affairs (VA)
Veterans Administration (I21)
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Rehabilitation Research and Development SPiRE Program (RRDS)
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Veterans Health Administration
United States
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