Effect of Lifestyle Changes on BDNF Level After Stroke

This is a substudy of the study entitled "Assessing a Multi-Disciplinary Lifestyle Medicine
Intervention Following Stroke," specifically looking at the effects of lifestyle change on
brain-derived neurotrophic factor (BDNF). BDNF has emerged as a key facilitator of
neuroplasticity to improve motor learning and rehabilitation after stroke. Aerobic exercise
has been shown to increase levels of BDNF in multiple parts of the central nervous system and
therefore may facilitate neuroplasticity and motor recovery. While BDNF levels appear to be
increased for up to 1 hour following a bout of aerobic exercise, it is unclear whether
regular aerobic exercise over weeks to months can increase baseline BDNF levels in humans
following stroke.

An single nucleotide polymorphism exists on the BDNF gene in 30-50% of the human population
that results in an amino acid change from valine (val) to methionine (met) at position 66
(val66met) of the precursor peptide proBDNF. The presence of the met allele results in a 25%
reduction in activity-dependent secretion of BDNF in the CNS.

The Wellness in Rehabilitation program at the VA Palo Alto Health Care System is a lifestyle
medicine intervention for patients following stroke. It is a 12-week program involving weekly
meetings that include exercise (particularly aerobic exercise), nutrition, stress management,
education, and group support. Participants are encouraged to perform healthy lifestyle
behaviors (i.e. exercise) daily at home, and a health coach calls each patient weekly to
support the behavior change process.

Participants in the Wellness in Rehabilitation program who elect to participate in the
research study will have blood drawn at baseline, week 6, and week 12. Blood draws will be
performed in the morning prior to exercise, and week 6 will additionally include a blood draw
within 30 minutes of completing a bout of aerobic exercise. Following completion of the
study, plasma BDNF levels (measured as nanograms per milliliter) will then be measured at all
4 time points (baseline, week 6 pre-exercise, week 6 post-exercise, and week 12). In
addition, BDNF genotype will be measured using the baseline sample. Participants will also
complete bike or treadmill exercise testing at baseline and week 12 to determine pre- and
post-program cardiovascular fitness levels (measured as VO2 max and estimated metabolic
equivalents), and will also complete a 6-minute walk test. They will be asked to record their
exercise daily and will additionally complete the Physical Activity Scale for Individuals
with Physical Disabilities at baseline and week 12 time points.

Inclusion Criteria:

- History of prior stroke (ischemic or hemorrhagic) or transient ischemic attack

- Ability to ambulate at least 10 feet with minimal to moderate assistance

- Ability to travel to intervention site on a weekly basis.

Exclusion Criteria:

- Cerebral aneurysm

- Concurrent pregnancy

- Serious terminal illnesses (e.g. end stage renal disease, heart failure (class IV),
cirrhosis (class C), metastatic cancer)

- Any injury or illness preventing participation in regular aerobic exercise

- Moderate-severe dementia or cognitive decline