Clinical trial NCT03158337: Effects of Regular Exercise on Cerebrovascular Reserve in Older Adults
Official title: Effects of Regular Exercise on Cerebrovascular Reserve in Older Adults: Role in the Prevention of Age-Related Cognitive Decline
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Aging
Physical Activity
Cognitive Function
Keywords: Exercise
Physical Activity
Brain blood flow
Cognition
Fitness
Lead sponsor: University of Calgary
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2017-05-18
Enrollment: 286
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: While it is well established that physical inactivity is a modifiable risk factor for vascular disease and cognitive decline, the mechanism by which exercise exerts its protective effect on the cerebral circulation and cognition is unknown. This knowledge gap was recognized recently in the Centers for Disease Control \& Prevention and the Alzheimer's Association document "National Public Health Road Map to Maintaining Cognitive Health". Our rationale for these studies is that the identification of physical exercise as a lifestyle factor able to improve cerebrovascular reserve and cognition would establish a strong scientific framework justifying design of a randomized clinical trial that could evaluate the role of physical activity in cerebrovascular health and function.

This research is based on data we obtained from a cross-sectional study that showed significant relations between physical fitness, vascular regulation and cognition. Cerebrovascular reserve and cognition were better maintained in women who were physically active but reduced in women who were sedentary. Our central hypothesis is that regular aerobic exercise mitigates age-related decreases in cerebrovascular reserve, which in turn imparts benefits in cognition. Further, we believe that these effects will persist after the structured aerobic exercise program is terminated.

Our 18 month study began with a 6-month baseline period, followed by a 6-month exercise intervention, and a 6-month follow-up period. In addition, there are 5-year and 10-year follow-up periods. Volunteers (men and women aged ≥ 55 years) from the community were recruited using a variety of recruitment methods including media and distribution lists. After the baseline (pre-training) measurements, participants underwent a six-month aerobic training program, following guidelines previously used by us and according to the new exercise guidelines for older adults established by American College of Sports Medicine and the American Heart Association. The study involves comprehensive assessments of physical fitness, cerebrovascular responses to carbon dioxide at rest and during sub-maximal exercise, and an extensive battery of cognitive function tests.


Eligibility criteria: Inclusion Criteria:

* sedentary status (engages in less than 30 minutes of moderate exercise four days per week or 20 continuous minutes of vigorous exercise two days per week), the ability to walk independently outside or on stairs, body mass index (BMI) \< 35 kg/m\^2, women were at least 12 months postmenopausal on entry into the study

Exclusion Criteria:

* heart/chest pain upon physical exertion, fainting spells/dizziness, surgery or major trauma in the previous 6 months, known asthma or sleep apnea, history of myocardial infarction, angina, arrhythmia, valve disease, chronic heart failure, history of stroke, cardiovascular or cerebrovascular disease, history of chronic headache or migraines, history of blood clots/thrombosis, smokers (within last 12 months), currently taking medication (beta-blockers, anti-depressants, digitalis/digoxin, blood thinners (warfarin), evista (raloxifene), corticosteroids (e.g., prednisone), adrenaline/epinephrine, anti-arrhythmics (e.g., norpace)).

Primary outcomes:
measure: Change in Cognition Assessed by Neuropsychological Test Battery
timeFrame: Measured at baseline (0 and 6 months), exercise intervention completion (12 months) and follow up (18,72 and 132 months)
Secondary outcomes:
measure: Change in Maximal Oxygen Uptake (VO2max) Assessed by Metabolic Cart
timeFrame: Measured at baseline (0 and 6 months), during the exercise intervention (9 months), exercise intervention completion (12 months) and follow up (18,72 and 132 months)
measure: Change in Cerebral Blood Flow Assessed by Transcranial Doppler Ultrasound
timeFrame: Measured at baseline (0 and 6 months), during the exercise intervention (9 months), exercise intervention completion (12 months) and follow up (18,72 and 132 months)
measure: Change in Blood Biomarkers Assessed by Elisa Assays
timeFrame: Measured at baseline (0 and 6 months), during the exercise intervention (9 months), exercise intervention completion (12 months) and follow up (18,72 and 132 months)
measure: Change in Risk/protective factors Assessed by Questionnaires
timeFrame: Measured at baseline (0 and 6 months), during the exercise intervention (9 months), exercise intervention completion (12 months) and follow up (18,72 and 132 months)
Other outcomes:
measure: Change in Sleep Quality Assessed by Polysomnography, Actigraphy and Questionnaires
timeFrame: A sub-sample of participants were assessed at baseline (6 months), exercise intervention completion (12 months) and follow up (18,72 and 132 months).
measure: Change in Brain Structure and Function Assessed by Neuroimaging Modalities
timeFrame: A sub-sample of participants were assessed at baseline (6 months), exercise intervention completion (12 months) and follow up (18,72 and 132 months).
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
Study officials:
affiliation: University of Calgary
name: Marc J Poulin, PhD, DPhil
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tyndall AV, Davenport MH, Wilson BJ, Burek GM, Arsenault-Lapierre G, Haley E, Eskes GA, Friedenreich CM, Hill MD, Hogan DB, Longman RS, Anderson TJ, Leigh R, Smith EE, Poulin MJ. The brain-in-motion study: effect of a 6-month aerobic exercise intervention on cerebrovascular regulation and cognitive function in older adults. BMC Geriatr. 2013 Feb 28;13:21. doi: 10.1186/1471-2318-13-21.
citation: Pannu T, Sharkey S, Burek G, Cretu D, Hill MD, Hogan DB, Poulin MJ. Medication use by middle-aged and older participants of an exercise study: results from the Brain in Motion study. BMC Complement Altern Med. 2017 Feb 10;17(1):105. doi: 10.1186/s12906-017-1595-5.
citation: Gill SJ, Friedenreich CM, Sajobi TT, Longman RS, Drogos LL, Davenport MH, Tyndall AV, Eskes GA, Hogan DB, Hill MD, Parboosingh JS, Wilson BJ, Poulin MJ. Association between Lifetime Physical Activity and Cognitive Functioning in Middle-Aged and Older Community Dwelling Adults: Results from the Brain in Motion Study. J Int Neuropsychol Soc. 2015 Nov;21(10):816-30. doi: 10.1017/S1355617715000880.
citation: Tyndall AV, Argourd L, Sajobi TT, Davenport MH, Forbes SC, Gill SJ, Parboosingh JS, Anderson TJ, Wilson BJ, Smith EE, Hogan DB, Hill MD, Poulin MJ. Cardiometabolic risk factors predict cerebrovascular health in older adults: results from the Brain in Motion study. Physiol Rep. 2016 Apr;4(8):e12733. doi: 10.14814/phy2.12733.
citation: Ishigami Y, Eskes GA, Tyndall AV, Longman RS, Drogos LL, Poulin MJ. The Attention Network Test-Interaction (ANT-I): reliability and validity in healthy older adults. Exp Brain Res. 2016 Mar;234(3):815-27. doi: 10.1007/s00221-015-4493-4. Epub 2015 Dec 8.
citation: Drogos LL, Gill SJ, Tyndall AV, Raneri JK, Parboosingh JS, Naef A, Guild KD, Eskes G, Hanly PJ, Poulin MJ. Evidence of association between sleep quality and APOE epsilon4 in healthy older adults: A pilot study. Neurology. 2016 Oct 25;87(17):1836-1842. doi: 10.1212/WNL.0000000000003255.