A Fit Brain is a Healthy Brain. Dane B. Cook, Ozioma Okonkwo, Ryan J. Dougherty, Stephanie A. Schultz & Elizabeth A. Boots

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1 A Fit Brain is a Healthy Brain Dane B. Cook, Ozioma Okonkwo, Ryan J. Dougherty, Stephanie A. Schultz & Elizabeth A. Boots

2 Strong evidence Lower risk of early death Lower risk of coronary heart disease Lower risk of colon cancer Lower risk of breast cancer Prevention of weight gain Weight loss, particularly when combined with reduced calorie intake Prevention of falls Better cognitive function (for older adults) Reduced depression Lower risk of stroke Lower risk of high blood pressure Lower risk of adverse blood lipid profile Lower risk of type 2 diabetes Lower risk of metabolic syndrome Improved cardiorespiratory and muscular fitness

3 Physical activity and exercise Physical Activity: any bodily movement produced by skeletal muscles that results in energy expenditure Exercise: a subset of physical activity that is planned, structured, and repetitive and has as a final or an intermediate objective the improvement or maintenance of physical fitness. Physical fitness: a set of attributes that are either health- or skill-related. The degree to which people have these attributes can be measured with specific tests.

4 Physical inactivity was found to be the greatest individual risk factor for dementia in the US 21% AD cases (>1.1 million) Barnes and Yaffe, 2011

5 Physical activity and cognition Greater physical activity is associated with: Improved cognitive performance Decreased risk for cognitive decline 20/24 longitudinal studies Moderate and vigorous activity was found to protect against cognitive decline over a 2.5 year span (N=17,710) Bherer et al., 2013; Aichberger et al., 2010; Etnier et al., 2006

6 Physical activity across the lifespan protects against cognitive impairment Prevalence (%) of cognitive impairment % 29.7% N=9, % 21.1% %=Reported being sedentary Active Inactive 0 Teenage Age 30 Age 50 Old Age Middleton et al. 2010

7 Fitness and cognition Colcombe and Kramer, 2003; Smith et al., 2010

8 Why not exercise? large-scale interventions intending to examine the disease-modifying potential of non-pharmacological approaches are rarely conducted to the extent, breadth, or rigor of pharmaceutical trials.. to a misunderstanding of the complexity of the pathways by which lifestyle factors (e.g. physical activity) exert their effects on the endogenous pharmacology of the brain. Erickson et al., 2012

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10 Both physical activity and fitness are associated with greater brain volume & improved cognitive function Physical Activity (n=299) Erickson et al., 2010 Range = 0 to 300 blocks

11 Both physical activity and fitness are associated with greater brain volume & improved cognitive function Fitness (n=142) Fitness was associated with improved cognitive function GMV in DLPFC mediated this relationship Weinstein et al. 2012

12 Both physical activity and fitness are associated with greater brain volume & improved cognitive function Exercise Training (n=120) Erickson et al. 2011

13 WRAP cohort data demonstrate that physical activity is associated with age-related AD biomarkers Okonkwo et al., 2014

14 WRAP cohort data demonstrate that estimated cardiorespiratory fitness is associated with age-related AD biomarkers Boots et al., In Press

15 Fitness, Aging & the Brain (FAB) study

16 Objective measures of physical activity and sedentary behaviors 60 Weekday Vigorous High-Moderate 30 Low-Moderate Average Minutes/Hour Average Minutes/Hour am 1-2am 2-3am 3-4am 4-5am 5-6am 6-7am 7-8am 8-9am 9-10am 10-11am 11am-12pm 12-1pm 12-1am 1-2am 2-3am 3-4am 4-5am 5-6am 6-7am 7-8am 8-9am 9-10am 10-11am 11am-12pm 12-1pm Weekend 1-2pm 2-3pm 3-4pm 4-5pm 1-2pm 2-3pm 3-4pm 4-5pm 5-6pm 6-7pm 7-8pm 8-9pm 9-10pm 10-11pm 11pm-12am 5-6pm 6-7pm 7-8pm 8-9pm 9-10pm 10-11pm 11pm-12am Light (standing still) Light (movement) Sedentary 60+ Sedentary Sedentary Sedentary Sedentary Sedentary Sedentary 0-10 Vigorous High-Moderate Low-Moderate Light (movement) Light (standing still) Sedentary 60+ Sedentary Sedentary Sedentary Sedentary Sedentary Sedentary 0-10 Average Minutes/Day Light Avg light 60+ Avg light Avg light Avg light Avg light Avg light Avg light 0-10 Average Minutes/Day Sedentary Avg sed 60+ Avg sed Avg sed Avg sed Avg sed Avg sed Avg sed 0-10

17 Future Directions

18 Exercise maintains/improves brain health Neurogenesis Oxidative Stress Angiogenesis Insulin Sensitivity Immune Amyloid & Tau Clearance

19 Study design and work out plan 60%-70% HRR 70%-80% HRR HR (bpm) %-60% HRR min/day 3 days/week min/day 3 days/week 50 min/day 3 days/week < 50% HRR < 50% HRR < 50% HRR Exercise Stretching min/day 3 days/week min/day 3 days/week 1 to 4 5 to 8 9 to 26 Weeks 50 min/day 3 days/week

20 Effect of Intervention: Depends on Extra-Intervention Behavior? Glucose Metabolism Control group Intervention group AND decreased sedentary behavior outside of intervention Intervention group BUT no change in sedentary behavior outside of intervention Intervention group BUT increased sedentary behavior outside of intervention Time Alzheimer s Association Grant # Aerobic exercise for AD prevention in at-risk middle-aged adults (Okonkwo PI)

21 Summary Physical activity and fitness are important determinants of healthy aging Exercise has the potential to impact numerous neurobiological pathways that can potentially modify the aging process and help to maintain cognitive function and QOL Future research is needed to determine: Dose Types of exercise Mechanisms For whom exercise is most beneficial PA measurement At-risk populations

22 Exercise Psychology Lab, UW-Madison Grad students Hawaii, 2012

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