Alzheimer’s Disease Annual Update 11/7/2014

1

A Fit Brain is a Healthy Brain

Dane B. Cook, Ozioma Okonkwo, Ryan J. Dougherty, Stephanie A. Schultz & Elizabeth A. Boots

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

http://www.health.gov/paguidelines/guidelines/chapter2.aspx

• 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.

Physical activity and exercise Physical inactivity was found to be the greatest individual risk factor for dementia in the US

Barnes and Yaffe, 2011

21% AD cases(>1.1 million)

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

Physical activity across the lifespan protects against cognitive impairment

0

2

4

6

8

10

12

14

16

18

Teenage Age 30 Age 50 Old Age

Pre

vale

nce

(%

) o

f co

gn

itiv

e im

pai

rmen

t

Active

Inactive

Middleton et al. 2010

N=9,34415.5%

29.7%28.1%

21.1%

%=Reported being sedentary

Alzheimer’s Disease Annual Update 11/7/2014

2

Fitness and cognition

Colcombe and Kramer, 2003; Smith et al., 2010

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

Erickson et al., 2010 Range = 0 to 300 blocks

Both physical activity and fitness are associated with greater brain volume & improved cognitive function

Physical Activity (n=299)

Both physical activity and fitness are associated with greater brain volume & improved cognitive function

Weinstein et al. 2012

• Fitness was associated with improved cognitive function• GMV in DLPFC mediated this relationship

Fitness (n=142)

Erickson et al. 2011

Both physical activity and fitness are associated with greater brain volume & improved cognitive function

Exercise Training (n=120)

Alzheimer’s Disease Annual Update 11/7/2014

3

WRAP cohort data demonstrate that physical activity is associated with age-related AD biomarkers

Okonkwo et al., 2014

WRAP cohort data demonstrate that estimated cardiorespiratory fitness is associated with age-related AD biomarkers

Boots et al., In Press

Fitness, Aging & the Brain (FAB) studyObjective measures of physical activity and sedentary behaviors

0

50

100

150

200

250

Ave

rag

e M

inut

es/D

ay

Light

Avg light 60+ duration

Avg light 50-60 duration

Avg light 40-50 duration

Avg light 30-40 duration

Avg light 20-30 duration

Avg light 10-20 duration

Avg light 0-10 duration

0

100

200

300

400

500

600

700

Ave

rage

Min

utes

/Day

Sedentary

Avg sed 60+ duration

Avg sed 50-60 duration

Avg sed 40-50 duration

Avg sed 30-40 duration

Avg sed 20-30 duration

Avg sed 10-20 duration

Avg sed 0-10 duration

-60

-50

-40

-30

-20

-10

0

10

20

30

40

50

60

12-1a

m

1-2am

2-3a

m

3-4am

4-5am

5-6a

m

6-7am

7-8a

m

8-9am

9-10

am

10-11

am

11am-1

2pm

12-1

pm

1-2p

m

2-3pm

3-4p

m

4-5pm

5-6pm

6-7p

m

7-8pm

8-9p

m

9-10pm

10-11

pm

11pm

-12a

m

Ave

rag

e M

inu

tes/

Ho

ur

Weekday

Vigorous

High-Moderate

Low-Moderate

Light (standing still)

Light (movement)

Sedentary 60+

Sedentary 50-60

Sedentary 40-50

Sedentary 30-40

Sedentary 20-30

Sedentary 10-20

Sedentary 0-10

-60

-50

-40

-30

-20

-10

0

10

20

30

40

50

60

12-1

am

1-2a

m

2-3am

3-4a

m

4-5am

5-6a

m

6-7am

7-8a

m

8-9am

9-10

am

10-11

am

11am

-12p

m

12-1

pm

1-2pm

2-3p

m

3-4pm

4-5p

m

5-6pm

6-7p

m

7-8p

m

8-9pm

9-10p

m

10-11

pm

11pm

-12a

m

Av

erag

e M

inu

tes/

Ho

ur

Weekend

Vigorous

High-Moderate

Low-Moderate

Light (movement)

Light (standing still)

Sedentary 60+

Sedentary 50-60

Sedentary 40-50

Sedentary 30-40

Sedentary 20-30

Sedentary 10-20

Sedentary 0-10

Future DirectionsExercise maintains/improves brain health

Neurogenesis

Angiogenesis

Immune

Amyloid & TauClearance

Insulin Sensitivity

Oxidative Stress

Alzheimer’s Disease Annual Update 11/7/2014

4

70

80

90

100

110

120

130

140

150

1 to 4 5 to 8 9 to 26

HR

(b

pm

)

Weeks

Exercise

Stretching

Study design and work out plan

50%-60% HRR

20 – 35 min/day3 days/week

< 50% HRR

20 – 35 min/day3 days/week

< 50% HRR

50 min/day3 days/week

70%-80% HRR

50 min/day3 days/week

60%-70% HRR

40-50 min/day3 days/week

< 50% HRR

40-50 min/day3 days/week

Glu

cose

Met

abo

lism

Time

Intervention group AND decreased sedentary behavior outside of intervention

Control group

Intervention group BUT increased sedentary behavior outside of intervention

Effect of Intervention: Depends on Extra-Intervention Behavior?

Intervention group BUT no change in sedentary behavior outside of intervention

Alzheimer’s Association Grant #305257 “Aerobic exercise for AD prevention in at-risk middle-aged adults” (Okonkwo PI)

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

Exercise Psychology Lab, UW-MadisonGrad students Hawaii, 2012