Exercise as an intervention across cognition and mood

Joe Verghese, MBBS, MS

Albert Einstein College of Medicine

Bronx, NY

Disclosure 1: Funding received from National Institutes On Aging (grants PO1 AGO3949 and RO1 AGO25119)

Disclosure 2: The speaker has not received any funding from these companies (not even a cup of coffee!)

Exercise

• Good for the brain?

• Good for mood?

• Which activities?

• How much?

• How do they work?

Strength of evidence?

• Mental exercise

• Physical exercise

• Social activities

Observational Vs. RCT

Fratiglioni, Lancet Neurol 2004

Bronx Aging Study

Inception: 1980-1983

488 volunteersAge 75-85

Community living 90% Caucasian 65% women

No dementia

Katzman R, Ann Neurol 1989, Verghese J, NEJM 2003

469 nondemented subjects

Clinical, neuropsychological evaluations at entry and at 12-18 mo follow-up visits

Study period: 1980-2001

124 Dementia30 Vascular dementia 25 Mixed dementia

Cognitive

Physical

7 : almost daily

4: several days

1: once weekly

0: < weekly or never

Leisure activity scales Cognitive activity scale (0-42)

Physical activity scale (0-77)

XX X X

X X

X X X X

X

Activity days

Hazard ratio (95% CI)

CognitivePhysical

Dementia 124 0.93 (0.90-0.97) 1.00 (0.98-1.03)

Vascular 30 0.92 (0.86-0.99) 1.01 (0.97-1.04)

Mixed 25 0.87 (0.78-0.93) 0.90 (0.83-1.03)

aMCI 58 0.95 (0.91-0.99) 0.97 (0.93-1.00)

VCI 83 0.94 (0.91-0.98) 1.01 (0.98-1.04)

Verghese NEJM 2003, Neurology 2006

Honolulu-Asia study2257 men 71-93y

Vs. 2mi/day<0.25: HR 1.770.25 to 1: HR 1.71

Abbott, et al. JAMA 2004

Nurses Health Study18,766 women 70-81y

Walking better baseline cognitionPhysical activity ↓ cognitive decline

Weuve J, et al. JAMA 2004

Bronx Aging studyWalking HR 0.67 (0.45-1.05)

Dancing and risk of dementia Adjusted Hazard Ratio 0.24 (0.06-0.99)

Verghese J, N Engl J Med 2003

Dancers Non-dancers p (24) (84)

------------------------------------------------------------ ------Blessed test 2.0 2.0 .92FCSRT 47.9 47.9 .79 Block design 23.1 23.1 .97Digit span 14.5 14.9 .52Digit Symbol 45.3 46.1 .75Verbal Fluency 39.1 37.8 .67Trail Making B 146.5 165.4 .95

Matched by age, sex, and education.

Dancers have better gait but not cognition

Verghese J, J Am Geriatr Soc 2006

Life-p

Table c.1.10.1. Cognitive tests at baseline and 12-mo in the entire cohort

Baseline 12 mo

Cognitive Test Mean SD Mean SDDSST 47.0 12.3 46.6 14.2

Rey Short 6.9 3.0 7.7 2.7Rey Long 6.1 3.3 6.9 3.1Rey Inference 3.7 1.6 3.9 1.43MS 90.6 6.4 91.0 6.5Stroop 40.8 22.3 39.7 22.0

Figure c.1.10.1Figure c.1.10.1

Ball, K. JAMA 2002

MemoryMnemonics, list recallN =703

ReasoningProblem solvingN = 699

Processing speedVisual searchN = 702

ControlN = 698

ACTIVE trial

Exercise and mood

• Two meta-analyses of RCT of exercise and depression.

Lawlor & Hopker, BMJ 2001

Stathopoulou G., et al. Clinical Psychology 2006

Lawlor & Hopker. BMJ 2001;322:763

Lawlor & Hopker. BMJ 2001

RCT: PHYSICAL EXERCISE Vs. No INTERVENTION

Pooled standardized mean difference in effect size: -1.1 (95% CI -1.5 to -0.6).

Pooled standardized mean difference in effect size: -0.3 (95% CI -0.7 to 0.1)

Lawlor & Hopker. BMJ 2001

RCT: EFFECT OF PHYSICAL EXERCISE Vs. COGNITIVE THERAPY

Stathopoulou, G., et al. Clinical Psychology: Science and Practice 2006, 13, 179–193.

• RCT with non-active comparison (wait list, placebo, low level exercise, health education)

• Depression secondary to medical illness excluded

Mean overall effect size: 1.39 (95% 0.89 to 1.82)

N Age Intervention Effect Ref

32 70 • Resistance training 3/wk• Health seminar 2/wk

No Singh, et al.1997

30 72.5 • Walk x 40 min - 3/wk• Chat x 1h - 2/wk• Wait list control

Social: NOWait list: YES

McNeill, et al. 1991

32 71.3 • Weight lifting 10 wk followed by unsupervised exercise 10 wk• Lectures x 10 wk

Beck DI

↓ at 26 mo

Singh, et al. 2005

156 57 • Exercise 3/wk x 16wk• Antidepressant• Combination

No difference20% drop out

Blumenthal, et al. 1999

86 63 •.Weight/stretch x 10wk• Health Education

p = 0.05 Mather, et al. 2002

All the world's a stage, And all the men and women merely players;They have their exits and their entrances; and one man in his time plays many parts, His acts being seven ages……………. Last scene of all, that ends this strange eventful history, Is second childishness and mere oblivion; Sans teeth, sans eyes, sans taste, sans everything."

Shakespeare Wm. As you like it. Act II, Scene VII

How much?

Cognitive Activity Scale (0-42)

Dementia Hazard ratio 0.93 (7% risk reduction)  

1

4

Low levels of participation!

TVRead

KnitPuzzles

ChessCards

ComputerWrite

MusicSing

MuseumTheatre

EducationGroups

0

1

2

3

4

5

6

73 urban elderlyMean age 80.5 y90% women

Ambrose AF, Poster A77: AGS 2005Mean activity scores

Mechanisms

• Cardiac fitness

• Neurobiological benefits of exercise:

Serotonin, endorphin, neurotrophic factors

• Stress

• Improved sleep patterns

• Cognitive reserve

Brain effects

6 month RCT 59 sedentary elderly Aerobic exercise group vs. stretching/toning

Colcombe et al. J Gerontol A Biol Sci Med Sci2006

11 subjects33y (21-45)Aerobic 4/wk x 11

Pereira As, et a. PNAS 2007

Can leisure activities be bad for you?

Daily TV viewing 1.32 (1.08 – 2.62)

Social activities 0.82 (0.68 – 0.98)Physical activities 1.11 (0.89 – 1.38)Intellectual activities 0.84 (0.72 – 0.98)

Adjusted for age, gender, education, and income.

Lindstrom, et al. Brain & Cognition, 2005

Exercise Challenges 1

• Small studies, volunteer populations

• Brief follow-up.

Effective short term but long term?

• Give up easily: 20% drop out rate

• Less active at baseline

• Poor maintenance behaviors: dyads

Exercise Challenges 2

• Aerobic vs. Anaerobic

• Physical, Cognitive, Social, or all three?

• Cognitive domain specific

• Biomarkers (track effect and change)