Cognitive Control and Physical Exercise

Epidemiological evidence suggest that a set of lifetime exposures including educational and
occupational attainment and leisure activities later in life are associated with more
preserved cognitive and day-to-day functioning and reduced risk of dementia. However, the
specific set of activities that can maintain or improve function in late life are relatively
unexplored. In the current study, we will test the combined efficacy of two such activities:
cognitive training and aerobic exercise. These activities have been shown to increase
cognitive function and brain plasticity, respectively. The cognitive intervention that we
will use is training with the Space Fortress task. This task is aimed at improving cognitive
control processes that underlie multiple activities and are particularly affected by aging.
We hypothesize that combining these two interventions will produce synergistic effects that
will significantly improve cognitive and day-to-day function in healthy older adults.

A total of 90 cognitively-healthy older adults will be recruited and randomly assigned to
one of three conditions: control video game, control exercise and combined exercise and
space fortress training. A range of cognitive and day-to-day functioning will be assessed at
baseline and after three months of training. We will also assess compliance with a
home-based version of the training program from the end of the 3-month laboratory-based
training and the effect of this compliance on measures of cognition and day-to-day
functioning. We hypothesize that the interventions can be sustained over a 1-year period and
that larger benefits will be observed in participants that adhere to the protocol.

We also propose two complementary approaches to investigating the neural correlates of the
beneficial effects of aerobic exercise on cognition: 1) imaging -- we will use a combination
of structural, metabolic, and cognitive activation fMRI studies to evaluate the neural
substrates of the effect of aerobic exercise on cognition. 2) important correlates -- we
will explore the effects of apolipoprotein E (APOE) genotype, inflammatory markers and
cognitive reserve on the cognitive effects of aerobic exercise.

Inclusion Criteria:

1. Age 60-75

2. English-speaking

3. Strongly right-handed

4. BMI > 18.5 and < 32

5. Post-menopausal (women only): no estrogen replacement therapy

6. Sedentary: VO2max < 36 ml/kg/min for men age 60-75; < 29 ml/kg/min for women age
60-75 (determined using Jones Formula Men = (60-(0.55*AGE)) Women = (48-(.37*AGE))

Exclusion Criteria:

1. MRI contraindications (e.g., metallic implants, pacemaker, weight > 350 lbs, waist >
55")

2. Hearing impaired/hearing aids, unable to read newspaper at arm's length with
corrective lenses

3. Objective cognitive impairment

4. Ischemic changes, abnormal blood pressure responses, or any significant ectopy during
aerobic capacity testing

5. Cardiovascular disease

6. Uncontrolled high blood pressure (systolic blood pressure ≥ 180 mmHg; or diastolic
blood pressure ≥ 105 mmHg on two measures)

7. Current or recent (evidence of disease x 5 years) non-skin neoplastic disease or
melanoma

8. Active hepatic disease (not a history of hepatitis) or primary renal disease
requiring dialysis, primary untreated endocrine diseases, e.g., Cushing's disease or
primary hypothalamic failure or insulin dependent diabetes (Type I or II).

9. HIV infection

10. Pregnant or lactating (participation allowed 3 months after ceasing lactation

11. Other medical disorders judge to interfere with study

12. Medications that target CNS (e.g., neuroleptics, anticonvulsants, antidepressants,
benzodiazepines) within the last month

13. Women: any selective estrogen receptor modulator or aromatase inhibitor Men: androgen
ablation/deprivation hormonal therapies

14. Any history of psychosis or electroconvulsive therapy

15. Psychotic disorder (lifetime)

16. Current or recent (within past 12 months) alcohol or substance abuse or dependence.
Recent use (past month) of recreational drugs.

17. Brain disorder such as stroke, tumor, infection, epilepsy, multiple sclerosis,
degenerative diseases, head injury, mental retardation

18. Imaged cortical stroke or large subcortical lacunae or infarct or space-occupying
lesion (≥ 2 cubic cm). Other findings, e.g., periventricular caps or small white
matter hyperintensities, do not result in exclusion

19. Diagnosed learning disability, dyslexia