Exercise, Age-Related Memory Decline, And Hippocampal Function

• cognitive function [ Time Frame: change from before (pre) to after (post) 12 weeks of training ] [ Designated as safety issue: No ]
  measures of memory, executive function, attention/processing speed, language, and general intelligence
• aerobic capacity [ Time Frame: change from before (pre) to after (post) 12 weeks of training ] [ Designated as safety issue: No ]
• cerebral blood flow [ Time Frame: change from before (pre) to after (post) 12 weeks of training ] [ Designated as safety issue: No ]
  arterial spin labeling fMRI

The purpose of this study is to test the hypothesis that aerobic exercise leads increased cerebral blood volume in the dentate gyrus of the hippocampus in a sample of young and older adults.

In the US, increased length of life and reduced morbidity and mortality have resulted in a growing number of older adults, the demographic "time bomb" often referred to in discussions of public policy. According to the Census Bureau, the population aged 65 and over will double in size within the next 25 years. Moreover, these older adults will live healthier lives than their predecessors. While this increased length of a healthy life is an undeniable societal benefit, it brings with it a major societal problem: an epidemic of aging-related cognitive decline. The need to develop interventions to address this growing problem is urgent. Aging-related cognitive dysfunction is not diffuse; rather it targets selected brain areas, in particular the frontal lobes and the hippocampal formation. The separate but interconnected subregions of the hippocampus are differentially vulnerable to pathogenic mechanisms, including the normal aging process. A range of in vivo and post-mortem studies have converged on the dentate gyrus (DG) as the hippocampal subregion differentially targeted by the aging process. As with pathogenic processes, any intervention that improves brain function does so with regional selectivity. One such intervention is physical exercise, which has been shown to improve both frontal lobe and hippocampal function. Using a high-resolution variant of functional magnetic resonance imaging (fMRI), the investigators have demonstrated that aerobic training selectively benefitted DG function both humans and mice. In addition, improvement in DG function was associated with improved performance on a word list learning task but not in tasks conventionally thought to be frontal lobe dependent. The human part of the study had significant shortcomings, however: it was small (N = 11), lacked a control group, enrolled only young subjects (age 20-45 years), and employed only a limited neuropsychological testing battery. The overall goal of this proposal is to use the high-resolution variant of fMRI to test the hypothesis that aerobic training will induce improvements in DG function in a sample of younger (age 20-35) and older (50-65) adults, assigned randomly to an active training condition or wait list control group. The investigators will use more comprehensive neuropsychological testing to examine the relationship between changes in DG function and selected cognitive capacities. Taken together with the observation that normal aging differentially targets the DG, this research program will establish that physical exercise is an effective approach for ameliorating the insidious cognitive slide that occurs in aging. Thus, the potential significance of this application is substantial.

• Cognitive Deterioration
• Disorder of Aging

• Behavioral: aerobic training
  12 weeks of aerobic training, 4X/week
  Other Name: Aerobic training
• Behavioral: Wait list
  wait list control condition
  Other Name: Wait list control

• Experimental: aerobic training
  12 weeks of aerobic training, 4X/week
  Intervention: Behavioral: aerobic training
• Placebo Comparator: wait list control
  wait list control condition, 12 weeks to parallel the active intervention group
  Intervention: Behavioral: Wait list

Inclusion Criteria:

1. Age 20-35 years, and 50-65 years
2. English-speaking
3. Ambulatory Interview
4. "Average" fitness as determined by AHA standards (VO2max < 43 and 36 ml/kg/min for men age 20-35 years and 50-65 years, respectively; < 36 and 29 ml/kg/min for women age 20-35 years and 50-65 years respectively)

Exclusion Criteria:

1. Ischemic changes, abnormal blood pressure responses, or any significant ectopy during aerobic capacity testing
2. Cardiovascular disease
3. Uncontrolled high blood pressure (systolic blood pressure ≥ 180 mmHg; or diastolic blood pressure ≥ 105 mmHg on two measures)
4. Current or recent (evidence of disease x 5 years) non-skin neoplastic disease or melanoma. Prostatic carcinoma will not be grounds for exclusion.
5. 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). Well-treated hypothyroidism will not be excluded.
6. HIV infection
7. Pregnant or lactating (participation allowed 3 months after ceasing lactation).
8. Medications that alter inflammation or autonomic nervous system activity
9. Any history of psychosis or ECT
10. Psychotic disorder (lifetime)
11. Current or recent (past 5 years) Major Depressive Disorder, Bipolar Disorder, or Anxiety disorder
12. Current or recent (within past 12 months) alcohol or substance abuse or dependence. Recent use (past month) of recreational drugs.
13. Dietary supplements that affect inflammation or the ANS
14. Cardiac Pacemaker
15. Internal Pump
16. Insulin Pump
17. Tattoo eyeliner
18. Wire Sutures
19. Internal Metal Objects
20. Metal Slivers in Eye
21. Prosthesis
22. Hearing Aid Implants
23. Neurostimulator
24. Metal Fragments
25. Brain Aneurysm Clips
26. Vascular Clips
27. Breast Expander
28. Vena Cava Filter
29. Heart Valve
30. Metal Stents
31. Asthma
32. Hay-Fever
33. Sickle Cell Disease
34. Kidney Disease
35. Pregnant
36. Machinist or ever worked with heavy metals
37. Contraindication to gadolinium, including prior adverse reaction to gadolinium, past or current history of severe breathing difficulty that has been treated by a physician (e.g., asthma, COPD, etc.), and sickle cell disease. History of renal impairment or estimated glomerular filtration rate <30 L/min/1.73m2 is also exclusionary.