**9. Limitations and suggestions**

The good news is, lines of inquiry utilizing neuroimaging are still rather novel and as such, there is much to study. The bad news is, these lines of inquiry utilizing neuroimaging are still rather novel and there is much to learn, so omissions and/or mistakes in research design are to be expected. Investigating how exercise impacts the brain is akin to the first studies investigating how exercise impacted the heart and its related vasculature several decades ago.

A limitation in several structural imaging studies (e.g., Marks et al. 2010; Bullitt et al. 2009; Colcombe et al., 2006) was lack of cognitive function testing – it is unknown if the improved brain structures found in the more active subjects would have translated into better cognitive function. Adding cognitive testing with magnetic resonance imaging (MRI) may help detect subtle changes that the standard cognitive test batteries if used alone, cannot. If the MRI is able to detect changes, independent of the cognitive tests, a therapeutic program could be implemented at an earlier stage of decline and perhaps be more effective in reducing further impairment.

MRI Techniques to Evaluate Exercise Impact on the Aging Human Brain 245

Aerobic fitness not only facilitates improved oxygen delivery and utilization in the cardiocerebral vascular systems, improved oxidative capacity has been shown to up-regulate expression of important neuronal growth factors such as insulin-like growth factor I (IGF-I), brain-derived neurotrophic factor (BDNF) and related protein precursors in animal models (Ding et al., 2006; van Praag et al., 2005). Furthermore, aerobic fitness may mediate improved cerebral white matter integrity via the intricate adaptations that take place on the neural-humoral level during exercise (Marks et al., 2010). Therefore, exercise outcome studies trials need to include not only structural imaging detailed in this paper, but also

In summary, the research questions that remain to be answered are: What is a sufficient exercise dose for the brain? How much, or how little, exercise is really needed to maintain brain structure and cognitive function? Will any type of physical activity do? Will the resultant health recommendations for the brain be complementary to the current guidelines

To move the future of brain training research forward, we must continue to revisit the past ground-breaking cardiovascular research studies and modify them for the brain. Ancient physicians and philosophers like Hippocrates and Cicero espoused the benefits of exercising both the body and the mind, and here we are, 2,000 years later, scientifically documenting the neurobiological benefits of exercise. Several investigators have been using a few standard cardiovascular disease risk reduction guidelines with success in maintaining brain volume in older adults, but so many more exercise options remain to be explored. Hopefully it will not take another 50 years to firmly establish exercise guidelines for maintaining and

The University of North Carolina at Chapel Hill's Libraries provided support for open

Allen, J.S., Damasio, H., Grabowskia, T.J., Brussa, J. and Zhang, W. (2003). Sexual

American College of Sports Medicine. (2009). *ACSM's Guidelines for Exercise Testing and Prescription*, 8th Edition, New York: Lippincott, Williams and Wilkins American College of Sports Medicine. (1990). The recommended quantity and quality of

Armstrong, L.E., Soto, J.A., Hacker, F.T., Casa, D.J., Kavouras, S.A., Maresh, C.M. (1998).

Borg GAV. (1985). *An introduction to Borg's RPE Scale*. Ithaca, NY:Movement Publications. Baumgartner, T.A. & Jackson, A.S. (1995). *Measurement for Evaluation in Physical Education and Exercise Science*, (p. 289) Brown & Benchmark Publ., Madison:WI

dimorphism and asymmetries in the gray–white composition of the human

exercise for developing and maintaining cardiorespiratory and muscular fitness in

Urinary indices during dehydration, exercise, and rehydration. I*nt. J. Sport Nutr.* 8:

**10. Conclusions** 

for cardiovascular health?

**11. Acknowledgment** 

345-355

access publication.

**12. References** 

enhancing brain health with exercise.

cerebrum, *NeuroImage*, 18:880-894

healthy adults. *Med Sci Sports Exerc*, 22:265-274

hormonal measurements and perfusion imaging.

*Directions: Query the participant regarding his/her extent of physical activity using the activity descriptors below as well as established metabolic tables for physical activity.* 

#### **A. No regular participation in programmed recreational sport or physical activity:**

0 = avoid walking or exertion (always use elevator, drive whenever possible instead of walking.)

1 = pleasure slow walking, routinely use stairs, occasionally heavy breathing or perspiration

**B. Regular participation modest/moderate physical activity ( e.g. golf, horseback riding, calisthenics, gymnastics, table tennis, bowling, weight lifting, yard work etc):** 

2 = 10 to 60 minutes per week

3 = over one hour per week

**C. Regular participation in heavy physical exercise (e.g. jogging, running, swimming, cycling, rowing, skipping rope, running in place, tennis, basketball, or handball etc.):** 

4 = run less than 1 mile per week or spend less than 30 minutes per week in comparable heavy physical activity

5 = run 1 to 5 miles per week or spend 30 to 60 minutes per week in comparable heavy physical activity

6 = run 5 to 10 miles per week or spend 1 to 3 hours per week in comparable heavy physical activity

7 = run over 10 miles per week or spend over 3 hours per week in comparable heavy physical activity

Table 3. Physical Activity Rating Scale (PARS; Baumgartner and Jackson, 1995).

There are also scanner issues to deal with when a study design goes from a single acute scan to repeated scans over several months or years. Your scanner must be intra-reliable (i.e, a measure today will yield relatively the same results tomorrow). It is well known among neuroimaging technicians that scanners "drift" over time, therefore it is important to keep track of the drift so you can be sure changes that are seen months from the initial scan are corrected for the drift. Along these same lines, in order to get larger sample sizes, multiple sites may be needed. Therefore all the scanners used must be determined to be inter-reliable. This is generally accomplished with phantom testing.

It is equally important to account for individual brain plasticity - the investigator must understand the normal brain changes over time independent of any treatment so that intervention changes seen can be distinguished from random occurrence or normal aging.

Lastly, dehydration is an issue that only recently has begun to be accounted for in neuroimaging research studies. Care must be taken to ensure the research volunteers are euhydrated, otherwise, the question that may arise when a brain volume increase is reported: Is the increase in brain volume "true"? Or is it due to dehydration known to plague not only the elderly but also exercisers who exercise in a hot environment and may not have hydrated sufficiently? A simple way to account for hydration status is to obtain a urine sample and test it for urine specific gravity using either a dip stick (aka chem. strip) or a small handheld refractometer. A non-smelly light straw-colored urine would suggest the person was adequately hydrated. If a more precise objective measure is needed, the urine specific gravity reading should be between 1.010 to 1.020 (Armstrong et al., 1998).
