Impact of Aerobic Fitness on Cerebral White Matter Integrity in the Cingulum
in Older Adults Bonita L. FACSM, Laurence M. Martin Styner4, Elizabeth Bullitt5, Michael Babbitt1, Jessica Hawkins1, J. Keith Smith6 Depts. of 1Exercise and Sport Science, 2Allied Health Sciences, 3Emergency Medicine, 4Computer Science and Psychiatry, 5Neurosurgery and 6Radiololgy University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-8700 Presented: ACSM Conference, May 29, 2008, Indianapolis, IN Marks1,2,3,
Katz1,3,
INTRODUCTION Research suggests that a positive relationship may exist between exercise and cognitive function, particularly executive function (e.g. planning, coordinating complex tasks, etc).1-3 Brain imaging studies have shown that cortical volumes and cerebral white matter (CWM) integrity in the prefrontal brain regions associated with executive function decline with aging.3,4 Furthermore, CWM loss appears to be non-linear, with a more rapid decline occurring after age 60.5 Diffusion Tensor Imaging (DTI) can provide detailed delineation of CWM pathways based on rates of microscopic water diffusion and may enable early detection of micro-structural changes related to cognitive decline. A higher degree of CWM integrity is represented by a greater degree of fractional anisotropy (FA) of diffusion.6 Preliminary research by Marks et al.7 suggested that higher predicted aerobic fitness levels were associated with greater CWM integrity in the cingulum region of the brain. The cingulum is a bundle of white matter fibers that encircle the corpus callosum and is believed to be involved with cardiovascular autonomic regulation. However the preliminary brain mapping7 was simplistic and based on a non-exercise aerobic fitness prediction model. 8 Thus, to better determine the potential anatomical impact of aerobic fitness on the cingulum, more sophisticated testing and analyses were needed. REFERENCES: 1. Etnier, Nowel et al. (2006). Brain Research Reviews, 52:119-130 2. Heyn, Beatriz et al. (2004). Arch Phys Med Rehabil, 85:1694-1700 3. Colcombe & Kramer (2003). Psychol Sci, 14:125-130 4. Madden, Whiting et al. (2004). Neuroimage, 21:1175-1181 5. Courchesne, Chisum et al (2000). Radiology, 216:672-682 6. Mori et al. (2005). MRI Atlas of Human White Matter, Elsevier Press 7. Marks, Madden et al. (2007). Annals of NY Acad Sci, 1097:171-174 8. Jackson, Blair, et al. (1990). Med Sci Sports Exerc, 22:863-870
RESULTS
PURPOSE
ABSTRACT # 1785 INTRODUCTION: Aerobic fitness may help maintain cognitive function in older adults. However, little is known about the potential mechanisms by which improvements in aerobic fitness may lead to these changes. One potential mechanism is cerebral white matter integrity (CWMI). Both CWMI and aerobic fitness decline with aging. Hence, different aerobic fitness levels may be related to varying amounts of CWMI, which then could impact cognitive function. PURPOSE: To determine brain regions with significant positive associations between CWMI and aerobic fitness in older adults. METHODS: 15 older adults (66 + 6 yrs) completed peak VO2 treadmill testing (Modified Pepper Protocol; VO2 peak range = 14 to 54 ml/kg/min). Magnetic resonance (MR) imaging was used to analyze multiple brain regions during rest on a separate day. Structural 3D T1 MP-Rage and diffusion tensor imaging (DTI, 21 directions, repeated 4x) was done using a 3.0 Tesla MR imaging unit. 3D fractional anisotropy (FA) maps were computed from the raw DTI data. Previous research has shown age-related FA declines in the frontal regions, therefore the specific regions of interest (ROI) identified for this study were the cingulum, genu of the corpus callosum, and uncinate fasciculus (UNC). All ROIs were outlined using InsightSNAP software on the FA maps (FA Coefficient of variance = 3.9%). RESULTS: Manova revealed no significant age and gender effects. Bivariate analysis showed an overall positive correlation between FA and VO2 peak for the entire cingulum (r = 0.536, p = 0.032). A multiple regression analysis indicated varying contributions of VO2 peak on the FA within specific segments of the cingulum (anterior: R2 = 0.32, p = 0.014; medial:R2 = 0.18, p = 0.056; posterior: R2 = 0.04, p = 0.25). Analyses of specific segments within the left and right cingulum resulted in significant correlations between FA and VO2peak in the left anterior (r = 0.559, p = 0.030) and left medial (r = 0.572, p = 0.026) segments. Multiple regression revealed that the greatest unique contribution of VO2 peak to the FA variance resided in the medial segment of the left cingulum (R2 =0.33, p = 0.026 ). Genu and UNC results: p > 0.08. CONCLUSION: There are segment and side-specific positive associations between CWMI and aerobic fitness in the cingulum. Med Sci Sports and Exerc, 40:1 Suppl, 2008.
This study determined if there were segmental and hemispheric differences in the impact of aerobic fitness on CWM integrity in the cingulum of the brain in healthy older adults.
Scatterplots Comparing FA to VO2 Peak in Select ROI r = 0.572, R2 = 0.327 R2adj. = 0.275 p = 0.026*
r = 0.559, R2 = 0.312 R2adj. = 0.259 p = 0.030*
r = 0.536, R2 = 0.287 R2adj.= 0.232 p = 0.039*
r = 0.623, R2 = 0.388 R2adj.= 0.341 p = 0.013**
METHODS Subjects Fifteen older adults between 60 - 76 years of age (8 males, 7 females) successfully completed all of the testing procedures. All were healthy and without orthopedic, cardiopulmonary, metabolic, or cognitive limitations Subjects reported exercising over 3 hours a week for the past 10 years or were active less than 90 minutes a week.This research was approved by UNC’s Biomedical Review Board for Human Subjects, Study #05-3151.
Diffusion Tensor Imaging . Structural images were acquired
with a head only 3.0 Tesla MRI unit (Allegra Siemens Medical Systems) with a maximum gradient strength of 40 mT/m and a maximum slew rate of 40 mT/m/msec. A spin echo diffusion tensor weighted sequence was used to acquire the MR images. A baseline image and 21 directional images were acquired (4x) at an isotropic resolution of 2 x 2 x 2 mm. The baseline image was acquired without a diffusion gradient (b = 0). The remaining gradients were b = 1000s/mm2. Fractional anisotropy (FA) and mean diffusivity (MD) was computed from the imaging data. Regions of interest (ROI) were outlined using the InsightSNAP tool (www.itksnap.org). An investigator blinded to subject characteristics outlined and analyzed the anterior, medial, posterior, and total cingulum regions on a slice by slice basis for each subject. High FA measurement stability (coefficient of variance = 3.9%) was measured via three repeated measurements over all datasets. SAMPLE: FAZ
SAMPLE: MDZ
MANOVA revealed no significant age or gender effects on FA (p > 0.27) Multiple Regression Analyses of VO2peak on FA (left + right hemispheres): Anterior Cingulum Medial Cingulum Posterior Cingulum
r = 0.57 R2 = 0.32, r = 0.43 R2 = 0.18, r = 0.19 R2 = 0.04,
R2adj. = 0.27 p = 0.014* R2adj. = 0.12 p = 0.112 R2adj. = - 0.04 p = 0.250
medial anterior
posterior
VO2Peak Assessment On a separate day, subjects underwent a physician-supervised, ECGmonitored ramped peak exercise stress test on a treadmill (TM) utilizing Duke’s Modified Pepper Protocol. Speed progressively increased from 1.5 to 3.3 mph; percent (%) grade increased from 0 to 20%. Oxygen consumption (VO2) was measured using the PARVO TrueMax VO2 Metabolic Cart System (ParvoMedics, Salt Lake City, Utah ). Blood pressure and ratings of perceived exertion were also recorded at every stage. The test was terminated when subjects reached volitional exhaustion. All subjects attained or slightly exceeded their age-predicted maximum heart rates.
VO2 peak: Mean = 31.5 ± 10 ml/kg/min; Range = 14 to 54 ml/kg/min. Total time on TM: Mean = 14.6 ± 3 min; Range = 10 to 21 min.
ACKNOWLEDGEMENT Funding was provided by the Biomedical Research Imaging Center (BRIC), School of Medicine, University of North Carolina at Chapel Hill.
CINGULUM
CONCLUSIONS This study demonstrates that greater aerobic fitness is related to greater CWM integrity in the cingulum in healthy older adults. Specifically, aerobic fitness is associated with greater CWM integrity in the anterior and medial segments of the cingulum on the left side of the brain in healthy older adults. There is no relationship between aerobic fitness and CWM integrity in the posterior portion of the cingulum in healthy older adults.
