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Cardiorespiratory fitness and brain volume and white matter
integrity.......Exercise Associated with Improved Brain
 
 
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"Greater physical fitness was associated with more brain volume and greater white matter integrity measured 5 years later in middle-aged adults........Per 1-minute-higher Maxdur, the odds ratio for having less whole brain volume was 0.85 (p = 0.04) and for having low white matter integrity was 0.80 (p = 0.02), adjusted for age, race, sex, clinic, body mass index, smoking, alcohol, diet, physical activity, education, blood pressure, diabetes, total cholesterol, and lung function (plus intracranial volume for white matter integrity). No significant associations were observed between Maxdur and abnormal tissue volume or blood flow in white matter. Findings were similar for associations with continuous brain MRI measures."
 
"We found that greater CRF (cardiorespiratory fitness) measured by Maxdur (maximal treadmill test duration) with the treadmill test was associated with higher WBV (whole brain volume) and white matter NTV (normal tissue volume) and integrity 5 years later among apparently healthy middle-aged adults. The results imply that CRF may play a role in the brain structure and function in this population. It is an interesting possibility that improvement in CRF through exercise may prevent or at least delay future WBV and white matter changes in older adulthood."
 
Cardiorespiratory fitness (CRF), measured by treadmill duration, correlates with reduced cardiovascular diseases and overall mortality rates.1-3 Since CRF level may be improved, especially by physical activity and weight loss,4,5 CRF could be used as an intervention to promote health. Brain atrophy (low brain tissue volume) in whole brain or certain regions, and white matter findings on brain MRI, including lower volume, fluid-attenuated inversion recovery (FLAIR)/T2 hyperintensity lesions, and reduced integrity as reflected by low fractional anisotropy (FA), have been associated with normal aging, cerebral small vessel disease, hypertension, impaired cognitive function, and Alzheimer disease.6-19 Recent studies showed that higher CRF was associated with higher whole brain volume (WBV), higher white matter volume and integrity (focal FA values), and higher cerebrovascular reserve in people with Alzheimer disease or multiple sclerosis (MS) and in elders.20-27
 
Therefore, we proposed to investigate the associations between CRF and WBV, and especially white matter measurements in black and white study participants to better understand the pathogenesis of brain atrophy and white matter lesions in middle adulthood.
 
We hypothesized that greater CRF, defined by longer symptom-limited maximal treadmill test duration (Maxdur), would be associated with lower odds of unfavorable brain MRI findings including less WBV, less normal tissue volume (NTV),more abnormal tissue volume (ATV), and lower integrity and blood flow in white matter in healthy middle-aged adults.
 
The population-based sample of healthy middle-aged white and black participants, who completed symptom-limited maximal treadmill tests 5 years before the brain MRI, are the main strengths of our study. The findings of the current study are generalizable because of community-based sampling at baseline, balanced by age, race, sex, and educational achievement, and the inclusion of adults with obesity and smokers.
 
DISCUSSION In the current period-cross-sectional study, higher CRF measured by Maxdur at average age 45 years was associated with more favorable brain MRI measurements 5 years later. Specifically, higher Maxdur was associated with higher WBV and white matter NTV and FA independent of demographic variables. In addition, participants with higher Maxdur were less likely to have low WBV and low FA as hypothesized irrespective of demographic, lifestyle, and clinical characteristics. Higher CRF was not significantly associated with higher ATV (hyperintensity) or lower blood flow in white matter.
 
In those with unfavorable WBV and white matter FA, after adjustment for age, race, and sex, Maxdur was lower compared with those who had favorable brain MRI values.......Mean alcohol intake was higher in those with unfavorable WBV, white matter NTV, and FA.......There were more hypertensive participants in those with unfavorably low WBV and high white matter ATV (tables e-1 and e-2).
 
Per 1 minute higher, Maxdur was associated with 0.18% more ICV in WBV (corresponding to 7% of an SD of WBV), 0.11% more ICV in white matter NTV (corresponding to 6% of an SD of white matter NTV), and 0.0009 higher whiter matter FA (corresponding to 5% of an SD of white matter FA) in models adjusted initially for age, race/sex groups, and field center (table 2, model 1), but not associated with white matter ATV and blood flow. The association between Maxdur and WBV and white matter NTV remained significant after adjusting for body mass the association between higher Maxdur and low WBV became 0.81 (95% CI, 0.70-0.94), and the associations between Maxdur and low white matter NTV became nonsignificant. The finding between higher Maxdur and low white matter FA was in the expected direction with further adjustment for ICV. Additional adjustment for clinical measurements including blood pressure, diabetes, total cholesterol, and lung function (model 3) yielded similar associations between higher Maxdur and low WBV with the OR of 0.85 (95% CI, 0.72-0.996), and between higher Maxdur and low FA with the OR of 0.80 (95% CI, 0.65-0.97). Sensitivity analysis with unfavorableMRI measurements defined by the extreme 25th percentile yielded similar findings (data not shown). No significant interactions were identified between Maxdur and race/sex groups on brain MRI measurements (all p . 0.05 with df 5 3).
 
Our findings of the association between CRF and WBV, white matter NTV, and white matter integrity are consistent with previous findings in cross-sectional studies and clinical trials in people with Alzheimer disease and MS, and in healthy older adults.20-26 In addition, we previously found that higher CRF was related to better cognitive function in participants of the CARDIA Study.34 Better cognitive function has been observed to relate to white matter integrity in several other large population studies of middle-aged and elderly individuals.11-14
 
In multivariable logistic models adjusted initially for age, race/sex groups, and field center (model 1), Maxdur was associated with lower odds of low WBV with the OR per 1-minute-higher Maxdur of 0.86 (95% CI, 0.76-0.96), and lower odds of low white matter NTV with the OR per 1-minute-higherMaxdur of 0.89 (95% CI, 0.79-0.996), but not associated with high white matter ATV, low white matter FA, or low white matter blood flow (table 3). After adjusting for body mass index, smoking, alcohol consumption, diet pattern, physical activity, and education (model 2), the OR of the association between higher Maxdur and low WBV became 0.81 (95% CI, 0.70-0.94), and the associations between Maxdur and low white matter NTV became nonsignificant. The finding between higher Maxdur and low white matter FA was in the expected direction with further adjustment for ICV. Additional adjustment for clinical measurements including blood pressure, diabetes, total cholesterol, and lung function (model 3) yielded similar associations between higher Maxdur and low WBV with the OR of 0.85 (95% CI, 0.72-0.996), and between higher Maxdur and low FA with the OR of 0.80 (95% CI, 0.65-0.97). Sensitivity analysis with unfavorable MRI measurements defined by the extreme 25th percentile yielded similar findings (data not shown). No significant interactions were identified between Maxdur and race/sex groups on brain MRI measurements (all p > 0.05 with df = 3).
 
Our findings of the association between CRF and WBV, white matter NTV, and white matter integrity are consistent with previous findings in cross-sectional studies and clinical trials in people with Alzheimer disease and MS, and in healthy older adults.20-26 In addition, we previously found that higher CRF was related to better cognitive function in participants of the CARDIA Study.34 Better cognitive function has been observed to relate to white matter integrity in several other large population studies of middle-aged and elderly individuals.11-14 Although these associations of CRF with cognitive function and of cognitive function with white matter characteristics do not necessarily mean that brain MRI parameters would be better in those with higher or improved treadmill duration, the evidence presented here is consistent with the hypothesis that brain volume and white matter integrity might respond to improved CRF. The stronger and significant association of CRF and integrity after adjustment for adiposity, lifestyles, and risk factors for cardiovascular .....
 
Given the age of our participants, the definition of low WBV and low NTV, high abnormal tissue, and low integrity (FA) and blood flow in the white matter may not have clinical significance at this point; however, clinical diseases including hypertension, cerebral small vessel disease, dementia, cognitive impairment, stroke, and MS have been found to be related to low white matter volume, high abnormal tissue, and low integrity.7-10,14,20-22,24 In addition, we found that participants who were defined as the worst 15% in most MRI variables reported drinking more alcohol than others. Because chronic alcohol consumption is known to be related to some irreversible white matter changes,38,39 it is very likely that the worst 15% MRI findings in our cohort represent some pathologic deterioration of white matter. We believe that the dichotomized outcomes defined in our study may represent subclinical brainMRI changes in an apparently healthy middle-aged population. The corresponding relations of CRF with the continuous white matter variables gave consistent findings.
 
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Cardiorespiratory fitness and brain volume and white matter integrity
 
Neurology
Published Ahead of Print on May 8, 2015
 
Na Zhu, PhD David R. Jacobs, Jr., PhD Pamela J. Schreiner, PhD Lenore J. Launer, PhD Rachel A. Whitmer, PhD Stephen Sidney, MD Ellen Demerath, PhD William Thomas, PhD Claude Bouchard, PhD Ka He, PhD Guray Erus, PhD Harsha Battapady, PhD R. Nick Bryan, MD
 
From the Divisions of Epidemiology and Community Health (N.Z., D.R.J., P.J.S., E.D.) and Biostatistics (W.T.), School of Public Health, University of Minnesota; St. Barnabas Hospital (N.Z.), affiliated with Albert Einstein College of Medicine; Neuroepidemiology Section (L.J.L.), NIA; Kaiser Permanente Division of Research (R.A.W., S.S.); Human Genomics (C.B.), Pennington Biomedical Research Center; School of Public Health (K.H.), Indiana University Bloomington; and Department of Radiology (G.E., H.B., R.N.B.), University of Pennsylvania.
 
The CARDIA Study
 
Abstract

Objective: We hypothesized that greater cardiorespiratory fitness is associated with lower odds of having unfavorable brain MRI findings.
 
Methods: We studied 565 healthy, middle-aged, black and white men and women in the CARDIA (Coronary Artery Risk Development in Young Adults) Study.
The fitness measure was symptom-limited maximal treadmill test duration (Maxdur); brain MRI was measured 5 years later. Brain MRI measures were analyzed as means and as proportions below the 15th percentile (above the 85th percentile for white matter abnormal tissue volume).
 
Results: Per 1-minute-higher Maxdur, the odds ratio for having less whole brain volume was 0.85 (p = 0.04) and for having low white matter integrity was 0.80 (p = 0.02), adjusted for age, race, sex, clinic, body mass index, smoking, alcohol, diet, physical activity, education, blood pressure, diabetes, total cholesterol, and lung function (plus intracranial volume for white matter integrity). No significant associations were observed between Maxdur and abnormal tissue volume or blood flow in white matter. Findings were similar for associations with continuous brain MRI measures.
 
Conclusions: Greater physical fitness was associated with more brain volume and greater white matter integrity measured 5 years later in middle-aged adults.
 
GLOSSARY
 
ATV =abnormal tissue volume; CARDIA = Coronary Artery Risk Development in Young Adults; CI = confidence interval; CRF = cardiorespiratory fitness; FA = fractional anisotropy; FLAIR = fluid-attenuated inversion recovery; ICV = intracranial volume; Maxdur = maximal duration; MS = multiple sclerosis; NTV = normal tissue volume; OR = odds ratio; WBV = whole brain volume.

 
 
 
 
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