Physical activity predicts gray matter volume in late adulthood: the Cardiovascular Health Study

Abstract

Objectives: Physical activity (PA) has been hypothesized to spare gray matter volume in late adulthood, but longitudinal data testing an association has been lacking. Here we tested whether PA would be associated with greater gray matter volume after a 9-year follow-up, a threshold could be identified for the amount of walking necessary to spare gray matter volume, and greater gray matter volume associated with PA would be associated with a reduced risk for cognitive impairment 13 years after the PA evaluation.

Methods: In 299 adults (mean age 78 years) from the Cardiovascular Health Cognition Study, we examined the association between gray matter volume, PA, and cognitive impairment. Physical activity was quantified as the number of blocks walked over 1 week. High-resolution brain scans were acquired 9 years after the PA assessment on cognitively normal adults. White matter hyperintensities, ventricular grade, and other health variables at baseline were used as covariates. Clinical adjudication for cognitive impairment occurred 13 years after baseline.

Results: Walking amounts ranged from 0 to 300 blocks (mean 56.3; SD 69.7). Greater PA predicted greater volumes of frontal, occipital, entorhinal, and hippocampal regions 9 years later. Walking 72 blocks was necessary to detect increased gray matter volume but walking more than 72 blocks did not spare additional volume. Greater gray matter volume with PA reduced the risk for cognitive impairment 2-fold.

Conclusion: Greater amounts of walking are associated with greater gray matter volume, which is in turn associated with a reduced risk of cognitive impairment.

e–Pub ahead of print

Figure 1 Subject inclusionary criteria and sample sizes We demonstrate the longitudinal design beginning in 1989–1990 and ending with the voxel-based morphometry (VBM) analysis on high-resolution MRI data collected in 1998–1999. All participants in this sample were free of dementia and mild cognitive impairment (MCI). Originally, 1,479 individuals had physical activity assessed and 924 had a low-resolution MRI. A total of 516 of these individuals returned 5 years later for a follow-up MRI session. From these individuals, we excluded 61 with dementia, 150 with MCI, and 6 because of missing white matter grades from the first MRI assessment. Our final sample size for the VBM analysis was 299 elderly individuals between 70 and 90 years of age. *Visual rating of white matter lesions, ventricular size, atrophy, and MRI-identified infarcts.

Figure 2 Brain regions associated with greater walking (A) Brain regions showing an association between greater amounts of physical activity (blocks walked) at baseline and greater gray matter volume. Statistical map is thresholded with a false discovery rate of p = 0.05 and a minimum cluster threshold of 100 contiguous voxels. (B) Brain regions showing greater volume in the highest quartile (>72 blocks walked in 2 weeks) compared to the bottom 3 quartiles. There were no reliable differences in brain volume among the bottom 3 quartiles.

Figure 3 Threshold effects on brain volume Mean volumes (and SEM) of 4 brain regions (precentral gyrus [A], supplementary motor area [B], precuneus [C], and hippocampus [D]) adjusted for variance due to age, total intracranial volume, gender, body mass index, race, white matter grade, presence of MRI infarcts, and education split into quartiles based on the amount of physical activity (Q1: 0–12 blocks, n = 91; Q2: 13–24 blocks, n = 57; Q3: 25–70 blocks, n = 78; Q4: 72–300 blocks, n = 73). The highest quartile group (Q4) had greater volume in all regions examined compared with the lower 3 quartiles. No significant differences were found among the lower 3 quartiles.