Cardiorespiratory fitness is differentially associated with cortical thickness in young and older adults
Introduction
Cerebral volume loss is a well-documented correlate of the aging process, accompanied by a reliable pattern of regional cortical thinning with advancing age (Fjell et al., 2009b, Salat et al., 2004, Shaw et al., 2016). Brain regions most susceptible to age-related cortical degeneration largely coincide with heteromodal association areas that support higher-level processing, and include lateral temporal, inferior parietal, and frontal regions, as well as the precuneus, temporoparietal junction, and fusiform gyrus (Fjell et al., 2009a, Fjell et al., 2009b, Shaw et al., 2016). Despite a general trend of cortical atrophy in healthy aging, individual differences have been observed in the rate and extent of degeneration, with some adults maintaining relatively more intact structural integrity throughout late life than same-aged peers (Pfefferbaum and Sullivan, 2015). Thus, in an effort to promote optimal brain health within a society where the population distribution is increasingly shifting towards older ages (Vincent and Velkoff, 2010), identifying relevant lifestyle factors that may protect against age-related neurostructural decline is warranted.
One factor that may play a role in mitigating age-associated brain decline is cardiorespiratory fitness1 (CRF). CRF reflects the efficiency of the circulatory and respiratory systems to provide oxygenated blood to musculature during sustained aerobic physical activity. As a modifiable health factor, CRF can be optimized through regular engagement in physical activity of moderate to vigorous intensity such as jogging, swimming, or biking. The gold standard of CRF assessment is treadmill-based graded maximal exercise testing, which yields a measure of peak volume of oxygen consumption (peak VO2) at maximum intensity exercise. Compared to self-report or estimated CRF metrics, peak VO2 provides an objective and reliable indicator of CRF. Whereas systemic benefits of enhanced CRF to both emotional and physical health are well documented (DiLorenzo et al., 1999, Myers et al., 2015, Papasavvas et al., 2016, Tozzi et al., 2016, Warburton et al., 2006), only recently have studies begun to explore the relation between CRF and brain structure, particularly in the context of aging.
Cross-sectional studies of older adults have generally reported a positive association of CRF with gray matter volume (Boots et al., 2015, Bugg and Head, 2011, Erickson et al., 2007, Gordon et al., 2008, Weinstein et al., 2012) as well as with cognitive performance in the domains of executive function and memory (Barnes et al., 2003, Hayes et al., 2016). Interestingly, reliable CRF effects have been observed primarily within lateral prefrontal and parietal gray matter regions (Erickson et al., 2014, Hayes et al., 2014), cortical areas most vulnerable to age-related atrophy (Fjell et al., 2009b). Given this apparent regional overlap between CRF and aging effects, it follows that enhanced CRF could lessen the degree of cortical decline in aging. In support of this concept, aerobic exercise intervention studies have provided evidence of CRF-related neuroplasticity, as exercising older adults show greater regional brain volume than age-matched controls (Colcombe et al., 2006, Erickson et al., 2011).
Although positive associations between CRF and gray matter volume have been previously reported, it is less clear how CRF may relate to cortical thickness in older adult populations. Given that the surface area component used to define volume captures additional variance related to head size and the degree of regional cortical folding, volumetric approaches have been shown to yield less sensitive estimates of age-associated cortical atrophy when compared to surface-based cortical thickness techniques (Hutton et al., 2009, Lemaitre et al., 2012, Panizzon et al., 2009). Studies of patient populations (mild cognitive impairment, heart failure, and schizophrenia) have demonstrated positive associations between cortical thickness and CRF (Alosco et al., 2013, Reiter et al., 2015, Scheewe et al., 2013), yet the association between CRF and cortical thickness in the context of healthy aging remains unknown. One recent study (Lee et al., 2016) demonstrated a positive relation between self-reported physical activity and cortical thickness in healthy older adults. However, given that subjective CRF measures do not align well with objectively quantified peak VO2 (Tager et al., 1998), additional study is warranted.
In the current cross-sectional study, we investigated age-dependent associations between objectively quantified CRF (peak VO2) and cortical thickness in healthy older and young adults using a whole-brain cortical surface-based approach. The primary goals of this study were 1) to assess whether CRF is differentially associated with cortical thickness in young and older adults, 2) to determine the spatial overlap between observed CRF and aging effects across the cortex, and 3) to examine whether higher CRF in late life may eliminate age-related cortical thickness decline. Based on the previously reported beneficial effects of CRF on gray matter volume in aging, as well as positive associations between cortical thickness and CRF in patient populations, we expected to observe similar positive associations between CRF and cortical thickness in our older adult cohort. In particular, we anticipated that regions where CRF is positively associated with cortical thickness in older adults would overlap with frontal and temporoparietal regions most susceptible to age-related cortical thinning. Given the dearth of studies in young adults, we had no strong prediction about the association between CRF and cortical thickness for this cohort. A recent study of early adolescents (aged 9–11 years) found that greater CRF was associated with thinner cortex within regions of superior frontal, superior temporal and lateral occipital cortex (Chaddock-Heyman et al., 2015), a finding that likely reflects successful maturational development and neural pruning. The fact that in some brain regions protracted maturational cortical thinning has been observed throughout young adulthood (Tamnes et al., 2013) raises the possibility that young adults may show a negative association between CRF and cortical thickness similar to that observed in adolescents. By examining young and older adults in the same study, we were able to directly assess age-dependent associations between CRF and cortical thickness, and additionally, whether age-related differences in cortical thickness are impacted by CRF.
Section snippets
Participants
Thirty-four young adults and 35 older adults were enrolled in the current study. Six older adults (four with incidental findings on MRI and two with excessive head motion) and two young adults (one with excessive head motion, the other whose peak VO2 value was a statistical outlier at greater than 3 standard deviations above the mean) were excluded from the current analyses. The final sample consisted of 32 young adults (age=18–31 years) and 29 older adults (age=55–82 years; see Table 1 for
Participant characteristics
Demographic characteristics of the young and older adult samples are provided in Table 1. No study participants had hypertension (blood pressure greater than 140/90 mmHg), as assessed by the exercise physiologist and cardiologist performing the cardiorespiratory exercise assessment. Groups were matched in sex, χ2 (1)=0.01, p=0.91, and race, χ2(1)=2.21, p=0.14, with both age groups consisting mostly of Caucasians. There were no group differences in estimates of pre-morbid intellectual functioning
Discussion
In the current study, we evaluated age-dependent associations between an objective indicator of CRF (peak VO2) and vertex-wise cortical thickness in a sample of healthy young and older adults. We observed a significant age group by CRF interaction in several cortical areas, with the strongest effect noted in the left supramarginal cortex that remained significant following multiple comparison correction. Follow-up analyses indicated that higher CRF was related to thicker cortex in older adults,
Conclusions
We observed differential associations between CRF and cortical thickness in young and older adults. After additionally controlling for age as a continuous variable within each group, CRF was positively associated with cortical thickness in older adults largely within multimodal association areas. These regional findings largely overlapped with cortical areas also vulnerable to age-related cortical decline. Higher fit older adults had greater cortical thickness than their lower fit peers, but
Acknowledgements
This work was supported by the Department of Veterans Affairs, Rehabilitation, Research & Development Service (Career Development Award e7822w awarded to S.M.H.), the Department of Veterans Affairs, Clinical Science Research & Development Services (M.V.), and the National Institute of Aging (K24AG035007 awarded to R.A.S.). Assistance with participant recruitment was provided by the Massachusetts Alzheimer's Disease Research Center (P50-AG005134), and the Boston University Alzheimer's Disease
References (62)
- et al.
Poorer physical fitness is associated with reduced structural brain integrity in heart failure
J. Neurol. Sci.
(2013) - et al.
Maximal oxygen intake and nomographic assessment of functional aerobic impairment in cardiovascular disease
Am. Heart J.
(1973) - et al.
Exercise moderates age-related atrophy of the medial temporal lobe
Neurobiol. Aging
(2011) - et al.
Cortical surface-based analysis. I. Segmentation and surface reconstruction
Neuroimage
(1999) - et al.
Long-term effects of aerobic exercise on psychological outcomes
Prev. Med.
(1999) - et al.
Physical activity, fitness, and gray matter volume
Neurobiol. Aging
(2014) - et al.
Interactive effects of fitness and hormone treatment on brain health in postmenopausal women
Neurobiol. Aging
(2007) - et al.
Cortical surface-based analysis. II: inflation, flattening, and a surface-based coordinate system
Neuroimage
(1999) - et al.
Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain
Neuron
(2002) - et al.
What is normal in normal aging? Effects of aging, amyloid and Alzheimer's disease on the cerebral cortex and the hippocampus
Prog. Neurobiol.
(2014)
Smoothing and cluster thresholding for cortical surface-based group analysis of fMRI data
Neuroimage
A comparison between voxel-based cortical thickness and voxel-based morphometry in normal aging
Neuroimage
Cardiorespiratory fitness is positively correlated with cerebral white matter integrity in healthy seniors
Neuroimage
Reliability and statistical power analysis of cortical and subcortical FreeSurfer metrics in a large sample of healthy elderly
Neuroimage
Physical activity and cardiorespiratory fitness as major markers of cardiovascular risk: their independent and interwoven importance to health status
Prog. Cardiovasc. Dis.
Cross-sectional versus longitudinal estimates of age-related changes in the adult brain: overlaps and discrepancies
Neurobiol. Aging
Differential aging of the brain: patterns, cognitive correlates and modifiers
Neurosci. Biobehav Rev.
Exercise therapy, cardiorespiratory fitness and their effect on brain volumes: a randomised controlled trial in patients with schizophrenia and healthy controls
Eur. Neuropsychopharmacol.
A hybrid approach to the skull stripping problem in MRI
Neuroimage
Age-related cortical thinning in cognitively healthy individuals in their 60s: the PATH Through Life study
Neurobiol. Aging
Brain development and aging: overlapping and unique patterns of change
Neuroimage
Exercise and the brain: something to chew on
Trends Neurosci.
The association between aerobic fitness and executive function is mediated by prefrontal cortex volume
Brain Behav. Immun.
Entorhinal volume, aerobic fitness, and recognition memory in healthy young adults: a voxel-based morphometry study
Neuroimage
A longitudinal study of cardiorespiratory fitness and cognitive function in healthy older adults
J. Am. Geriatr. Soc.
Cardiorespiratory fitness is associated with brain structure, cognition, and mood in a middle-aged cohort at risk for Alzheimer's disease
Brain Imaging Behav.
The role of aerobic fitness in cortical thickness and mathematics achievement in preadolescent children
PLoS One
Shorter term aerobic exercise improves brain, cognition, and cardiovascular fitness in aging
Front. Aging Neurosci.
A power primer
Psychol. Bull.
Aerobic exercise training increases brain volume in aging humans
J. Gerontol. A Biol. Sci. Med. Sci.
Exercise training increases size of hippocampus and improves memory
Proc. Natl. Acad. Sci. USA
Cited by (50)
Cross-sectional associations between cortical thickness and physical activity in older adults with spontaneous memory complaints: The MAPT Study: Aging, physical activity, and cortical thickness
2023, Journal of Sport and Health ScienceCitation Excerpt :Taken together, these data suggest that the relationship between CT and PA may be dependent on brain status in the sense that PA might be preferentially associated with CT in the most vulnerable areas at a given time point in the life course. Similarly, some authors have demonstrated that, in older adults, cardiorespiratory fitness was positively associated with CT in regions showing significant age-related atrophy.49 Thus, the association between PA and CT might follow the age-related pattern of cortical thinning described above, with a shift from the frontal to the temporal lobes after the age of 60 years.
Understanding the Neurophysiological and Molecular Mechanisms of Exercise-Induced Neuroplasticity in Cortical and Descending Motor Pathways: Where Do We Stand?
2021, NeuroscienceCitation Excerpt :These authors also found that highly fit, older adults had greater cortical thickness than low fit, older adults in the same brain areas, which are also the most vulnerable to age-related atrophy. Additionally, cortical thickness of some brain regions did not differ in highly fit, older versus young adults, suggesting that cardiorespiratory fitness attenuates age-related cortical decline in older adults, particularly in the precentral gyrus (M1), pars triangularis, and non-dominant precuneus (Williams et al., 2017). Further, Jonasson et al. (2017) showed that cardiorespiratory fitness was linked to greater cortical thickness in the dorsolateral prefrontal cortex in older adults, while Wood et al. (2016) reported that old Masters athletes, who started competitive aerobic training early in life, sustained it for over 30 years, and had high levels of cardiorespiratory fitness, exhibited greater cortical thickness throughout a wide range of cortical areas, especially in the pre- and postcentral gyri, medial prefrontal cortex, and insula, compared to age-matched, healthy individuals (Wood et al., 2016).
Objective aerobic fitness level and neuropsychological functioning in healthy adolescents and emerging adults: Unique sex effects
2020, Psychology of Sport and Exercise