Beyond vascularization: aerobic fitness is associated with N-acetylaspartate and working memory.
Open accessAbstract
Aerobic exercise is a promising form of prevention for cognitive decline; however, little is known about the molecular mechanisms by which exercise and fitness impacts the human brain. Several studies have postulated that increased regional brain volume and function are associated with aerobic fitness because of increased vascularization rather than increased neural tissue per se. We tested this position by examining the relationship between cardiorespiratory fitness and N-acetylaspartate (NAA) levels in the right frontal cortex using magnetic resonance spectroscopy. NAA is a nervous system specific metabolite found predominantly in cell bodies of neurons. We reasoned that if aerobic fitness was predominantly influencing the vasculature of the brain, then NAA levels should not vary as a function of aerobic fitness. However, if aerobic fitness influences the number or viability of neurons, then higher aerobic fitness levels might be associated with greater concentrations of NAA. We examined NAA levels, aerobic fitness, and cognitive performance in 137 older adults without cognitive impairment. Consistent with the latter hypothesis, we found that higher aerobic fitness levels offset an age-related decline in NAA. Furthermore, NAA mediated an association between fitness and backward digit span performance, suggesting that neuronal viability as measured by NAA is important in understanding fitness-related cognitive enhancement. Since NAA is found exclusively in neural tissue, our results indicate that the effect of fitness on the human brain extends beyond vascularization; aerobic fitness is associated with neuronal viability in the frontal cortex of older adults.
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Growth in hippocampal volume and, in some cases, improvements in working memory performance are correlated with higher concentrations of NAA.
“N-acetylaspartate (NAA) is a metabolite indicative of neuronal integrity and a number of AE studies have demonstrated that the growth in hippocampal volume (Pajonk et al., 2010; Erickson et al., 2012; Gonzales et al., 2013; Wagner et al., 2015) and in some cases, improvements in working memory performance (Erickson et al., 2011) are both correlated with higher concentrations of NAA.”
From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Erickson et al., 2012
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Cognitive and Motor Perseveration Are Associated in Older Adults
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- Authors
- Erickson, K. I., Weinstein, A. M., Sutton, B. P., Prakash, R. S., Voss, M. W., Chaddock, L., Szabo, A. N., Mailey, E. L., White, S. M., Wojcicki, T. R., McAuley, E., & Kramer, A. F.
- Affiliations
- University of Pittsburgh (US)
- University of Illinois Urbana-Champaign (US)
- The Ohio State University (US)
- Corresponding author
- Erickson, Kirk I.
- ORCID
- Venue
- Brain and Behavior
- Publisher
- Wiley
- Published
- 2012-01
- Volume
- 2
- Issue
- 1
- Pages
- 32-41
- ISSN
- 2157-9032 (ISSN-L)
- 2162-3279
- PMC
- PMC3343297
- OpenAlex
- W1601536642
- Cited by
- 110
- References
- 56
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 5 · 2022: 10 · 2021: 9 · 2020: 6 · 2019: 13 · 2018: 12 · 2017: 5 · 2016: 5 · 2015: 13 · 2014: 9 · 2013: 8 · 2012: 7
- FWCI
- 7.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Brain and Behavior (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- University of Pittsburgh (P50 AG005133, P30-AG024827)
- National Institutes of Health (AG005133, AG024827)
- University of Illinois at Urbana-Champaign
- National Institute on Aging (RO1 AG25667, R01AG025032, AG-005133, P50AG005133, AG 024827, RO1 AG25032, R01AG025667, P30AG024827)
- National Institute of General Medical Sciences (T32GM081760)
- Topics
- Health Sciences › Medicine › Physiology › Physical Activity and Health
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Keywords
- cardiorespiratory fitness, N-acetylaspartate, neuronal viability, working memory, cognitive aging, older adults, frontal cortex, brain vascularization, cognitive decline prevention, backward digit span, brain metabolites
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