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Author response: Circulating cortisol and cognitive and structural brain measures: The Framingham Heart Study

  • Justin Echouffo-Tcheugui, Physician, Johns Hopkins University
  • Sarah C. Conner, Biostatistician, Boston University
  • Jayandra J. Himali, Biostatistician, Boston University
  • Alexa S. Beiser, Biostatistician, Boston University
  • Sudha Seshadri, Physician, University of Texas Health Sciences Center, San Antonio
Submitted May 10, 2019

Jiménez-Pavón et al. suggest that we should have considered physical activity or cardiorespiratory fitness as a factor that mediates the relation between cortisol and brain volumes in our study.1 We agree that physical activity may be associated with circulating levels of cortisol. However, there are reasons not to consider physical activity (or cardiorespiratory fitness) as a mediating factor in an analysis linking cortisol levels to brain-related outcomes. The biological framework connecting physical activity, cortisol, and the brain suggests that cortisol is on the pathway between physical activity and brain morphology rather than physical activity being an intermediary between cortisol and brain outcomes.2 Consequently, it would make more sense to examine the mediating effect of cortisol on the relation between physical activity (or cardiorespiratory fitness) and brain volumes, rather than assessing the mediating effect of physical activity in the link between cortisol and brain morphology. Such an approach is corroborated by the results presented in the reference cited by Jiménez-Pavón et al., which described an intervention to increase physical activity leading to a modulation of the levels of cortisol.3

It is neither appropriate to adjust for physical activity (an antecedent to cortisol in the biological pathway; thus possibly an overadjustment) while relating cortisol to brain volumes, nor to assess its mediating effect on the association of cortisol and brain morphology. However, we are open to the interesting idea of examining the mediating effect of cortisol on the association of physical activity with brain volumes.

Disclosure​

The authors report no relevant disclosures. Contact journal@neurology.org for full disclosures.

References

  1. Echouffo-Tcheugui JB, Conner SC, Himali JJ, et al. Circulating cortisol and cognitive and structural brain measures: The Framingham Heart Study. Neurology 2018;91:e1961–e1970.
  2. McEwen BS, Gianaros PJ. Stress- and allostasis-induced brain plasticity. Annu Rev Med 2011;62:431–445.
  3. Tada A. Psychological effects of exercise on community-dwelling older adults. Clin Interv Aging 2018;13:271–276.

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Neurology | Print ISSN:0028-3878
Online ISSN:1526-632X

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