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Is there a link between gray matter and cardiorespiratory fitness?

by P. Debraux | 14 January 2020

dementia, sport, health, physical activity, cardio, cardiorespiratory fitness, heart, vascular, alzheimer

According to the World Health Organization (WHO), dementia is a global epidemic which would count around 50 million people in the world (with 10 million new cases each year...) and whose global economic cost would be estimated at 818 billion a year. Dementia is a syndrome, usually chronic or progressive, in which an impairment of cognitive function (ability to perform mental operations) is observed, and which is more important than that expected from normal aging. It affects memory, reasoning, orientation, comprehension, calculation, learning ability, language and judgment (see the WHO site on the subject). Alzheimer's disease is the most common cause and is thought to account for around 60-70% of cases.

We regularly discuss studies showing the health benefits of physical activity. And in the case of dementia and cognitive disorders, physical and sports activity is recognized for its benefits on slowing cognitive decline. However, few studies have yet examined the real impact of the level of physical activity on dementia. And there is not yet a consensus on which variable quantifying physical activity would be the most relevant for studying this relationship. The circulatory and respiratory systems ability to provide the necessary oxygen during physical activity (i.e., the cardiorespiratory fitness), often quantified by VO2peak in sedentary people or VO2MAX in athletes, is a validated and objective measurement of the state of form of an individual. We have already discussed in previous articles its interest in cardiovascular and metabolic health. And the scientific literature suggests that there is a link between the cardiorespiratory fitness and the volume of gray matter in the hippocampus and the prefrontal cortex. However, dementia is generally characterized by a decrease in brain volume. And this atrophy is much more accentuated than that observed in a healthy person, at equal age. However, the few studies that have looked at this topic were limited by very small samples of subjects. Therefore, the question remains: is there an association between the volume of the brain, the volume of gray matter and the level of physical activity?

The Study

To answer this question, a team of German researchers wanted to understand if there was a link between VO2peak and total and local brain volumes. To increase the power of their analysis, the researchers used 2 populations of independent cohorts. And 2103 adults (1104 women and 999 men) aged 21 to 84 years participated in this study. To ensure the actual level of physical activity, all the participants carried out a laboratory effort test on a cyclo-ergometer in order to obtain VO2peak, VO2 at the anaerobic threshold and the maximum aerobic power (PMAX). For brain volume measurements, the researchers used magnetic resonance imaging (MRI). Thus, they obtained measurements of total brain volume (TBV), total gray matter (TGM), total white matter (TWM). For a more detailed analysis of the different brain regions, the researchers used voxel-based morphometry (roughly, three-dimensional pixels). Data were adjusted for age, gender, education, tobacco use, body mass, blood pressure, glycated hemoglobin level and intracranial volume.

Results & Analyzes

The main results of this study show that the level of cardiorespiratory fitness represented by VO2peak is significantly and positively associated with greater total brain volume and greater gray matter volume, but no significant association with white matter was observed. For each increase in one standard deviation in VO2peak, the TBV increases by 19.93 cm3 and the TGM volume by 5.31 cm3. The lack of association with the white matter could be linked to the measurement technique used which is not perfectly suited.

Voxel-based morphometry analysis made it possible to highlight a positive and significant association between VO2peak and the gray matter volume of the left middle temporal gyrus, the right parahippocampal gyrus, the left orbitofrontal cortex and the bilateral cingulate gyrus. The hippocampus plays a central role in memory-related functions and is associated with several diseases such as Alzheimer, depression and schizophrenia. The orbitofrontal cortex is involved in decision-making for emotional and reward-related behaviors.

The authors explain that endocrine mechanisms of anti-inflammatory factors and neurotrophins such as brain-derived neurotrophic factor (protein involved in the growth and differentiation of new neurons and synapses) whose it has been shown a link to exist with a higher level of cardiorespiratory fitness could play a major role in brain protection, which in turn could play on improving cognitive health and slowing down its decline.

In addition, the authors found a link between age and VO2peak and PMAX in relation to the hippocampal volume, which indicates higher benefits for people over the age of 45 who have a higher cardiorespiratory fitness. The decrease in hippocampal volume is linked to the decline in short memory during aging.

Practical Applications

The strength of this study lies in the number of participants and in the fact that the level of physical activity was actually evaluated via the measurement of VO2peak during an exercise test. The results demonstrate a positive and significant association between the cardiorespiratory fitness and the total brain volume as well as the volume in gray matter. However, this study does not demonstrate a cause and effect relationship. VO2 is not only affected by regular training but also by risky behaviors, genetics, other health conditions. It is impossible to know if a high VO2peak increases the brain volume or if a high brain volume allows a higher VO2peak.

This study represents the beginnings of the analysis about the impact of physical activity on cognitive decline and dementia. A randomized controlled study will be necessary to know the impact of the level of physical activity on these diseases.


  1. Wittfeld K, Jochem C, Dörr M, Schmike U, Gläser S, Bahls M, Markus MRP, Felix SB, Leitzmann MF, Ewert R, Bülow R, Völzke H, Janowitz D, Baumeister SE and Grabe HJ. Cardiorespiratory Fitness and Gray Matter Volume in the Temporal, Frontal, and Cerebellar Regions in the General Population. Mayo Clin Proc 95 (1) : 44-56, 2020.

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