Cardiorespiratory exercise improves gray matter volume in areas of the brain associated with age-related cognitive decline


Cardiorespiratory exercise — walking briskly, running, biking and just about any other exercise that gets your heart pumping — is good for your body, but can it also slow cognitive changes in your brain?

A study in Mayo Clinic Proceedings from the German Center for Neurodegenerative Diseases provides new evidence of an association between cardiorespiratory fitness and brain health, particularly in gray matter and total brain volume — regions of the brain involved with cognitive decline and aging.

Brain tissue is made up of gray matter, or cell bodies, and filaments, called white matter, that extend from the cells.

The volume of gray matter appears to correlate with various skills and cognitive abilities. The researchers found that increases in peak oxygen uptake were strongly associated with increased gray matter volume.

The study involved 2,013 adults from two independent cohorts in northeastern Germany. Participants were examined in phases from 1997 through 2012.

Cardiorespiratory fitness was measured using peak oxygen uptake and other standards while participants used an exercise bike. MRI brain data also were analyzed.

The results suggest cardiorespiratory exercise may contribute to improved brain health and decelerate a decline in gray matter.

An editorial by three Mayo Clinic experts that accompanies the Mayo Clinic Proceedings study says the results are “encouraging, intriguing and contribute to the growing literature relating to exercise and brain health.”

Ronald Petersen, M.D., Ph.D., a Mayo Clinic neurologist and first author of the editorial, says the most striking feature of the study is the measured effect of exercise on brain structures involved in cognition, rather than motor function.

“This provides indirect evidence that aerobic exercise can have a positive impact on cognitive function in addition to physical conditioning,” he says. “Another important feature of the study is that these results may apply to older adults, as well.

There is good evidence for the value of exercise in midlife, but it is encouraging that there can be positive effects on the brain in later life as well.”

Dr. Petersen is the Cora Kanow Professor of Alzheimer’s Disease Research and the

Chester and Debbie Cadieux Director of the Mayo Clinic Alzheimer’s Disease Research Center.

The study’s finding of higher gray matter volume associated with cardiorespiratory exercise are in brain regions clinically relevant for cognitive changes in aging, including some involved in Alzheimer’s disease.

The editorial calls those associations interesting but cautions against concluding that cardiorespiratory fitness correlations would affect Alzheimer’s disease.

The results suggest cardiorespiratory exercise may contribute to improved brain health and decelerate a decline in gray matter.

“This is another piece of the puzzle showing physical activity and physical fitness is protective against aging-related cognitive decline,” says Michael Joyner, M.D., a Mayo Clinic anesthesiologist and physiologist, and editorial co-author. “There’s already good epidemiological evidence for this, as well as emerging data showing that physical activity and fitness are associated with improved brain blood vessel function. This paper is important because of the volumetric data showing an effect on brain structure.”

Dr. Joyner is the Frank R. and Shari Caywood Professor at Mayo Clinic.

Long-term studies on the relationship between exercise and brain health are needed, which will be costly and logistically challenging to produce. “Nevertheless, these data are encouraging,” says Clifford Jack Jr., M.D., a Mayo Clinic neuroradiologist and co-author of the editorial. “The findings regarding cardiorespiratory fitness and certain brain structures are unique.”

Dr. Jack is the Alexander Family Professor of Alzheimer’s Disease Research.

According to Mayo Clinic experts, moderate and regular exercise — about 150 minutes per week — is recommended. Good cardiorespiratory fitness also involves:

  • Not smoking
  • Following healthy eating habits
  • Losing weight or maintaining a healthy weight level
  • Managing blood pressure and avoiding hypertension
  • Controlling cholesterol levels
  • Reducing blood sugar, which over time can damage your heart and other organs

University Medicine Greifswald, Germany, also was part of the research project. Katharina Wittfeld, Ph.D., a researcher at the German Center for Neurodegenerative Disease, is first author.

In our growing elderly population, Alzheimer’s disease (AD) is the central form of dementia with a massive socio-economic impact, representing one of the most expensive diseases for our health systems (Gustavsson et al., 2011).

Despite being highly relevant for our society, medical treatment for preventing cognitive decline is still sparse (Moniz-Cook et al., 2011). Therefore, alternative forms of treatment, which can be well implemented in patients’ daily routine, are gaining the attention of current research. In this context, physical activity is a viable promising low-cost, low-risk, individual and widely available option, which is already known for its reduction impact in health risks, such as cardiovascular diseases, cancer and mental health problems (Nelson et al., 2007).

Accordingly, beneficial effects of exercise and fitness on cognition and brain structure have also been described and offer a promising tool for preventing cognitive decline during the aging process (Van Der Borght et al., 2009Eadie et al., 2005Kronenberg et al., 2003Van Praag et al., 1999Redila et al., 2006Norton et al., 2014). Several randomized controlled trials (RCTs) in young, as well as elderly, healthy humans showed that physical exercise lead to an improvement in cognition, especially in spatial and executive functioning (Gates et al., 2013Hess et al., 2014Zheng et al., 2016). Some studies also report a reduced risk of development of dementia (Burns et al., 2008Lautenschlager et al., 20122008Ngandu et al., 2015Tolppanen et al., 2015Vidoni et al., 2012b).

There are further indications that physical activity might slow down progression of dementia and that cardiorespiratory fitness can help reducing the detrimental effects of cerebral amyloid on cognition in AD (Schultz, 2015) and could decrease the amount of amyloid beta 1–42 in cerebrospinal fluid (CSF) (Baker et al., 2010).

Despite such evidence of the advantageous effect of exercise in many aspects, the structural changes at the cerebral level in neurodegenerative diseases are still poorly understood, especially when comparing to cognitively healthy older adults.

This understanding, however, is crucial for offering an optimized treatment adapted to disease state. In this context, MRI represents a neuroimaging tool, easy to implement in clinical routine, to further examine alterations on brain level corresponding to cognitive improvements in neurodegenerative disease.

Next to structural changes, such as regional volume alterations, MRI can further serve to detect functional alterations, network shifting and even metabolic alterations in neurodegenerative disease progression (Reetz et al., 2012Romanzetti et al., 2014). It is also able to monitor intervention effects (Hohenfeld et al., 2017) and disease progression, which makes it a most valuable biomarker.

So far, longitudinal MRI studies on MCI have shown that initial degeneration focusses on substructures of the temporal lobe, spreading to the parietal lobe and finally extending to frontal lobe regions when converting to AD (Chételat et al., 2005Whitwell et al., 2007). Recent findings via diffusion-tensor-imaging (DTI) have proved that not only gray matter, but also white matter is affected in MCI and AD, leading to changes in the connections of hippocampus (Fellgiebel et al., 2004Fellgiebel et al., 2005), posterior cingulum (Fellgiebel et al., 2004Medina et al., 2006), thalamus (Rose, 2006) and regions in the posterior white matter in MCI, also correlating with cognitive impairment. In functional MRI (fMRI) studies on MCI, there have been several discrepant results. On the one hand, studies showed decreased activity in the medial temporal lobe (MTL) in AD and their genetic-at-risk population (Johnson et al., 2006Machulda et al., 2003Mondadori et al., 2007Petrella et al., 2006Ringman and Coppola, 2013).

On the other hand, other studies reported an increase of activity in temporal regions, especially in very early MCI (Kircher et al., 2007Lenzi et al., 2011), which is discussed as a possible compensatory increase of activity brain response, reflecting recruitment of supplementary neural resources to counteract the effects of AD pathology, or could in contrary, as indicated in a pharmacological intervention study, represent a dysfunctional condition (Bakker et al., 2012).

When taking these described brain alterations into account, several relevant questions arise when considering the effects of physical exercise on brain integrity in MCI/AD: What is the specific effect of physical exercise on the brain?

Are only certain brain regions/networks responsive to physical activity, regions which are mainly affected by disease state, as described above? The aim of this systematic review is to give an overview of studies examining the brain changes detectable by MRI after physical exercise intervention of individuals with MCI and/or AD, which may support planning of future interventional studies. In the first section of this review, we describe our search methods.

In a second part, we rate the quality of RCTs according to criteria from the Cochrane Library, the PEDro Scale and the Evidence-based Medicine Working Group (Forbes et al., 2008Guyatt et al., 1993Guyatt et al., 1994Liu and Latham, 2009Maher et al., 2003) introduced by Pitkälä et al., 2013.

We additionally visualize the rating results, ordered by interventions, and compare cerebral changes induced by exercise between cognitively healthy older adults and patients with cognitive impairment. Finally, we discuss potential study designs and provide an outlook of future work.

Mayo Clinic
Media Contacts:
Susan Barber Lindquist – Mayo Clinic

Original Research: Open access
“Cardiorespiratory Fitness and Brain Volumes”. Ronald C. Petersen, Michael J. Joyner, Clifford R. Jack Jr..
Mayo Clinic Proceedings doi:10.1016/j.mayocp.2019.11.011.


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