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Ciria LF, Román-Caballero R, Vadillo MA, Holgado D, Luque-Casado A, Perakakis P, Sanabria D. An umbrella review of randomized control trials on the effects of physical exercise on cognition. Nat Hum Behav. 2023 Mar 27; PubMed.
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Columbia University
Biostat, Inc.
This paper focuses on the mean effect size across many meta-analyses. The authors argue that the mean is small (around 0.25). Additionally, they argue that this mean is actually incorrect. If the mean is adjusted to account for various errors, the corrected mean could be as low as zero. They conclude that “… the available causal evidence from RCTs on the exercise–cognition link is far from conclusive.”
However, the approach used in this paper does not take into account the variability in effect sizes across studies. The data presented here indicate that there is a lot of variability in effect sizes; with some meta-analyses reporting effects approaching 0.5. Again, this refers to the means, suggesting that there are studies where effect sizes are even larger than that.
Given this dispersion, it would be important to identify factors in studies that are associated with larger versus smaller effect sizes. The paper does make that point when it discusses pluses and minuses of various studies. These include whether or not baseline cognition was considered, the type and extent of the exercise intervention, and the nature of the control conditions. Notably, the authors “discover” the fact that each analysis reflects one “slice” of the larger universe. This should have led them to rethink their basic idea of focusing on the mean, but it did not.
There are other technical issues that could be addressed. For example, the authors attempt to correct for publication bias. There are alternate ways to address this issue that would be more appropriate, considering that the quality of studies must be taken into account.
From my point of view, there are many excellent studies, implemented in the most careful way, that have shown strong effects of exercise on cognition. So overall, I do not find this study convincing in arguing that there is minimal effect of exercise on cognition.
We published an exercise study that was not included in any of these meta-analyses. It adhered to many of the better aspects of study design mentioned in this paper. We found a strong effect of exercise on cognition (Stern et al., 2019).
References:
Stern Y, MacKay-Brandt A, Lee S, McKinley P, McIntyre K, Razlighi Q, Agarunov E, Bartels M, Sloan RP. Effect of aerobic exercise on cognition in younger adults: A randomized clinical trial. Neurology. 2019 Feb 26;92(9):e905-e916. Epub 2019 Jan 30 PubMed.
View all comments by Michael BorensteinUniversity of British Columbia
The finding of a small exercise-related benefit (d=0.22) on cognitive function is not new. This has been reported in prior systematic reviews and meta-analysis, including those by Falck and Northey (Falck et al., 2019; Northey et al., 2018). Despite the small effect size—engaging in exercise (or not) is within someone’s control. The choice to exercise directly combats physical inactivity, which is a key and modifiable risk factor for dementia as highlighted by the Lancet 2020 report (Livingston et al., 2020). By reducing physical inactivity (via engagement in exercise or physical activity)—one can reduce dementia risk by 2 percent. We know regular physical activity and exercise also impact one’s risk for obesity, hypertension, and diabetes—and thus, potentially reducing dementia risk by another 4 percent.
One key aspect we also need to remember is that exercise trials (randomized controlled trials) typically run for three to 12 months. This is a very short period within a person’s lifespan. Thus, should we expect a very large effect (i.e., d > .7) on cognitive function among otherwise healthy individuals? However, long-term adoption of positive lifestyle behaviors, such as regular exercise, can significantly impact one’s overall cognitive trajectory. Many epidemiological studies have shown this—those who are more physically active have reduced dementia risk.
In regard to the critique that “most meta-analyses have not included most of the available studies which would meet their inclusion criteria”—one needs to be careful. A systematic review (SR), by definition, involves a detailed and comprehensive plan and search strategy, derived a priori, with the goal of reducing bias by identifying, appraising, and synthesizing all relevant studies on a particular topic. The specific research question(s) being asked by the SR and meta-analysis dictates what papers will be included. Thus, it is very possible that one SR and meta-analysis in the broader area of exercise and cognitive function may not include the same exact set of studies as another because of differences in specific details/questions. For example, for an exercise trial to be included in the SR and meta-analysis Ryan Falck in my lab did, the trial must have included both physical and cognitive outcomes. For a study to be included in the SR and meta-analysis we did led by Cindy Barha, the studies must have included information on the breakdown of female vs. male participants (Barha et al., 2017).
References:
Falck RS, Davis JC, Best JR, Crockett RA, Liu-Ambrose T. Impact of exercise training on physical and cognitive function among older adults: a systematic review and meta-analysis. Neurobiol Aging. 2019 Jul;79:119-130. Epub 2019 Mar 26 PubMed.
Northey JM, Cherbuin N, Pumpa KL, Smee DJ, Rattray B. Exercise interventions for cognitive function in adults older than 50: a systematic review with meta-analysis. Br J Sports Med. 2018 Feb;52(3):154-160. Epub 2017 Apr 24 PubMed.
Barha CK, Davis JC, Falck RS, Nagamatsu LS, Liu-Ambrose T. Sex differences in exercise efficacy to improve cognition: A systematic review and meta-analysis of randomized controlled trials in older humans. Front Neuroendocrinol. 2017 Jul;46:71-85. Epub 2017 Apr 22 PubMed.
View all comments by Teresa Liu-AmbroseUCL
This study shows small exercise-related benefits on cognition. The full model found effects size = 0.22. They looked for publication bias using three methods and this reduced effect size but the finding was still positive.
In the 2020 Lancet Commission report we previously discussed the complexity of the link between physical activity and dementia. Physical activity changes over a person’s lifetime, decreasing when someone becomes ill, varying across cultures and socioeconomic class and between genders, making it difficult to be clear, but the balance of evidence is that the link between exercise and dementia is bidirectional. Exercise might also be required to be sustained and continue nearer the time of risk to be effective.
I do not think there is anything contradictory in these findings. While not discussed in this interesting paper, RCTs tend by their nature to be short and recruit people who are highly motivated and knowledgeable—and both groups may change their behavior knowing there is an intervention. A recent RCT, which the authors quoted here as a high-quality exception, had, with 945 participants, high power (Zotcheva et al., 2022). Interestingly, at five years, 96 percent of controls followed national guidelines for exercise, which was up from 87 percent at baseline. It is difficult to show much effect if the control group are highly motivated exercisers.
References:
Zotcheva E, Håberg AK, Wisløff U, Salvesen Ø, Selbæk G, Stensvold D, Ernstsen L. Effects of 5 Years Aerobic Exercise on Cognition in Older Adults: The Generation 100 Study: A Randomized Controlled Trial. Sports Med. 2022 Jul;52(7):1689-1699. Epub 2021 Dec 8 PubMed.
View all comments by Gill LivingstonRush Medical College
This study examined the relationship between exercise and cognition by conducting an umbrella review of 24 meta-analyses of randomized controlled trials. Trial participants were of varying age and generally healthy.
The authors indicate that this relationship may not be as established as we think. They point to the importance of replicating findings in the area of exercise and cognition.
Interestingly, the authors found that few studies were the same across more than one meta-analysis. Meta-analyses may have missed including eligible studies slightly under 50 percent of the time. They also varied in terms of analytical approaches and methods.
Overall, I think the authors should be commended for addressing publication bias in great detail.
It may be worth noting that an established model does not exist to describe the mechanisms behind the relationship between exercise and cognition.
View all comments by Pankaja DesaiMake a Comment
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