Effects of physical activity on cognition, well-being, and brain: Human interventions Arthur F. Kramer*, Kirk I. Erickson Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA Abstract This article provides a review of the human intervention literature that has examined the influence of fitness training on cognition, well-being, brain structure, and brain function. Meta-analyses of this literature, which are reviewed here, suggest robust effects of fitness training on cognition and well-being. Although there are currently few human intervention studies that have examined fitness effects on human brain function and structure, the studies that have been conducted report promising results. © 2007 The Alzheimer’s Association. All rights reserved. Keywords: Aging; Fitness training; Brain function and structure; Cortical plasticity 1. Introduction During the past several years, there has been growing scientific and public interest in the effects of physical ac- tivity on cognitive maintenance and brain health. This in- terest has been driven in large part by epidemiologic studies reported during the past decade, in which physical fitness has emerged as one of the critical lifestyle factors associated with perseverance of cognitive function in older adults. In addition, a growing body of data from laboratory and animal studies has begun to reveal the potential cellular and mo- lecular mechanisms by which physical activity might influ- ence brain structure and function, with concomitant benefits to cognitive processes. The confluence of epidemiologic and animal data sup- porting beneficial brain effects of physical activity (re- viewed elsewhere in this supplement), combined with the prospect of a looming public health crisis as a result of an aging population at greater risk for cognitive decline and dementia, has fueled interest in developing fitness-based public health interventions that might interrupt, prevent, or at least delay cognitive decline. Toward that end, a small number of randomized, controlled human clinical studies have examined the effects of various fitness training regi- mens on cognitive skills and, more recently, on brain struc- ture and patterns of neural activity. The results of these studies have been mixed, with some showing a significant effect of fitness training on cognition and the delay of dementia and others finding no effect. There are a number of reasons why this might be the case. For one, researchers have used a number of different fitness training regimens, which have varied in program duration, session length and intensity, and type of activity (eg, aerobic vs nonaerobic). Methodologies, study subjects, and cognitive tasks used to assess fitness effects have also varied among the studies, making it difficult to generalize results. Critically, sample sizes in many studies have been very small, and thus they lack the power to make strong conclusions about cause and effect. Meta-analytic studies have combined data from smaller trials to increase the statistical power of the evidence and, at the same time, have shed light on po- tential moderators of the fitness effect and provided di- rections for additional research. Despite the many ques- tions that remain, the emerging view from this growing literature supports a neuroprotective effect of fitness training for aging humans. Here we focus on three meta-analyses that have exam- ined physical activity training studies dating back to the 1960s. We also review the results of a recent study designed to examine interactions between physical fitness and hor- mone replacement therapy, which is one variable that might help explain mixed results in epidemiologic and interven- tion studies. *Corresponding author. Tel.: 217-244-1933; Fax: 217-333-2922. E-mail address: akramer@s.psych.uiuc.edu Alzheimer’s & Dementia 3 (2007) S45–S51 1552-5260/07/$ – see front matter © 2007 The Alzheimer’s Association. All rights reserved. doi:10.1016/j.jalz.2007.01.008