Cardiorespiratory Fitness, Hippocampal Volume and Frequency of Forgetting in Older Adults

The forthcoming decades will witness a dramatic increase in the population of older adults in the United States, resulting in an increased prevalence of individuals at risk for, and living with, chronic disease and functional disability (CDC, 2008). To some extent, preventive health behaviors such as a healthy diet and regular physical activity can reduce these risks. In particular, physical activity can enhance cardiorespiratory fitness, which is associated with a decreased risk of all-cause mortality and chronic illnesses, especially cardiovascular disease (Blair et al., 1996; Carnethon, Gulati, & Greenland, 2005). Importantly, cross-sectional studies and randomized clinical trials suggest that cardiorespiratory fitness is associated with brain structure and function. For example, Colcombe, et al. (2003) reported loss of tissue densities in the frontal, parietal, and temporal cortices due to aging were substantially reduced in adults with higher levels of cardiorespiratory fitness. Additionally, improvements in fitness brought about by exercise training have been associated with improvements in processing speed and executive function (Kramer et al., 1999). Colcombe et al. (2004) also demonstrated that aerobically trained older adults had greater task-related activity in regions of the prefrontal and parietal cortices that are involved in selective attention and inhibitory functioning. The aging process has well-documented effects on brain structure, in particular, the hippocampal region (Raz & Rodrigue, 2006). Longitudinal studies suggest that hippocampal volume shrinks at a median rate of 1.23% per year (Raz, 2004) and this rate is twice as great in healthy older adults than younger adults (Raz et al., 2004). Compromised hippocampal volume has, in turn, been associated with poor spatial working memory in humans (Kelley et al., 1998; Maguire, Frackowiak, & Frith, 1997) and rodents (Seamans, Floresco, & Phillips, 1998). Importantly, spatial working memory tasks are often composed of cognitive skills that are largely dependent on a fully functioning hippocampus (Lee, Jerman, & Kesner, 2005). Whether higher levels of cardiorespiratory fitness play a protective role in the preservation of hippocampal volume is an important research question, given that fitness is modifiable with increased exercise participation. This relationship has been studied in animals and this literature provides evidence that exercise facilitates hippocampal neurogenesis (Pereira et al., 2007; van Praag, Kempermann, & Gage, 1999; van Praag, Shubert, Zhao, & Gage, 2005), which has been associated with learning and memory (Leuner, Waddell, Gould, & Shors, 2006). In a recent report, Erickson and his colleagues (2009) suggested that higher levels of aerobic fitness were associated with greater hippocampal volume in a large sample of older adults. In turn, greater volume was associated with better performance on a spatial memory task. In these analyses, Erickson et al. statistically controlled for the potential confounding influence of demographic characteristics such as age, sex, and education. However, a number of other factors associated with lifestyle that have previously been associated with cognitive function, including physical activity (Weuve et al., 2004) and body composition (Gunstad et al., 2007), were not considered. However, these latter factors, coupled with age, education and sex represent legitimate foundational elements of fitness, rather than being treated as simply noise in the system (i.e., covariates). Given that the prevalence of memory problems in older adults range from 25–60% (De Jager, Blackwell, Budge, & Sahakian, 2005; Jonker, Geerlings, & Schmaud, 2000), understanding the biological, behavioral, and physiological factors that may influence these problems is an important public health issue. This is particularly the case if some of these factors are modifiable through lifestyle change. Given that self-appraisals of memory have been associated with subsequent cognitive decline in older adults (Schofield et al., 1997) and with brain function (Small, Larue, Komo, Kaplan, & Mandelkern, 1995), we were interested in further examining the association between cardiorespiratory fitness and self-appraisals of memory (i.e., frequency of forgetting). To do so, we significantly extend the data published by Erickson et al. (2009) in the following manner. First, we treated sex, age, education, physical activity, and body composition (i.e., body mass index; BMI) as determinants of fitness. Second, based upon the animal and human literature that indicates a well-functioning hippocampus is associated with spatial working memory and that exercise-induced fitness is associated with hippocampal preservation, we hypothesized that the relationship between fitness and memory self-appraisals (frequency of forgetting) would be mediated first by hippocampal volume and, in turn, by spatial working memory. Third, we use path analysis within a covariance modeling framework to test the hypothesized models. Fourth, in examining relationships among the hippocampus, spatial working memory, and frequency of forgetting, we used sex, age, and education as covariates. Finally, because hypertension and cardiovascular risk factors are associated with hippocampal atrophy (Raz & Rodrigue, 2006) and depression is correlated with more frequent memory complaints (Zelinski & Gilewski, 2004), we used these factors as covariates in preliminary model testing. This allowed for a very stringent test of the following two path models. In both, we hypothesized that being male, younger, more active, better educated, and having lower BMI would be associated with greater levels of fitness. In addition, being fitter was hypothesized to be associated with greater hippocampal volume which would, in turn, be associated with better spatial memory performance (i.e. in Model 1, faster reaction time and in Model 2, better accuracy). Finally, we hypothesized that better spatial memory would be associated with less frequent episodes of forgetting. The hypothesized model is shown in Figure 1. Figure 1 Hypothesized Path Model