There were significant correlations between VO2 peak and age (r = −0.41; P < 0.001), sex (r = −0.50; P < 0.001), and years of education (r = 0.23; P < 0.003), thereby highlighting the necessity to control for these confounding factors to isolate effects associated with fitness. In the HLR analysis, the variables age, sex, and years of education (M = 15.65; SD = 2.91) were entered first as covariates to isolate the influence of VO2 peak (M = 21.11; SD = 4.80) on hippocampal volume. With all four factors entered the overall model was significant for the right hemisphere (F (4,163) = 21.43; P < 0.001) with all four variables accounting for 35.0% of the total variance in adjusted right hippocampal volume. Consistent with our hypotheses, VO2 peak significantly predicted adjusted right hippocampal volume (t = 4.38; β = 0.36; P < 0.001) with higher fitness levels associated with greater volume (see ). In this analysis, 17.1% of the variation in right hippocampal volume was accounted for by age (F(1,162) = 33.34; P < 0.001) with older individuals having smaller hippocampal volumes. Sex explained additional variance in right hippocampal volume with a R2 change of 9.9% (F(1,161) = 21.89; P < 0.001) with women having larger adjusted hippocampal volumes than men. Years of education explained a nonsignificant 0.02% of additional variance in volume (F(1,160) = 0.40; P < 0.53). Fitness measurements, however, explained 7.8% of the variance in the right hippocampus volume (F(1,159) = 19.18; P < 0.001) after accounting for the variance from age, sex, and years of education. The age × fitness interaction did not account for any significant variation in right hippocampal volume (F(1,158) = 0.762; P < 0.38, R2 = 0.03).
FIGURE 2 Scatterplots showing that with an increase in fitness (VO2 peak) there is an increase in hippocampal volume (cm3). Correlations for both the left and right hippocampus with fitness remained significant even after including age, sex, and years of education (more ...)
We performed the same analysis on the left hemisphere hippocampus. The overall model was significant with all four factors entered (F(4,163) = 21.22; P < 0.001) and explained 34.8% of the total variance in adjusted left hippocampal volume. Similar to the right hippocampus, aerobic fitness levels were positively associated with left adjusted hippocampal volume (t = 5.45; β = 0.45; P < 0.001). Age explained 15% of the variation in volume (F(1,162) = 28.58; P < 0.001). The addition of sex to the model explained an additional 7.5%, a significant increase in explained variance (F(1,161) = 15.69; P < 0.001), but years of education only explained 0.01% of additional variance after age and sex (F(1,160) = 0.20; P < 0.65). Like the right hippocampus, fitness measurements explained 12.2% of additional variance in hippocampal volume after variance associated with age, sex, and years of education were accounted for (F(1,159) = 29.65; P < 0.001). Similar to the right hemisphere, the age × fitness interaction was not significant (F(1,158) = 0.16; P < 0.69) and only accounted for 0.01% of the variation in left hippocampal volume. These analyses clearly identify aerobic fitness levels, along with age and sex, as an important factor in explaining both left and right hippocampal volume in older adults ().
For the spatial memory task, we found comparable results to other studies using this paradigm and other similar spatial memory paradigms (Greenwood et al., 2005
; Beigneux et al., 2007
). Computer errors resulted in lost data for four individuals leaving a total of 161 individuals for all analyses with memory performance (see ). A repeated-measures analysis revealed that accuracy rates significantly decreased from the 1-item set size to the 3-item set size (F(2,320) = 74.62; P
< 0.001) and response times significantly increased from the 1-item to 3-item set size (F(2,320) = 487.60; P
< 0.001). Planned comparisons demonstrated that both accuracy rates and response times were reliably different between each of the three set sizes (all P
Mean Scores and Standard Deviations for the Spatial Memory Task Along With Correlation Coefficients and Partial Correlation Coefficients (Controlling for Age, Sex, and Years of Education) for Each Independent Variable
In a HLR analysis with age, sex, and years of education entered as covariates, we found that fitness levels were reliably associated with accuracy rates for the 3-item memory condition, with 5.0% of the variance (t = 3.09; β = 0.29; P < 0.002) in accuracy accounted for by fitness levels (F(1,155) = 9.58; P < 0.002). Fitness was not related to 1-item or 2-item accuracy rates (see for a list of partial correlations associated with fitness and hippocampal volume). Furthermore, with age, sex, and years of education entered first in the HLR, a significant amount of variance in accuracy rates for the 3-item memory condition were accounted for by right hippocampal volume (F(1,155) = 6.73; P < 0.01) with 3.6% of the variation explained. Right hippocampal volume, however, did not account for variance in either 1-item or 2-item accuracy rates (both P > 0.05). The left hemisphere accounted for 5.3% of the variance in 3-item accuracy rates after accounting for age, sex, and years of education (F(1,155) = 10.09; P < 0.002), 3.1% of the variation in 2-item accuracy rates (F(1,155) = 5.32; P < 0.02), and 4.4% of the variance in 1-item accuracy rates (F(1,155) = 7.56; P < 0.007). Therefore, the right hippocampal volume was significantly related to spatial memory performance for the 3-item set-size and the left hemisphere hippocampal volume was related to memory performance regardless of the set-size (see for the partial correlations). Because higher levels of fitness were associated with enhanced performance in the 3-item memory condition and not in the 1-item or 2-item conditions, only the 3-item memory condition could be assessed in a mediation analysis.
In the exploratory mediation analysis, we found that the effect of fitness on 3-item spatial memory (accuracy) was attenuated, but still significant when age, sex, years of education, and right hippocampal volume were entered into the model (F(1,154) = 5.81; P < 0.01) with fitness level explaining 3.0% (t = 2.41; β = 0.23) of the variance in 3-item memory performance (). As noted earlier, without including the right hippocampus as a mediator, fitness levels explained 5% of spatial memory performance. This amounted to a drop in 2% of explained variance when right hippocampal volume was entered into the model, or an attenuation of 40% of the fitness-spatial memory relationship. However, using a modified Sobel test (see Materials and Methods) we found that the right hippocampal volume was not a significant mediator in the fitness-spatial memory relationship (z = 1.57; P < 0.116).
FIGURE 3 In this bar graph, we represent on the Y-axis the variance (R2) in accuracy on the 3-item spatial memory task explained by each factor or combination of factors on the X-axis. A test of mediation examines whether controlling for the variance associated (more ...)
For the left hippocampus volume, we found that the effect of fitness on 3-item spatial memory (accuracy) was attenuated, but still significant when age, sex, years of education, and left hippocampal volume were entered into the model (F(1,154) = 4.25; P < 0.04) with fitness level explaining 2.2% (t = 2.06; β = 0.20) of the variance in 3-item memory performance (). This amounted to a drop in 2.8% of explained variance when left hippocampal volume was entered into the model, or in other words, an attenuation of 56% of the fitness-spatial memory relationship. Using a Sobel test of significance, we found that the left hippocampus volume was a significant partial mediator between fitness and spatial memory (z = 2.056; P < 0.03), suggesting that the volume of the left hippocampus contributes to the memory benefits associated with higher fitness levels.
We conducted similar analyses with the RT data. In the HLR analysis, fitness was marginally related to the 1-item RT (t = −1.96; β = −0.19; P < 0.05) and 2-item RT (t = −1.95; β = −0.19; P < 0.052) conditions with 2.2 and 2.1% of the variance explained respectively after age, sex, and years of education were entered into the model. There was also a trend for RT for the 3-item condition to be negatively related to fitness levels (t = −1.56; β = −0.15; P < 0.12). Furthermore, we found that 4.2% of the variance in 1-item RT (F(1,155) = 7.38; P < 0.007) was accounted for by the right hippocampus volume after age, sex, and years of education were entered into the model. The right hippocampus volume did not explain a significant amount of variance in 2-item RT or 3-item RT scores (both P > 0.05). The left hippocampus volume explained 8.5% of the variance in 1-item RT scores (F(1,155) = 15.97; P < 0.001), 3.6% of the variance in 2-item RT scores (F(1,155) = 6.74; P < 0.01), and 2.1% of the variance in 3-item RT scores (F(1,155) = 3.74; P < 0.055) after age, sex, and years of education were entered into the model. Because of the constraints of the mediation criteria, only the 1-item and 2-item RT scores were subjected to a mediation analysis with the left and right hippocampus volumes.
In an exploratory mediation analysis we found that the right hippocampal volume completely mediated the effect of fitness on 1-item RT scores. Specifically, the fitness-memory relationship dropped from 2.2% to a nonsignificant 0.08% for the 1-item RT scores indicating that the fitness-RT relationship for the 1-item memory condition was completely mediated by right hippocampal volume (z = −2.71; P < 0.006). The right hippocampus also reduced the relationship between fitness and RT for the 2-item memory condition from 2.1% to a nonsignificant 1.2%, yet this failed to reach significance using a modified Sobel test (z = −1.81; P < 0.06). The left hippocampus volume also partially mediated the fitness-RT relationship for the 1-item memory condition. Specifically, fitness explained 8.5% of the 1-item RT scores, but this dropped to 2.2% when the left hippocampus volume was included in the regression (z = −2.04; P < 0.04). The left hippocampus did not significantly mediate the 2-item RT scores (P > 0.05). These results indicate that the volume of the left and right hippocampus mediates the fitness-RT relationship for the easier 1-item memory condition, but not for the more challenging 2-item condition.