Processing speed declines with age and is a strong predictor of age-related cognitive decline in other domains, and in predicting who will need help with tasks of daily living in later years. Higher cardiorespiratory fitness (CRF) reflects better cardiopulmonary health and is related to maintenance of processing speed and cognition into late life. On the other hand, white matter lesions (WML) are reflective of age-related brain network disconnections from damage to white matter tracts in the brain. Lower CRF and higher WML burden have each been related to poorer cognitive performance. Although higher CRF provides a protective effect on cognition, the combined effects of CRF and WML on processing speed have yet to be determined. Specifically, whether CRF and WML independently affect processing speed or if WML moderates the effect of CRF on processing speed is yet to be established. We predicted WML may moderate CRF benefits on cognitive aging if CRF-related cognitive benefits are weakened by high WML load. Here, we test this question with the gold-standard measure of CRF, maximal exercise oxygen uptake (relative VO2 max, mL/kg/min) during a graded exercise test, and a validated neuropsychological measure of processing speed, the Digit Symbol Substitution Test (DSST).

CRF, DSST scores, and WML volumes of cognitively normal adults (n=91) aged 55-80 years were included in this analysis. The WML data was corrected for total intracranial volume and was log transformed. A linear regression model included the number of accurately completed items on the DSST as the dependent variable and age, sex, relative VO2 max, WML volumes and the interaction between relative VO2 max and WML volume as the predictor variables.

Main effects of age, sex, VO2 max and WML volume on the DSST were observed. Greater age, higher WML volume, and lower relative VO2 max were associated with poorer performance on the DSST. In addition, females (n=55) performed better than males (n=36) on the DSST. No significant interaction was observed between VO2 max and WML volume on DSST scores.

Our results show that 1) WML and relative VO2 max independently contribute to processing speed performance in older adults as measured by the DSST, and 2) WML do not moderate the relation between VO2 max and the DSST. Strengths of this study include gold-standard measurement of CRF and WML volumes as predictors of performance on the DSST in older adults. Further research is warranted to understand how vascular aging and brain health indicators interactively or interdependently impact cognition in aging.