One of the results of the Lifestyle Interventions and Independence for Elders (LIFE) pilot trial was that the digit symbol substitution test (DSST) score, a test of processing speed and executive control function, remained stable over time in the intervention group, while the DSST score of the control group declined over the same period of time. There is recent emerging evidence that older adults who are engaged in physical exercise are more likely to maintain high cognitive function and less likely to develop dementia or other functional impairments compared to those who do not exercise. Aerobic muscular activity may increase cerebral blood flow, and greater cerebral oxygenation can in turn prevent the age-related processes of neuronal degeneration and help delay the brain functional decline. It is possible that the increased level of aerobic activity from the LIFE intervention program had positive cerebrovascular effects in the intervention vs. the control group. Such enhanced cerebrovascular effects may have contributed to delay age-related neuronal death and would thus explain the difference in DSST scores that were measured between the two groups. It is important to understand whether this type of aerobic intervention is associated with such changes in brain functioning, because the brain plays an important role in controlling mobility. ? Brain integrity is associated with mobility. In older adults, cognitive performance in executive control domains, and specifically the DSST score, are associated with faster gait speed and with better performance on several mobility measures, independently of other health-related risk factors for mobility impairment. In addition to brain function, there are distinct aspects of brain structure, as measured on MRI, which are also associated with motor performance. Dr. Rosanos research group has shown that the burden of brain connectivity disease (e.g. white matter hyperintensities volume), and the severity of neuronal atrophy in selected mobility-related areas, are both associated with gait speed and balance difficultied, and that these associations are independent of confounders. ? Functional brain MRI is a reliable tool to measure the brain functional integrity. Brain imaging studies have shown that the neuronal activation and metabolism in regions that are involved in executive control function declines with older age, and that this declining neuronal signal is associated with declining cognitive performance. Dr. Rosano has previously measured the intensity of neuronal activation in a population of older adults by using the functional brain MRI (fMRI) technique. She found that cognitively normal older adults have greater activation in the dorsolateral prefrontal cortex, in the posterior parietal cortex and in the anterior cingulated cortex while they are engaged in executive control function tasks, such as the modified Stroop task 28 and the fMRI signal from these regions was strongly correlated with the actual performance on the modified Stroop test. ? Based on these discoveries, we will acquire brain fMRI concurrently with 1 year follow-up data on physical function (400 meter walk and SPPB) and measures of cognitive function (digit symbol substitution test (DSST), Stroop and Teng Modified Minimental State Exam (MMSE). It is hypothesized that the intervention group has greater fMRI signal activation in the executive control function regions, higher long term executive control function scores (as measured by DSST) and better mobility measures than the control group. It is also hypothesized that these associations will be independent of global cognitive function, as measured by the MMSE. This finding would suggest that this type of aerobic intervention is linked with greater neuronal activation.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Intramural Research (Z01)
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National Institute on Aging
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Liu, Ge; Allen, Ben; Lopez, Oscar et al. (2015) Racial Differences in Gray Matter Integrity by Diffusion Tensor in Black and White Octogenarians. Curr Alzheimer Res 12:648-54