Fatigue is associated with increased mortality in older adults and is the leading cause of activity restrictions in this population. Unfortunately, our understanding of the causes of fatigue in older adults is quite limited and we have no proven treatments. While it is known that aging has profound effects on the central nervous system (CNS) and cognitive function there have been no studies to date attempting to understand how CNS and cognitive factors contribute to fatigue complaints and activity restrictions in older adults. This is a striking gap as CNS and cognitive factors may play a central role in many processes suspected to drive fatigue in older adults and would thus be a potent target for therapeutic interventions. Fatigue is a complex construct which includes subjective perceptions (perceived fatigue) and objective changes in performance (fatigability). The research objectives of this proposal are to: 1) Determine the association between an objective measure of cognitive performance fatigability and activity levels in older adults;and 2) Identify potential neuronal mechanisms of this fatigability. The long-term goal is to determine whether interventions directed at cognition and/or CNS targets restore activity levels in older adults afflicted by fatige. The central hypothesis is that cognitive performance fatigability in older adults contributes to activity restrictions and is due to aging related neurocognitive changes. This hypothesis has been formulated on the basis of our preliminary data showing: 1) Significant correlations between cognitive fatigability and both age and fatigue complaints in older adults;and 2) Associations between physiologic markers of cognitive reserve and cognitive fatigability. The rationale for the proposed research is that better objective measures of cognitive and CNS factors are needed to advance our understanding of fatigability in older adults and to identify targets for therapeutic interventions. The hypothesis will be tested through two Specific Aims: 1) Determine the correlation between cognitive performance fatigability and activity levels in older adults;and 2) Determine the relationship between cognitive fatigability and neurophysiological markers of cognitive reserve using electroencephalography (EEG). The approach is innovative because it represents the first study to examine objective cognitive fatigability as a cause of restricted activity in older adults and is the first study to determine whether physiologic measures of cerebral reserve impact cognitive fatigability. The proposed research is significant because it is expected to advance out understanding of the mechanisms of fatigability in older adults and to contribute new tools, mechanistic insights and therapeutic targets essential for advancing this field. The knowledge and techniques developed in this R21 proposal will serve as a foundation for future R01 proposals to investigate the potential for cognitive interventions t improve activity restrictions in older adults and mechanistic studies to better understand the relationship and interaction of potential causes of restricted activity in older adults including cognitive, CNS, muscular, cardiovascular and metabolic factors.
Fatigue in older adults is associated with decreased quality of life, increased mortality, and is the leading cause of restrictions in activity in this population et little is known about its causes and there are no effective interventions. Our preliminary data suggest that increased fatigability of cognitive abilities and attention in older adults is a potentially important cause of activity restrictions in this population and may be related to changes in brain function associated with aging. This proposal will validate a novel objective measure of cognitive fatigability in older adults and determine whether this cognitive fatigability is associated with activity restrictions and age-related changes in brain function.