The proposed research is aimed at better understanding the neural underpinnings of cognitive reserve (CR). We have postulated that CR moderates the relationship between age- or Alzheimer?s disease (AD)-related brain pathology and the clinical impact of that pathology. Our findings suggest that CR operates through individual differences in how tasks are processed in the brain and that we can use fMRI-measured task-related activation to understand these processing differences. We have also begun to look at the factors influencing brain integrity, or brain reserve (BR). The promise of better understanding CR and BR is that these concepts have implications for preservation of function over time, so the neural mechanisms underlying reserve are optimally studied in a longitudinal context. We propose to initiate longitudinal follow-up at 5 years of a large, well characterized, initially healthy group of young (n=50) and older (N=150) adults, in order to elucidate the neural mechanism underlying CR that help maintain BR and successful cognitive performance in the face of advancing age-related brain changes and AD pathology. These participants have already been studied at baseline with two fMRI tasks, as well as quantified measures of age- and AD-related brain changes and pathology, including MR measures of brain volume, cortical thickness, white matter hyperintensities, resting cerebral blood flow and default network integrity, as well quantified amyloid burden from Florbetaben PET. We have already identified candidate neural mechanisms for CR. We will determine whether differential expression of these CR networks in healthy elders is associated with reduced risk of important clinical outcomes including cognitive decline and developing mild cognitive impairment MCI or AD. We will also explore how measured CR and CR networks maintain BR and how they moderate the effect of observed brain changes and advancing AD pathology in order to preserve cognitive functioning.
Impact This work will lead to better understanding of how age-related brain changes and advancing AD pathology impact on the neural systems that mediate cognitive function and elucidate the neural mechanisms that differentiate successful from unsuccessful aging. In turn, it should provide clues for remediating or preventing age-related cognitive changes and delaying the onset of AD.
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