Tuesday, May 14, 2024
5/14/2024
PROJECT SUMMARY Declines in fluid, speed-dependent cognition (e.g., attention and memory) are a hallmark feature of Alzheimer’s disease (AD), but some degree of decline is also seen even in healthy older adults. Based on magnetic resonance imaging (MRI) studies using diffusion-weighted imaging (DWI), the cortical disconnection theory proposes that normal age-related cognitive decline is at least partly explained by the degradation of white matter pathways connecting distributed brain regions, with greater white matter degradation in AD. An important extension of this theory is to understand how white matter disconnection affects brain function in both healthy aging and AD. However, the examination of age- and AD-related differences in white matter connectivity, and its relation to brain function, is constrained by the relatively low resolution of standard DWI data, which cannot accurately resolve fine-grained white matter regions with crossing fiber bundles or high curvature. To address these limitations, this proposal will capitalize on a high-resolution multi-shot DWI protocol that achieves spatial resolutions = 1 mm3 on clinical 3T MRI scanners. Several studies of rodents and younger adults already suggest that high-resolution DWI estimates white matter structural connectivity more accurately than standard resolution DWI. This proposal will translate this earlier work by examining whether standard (1.5 mm3 voxels; 3.375 l volume) and high-resolution (1 mm3; 1l volume) measures of white matter structural connectivity differ in their relations to age and ability to explain age-related differences in cognitive performance (Aim 1) or functional connectivity (Aim 2) in healthy adults across the lifespan (n = 140; ages 18- 80 years). This proposal will also examine the sensitivity of high-resolution DWI to white matter disconnection and aberrant structure-function relations in adults with AD (n = 30; Aim 3). Cognition in the healthy adults will be assessed using 12 tests of memory, executive function, and perceptual-motor speed. Structural (DWI) and functional (resting-state functional MRI) connectivity will be assessed using a graph theoretical approach, providing a novel basis for comparison between these different MRI modalities. Results from this clinically feasible high-resolution DWI protocol will help answer fundamental questions about relations between neurocognitive aging, brain structure, and brain function, which is important as the field is moving toward large- scale, multimodal datasets. Ultimately, this project may identify additional age- and AD-related differences in white matter connectivity that cannot be identified using only standard resolution DWI and may inform future interventions targeting white matter connectivity to slow atypical cognitive decline. The wealth of neuroimaging and aging resources available to the applicant at Duke University Medical Center will help her establish an independent research program focused on multiple cognitive domains, graph theory, and advanced DWI methodology, thereby propelling her toward her career goal of becoming a professor at a four-year university.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
