UC Riverside

One of the central goals of neuroscience is to understand how the brain impacts behavior, this understanding can help explain why some individuals undergo normal age- related memory decline while others develop dementia. To this end, the current body of work utilized multi-compartment diffusion imaging to characterize brain wide differences in gray matter microstructure and examined relationships to memory performance, using young and older adults. This approach was sensitive to restricted, hindered, and free diffusion compartments, which are thought to reflect intra- and extra-cellular diffusion, and cerebral spinal fluid, respectively. Initial results with 51 participants (chapter 1) in the hippocampus revealed that multi-compartment diffusion measures outperformed traditional single-tensor measures to capture differences in age and memory performance, likely to improved sensitivity to gray matter microstructure including differences in the free water compartment. A follow up with 146 participants (chapter 2) revealed that the previously observed effects extended to gray matter regions beyond the hippocampus.Frontal lobe free diffusion was the top ranked predictor of age and was negatively, strengthening the association between of free water and age. Within hippocampus, relationships to memory performance revealed that hindered and restricted diffusion were selective to different facets of memory performance; negative associations were observed between hindered diffusion and mnemonic discrimination, and between restricted diffusion and recall performance. This negative association with recall, in addition to an age-related increase in restricted diffusion suggested that diffusion measures may be sensitive to gray matter gliosis. The last experiment with a subset of 63 participants from the previous chapter (chapter 3) supported this theoretical framework by demonstrating that diffusion measures were positively associated with iron content, consistent with the model of iron-related inflammation and gliosis established in animals. The shared variance between iron and restricted diffusion also helped explain differences in recall memory performance, since higher restricted diffusion was associated with poorer memory performance. Overall, this body of work moves the field of neuroscience forward by demonstrating that gray matter microstructure differs between young and older adults in specific ways and identifies gliosis as a contributor to differences in human memory.