Description (from grant):
The main goal of this research initiative is to further expand our current research to investigate the relationship of myelination and axonal density in the brain to cognitive and functional outcomes, as well as the interplay of iron deposition, local myelination, and axonal density, using myelin water fraction (MWF) metrics for myelin quantification, multi-shell diffusion tensor imaging (MSDTI) for axonal density mapping, and susceptibility imaging (SWI) for local iron content quantification. A further important correlate to these studies is the vulnerability of oligodendrocyte metabolism and axonal density to local cerebral blood flow (CBF) through combined MRI measurements of MWF, MSDTI, SWI, and CBF, in the setting of normative aging (NA), mild cognitive impairment (MCI), and dementia. Further, in addition to cognitive decline, dementia is accompanied by neuropsychiatric symptoms including disturbances in mood, emotion and sleep, as well as confusion, agitation and depression. All of this suggests significant brainstem involvement in the development of dementia. This region is remarkably understudied in the investigation of cognitive impairment and dementia. Significant progress has been achieved during the last fiscal year. Using our advanced MRI techniques for MWF and CBF quantifications: 1- We demonstrated a quadratic, inverted U-shape, relationship between MWF and age in all brain regions investigated, suggesting that myelination continues until middle age followed by decreases at older ages. We also observed that these age-related differences vary across different brain regions, as expected. Finally, our results provide reference values for MWF values in normative aging. This work was motivated by the fact that age is the main risk factor for degenerative central nervous system (CNS) disease and associated cognitive and functional impairment. It is therefore crucial to characterize microstructural changes in the brain that occur with normal aging to distinguish them from changes caused by disease.