Early biomarkers for Alzheimer's disease and other forms of dementia in human patients include a 20-30% reduction in cerebral blood flow, the appearance of white matter hyperintensities with magnetic resonance imaging, and significant deficits in cerebral blood oxygen. To study the related mechanisms underlying these changes, we are performing three-photon microscopy in live mice, which allows for the necessary deep in vivo imaging to reach the white matter and results in label-free third harmonic generation (THG) signals from myelin and red blood cells.We first optimized our THG imaging technique of myelin to reliably produce high-quality images of subcortical white matter for longitudinal studies. By imaging myelin in a severe mouse model of demyelination over several weeks, we developed several metrics to quantify myelin degeneration. We successfully applied these metrics in preliminary experiments on two new mouse models of dementia, based on genetic and environmental risk factors for dementia in patients. We also demonstrated the ability to track myelin degradation in parallel with blood flow measurements, without the need for extrinsic fluorophores. Further, to explore the blood oxygen changes observed in humans, we introduce THG spectroscopy in mice to measure blood oxygen concentration at the capillary level. Our technique capitalizes on the oxygen-dependent absorption spectrum changes of hemoglobin and the resonantly enhanced THG signal from hemoglobin due to real electronic transitions at the THG photon energies. While our work suggests that an absolute measurement of blood oxygen concentration will require a more complete understanding of the relationship between enhancement of THG and linear reabsorption of that same THG, relative changes in oxygenation are already readily detected by our system. We also implemented an adaptive optics system to improve THG imaging in the subcortical white matter, but caution against using THG signal alone as a metric for correcting wavefront aberrations. Finally, a preliminary experiment demonstrates the feasibility of imaging retinal vasculature as a means of correlating retinal and neural pathologies, with the goal of motivating retinal imaging in humans as an early diagnostic. Together, we propose that these novel label-free metrics may help increase our understanding of the mechanisms underlying neurodegeneration.