| dc.description.abstract | Cerebrovascular and Alzheimer’s disease (AD) pathology often co-occur, complicating clinical diagnosis, treatment strategies, and understanding of the leading causes of dementia. Cerebral hemodynamic and metabolic rate markers, non-invasively quantifiable on magnetic resonance imaging (MRI), may provide early insight into distinct or co-pathological neurodegenerative and cerebrovascular processes occurring during abnormal brain aging.
The first objective of this project was to characterize associations between cognitive diagnosis and cerebral metabolic rate of oxygen (CMRO2) variables, determining if associations were modified by genetic risk for AD (APOE-ε4 carrier status) or stroke risk. 3T multimodal MRI captured cerebral blood flow (CBF) and oxygen extraction fraction (OEF); CMRO2 was quantified by the Fick principle. Findings indicated that CBF and CMRO2 were lower among individuals with dementia. OEF was lower among APOE-ε4 carriers with mild cognitive impairment (MCI) relative to APOE-ε4 non-carriers with MCI. Interaction models among cognitively impaired individuals suggested that OEF may be lower with greater stroke risk in APOE-ε4 carriers and higher with greater stroke risk in APOE-ε4 non-carriers.
The second and third objectives were to examine the association between a marker of arterial transit time, the arterial spin-labeling spatial coefficient of variation (ASL-sCoV), and neuroimaging markers of cerebral small vessel disease (SVD) and to assess whether ASL-sCoV mediated associations between brain artery lumen diameters and SVD burden. ASL-sCoV, SVD markers, and brain large artery lumen diameters were quantified on 3T multimodal MRI. Higher ASL-sCoV was associated with higher white matter hyperintensity (WMH) and basal ganglia enlarged perivascular spaces volumes. Higher baseline ASL-sCoV was associated with a faster longitudinal increase in WMH volume. The association between larger internal carotid artery lumen diameter and higher anterior WMH volume was partially mediated by higher anterior ASL-sCoV.
Taken together, this research indicates that MRI markers of hemodynamic timing and oxygen metabolism provide useful insights into neurodegenerative and cerebrovascular pathologies which often overlap in the aging brain. Distinct changes in OEF with genetic risk for AD and stroke risk highlight its potential to help disentangle co-pathological mechanisms and assist with differential diagnosis. Finally, hemodynamic timing markers show promise in advancing understanding and early detection of SVD pathophysiology. | |
