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Principal Investigator  
Principal Investigator's Name: Katherine Bangen
Institution: University of California, San Diego
Department: Psychiatry
Proposed Analysis: Recent evidence using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) demonstrated that amyloid-beta pathology is associated with hypoperfusion (Mattsson et al., 2014, Brain). Mattsson et al. (2014) reported that, in a sample of 182 ADNI participants, amyloid-beta pathology was associated with reduced cerebral blood flow in early stages of the Alzheimer's disease (AD) course and reduced brain volume later in the course of AD. Overall, findings from this recent study suggest that amyloid-beta pathology shows different relations with cerebral blood flow and volume across the spectrum from normal cognition to AD with dementia. Our recent research suggests that vascular risk burden influences the trajectory of cognitive decline in preclinical AD (e.g., Bangen et al., 2013, Journal of Cerebrovascular Diseases and Stroke). Even in those without cognitive impairment, vascular risk factors have been associated with cerebrospinal fluid markers of amyloid and tau (Nation et al., 2014, Neurology). Although it is well established that vascular risk factors are risk factors for AD, the underlying mechanisms are unclear. We hypothesize that the associations between cerebral blood flow and amyloid-beta pathology variy based on vascular risk burden. We aim to examine how elevated vascular risk burden (based on history of hypertension, type 2 diabetes, hypercholesterolemia, obesity, cardiovascular disease, smoking, and transient ischemic attack) modifies the relationship between amyloid-beta pathology and cerebral blood flow. We plan to incorporate ADNI data from medical history, laboratory analysis (blood glucose, cholesterol), arterial spin labeling MRI, and AV45 amyloid. We will use regression models adjusting for age, sex, and anti-hypertensive medication use to examine the modifying effects of vascular risk burden on the association between cerebral blood flow and amyloid.
Additional Investigators  
Investigator's Name: Lauren Edwards
Proposed Analysis: Lauren Edwards, a PhD student working in my research laboratory, will pursue analyses examining associations of cognition, tau and amyloid biomarkers, and vascular factors in older adults with and without mild cognitive impairment.