Peter Kang, M.D., MSCI
ABSTRACT:
The candidate is a neurologist, intensivist and an early-career clinical investigator pursuing a clinical and
translational research program using advanced multimodal neuroimaging methods to study the pathophysiology underlying cerebral small vessel disease (CSVD) and the vascular contributions to cognitive impairment and dementia (VCID). This proposal focuses on using neuroimaging as well as serum and cerebrospinal fluid (CSF) biomarkers to understand the role neuroinflammation plays in CSVD and VCID pathogenesis. The proposed work is a prospective, observational study utilizing neuroimaging, biomarkers, and cognitive assessments in participants with low to high risk of VCID progression. This work is made possible by the utilization of diffusion basis spectrum imaging (DBSI), a technique developed at Washington University which is capable of detecting and differentiating inflammatory cell infiltration and inflammation-associated vasogenic edema from axon loss and myelin injury, which traditional diffusion imaging cannot do. Aim 1 will determine if serum and CSF biomarkers of inflammation (primarily sTREM2 and YKL-40) are associated with DBSI metrics of neuroinflammation. Aim 2 will determine if DBSI metrics of neuroinflammation are predictive of severity in the imaging endpoints of CSVD (white matter hyperintensity volume and loss of microstructural integrity on diffusion tensor imaging) as well as cognitive impairment in VCID. The role of serum and CSF biomarkers in mediating this relationship will be investigated. Ultimately this work seeks to provide evidence for a novel mechanistic pathway in VCID, leading to the development of novel targeted therapeutic agents for the treatment and prevention of VCID.
LAY SUMMARY:
Cerebral Small Vessel Disease (CSVD) and Vascular Contributions to Cognitive Impairment and Dementia (VCID) are leading causes of disability and cognitive impairment in older adults. Though manifestations of CSVD and VCID are common, the underlying mechanisms of disease remain unknown. This project will use novel, noninvasive MRI techniques and fluid biomarkers to understand the role neuroinflammation plays in the development of CSVD/VCID, and to help determine who is at highest risk for disease progression.
