Cerebral Small Vessel Disease and Dementia: Defining Global Resilience and Disruption in Brain Networks - Summary/Abstract My goal is to establish myself as an independent biomedical researcher in brain aging and Alzheimer's disease (AD) and AD related dementias (ADRD). My passion to build a career in aging stems from my profound desire to help older people to maintain their functionality and quality of life. AD/ADRD are particularly interesting to me due their complex heterogeneous nature and my enthusiasm to work on complex health problems. The Wake Forest School of Medicine provides an exceptional environment to build a career in this field as it's a nationally recognized leader in geriatric research with multiple NIH-funded P30 centers (P30AG072947 ADRC and P30 Pepper OAIC) focused on aging process and age-related disorders. The K25 Mentored Career Development Award will provide a unique opportunity for me to build a rigorous foundation in this new direction by leveraging the didactic research and training opportunities offered by this environment. I have briefly described my research and training objectives for this award. Research. The most common form of neuropathology in older adults is mixed cerebral small vessel disease and AD pathologies. Despite this, we have major gaps in our practical understanding of small vessel disease contribution to cognitive dysfunction and decline. Specifically, the impacts of small vessel disease on brain networks are largely unknown. In my K25 application, by focusing on cerebral microbleeds (CMB), as common manifestations of small vessel disease, I seek to address this critical gap. My specific aims are to: 1) utilize advanced brain network modeling to uncover and quantify network resilience/disruption from CMB, 2) use an integrative machine learning model with novel brain network biomarkers of CMB to improve predicting cognitive impairment, and 3) develop and deploy software packages to disseminate the developed methods that enable researchers to ask similar questions with other biomarkers of neuropathology and verify findings of this study. My proposed research can provide novel tools and insights to enable a translational shift in our practical understanding of mechanistic impacts of CMB on the brain to allow incorporating them into current diagnostic and treatment frameworks. Training. My specific training objectives for the protected time provided by this award are to: 1) establish knowledge of healthy and abnormal aging within the context of AD/ADRD, 2) gain expertise in the vascular contributions to AD/ADRD, 3) acquire in-depth knowledge about imaging biomarkers of small vessel disease, and 4) improve collaborative research, networking, and grant writing skills. I will be guided by an outstanding team of multidisciplinary clinicians and scholars in aging and AD/ADRD, neuroscience, and statistics to accomplish these objectives through attending courses, conferences, seminars, workshops, and shadowing geriatric clinicians and neuroradiologists. The preliminary work from this study will open opportunities to study the effect of small vessel disease and other age-related pathology on brain health and risk for AD/ADRD and preclinical results for future R01 submissions.
