Projects

Multi-modal modeling of VCID: deep molecular and clinical phenotyping for therapeutic discoveries in early disease

Our team is developing new ways to measure vascular contributions to cognitive impairment and dementia in living humans. We operate at the juncture of preclinical and clinical research. Our focus is on the discovery of dysregulated molecular pathways in VCID and identification of plasma biomarkers for risk stratification and ultimately clinical trials for VCID. This discovery process requires new approaches for quantification of molecular and clinical abnormalities.

What we measure to map VCID trajectories

  • plasma, cerebrospinal fluid, and brain tissue

  • retinal and brain imaging

  • cognitive and psychiatric measures

  • movement and sleep tracking with wearables

  • video-based evaluations of voice and facial movement

Brain borders: where social determinants of health meet brain

Understanding vascular molecular pathologies will contribute to the development of quantitative measures of adverse socio-economic experiences on health.

VCID has genetic vulnerabilities (e.g. NOTCH3 mutations or APOE4 genotype) while environmental factors such as stress, lifestyle and diet can also contribute and accelerate decline.

Modeling monogenic disease to identify resilience

Genetic variant doesn’t always mean brain degeneration and decline. By studying individuals who defy predictive models, we seek to uncover the molecular underpinnings of resilience that boost the brain’s ability to resist pathology and maintain function.

We are especially focused on understanding resilience and resistance to mutations in NOTCH3 (CADASIL study ) and super-agers with elevated genetic risk for dementia.

Thank you to our sponsors for making this work possible.