Proteomics and Cognitive Decline Following Intracerebral Hemorrhage - Dementia rates are rising in the U.S., with new cases expected to nearly double to 1 million annually by 2060. Vascular Contributions to Cognitive Impairment and Dementia (VCID) — like reduced blood flow, strokes, or small vessel damage—has emerged as both an independent cause of dementia as well as an accelerant in other forms of dementia (such as Alzheimer’s disease). Intracerebral hemorrhage (ICH) stroke subtype caused by a bleed in the brain resulting from the rupture of a blood vessel within the brain and carries the highest risk for dementia among stroke survivors. This may be due to pre-existing risk factors (e.g., age, education, cerebral atrophy, and severity of pre-existing cerebrovascular disease) and ICH characteristics (ICH size, location, and intraventricular involvement) as well as concurrent cerebral amyloid angiopathy (another risk factor for VCID) and/or Alzheimer’s disease. However, the mechanisms by which these risk factors/characteristics produce post-ICH VCID remain unknown. Furthermore, there are currently no clear biomarker candidates or therapeutic targets for post-ICH VCID. Our central hypothesis is that the peripheral proteome at the time of ICH reflects brain health and systemic response to ICH and is associated with post-ICH VCID. To test this hypothesis, we will leverage biospecimens and long-term ICH cognitive outcomes from the Recovery of StrokE, Longitudinal Assessment With Neuroimaging (ROSE-LAWN, R01NS120493). The ROSELAWN study is the largest and longest study on ICH outcomes and follows 250 ICH patients with serial advanced neuroimaging as well as comprehensive motor, cognitive, and functional assessments beginning approximately 36 months post-ICH and continuing for an additional 12–24-month post-ICH. The plasma proteome will be characterized at the time of ICH using the unbiased SOMAscan assay, immune cells intracellular proteome will be characterized using Mass Spectrometry, and immune cell surface proteins will be characterized using flow cytometry. The association between peripheral proteins and MRI features of brain health and ICH characteristics will be tested. Additionally, the association between peripheral proteins and post-ICH VCID will be tested. A subset will undergo longitudinal proteome assessment. This R01 project will serve as the foundation for studying longitudinal changes in peripheral proteins and post-ICH VCID, as well as a springboard for translational research aimed at reducing post-ICH cognitive decline and dementia.
