Project Summary / Abstract Purpose: The REpeated ASSEssment of SurvivorS in ICH study will conduct long-term cognitive, functional, and neuropsychiatric performance assessments to determine if evacuation of spontaneous intracerebral hemorrhage (ICH) reduces the risk of later cognitive decline in the ageing brain. This study will compare rates of cognitive decline under two treatment strategies for intracerebral hemorrhage: the use of minimally invasive surgery with two similar techniques as performed in the recently completed MISTIE III and ENRICH trials, and the current standard of care using data from both controls in MISTIE III and ENRICH and comparative data from The Ethnic/Racial Variations of ICH (ERICH) study (U-01-NS067963) extended into the ERICH- Longitudinal study (R01-NS093870) which followed over 900 of the cases with serial cognitive examinations. Rationale: Intracerebral hemorrhage has the highest disability rate among stroke survivors. ICH survivors are at particularly high risk for progressive cognitive impairment which is strongly associated with greater hematoma volume, but also with cerebral amyloid angiopathy. Compared with standard of care, minimally invasive surgery with effective hematoma volume reduction may improve long-term functional outcomes while also reducing mortality. As such, reducing hematoma volume after ICH may reduce the risk of post ICH cognitive decline. Design: REASSESS ICH is a longitudinal structured serial telephone interview follow-up plus one-time in- person visit of an anticipated 359 ICH survivors enrolled in MISTIE III (2013-2017) or ENRICH (2018-2022). Cognitive and functional outcome data will be compared with up to 900 patients enrolled in ERICH-L, to determine if surgical ICH reduction leads to reduced risk of progressive cognitive decline. Primary Aim 1: To determine if surgical clot reduction after ICH reduces the risk of progressive cognitive decline. Hypothesis: The final residual volume of ICH will correlate with risk of cognitive decline after controlling for age, sex, initial volume of ICH, leukoaraiosis, APOE genotype, and hypertension treatment among operated and non-operated survivors of MISTIE III/ENRICH and survivors of ERICH, and effective clot reduction (<20 mL end of treatment volume), will be associated with lower risk of cognitive decline compared to non-operated patients. Primary Aim 2: To determine if there is a long-term benefit in survival and functional outcome from minimally invasive surgery and the interaction with cognitive decline. Hypothesis: Effective clot reduction will be associated with a decreased risk of death/major disability compared to non-operated patients. Exploratory Aim 3: To determine if inflammatory gene pathway expression predicts risk of cognitive decline. Hypothesis: Chronic brain inflammation contributes to progressive cognitive impairment post ICH. Our preliminary data identifies that inflammation appears to occur chronically after ICH; not just ac...