Program Director/Principal Investigator (Last, First, Middle): Woo, Daniel; Anderson, Christopher 3. Project Summary/Abstract We have recently completed analyses which identifies a population of patients that have a markedly increased risk of developing dementia/progressive cognitive impairment. Intracerebral hemorrhage patients had been reported to have a 42% risk of progressive cognitive impairment roughly 3 and a half years after their stroke and we have found a 39% risk in an independent population of patients. This extraordinarily high rate among survivors of ICH without a prior history of dementia yields multiple different hypotheses. First, it may be that the causes of ICH itself are also risk factors for dementia. If so, then those that develop dementia should demonstrate worsening markers of these causes such as cerebral small vessel disease and cerebral amyloid angiopathy. However, another prominent hypothesis in the field is that the hemorrhage itself is markedly inflammatory. If this inflammatory response were to trigger a progressive cognitive decline, then these cases should demonstrate differential inflammatory gene expression changes. The Recovery of StrokE (NS100417) study has recruited 163 cases out of a planned 500 total cases of ICH including 3T MRI, baseline and 3 month samples for DNA, RNA-sequencing and detailed baseline, 3 and 6 month motor, cognitive, behavioral and functional examinations. The current proposal seeks to re-enroll 250 cases of the planned 500 for 12 to 24 month follow-up neuroimaging, RNA sampling and repeated examination measures to address the following aims: 1) Determine if progressive cognitive impairment correlates with an increase in markers of cerebral small vessel disease and cerebral amyloid angiopathy; 2) Determine if inflammation as measured by RNA-sequencing markers of inflammation correlates with progressive cognitive impairment and 3) identify novel neuroimaging markers associated with progressive cognitive decline. If successful, we will provide the largest longitudinal multiple assessment evaluation of ICH and answer the major hypotheses on the development of dementia among survivors of ICH. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page
Woo, Daniel 4. Project Narrative We have identified a population in which the rate of development of dementia is extraordinarily high. Survivors of brain hemorrhage, also called intracerebral hemorrhage, develop progressive dementia at a rate of approximately 40% within several years of the hemorrhage. We seek to evaluate if this high risk is due to the underlying causes or to inflammation from the hemorrhage. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page
