Background and purpose: NMDA receptor antagonists have been found to reduce inflammation after intracerebral hemorrhage (ICH) in animal models. Here, we evaluated the potential role for dementia treatment (including memantine, an NMDA receptor antagonist and donepezil, an AchE inhibitor) in decreasing risk of ICH and effect on functional outcome.
Methods: The study population was comprised of the Genetic and Environmental Risk Factors for Hemorrhagic Stroke study (GERFHS), a case-control study of hemorrhagic stroke that recruited 1,000 cases of ICH and 3,000 controls (1997 -2013), and the Ethnic/Racial Variations of Intracerebral Hemorrhage study, a multi-center, case-control study to recruit 3,000 cases of ICH and 3,000 demographically matched controls from 2010 to the present. A subset of cases and controls with history of or treatment of Alzheimer’s disease or dementia was created to account for the higher risk of ICH with dementia. A review of each subject’s medication history was performed to evaluate the frequency of treated dementia. Three month survival was evaluated using multivariate logistic regression analysis.
Results: Frequency of memantine use among cases (N=234) and controls (N=36) with Alzheimer’s disease was 19.2% and 25.0%, respectively (OR 0.714, 95% CI [0.314-1.624], p=0.42). Frequency of donepezil use among cases (32.1%) was lower than controls (61.1%) (OR 0.300, CI [0.146-0.619], p=.0011). Cases on Alzheimer treatment did not demonstrate significantly better mortality at 3 months than untreated patients (p=0.15). Overall, treated dementia/AD was associated with a decreased risk of ICH (OR 0.18, CI [0.08-0.44], p=0.0002) independent of anticoagulant use, hypertension, and high cholesterol and prestroke disability.
Conclusions: While preliminary analysis was unable to identify an association between memantine and risk of ICH, treated dementia was associated with a decreased risk of ICH. In addition, despite putative benefits of NMDA antagonism, no benefit on survival was observed. Further studies are needed to determine the mechanism by which treatment of dementia may be associated with lower risk of ICH.