Cerebral amyloid deposition predicts long-term cognitive decline in hemorrhagic small vessel disease.

Abstract

To investigate the association between cerebral amyloid deposition and long-term cognitive outcomes in patients with hemorrhagic small vessel disease (SVD) and survivors of intracerebral hemorrhage (ICH). Patients experiencing an ICH without overt dementia were prospectively recruited (n=68) for brain MRI and Pittsburgh compound B (PiB) positron emission tomography scans at baseline. Cognitive function was assessed using the mini-mental status examination (MMSE) and clinical dementia rating after an overall median follow-up of 3.8 years. A positive amyloid scan was defined as a global PiB standardized uptake value ratio >1.2. Associations between follow-up cognitive outcomes and neuroimaging markers were explored using multivariable Cox regression models. PiB(+) patients were older (72.1±7.8 vs. 59.9±11.7, p=.002) and more frequently had cerebral amyloid angiopathy (CAA) (63.6% vs. 15.8%, p=.002) than PiB(-) patients. PiB(+) was associated with a higher risk of dementia conversion (32.9 vs. 4.0 per 100-person-years, hazard ratio [HR]=15.7 [3.0-80.7], p=.001) and MMSE score decline (58.8 vs. 9.9 per 100-person-years, HR=6.2 [1.9-20.0], p=.002). In the non-CAA subgroup (n=52), PiB(+) remained an independent predictor of dementia conversion, p=.04). In the Cox models, PiB(+) was an independent predictor of dementia conversion (HR=15.8 [2.6-95.4], p=.003) and MMSE score decline (HR=5.7 [1.6-20.3], p=.008) after adjusting for confounders. Cerebral amyloid deposition potentially contributes to long-term cognitive decline in SVD-related ICH.