Abstract

Background: To investigate the role of cerebral amyloid deposition for long-term cognitive outcomes in spontaneous intracerebral hemorrhage (ICH) survivors. Methods: Patients experiencing an ICH without over dementia were included (n = 68). Each patient received the brain MRI and Pittsburgh Compound B (PiB) PET at baseline, and the cognitive function was followed up using Mini-mental Status Examination (MMSE) and clinical dementia rating (CDR) with an overall median of 3.8 years. The association between follow-up cognitive outcomes and neuroimaging markers was explored using multivariable Cox regression models. Positive amyloid scan was defined as global PiB standardized uptake value ratio > 1.2. Results: Patients with PiB(+) were older (72.1 ± 7.8 vs. 59.9 ± 11.7, p = 0.002) and were more frequently associated with probable CAA (54.5% vs. 8.8%, p=0.001) than patients with PiB(-). PiB(+) was associated with a higher risk of dementia conversion (32.9 vs. 4.0 per 100-person-years, HR=16.4 [3.5-75.5], p <0.001) and cognitive decline (defined as MMSE decline≥ 2, 58.8 vs.9.9 per 100-person-years, HR=6.1 [2.0-18.8], p=0.002) compared to PiB(-). Higher lobar microbleed number and the presence of lacune were also associated with cognitive worsening (both p<0.005). In the cox models, PiB(+) was an independent predictor of dementia conversion (HR=12.3 [2.9-52.6], p=0.001) or cognitive decline (HR=7.9 [2.4-26.0], p=0.001) after adjustment for age, sex, educational years, lobar microbleeds and lacune. In the subgroup of patients who were non-CAA (n=57), PiB(+) remained an independent predictor of cognitive worsening (both p<0.005). Conclusions: We demonstrate the strong association between positive amyloid scan and long-term cognitive change in ICH survivors, suggesting cerebral amyloid deposition as an important driving factor for cognitive impairment in hemorrhagic small vessel disease.

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