Abstract
Predicting recurrent intracerebral hemorrhage (ICH) related to cerebral amyloid angiopathy (CAA) currently relies on brain images. We aimed to investigate whether blood neurodegenerative biomarkers predict disease severity and ICH recurrence in CAA. We recruited 68 first probable CAA-ICH cases from a Chinese prospective cohort, and 95 controls. We used the single-molecule array to measure acute phase blood amyloid-40, amyloid-42, total tau and neurofilament light chain (NfL). We used multivariable Cox regression models to assess the association between blood biomarkers and CAA-ICH recurrence, and used the concordance (c-) index to assess prediction models. Blood amyloid-42/40, total tau, and NfL levels changed in CAA-ICH cases than controls. During a median follow-up of 2.4 years, NfL was associated with CAA-ICH recurrence (adjusted hazard ratio 2.14, 95% CI 1.57-2.93) independent of MRI burden of small vessel disease (SVD). The performance of a model to predict CAA-ICH recurrence using MRI burden of SVD alone (c-index 0.77) increased with the addition of NfL (c-index 0.88, 95% CI 0.73-1.00, p=0.019). Further, NfL was associated with baseline ICH volume, NIHSS and 6-month mRS score. Blood NfL is associated with severity and prognosis of CAA-ICH and is a promising addition to MRI burden of SVD to predict CAA-ICH recurrence.
Highlights
Cerebral amyloid angiopathy (CAA) is one of the leading causes for spontaneous lobar intracerebral hemorrhage (ICH) in the elderly
A total of 144 cases with primary lobar ICH were admitted in two independent hospitals in China during the study period, and 68 cases with first-ever probable CAA-ICH (Figure 1) and 95 healthy elder controls were included in the study
The ICH recurrence was associated with older age, higher degree of periventricular spaces in the centrum semiovale (CSO-PVS) and heavier total MRI burden of small vessel disease (SVD), but not lobar cerebral microbleeds (CMBs) count, cortical superficial siderosis (cSS) presence or extent, or white matter hyperintensities (WMH) Fazekas score in univariable Cox regression analyses in our cohort (Table 2)
Summary
Cerebral amyloid angiopathy (CAA) is one of the leading causes for spontaneous lobar intracerebral hemorrhage (ICH) in the elderly. The prediction of ICH recurrence and disease severity for CAA mostly depends on brain imaging features, including the number of previous ICH and cerebral microbleeds (CMBs), posterior white matter hyperintensities (WMH) [1, 5] and cortical superficial siderosis (cSS), among which cSS is most clinically relevant [2, 3]. CAA-related MRI features represent vascular endpoints of CAA rather than neurodegenerative processes that might influence disease progression and recurrence risk [6]. The utilities of circulating biomarkers for CAA are still underexplored except for the diagnostic value of APOE genotype, β-amyloid (Aβ) 42 and Aβ40. We aimed to examine whether blood biomarkers of Aβ42, Aβ40, total tau and NfL in CAA indicate disease severity and predict prognosis
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