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APOE and Cerebral Small Vessel Disease Markers in Patients With Intracerebral Hemorrhage

Hostettler, Isabel Charlotte; Seiffge, David; Wong, Andrew; Ambler, Gareth; Wilson, Duncan; Shakeshaft, Clare; Banerjee, Gargi; ... Werring, David; + view all (2022) APOE and Cerebral Small Vessel Disease Markers in Patients With Intracerebral Hemorrhage. Neurology , 99 (12) e1290-e1298. 10.1212/WNL.0000000000200851. Green open access

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Abstract

BACKGROUND AND OBJECTIVE: We investigated the associations between Apolipoprotein E (APOE) genotype, intracerebral haemorrhage (ICH) and neuroimaging markers of cerebral amyloid angiopathy (CAA). METHODS: We included patients from a prospective, multi-centre UK observational cohort study of patients with ICH and representative UK population controls. First, we assessed association of APOE genotype with ICH (compared to controls without ICH). Second, among patients with ICH, we assessed the association of APOE status with haematoma location (lobar or deep) and brain computed tomography (CT) markers of CAA (finger like projections [FLP] and subarachnoid extension [SAE]). RESULTS: We included 907 patients with ICH and 2636 controls. Mean age was 73.2 (12.4 SD) years for ICH cases vs. 69.6 (0.2 SD) for population controls; 50.3% of cases and 42.1% of controls were female. Compared to controls, APOE ε2 allele was associated with all (lobar and non-lobar) as well as lobar ICH on its own in the dominant model, i.e. any APOE ε2 allele (OR 1.38, 95%CI 1.13-1.7, p=0.002 and OR 1.50, 95%CI 1.1-2.04, p=0.01, respectively), but not deep ICH in an age-adjusted analyses (OR 1.26, 95%CI 0.97-1.63, p=0.08) compared to controls. In the cases only analysis, APOE ε4 allele was associated with lobar compared to deep ICH in an age-adjusted analyses (OR 1.56, 95%CI 1.1-2.2, p=0.01). When assessing CAA markers, APOE alleles were independently associated with FLP (ε4: OR 1.74, 95%CI 1.04-2.93, p=0.04 and ε2/ε4: 2.56, 95%CI 0.99-6.61, p=0.05). We did not find an association between APOE alleles and SAE. DISCUSSION: We confirmed associations between APOE alleles and ICH including lobar ICH. Our analysis shows selective associations between APOE ε2 and ε4 alleles with FLP, a CT marker of CAA. Our findings suggest that different APOE alleles might have diverging influences on individual neuroimaging biomarkers of CAA-associated ICH.

Type: Article
Title: APOE and Cerebral Small Vessel Disease Markers in Patients With Intracerebral Hemorrhage
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1212/WNL.0000000000200851
Publisher version: https://doi.org/10.1212/WNL.0000000000200851
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Institute of Prion Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10152831
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