Observational Study

. 2022 Sep 20;99(12):e1290-e1298.

doi: 10.1212/WNL.0000000000200851. Epub 2022 Jul 8.

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

Isabel Charlotte Hostettler¹, David Seiffge¹, Andrew Wong¹, Gareth Ambler¹, Duncan Wilson¹, Clare Shakeshaft¹, Gargi Banerjee¹, Nikhil Sharma¹, Hans Rolf Jäger¹, Hannah Cohen¹, Tarek A Yousry¹, Rustam Al-Shahi Salman¹, Gregory Y H Lip¹, Martin M Brown¹, Keith Muir¹, Henry Houlden¹, David J Werring²

Affiliations

¹ From the Stroke Research Centre (I.C.H., D.S., Duncan Wilson, C.S., G.B., M.M.B., David Werring), University College London, Institute of Neurology; Neurogenetics Laboratory (I.C.H., H.H.), The National Hospital of Neurology and Neurosurgery, London, UK; Department of Neurosurgery (I.C.H.), Cantonal Hospital St. Gallen, Switzerland; Stroke Centre (D.S.), Department of Neurology and Department of Clinical Research, University of Basel and University Hospital Basel; Department of Neurology and Stroke Centre (D.S.), University Hospital Berne; MRC Unit for Lifelong Health and Ageing at UCL (A.W.), London; Department of Statistical Science (G.A.), UCL, London; Department of Clinical and Movement Neuroscience (N.S.), Institute of Neurology, London; Neuroradiological Academic Unit (H.R.J., T.A.Y.), Department of Brain Repair & Rehabilitation, University College London, Institute of Neurology; Haemostasis Research Unit (H.C.), Department of Haematology, University College London; Centre for Clinical Brain Sciences (R.A.-S.S.), School of Clinical Sciences, University of Edinburgh; Liverpool Centre for Cardiovascular Science (G.Y.H.L.), University of Liverpool and Liverpool Heart & Chest Hospital; Department of Clinical Medicine (G.Y.H.L.), Aalborg University, Denmark; and Institute of Neuroscience & Psychology (K.M.), University of Glasgow, Queen Elizabeth University Hospital, UK.
² From the Stroke Research Centre (I.C.H., D.S., Duncan Wilson, C.S., G.B., M.M.B., David Werring), University College London, Institute of Neurology; Neurogenetics Laboratory (I.C.H., H.H.), The National Hospital of Neurology and Neurosurgery, London, UK; Department of Neurosurgery (I.C.H.), Cantonal Hospital St. Gallen, Switzerland; Stroke Centre (D.S.), Department of Neurology and Department of Clinical Research, University of Basel and University Hospital Basel; Department of Neurology and Stroke Centre (D.S.), University Hospital Berne; MRC Unit for Lifelong Health and Ageing at UCL (A.W.), London; Department of Statistical Science (G.A.), UCL, London; Department of Clinical and Movement Neuroscience (N.S.), Institute of Neurology, London; Neuroradiological Academic Unit (H.R.J., T.A.Y.), Department of Brain Repair & Rehabilitation, University College London, Institute of Neurology; Haemostasis Research Unit (H.C.), Department of Haematology, University College London; Centre for Clinical Brain Sciences (R.A.-S.S.), School of Clinical Sciences, University of Edinburgh; Liverpool Centre for Cardiovascular Science (G.Y.H.L.), University of Liverpool and Liverpool Heart & Chest Hospital; Department of Clinical Medicine (G.Y.H.L.), Aalborg University, Denmark; and Institute of Neuroscience & Psychology (K.M.), University of Glasgow, Queen Elizabeth University Hospital, UK. d.werring@ucl.ac.uk.

PMID: 36123141
PMCID: PMC9576291
DOI: 10.1212/WNL.0000000000200851

Observational Study

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

Isabel Charlotte Hostettler et al. Neurology. 2022.

. 2022 Sep 20;99(12):e1290-e1298.

doi: 10.1212/WNL.0000000000200851. Epub 2022 Jul 8.

Authors

Affiliations

¹ From the Stroke Research Centre (I.C.H., D.S., Duncan Wilson, C.S., G.B., M.M.B., David Werring), University College London, Institute of Neurology; Neurogenetics Laboratory (I.C.H., H.H.), The National Hospital of Neurology and Neurosurgery, London, UK; Department of Neurosurgery (I.C.H.), Cantonal Hospital St. Gallen, Switzerland; Stroke Centre (D.S.), Department of Neurology and Department of Clinical Research, University of Basel and University Hospital Basel; Department of Neurology and Stroke Centre (D.S.), University Hospital Berne; MRC Unit for Lifelong Health and Ageing at UCL (A.W.), London; Department of Statistical Science (G.A.), UCL, London; Department of Clinical and Movement Neuroscience (N.S.), Institute of Neurology, London; Neuroradiological Academic Unit (H.R.J., T.A.Y.), Department of Brain Repair & Rehabilitation, University College London, Institute of Neurology; Haemostasis Research Unit (H.C.), Department of Haematology, University College London; Centre for Clinical Brain Sciences (R.A.-S.S.), School of Clinical Sciences, University of Edinburgh; Liverpool Centre for Cardiovascular Science (G.Y.H.L.), University of Liverpool and Liverpool Heart & Chest Hospital; Department of Clinical Medicine (G.Y.H.L.), Aalborg University, Denmark; and Institute of Neuroscience & Psychology (K.M.), University of Glasgow, Queen Elizabeth University Hospital, UK.
² From the Stroke Research Centre (I.C.H., D.S., Duncan Wilson, C.S., G.B., M.M.B., David Werring), University College London, Institute of Neurology; Neurogenetics Laboratory (I.C.H., H.H.), The National Hospital of Neurology and Neurosurgery, London, UK; Department of Neurosurgery (I.C.H.), Cantonal Hospital St. Gallen, Switzerland; Stroke Centre (D.S.), Department of Neurology and Department of Clinical Research, University of Basel and University Hospital Basel; Department of Neurology and Stroke Centre (D.S.), University Hospital Berne; MRC Unit for Lifelong Health and Ageing at UCL (A.W.), London; Department of Statistical Science (G.A.), UCL, London; Department of Clinical and Movement Neuroscience (N.S.), Institute of Neurology, London; Neuroradiological Academic Unit (H.R.J., T.A.Y.), Department of Brain Repair & Rehabilitation, University College London, Institute of Neurology; Haemostasis Research Unit (H.C.), Department of Haematology, University College London; Centre for Clinical Brain Sciences (R.A.-S.S.), School of Clinical Sciences, University of Edinburgh; Liverpool Centre for Cardiovascular Science (G.Y.H.L.), University of Liverpool and Liverpool Heart & Chest Hospital; Department of Clinical Medicine (G.Y.H.L.), Aalborg University, Denmark; and Institute of Neuroscience & Psychology (K.M.), University of Glasgow, Queen Elizabeth University Hospital, UK. d.werring@ucl.ac.uk.

PMID: 36123141
PMCID: PMC9576291
DOI: 10.1212/WNL.0000000000200851

Abstract

Background and objective: We investigated the associations between the APOE genotype, intracerebral hemorrhage (ICH), and neuroimaging markers of cerebral amyloid angiopathy (CAA).

Methods: We included patients from a prospective, multicenter UK observational cohort study of patients with ICH and representative UK population controls. First, we assessed the association of the APOE genotype with ICH (compared with controls without ICH). Second, among patients with ICH, we assessed the association of APOE status with the hematoma location (lobar or deep) and brain CT markers of CAA (finger-like projections [FLP] and subarachnoid extension [SAE]).

Results: We included 907 patients with ICH and 2,636 controls. The 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 with controls, any APOE ε2 allele was associated with all ICH (lobar and nonlobar) and lobar ICH on its own in the dominant model (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). In the cases-only analysis, the APOE ε4 allele was associated with lobar compared with 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.

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Figures

**Figure 2. Example of Subarachnoid Extension (SAE; A) and Finger-Like Projections (FLP; B)**

See this image and copyright information in PMC

References

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

Affiliations

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

Authors

Affiliations

Abstract

Figures

References

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LinkOut - more resources

Full Text Sources

Miscellaneous