Predictors for Late Post-Intracerebral Hemorrhage Dementia in Patients with Probable Cerebral Amyloid Angiopathy.

BACKGROUND AND OBJECTIVE Cerebral amyloid angiopathy (CAA) accounts for the majority of lobar intracerebral hemorrhage (ICH); however, the risk factors for dementia conversion after ICH occurrence in CAA patients is unknown, especially in the long-term period after ICH. Therefore, we aimed to unravel the predictors for late post-ICH dementia (6 months after ICH event) in probable CAA patients. METHODS From a large consecutive MRI prospective cohort of spontaneous ICH (2006-2017), we identified probable CAA patients (modified Boston criteria) without dementia 6 months post-ICH. Cognitive outcome during follow-up was determined based on the information from standardized clinical visit notes. We used Cox regression analysis to investigate the association between baseline demographic characteristics, past medical history, MRI biomarkers, and late post-ICH dementia conversion (dementia occurred after 6 months). RESULTS Among 97 non-demented lobar ICH patients with probable CAA, 25 patients (25.8%) developed dementia during a median follow-up time of 2.5 years (IQR 1.5-3.8 years). Pre-existing mild cognitive impairment, increased white matter hyperintensities (WMH) burden, the presence of disseminated cortical superficial siderosis (cSS), and higher total small vessel disease score for CAA were all independent predictors for late dementia conversion. CONCLUSION In probable CAA patients presenting with lobar ICH, high WMH burden and presence of disseminated cSS are useful neuroimaging biomarkers for dementia risk stratification. These findings have implications for clinical practice and future trial design.

[1]  M. Frosch,et al.  Histopathology of diffusion imaging abnormalities in cerebral amyloid angiopathy , 2019, Neurology.

[2]  O. Wu,et al.  Spatial Signature of White Matter Hyperintensities in Stroke Patients , 2018, bioRxiv.

[3]  S. Greenberg,et al.  Cortical superficial siderosis and first-ever cerebral hemorrhage in cerebral amyloid angiopathy , 2017, Neurology.

[4]  D. Blacker,et al.  Dementia incidence and predictors in cerebral amyloid angiopathy patients without intracerebral hemorrhage , 2017, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[5]  S. Greenberg,et al.  Cortical superficial siderosis predicts early recurrent lobar hemorrhage , 2016, Neurology.

[6]  S. Greenberg,et al.  Risk Factors Associated With Early vs Delayed Dementia After Intracerebral Hemorrhage. , 2016, JAMA neurology.

[7]  M. Frosch,et al.  Total Magnetic Resonance Imaging Burden of Small Vessel Disease in Cerebral Amyloid Angiopathy: An Imaging-Pathologic Study of Concept Validation. , 2016, JAMA neurology.

[8]  D. Leys,et al.  Dementia risk after spontaneous intracerebral haemorrhage: a prospective cohort study , 2016, The Lancet Neurology.

[9]  Y. Reijmer,et al.  Intracerebral hemorrhage and cognitive impairment. , 2016, Biochimica et biophysica acta.

[10]  K. Abe,et al.  High Incidence of Dementia Conversion than Stroke Recurrence in Poststroke Patients of Late Elder Society. , 2015, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[11]  M. Frosch,et al.  Cerebral amyloid angiopathy with and without hemorrhage , 2015, Neurology.

[12]  Benjamin S. Aribisala,et al.  White matter hyperintensities and normal-appearing white matter integrity in the aging brain , 2015, Neurobiology of Aging.

[13]  N. Beauchamp,et al.  Brain Imaging Findings in Elderly Adults and Years of Life, Healthy Life, and Able Life over the Ensuing 16 Years: The Cardiovascular Health Study , 2014, Journal of the American Geriatrics Society.

[14]  V. Caso,et al.  Neuroimaging in Intracerebral Hemorrhage , 2014, Stroke.

[15]  M. Dichgans,et al.  Prevalence of cortical superficial siderosis in patients with cognitive impairment , 2014, Journal of Neurology.

[16]  J. Baron,et al.  White matter perivascular spaces , 2014, Neurology.

[17]  Nick C Fox,et al.  Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration , 2013, The Lancet Neurology.

[18]  S. Greenberg,et al.  The Pathophysiology and Clinical Presentation of Cerebral Amyloid Angiopathy , 2012, Current Atherosclerosis Reports.

[19]  Morten Wang Fagerland,et al.  Impact of White Matter Lesions on Cognition in Stroke Patients Free from Pre-Stroke Cognitive Impairment: A One-Year Follow-Up Study , 2012, Dementia and Geriatric Cognitive Disorders Extra.

[20]  R. Petersen Clinical practice. Mild cognitive impairment. , 2011, The New England journal of medicine.

[21]  J. Morris,et al.  The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease , 2011, Alzheimer's & Dementia.

[22]  Nick C Fox,et al.  The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease , 2011, Alzheimer's & Dementia.

[23]  S. Greenberg,et al.  Cerebral Amyloid Angiopathy: A Systematic Review , 2011, Journal of clinical neurology.

[24]  W. Brown,et al.  Review: Cerebral microvascular pathology in ageing and neurodegeneration , 2011, Neuropathology and applied neurobiology.

[25]  S. Leurgans,et al.  Cerebral amyloid angiopathy pathology and cognitive domains in older persons , 2011, Annals of neurology.

[26]  Arno Klein,et al.  A reproducible evaluation of ANTs similarity metric performance in brain image registration , 2011, NeuroImage.

[27]  M. van Buchem,et al.  Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy , 2010, Neurology.

[28]  C. Jack,et al.  Mild cognitive impairment: ten years later. , 2009, Archives of neurology.

[29]  Istvan Csapo,et al.  Spatial Distribution of White-Matter Hyperintensities in Alzheimer Disease, Cerebral Amyloid Angiopathy, and Healthy Aging , 2008, Stroke.

[30]  M. Wiesmann,et al.  Subarachnoid Hemosiderosis and Superficial Cortical Hemosiderosis in Cerebral Amyloid Angiopathy , 2008, American Journal of Neuroradiology.

[31]  S. Greenberg,et al.  White matter lesions, cognition, and recurrent hemorrhage in lobar intracerebral hemorrhage , 2004, Neurology.

[32]  Y. Stern,et al.  Incidence of Dementia After Ischemic Stroke: Results of a Longitudinal Study , 2002, Stroke.

[33]  J. Szaflarski,et al.  Genetic and Environmental Risk Factors for Intracerebral Hemorrhage: Preliminary Results of a Population-Based Study , 2002, Stroke.

[34]  R. Roos,et al.  Dementia in hereditary cerebral hemorrhage with amyloidosis‐Dutch type is associated with cerebral amyloid angiopathy but is independent of plaques and neurofibrillary tangles , 2001, Annals of neurology.

[35]  F Barkhof,et al.  Inter-and Intraobserver Reproducibility of Cerebral Atrophy Assessment on MRI Scans with Hemispheric Infarcts , 1996, European Neurology.

[36]  T Brott,et al.  The ABCs of measuring intracerebral hemorrhage volumes. , 1996, Stroke.

[37]  F. Fazekas,et al.  Pathologic correlates of incidental MRI white matter signal hyperintensities , 1993, Neurology.

[38]  A. Alavi,et al.  MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. , 1987, AJR. American journal of roentgenology.

[39]  Christos Davatzikos,et al.  Correlating Cognitive Decline with White Matter Lesion and Brain Atrophy Magnetic Resonance Imaging Measurements in Alzheimer's Disease. , 2015, Journal of Alzheimer's disease : JAD.

[40]  D. Werring,et al.  Edinburgh Research Explorer Cognitive Impairment Before Intracerebral Hemorrhage Is Associated With Cerebral Amyloid Angiopathy , 2022 .