title: Vascular cognitive impairment neuropathology guidelines (VCING): the contribution of cerebrovascular pathology to cognitive impairment.
abstract: There are no generally accepted protocols for post-mortem assessment in cases of suspected vascular cognitive impairment. Neuropathologists from seven UK centres have collaborated in the development of a set of vascular cognitive impairment neuropathology guidelines (VCING), representing a validated consensus approach to the post-mortem assessment and scoring of cerebrovascular disease in relation to vascular cognitive impairment. The development had three stages: (i) agreement on a sampling protocol and scoring criteria, through a series of Delphi method surveys; (ii) determination of inter-rater reliability for each type of pathology in each region sampled (Gwet's AC2 coefficient); and (iii) empirical testing and validation of the criteria, by blinded post-mortem assessment of brain tissue from 113 individuals (55 to 100 years) without significant neurodegenerative disease who had had formal cognitive assessments within 12 months of death. Fourteen different vessel and parenchymal pathologies were assessed in 13 brain regions. Almost perfect agreement (AC2 > 0.8) was found when the agreed criteria were used for assessment of leptomeningeal, cortical and capillary cerebral amyloid angiopathy, large infarcts, lacunar infarcts, microhaemorrhage, larger haemorrhage, fibrinoid necrosis, microaneurysms, perivascular space dilation, perivascular haemosiderin leakage, and myelin loss. There was more variability (but still reasonably good agreement) in assessment of the severity of arteriolosclerosis (0.45-0.91) and microinfarcts (0.52-0.84). Regression analyses were undertaken to identify the best predictors of cognitive impairment. Seven pathologies-leptomeningeal cerebral amyloid angiopathy, large infarcts, lacunar infarcts, microinfarcts, arteriolosclerosis, perivascular space dilation and myelin loss-predicted cognitive impairment. Multivariable logistic regression determined the best predictive models of cognitive impairment. The preferred model included moderate/severe occipital leptomeningeal cerebral amyloid angiopathy, moderate/severe arteriolosclerosis in occipital white matter, and at least one large infarct (area under the receiver operating characteristic curve 77%). The presence of 0, 1, 2 or 3 of these features resulted in predicted probabilities of vascular cognitive impairment of 16%, 43%, 73% or 95%, respectively. We have developed VCING criteria that are reproducible and clinically predictive. Assuming our model can be validated in an independent dataset, we believe that this will be helpful for neuropathologists in reporting a low, intermediate or high likelihood that cerebrovascular disease contributed to cognitive impairment.10.1093/brain/aww214_video_abstractaww214_video_abstract.
authors: Dementia Research Group, School of Clinical Sciences, Faculty of Health Sciences, University of Bristol, Learning and Research Level 1, Southmead Hospital, Bristol, BS10 5NB, UK.
authors: Olivia A
authors: OA
authors: Skrobot
authors: Institute of Neuroscience and Newcastle Institute for Ageing, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK.
authors: Johannes
authors: J
authors: Attems
authors: Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, OX3 9DU, UK.
authors: Margaret
authors: M
authors: Esiri
authors: Department of Neuropathology, Institute of Pathology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, Debrecen, 4032, Hungary.|Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK.
authors: Tibor
authors: T
authors: Hortobágyi
authors: Centre for Clinical Brain Sciences, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, Midlothian, EH4 2XU, UK.
authors: James W
authors: JW
authors: Ironside
authors: Institute of Neuroscience and Newcastle Institute for Ageing, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK.
authors: Rajesh N
authors: RN
authors: Kalaria
authors: Department of Clinical Neuropathology, First floor, Academic Neuroscience Building, King's College Hospital, Denmark Hill, London, SE5 9RS, UK.
authors: Andrew
authors: A
authors: King
authors: Institute of Cancer and Genetics, Cardiff University School of Medicine, Institute of Medical Genetics Building, Heath Park, Cardiff, CF14 4XN, UK.
authors: George A
authors: GA
authors: Lammie
authors: Institute of Brain, Behaviour and Mental Health, Clinical and Cognitive Neuroscience Research Group, University of Manchester, A304 Clinical Sciences Building, Salford Royal Hospital, Stott Lane, Salford M6 8HD, UK.
authors: David
authors: D
authors: Mann
authors: Institute of Infection and Immunity, Cardiff University School of Medicine, Henry Wellcome Building, Heath Park, Cardiff CF14 4N, UK.
authors: James
authors: J
authors: Neal
authors: Institute of Infection and Immunity, Cardiff University School of Medicine, Henry Wellcome Building, Heath Park, Cardiff CF14 4N, UK.
authors: Yoav
authors: Y
authors: Ben-Shlomo
authors: Dementia Research Group, School of Clinical Sciences, Faculty of Health Sciences, University of Bristol, Learning and Research Level 1, Southmead Hospital, Bristol, BS10 5NB, UK.
authors: Patrick G
authors: PG
authors: Kehoe
authors: Dementia Research Group, School of Clinical Sciences, Faculty of Health Sciences, University of Bristol, Learning and Research Level 1, Southmead Hospital, Bristol, BS10 5NB, UK.
authors: Seth
authors: S
authors: Love
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D002561:Cerebrovascular Disorders / Q000150:complications* / Q000175:diagnosis* / Q000235:genetics; D060825:Cognitive Dysfunction / Q000175:diagnosis* / Q000209:etiology* / Q000235:genetics; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D000069338:Neuropathology / Q000379:methods* / Q000592:standards; D011336:Probability; D015203:Reproducibility of Results
chemical_list: D053327:Apolipoprotein E4
keywords: cerebrovascular disease; neuropathology; vascular cognitive impairment; vascular dementia