title: MRI visual rating scales in the diagnosis of dementia: evaluation in 184 post-mortem confirmed cases.
abstract: Accurately distinguishing between different degenerative dementias during life is challenging but increasingly important with the prospect of disease-modifying therapies. Molecular biomarkers of dementia pathology are becoming available, but are not widely used in clinical practice. Conversely, structural neuroimaging is recommended in the evaluation of cognitive impairment. Visual assessment remains the primary method of scan interpretation, but in the absence of a structured approach, diagnostically relevant information may be under-utilized. This definitive, multi-centre study uses post-mortem confirmed cases as the gold standard to: (i) assess the reliability of six visual rating scales; (ii) determine their associated pattern of atrophy; (iii) compare their diagnostic value with expert scan assessment; and (iv) assess the accuracy of a machine learning approach based on multiple rating scales to predict underlying pathology. The study includes T1-weighted images acquired in three European centres from 184 individuals with histopathologically confirmed dementia (101 patients with Alzheimer's disease, 28 patients with dementia with Lewy bodies, 55 patients with frontotemporal lobar degeneration), and scans from 73 healthy controls. Six visual rating scales (medial temporal, posterior, anterior temporal, orbito-frontal, anterior cingulate and fronto-insula) were applied to 257 scans (two raters), and to a subset of 80 scans (three raters). Six experts also provided a diagnosis based on unstructured assessment of the 80-scan subset. The reliability and time taken to apply each scale was evaluated. Voxel-based morphometry was used to explore the relationship between each rating scale and the pattern of grey matter volume loss. Additionally, the performance of each scale to predict dementia pathology both individually and in combination was evaluated using a support vector classifier, which was compared with expert scan assessment to estimate clinical value. Reliability of scan assessment was generally good (intraclass correlation coefficient > 0.7), and average time to apply all six scales was <3 min. There was a very close association between the pattern of grey matter loss and the regions of interest each scale was designed to assess. Using automated classification based on all six rating scales, the accuracy (estimated using the area under the receiver-operator curves) for distinguishing each pathological group from controls ranged from 0.86-0.97; and from one another, 0.75-0.92. These results were substantially better than the accuracy of any single scale, at least as good as expert reads, and comparable to previous studies using molecular biomarkers. Visual rating scores from magnetic resonance images routinely acquired as part of the investigation of dementias, offer a practical, inexpensive means of improving diagnostic accuracy.
authors.affiliation: Dementia Research Centre, University College London Institute of Neurology, London WC1N 3BG, UK.
authors.forename: Lorna
authors.initials: L
authors.lastname: Harper
authors.affiliation: Neurology Unit, Department of Physiopathology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan, Italy.
authors.forename: Giorgio G
authors.initials: GG
authors.lastname: Fumagalli
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Centre, 1081 HZ Amsterdam, The Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: Alzheimer Centre, VU University Medical Centre, 1081 HZ Amsterdam, The Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge CB2 0SZ, UK.
authors.forename: John T
authors.initials: JT
authors.lastname: O'Brien
authors.affiliation: Alzheimer Centre, VU University Medical Centre, 1081 HZ Amsterdam, The Netherlands.
authors.forename: Femke
authors.initials: F
authors.lastname: Bouwman
authors.affiliation: Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK.
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Burton
authors.affiliation: Dementia Research Centre, University College London Institute of Neurology, London WC1N 3BG, UK.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Rohrer
authors.affiliation: Dementia Research Centre, University College London Institute of Neurology, London WC1N 3BG, UK.
authors.forename: Nick C
authors.initials: NC
authors.lastname: Fox
authors.affiliation: FMRIB Centre, Nuffield Department of Clinical Neurosciences, University of Oxford OX3 9DU, UK Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, London WC1N 3BG, UK.
authors.forename: Gerard R
authors.initials: GR
authors.lastname: Ridgway
authors.affiliation: Dementia Research Centre, University College London Institute of Neurology, London WC1N 3BG, UK j.schott@ucl.ac.uk.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Schott
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000473:pathology*; D001344:Autopsy; D002540:Cerebral Cortex / Q000473:pathology*; D003704:Dementia / Q000175:diagnosis / Q000473:pathology; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000175:diagnosis / Q000473:pathology*; D006801:Humans; D020961:Lewy Body Disease / Q000175:diagnosis / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods / Q000592:standards*; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results
keywords: MRI; brain atrophy; dementia; neuropathology; visual rating