Diagnostic Utility of Measuring Cerebral Atrophy in the Behavioral Variant of Frontotemporal Dementia and Association With Clinical Deterioration
Abstract
Importance: The presence of atrophy on magnetic resonance imaging can support the diagnosis of the behavioral variant of frontotemporal dementia (bvFTD), but reproducible measurements are lacking.
Objective: To assess the diagnostic and prognostic utility of 6 visual atrophy scales (VAS) and the Magnetic Resonance Parkinsonism Index (MRPI).
Design, setting, and participants: In this diagnostic/prognostic study, data from 235 patients with bvFTD and 225 age- and magnetic resonance imaging-matched control individuals from 3 centers were collected from December 1, 1998, to September 30, 2019. One hundred twenty-one participants with bvFTD had high confidence of frontotemporal lobar degeneration (FTLD) (bvFTD-HC), and 19 had low confidence of FTLD (bvFTD-LC). Blinded clinicians applied 6 previously validated VAS, and the MRPI was calculated with a fully automated approach. Cortical thickness and subcortical volumes were also measured for comparison. Data were analyzed from February 1 to June 30, 2020.
Main outcomes and measures: The main outcomes of this study were bvFTD-HC or a neuropathological diagnosis of 4-repeat (4R) tauopathy and the clinical deterioration rate (assessed by longitudinal measurements of Clinical Dementia Rating Sum of Boxes). Measures of cerebral atrophy included VAS scores, the bvFTD atrophy score (sum of VAS scores in orbitofrontal, anterior cingulate, anterior temporal, medial temporal lobe, and frontal insula regions), the MRPI, and other computerized quantifications of cortical and subcortical volumes. The areas under the receiver operating characteristic curve (AUROC) were calculated for the differentiation of participants with bvFTD-HC and bvFTD-LC and controls. Linear mixed models were used to evaluate the ability of atrophy measures to estimate longitudinal clinical deterioration.
Results: Of the 460 included participants, 296 (64.3%) were men, and the mean (SD) age was 62.6 (11.4) years. The accuracy of the bvFTD atrophy score for the differentiation of bvFTD-HC from controls (AUROC, 0.930; 95% CI, 0.903-0.957) and bvFTD-HC from bvFTD-LC (AUROC, 0.880; 95% CI, 0.787-0.972) was comparable to computerized measures (AUROC, 0.973 [95% CI, 0.954-0.993] and 0.898 [95% CI, 0.834-0.962], respectively). The MRPI was increased in patients with bvFTD and underlying 4R tauopathies compared with other FTLD subtypes (14.1 [2.0] vs 11.2 [2.6] points; P < .001). Higher bvFTD atrophy scores were associated with faster clinical deterioration in bvFTD (1.86-point change in Clinical Dementia Rating Sum of Boxes score per bvFTD atrophy score increase per year; 95% CI, 0.99-2.73; P < .001).
Conclusions and relevance: Based on these study findings, in bvFTD, VAS increased the diagnostic certainty of underlying FTLD, and the MRPI showed potential for the detection of participants with underlying 4R tauopathies. These widely available measures of atrophy can also be useful to estimate longitudinal clinical deterioration.
Authors
![Ignacio Illan-Gala](/sites/default/files/styles/image_1x1_small/public/profile/ignacio_illan-gala.jpg?h=87136cbf&itok=50d8RSu0)
Ignacio Illán-Gala, MD, PhD
Neurologist
![Neus Falgas](/sites/default/files/styles/image_1x1_small/public/profile/neus_falgas.jpg?h=87136cbf&itok=TquqlhVe)
Neus Falgàs, MD, PhD
Neurologist
![Adit Friedberg](/sites/default/files/styles/image_1x1_small/public/profile/Adit_Friedberg.jpg?h=203f7f37&itok=RovhprzN)
Adit Friedberg, MD
Behavioral Neurologist
![Sheila Castro-Suarez](/sites/default/files/styles/image_1x1_small/public/profile/Sheila%20Castro-Suarez.jpg?h=87136cbf&itok=j7MDQp0s)
Sheila Castro-Suarez, MD
Neurologist
![Ophir Keret](/sites/default/files/styles/image_1x1_small/public/profile/_MG_9415.jpg?h=32b2d9d4&itok=r0jHR01b)
Ophir Keret, MD
Neurologist
![Nicole Rogers](/sites/default/files/styles/image_1x1_small/public/profile/Nicole_Rogers.jpg?h=dd5158f1&itok=u0HIPIe_)
Nicole Rogers, MD, PhD
Neurologist
![Didem Oz](/sites/default/files/styles/image_1x1_small/public/profile/Didem_Oz.jpg?h=3bb50dea&itok=UXJW4bOb)
Didem Öz, MD, PhD
Behavioral Neurologist, Epileptologist
![Lea Grinberg headshot 2021](/sites/default/files/styles/image_1x1_small/public/profile/Grinberg_Lea%20%281%29.jpg?h=a09a6676&itok=ispOx_-8)
Lea Tenenholz Grinberg, MD, PhD
Professor of Neurology and Pathology
![Salvo Spina](/sites/default/files/styles/image_1x1_small/public/profile/Salvo_Spina.jpg?h=ca529fcb&itok=-h2xiPYX)
Salvo Spina, MD, PhD
Associate Professor of Neurology
![Joel Kramer](/sites/default/files/styles/image_1x1_small/public/profile/Joel_Kramer.jpg?h=17c4d544&itok=WDjIGUzD)
Joel Kramer, PsyD
Professor of Neuropsychology
![Marilu Gorno Tempini](/sites/default/files/styles/image_1x1_small/public/profile/Marilu_GornoTempini.jpg?h=9ae984f7&itok=l7fhpDIF)
Marilu Gorno Tempini, MD, PhD
Professor of Neurology and Psychiatry
![Bruce Miller](/sites/default/files/styles/image_1x1_small/public/profile/Bruce%20Miller.jpg?h=3334e0bf&itok=3zITuREU)
Bruce Miller, MD
Founding Director, University of California, San Francisco
![Bill Seeley](/sites/default/files/styles/image_1x1_small/public/profile/Bill-Seeley.jpg?h=0d3353d8&itok=iyfBQb_O)
Bill Seeley, MD
Professor of Neurology and Pathology
![Howie Rosen headshot](/sites/default/files/styles/image_1x1_small/public/profile/20211019_1_0128%20%281%29.jpg?h=c2857175&itok=0k88_56I)
Howie Rosen, MD
Professor of Neurology