Diagnostic Utility of Measuring Cerebral Atrophy in the Behavioral Variant of Frontotemporal Dementia and Association With Clinical Deterioration

• Published in: JAMA network open 2021-03, Vol.4 (3), p.e211290-e211290
• Main Authors: Illán-Gala, Ignacio, Falgàs, Neus, Friedberg, Adit, Castro-Suárez, Sheila, Keret, Ophir, Rogers, Nicole, Oz, Didem, Nigro, Salvatore, Quattrone, Andrea, Quattrone, Aldo, Wolf, Amy, Younes, Kyan, Santos-Santos, Miguel, Borrego-Écija, Sergi, Cobigo, Yann, Dols-Icardo, Oriol, Lladó, Albert, Sánchez-Valle, Raquel, Clarimon, Jordi, Blesa, Rafael, Alcolea, Daniel, Fortea, Juan, Lleó, Alberto, Grinberg, Lea T, Spina, Salvatore, Kramer, Joel H, Rabinovici, Gil D, Boxer, Adam, Gorno Tempini, Maria Luisa, Miller, Bruce L, Seeley, William W, Rosen, Howard J, Perry, David C
• Format: Article
• Language: English
• Subjects: Aged; Atrophy; Brain - pathology; Clinical Deterioration; Dementia; Female; Frontotemporal Dementia - classification; Frontotemporal Dementia - complications; Frontotemporal Dementia - diagnostic imaging; Frontotemporal Dementia - pathology; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Mental Disorders - etiology; Middle Aged; Movement disorders; Neurology; Online Only; Original Investigation; Parkinson's disease; Prognosis; Vital signs
• ISSN: 2574-3805; 2574-3805
• DOI: 10.1001/jamanetworkopen.2021.1290

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. To assess the diagnostic and prognostic utility of 6 visual atrophy scales (VAS) and the Magnetic Resonance Parkinsonism Index (MRPI). 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. 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. 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