Individualized Atrophy-Based Prediction of Dementia Progression in Familial Frontotemporal Lobar Degeneration With Bayesian Linear Mixed-Effects Modeling.
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Dutt Shubir, Leichter Dana, Cobigo Yann, Wolf Amy, Kornak John, Clark Annie, Russell Lucy L, Bouzigues Arabella, Cash David M, Bocchetta Martina, Olzinski Molly, Appleby Brian, Bayram Ece, Borroni Barbara, Bozoki Andrea, Butler Chris R, Clark David, Convery Rhian S, Darby R Ryan, de Mendonça Alexandre, Dickerson Bradford, Domoto-Reilly Kimiko, Ducharme Simon, Ferry-Bolder Eve, Finger Elizabeth, Foster Phoebe H, Galasko Douglas R, Galimberti Daniela, Gerhard Alexander, Ghoshal Nupur, Graff Caroline, Graff-Radford Neill, Grant Ian M, Hales Chadwick M, Honig Lawrence S, Hsiung Ging-Yuek, Huey Edward D, Irwin David, Jiskoot Lize C, Kremers Walter, Kwan Justin Y, Laforce Robert, Le Ber Isabelle, Léger Gabriel C, Levin Johannes, Litvan Irene, Mackenzie Ian R, Masellis Mario, Mendez Mario F, Moreno Fermin, Onyike Chiadi, Otto Markus, Pascual Belen, Pressman Peter, Rademakers Rosa, Ramos Eliana Marisa, Ritter Aaron, Roberson Erik D, Rowe James B, Sanchez-Valle Raquel, Santana Isabel, Seelaar Harro, Snyder Allison, Sorbi Sandro, Synofzik Matthis, Tartaglia Maria Carmela, Tiraboschi Pietro, van Swieten John C, Vandebergh Marijne, Vandenberghe Rik, Heuer Hilary W, Miller Bruce L, Seeley William W, Gorno-Tempini Maria Luisa, Kramer Joel H, Forsberg Leah, Kantarci Kejal, Boeve Bradley F, Boxer Adam L, Rohrer Jonathan D, Rosen Howard J, Staffaroni Adam M, FTD Prevention Initiative (FPI) investigators
Аннотация
METHODS: Participants included 234 asymptomatic or prodromal carriers of C9orf72, GRN, or MAPT mutations (including 21 dementia converters) with ≥3 longitudinal magnetic resonance imaging (MRI) T1-weighted scans. The BLME models established individual voxel-wise gray matter trajectories using the first 2 scans. Person-specific clusters of accelerated volume loss were estimated in subsequent scans and tested as predictors of dementia conversion compared with other approaches in time-varying Cox proportional hazard models covarying for age. Receiver-operating characteristic (ROC) curves estimated utility of cluster volume in discriminating which participants converted to dementia within 24 months.
RESULTS: The BLME cluster volume predicted conversion to dementia in f-FTLD mutation carriers overall and separately in C9orf72, GRN, and MAPT, with comparable hazard ratios observed for atrophy W-maps and regional volumes. Within a 24-month timeframe, BLME cluster volume discriminated dementia converters from non-converters with larger areas under the curve (AUCs) than other approaches.
INTERPRETATION: Bayesian-modeled individualized atrophy scores predict dementia progression among asymptomatic f-FTLD mutation carriers and may have increased utility compared with other structural imaging methods when studying individuals over shorter timeframes that align with clinical trial design. ANN NEUROL 20269999:n/a-n/a.