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1 Supplementary Online Content Devenney E, Bartley L, Hoon C, et al. Progression in behavioral variant frontotemporal dementia: a longitudinal study. JAMA Neurol. Published online October 26, doi: /jamaneurol etable 1. Neuropsychological Test Results in Probable and Possible BVFTD and Controls at Baseline etable 2. Voxel-Based Morphometry Results for Probable BVFTD vs Controls, Possible BVFTD vs Controls, and Probable vs Possible BVFTD at Presentation etable 3. Voxel-Based Morphometry Results for Changed Status vs Controls and Unchanged Status vs Controls at Presentation efigure 1. Progression in Probable and Possible BVFTD efigure 2. Demographic and Genetic Information for Group With Changed Status With Illustrative Coronal MRI Images efigure 3. Patterns of Gray Matter Atrophy in Changed vs Unchanged Status Uncorrected at p <.001 This supplementary material has been provided by the authors to give readers additional information about their work American Medical Association. All rights reserved. 1

2 etable 1. Neuropsychological Test Results in Probable and Possible BVFTD and Controls at Basxeline Domain Cognitive Sub-test Scores (Mean) SD P values Test Probable Possible Controls Prob vs. Poss Prob vs Controls Poss vs Controls General ACE-R 72.4 (14.9) 83 (8) 94.5 (3.1) 0.01 <0.001 <0.001 Executive Trail-Making Test Time difference (98.9) 95.2 (62.4) 76.1 (32) 0.05 <0.001 <0.001 Digit Span Backwards 3.5 (1.4) 4.2 (1.2) 5.4 (1.2) 0.05 <0.001 <0.001 Hayling Cat A errors 7.2 (5) 2.4 (2.5).14 (.4) <0.001 <0.001 <0.001 Cat B errors 2.6 (2.4) 2.8 (2.2) 1 (1) <0.001 Letter Fluency 7.5 (3.7) 9.0 (5.3) 13.1 (3.2) 0.23 <0.001 <0.001 Memory RAVLT Immediate Recall 6.3 (4.2) 9.3 (4.2) 9.6 (2.7) Delayed Recall 4.6 (4) 6.3 (3.8) 10 (2.3) 0.15 <0.001 <0.001 RCF: 3 min recall 6.6 (6.1) 12.6 (7.1) 18 (6) 0.01 < Doors: Combined 5.9 (7.6) 12.3 (8.2) 19 (15) 0.01 <0.001 <0.001 Visuospatial RCF: Copy score 28 (5.5) 25.8 (6.7) 32 (3.3) 0.23 <0.001 <0.001 Emotion Ekman (9.7) 40.3 (6.1) 49.3 (4.2) 0.01 <0.001 <0.001 Processing Tasit 13.5 (5.8) 18.9 (3.3) 24 (1.8) <0.001 <0.001 <0.001 Language Sydbat Naming 19.9 (6.4) 23.1 (3.1) 27 (2) 0.18 <0.001 < American Medical Association. All rights reserved. 2

3 ACE-R = Addenbrooke s Cognitive Examination Revised. RAVLT = Rey Auditory Verbal Learning Test. RCF = Rey-Osterrith Complex Figure. Sydbat = Sydney Language Battery 2015 American Medical Association. All rights reserved. 3

4 etable 2. Voxel-Based Morphometry Results for Probable BVFTD vs Controls, Possible BVFTD vs Controls, and Probable vs Possible BVFTD at Presentation Regions Hemisphere (L/R/B) MNI coordinates for voxels of maximal intensity X Y Z No. of voxels Probable vs. controls 2 Cerebellum, temporal fusiform cortex, parahippocampal gyrus, inferior, middle and superior temporal gyrus, temporal fusiform gyrus, temporal pole, precuneus cortex, supracalcarine cortex, lateral occipital cortex, occipital pole, lingual gyrus, insula, hescl's cortex, parietal operculum cortex, parietal cortex, angular gyrus, frontal operculum cortex, planum polare, amygdala, hippocampus, putamen, caudate, thalamus, orbitofrontal cortex, subcallosal cortex, frontal pole, paracingulate gyrus, anterior cingulate gyrus, superior and middle frontal gyrus, precentral gyrus B Probable vs. possible Parahippocampal gyrus, hippocampus, amygdala, temporal fusiform cortex, planum polare, insula, superior, middle and inferior temporal gyrus, temporal pole, orbitofrontal cortex, caudate, accumbens, putamen, frontal and central operculum cortex, Heschls gyrus, subcallosal cortex Intracalarine cortex, lingual gyrus, precuneus cortex B R T value 2015 American Medical Association. All rights reserved. 4

5 Possible vs. control Frontal pole, paracingulate gyrus, superior, B middle and inferior frontal gyrus, anterior cingulate gyrus, frontal operculum cortex, insula, putamen, caudate, orbitofrontal cortex, subcallosal cortex, temporal pole, superior, middle and inferior temporal gyrus, hippocampus, amygdala, parahippocampal gyrus, thalamus, planum polare, central operculum cortex, Heschl s gyrus, parietal operculum gyrus, postcentral gyrus, precentral gyrus, supramarginal gyrus Cerebellum B Frontal pole, orbitofrontal cortex, inferior frontal R gyrus Precuneus cortex, postcentral gyrus, lateral L occipital cortex, superior parietal lobule Inferior, middle and superior temporal gyrus, R temporal fusiform gyrus Postcentral gyrus, superior parietal lobule, precentral gyrus L Corrected for FWE at p <.05, at a cluster threshold of greater than 100 contiguous voxels. No significant clusters for possible vs. probable bvftd American Medical Association. All rights reserved. 5

6 etable 3. Voxel-Based Morphometry Results for Changed Status vs Controls and Unchanged Status vs Controls at Presentation Regions No. of voxels T value Hemisphere (L/R/B) MNI coordinates for voxels of maximal intensity X Y Z Changed Status vs. Controls 2 Temporal pole, orbitofrontal L cortex, insula, putamen Insula, opercular cortex, inferior R frontal gyrus putamen Insula, opercular cortex L Occipital pole L Occipital pole, orbitofrontal gyrus L Middle and superior temporal L gyrus Inferior frontal gyrus L Unchanged Status vs. Controls 2 Frontal pole R Corrected at p <.05, at a cluster threshold of greater than 100 contiguous voxels. No significant clusters for changers vs non-changers and non-changers vs changers 2015 American Medical Association. All rights reserved. 6

7 efigure 1. Progression in Probable and Possible BVFTD A Probable bvftd at First Presentation (n=38) Probable (n=19) Definite (n=17) Other (n=2) MND (n=3) Pathology (n=4) Genetics (n=13) Alzheimer s Pathology TDP-43 (n=2) FUS (n=1) Pick s (n=1) C9orf72 (n=7) GRN (n=5) MAPT (n=1) B Possible bvftd at First Presentation (n=20) Followup (3.5 ± 1.2 years) Possible Unchanged non changers Status (n=9) Probably/Definite Changed Changers Status (n=11) Probable (n=3) C9orf72 (n=8) 2015 American Medical Association. All rights reserved. 7

8 efigure 2. Demographic and Genetic Information for Group With Changed Status With Illustrative Coronal MRI Images Expansion Status C9orf72 Legend: Detailed information regarding age, sex and expansion status for each patient in the changer group. Coronal T1 MRI images are shown at baseline and follow-up where available American Medical Association. All rights reserved. 8

9 efigure 3. Patterns of Gray Matter Atrophy in Changed vs Unchanged Status Uncorrected at p < Description: Results from voxel-based morphometry analyses demonstrating areas of gray matter density decrease for i) changed vs unchanged status. Coloured voxels show regions significant in the analyses for p < uncorrected American Medical Association. All rights reserved. 9