TY - JOUR
T1 - Disease specific and nonspecific metabolic brain networks in behavioral variant of frontotemporal dementia
AU - Rus, Tomaž
AU - Perovnik, Matej
AU - Vo, An
AU - Nguyen, Nha
AU - Tang, Chris
AU - Jamšek, Jan
AU - Šurlan Popović, Katarina
AU - Grimmer, Timo
AU - Yakushev, Igor
AU - Diehl-Schmid, Janine
AU - Eidelberg, David
AU - Trošt, Maja
N1 - Funding Information:
The aspects of this work were supported by the Slovenian Research Agency through the research programme P1‐0389, research project J7‐2600. T.R. is a recipient of the Fulbright Foreign Student Program sponsored by the U.S. Department of State's Bureau of Educational and Cultural Affairs.
Funding Information:
The authors report no competing interests with regard to the submitted manuscript. Outside the submitted manuscript DE serves on the scientific advisory boards of and has received fees from The Michael J. Fox Foundation for Parkinson's Research and Ovid Therapeutics, receives consulting fees from MeiraGTx, has received grants from NIH (NINDS, NIAID), and is the coinventor of patents re: Markers for use in screening patients for nervous system dysfunction and a method and apparatus for using same, without financial gain. TG received consulting fees from Abbvie, Alector, Anavex, Biogen, Eli Lilly, Functional Neuromodulation, Grifols, Iqvia/Quintiles, Novo Nordisk, Noselab, NuiCare, Roche Diagnostics, Roche Pharma, Toyama, UCB, and Vivoryon; lecture fees from Biogen, Life Molecular Imaging, Novo Nordisk, Roche Pharma, and Schwabe; and grants to his institution from Actelion and Novartis.
Publisher Copyright:
© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.
PY - 2023/2/15
Y1 - 2023/2/15
N2 - Behavioral variant of frontotemporal dementia (bvFTD) is common among young-onset dementia patients. While bvFTD-specific multivariate metabolic brain pattern (bFDRP) has been identified previously, little is known about its temporal evolution, internal structure, effect of atrophy, and its relationship with nonspecific resting-state networks such as default mode network (DMN). In this multicenter study, we explored FDG-PET brain scans of 111 bvFTD, 26 Alzheimer's disease, 16 Creutzfeldt-Jakob's disease, 24 semantic variant primary progressive aphasia (PPA), 18 nonfluent variant PPA and 77 healthy control subjects (HC) from Slovenia, USA, and Germany. bFDRP was identified in a cohort of 20 bvFTD patients and age-matched HC using scaled subprofile model/principle component analysis and validated in three independent cohorts. It was characterized by hypometabolism in frontal cortex, insula, anterior/middle cingulate, caudate, thalamus, and temporal poles. Its expression in bvFTD patients was significantly higher compared to HC and other dementia syndromes (p <.0004), correlated with cognitive decline (p =.0001), and increased over time in longitudinal cohort (p =.0007). Analysis of internal network organization by graph-theory methods revealed prominent network disruption in bvFTD patients. We have further found a specific atrophy-related pattern grossly corresponding to bFDRP; however, its contribution to the metabolic pattern was minimal. Finally, despite the overlap between bFDRP and FDG-PET-derived DMN, we demonstrated a predominant role of the specific bFDRP. Taken together, we validated the bFDRP network as a diagnostic/prognostic biomarker specific for bvFTD, provided a unique insight into its highly reproducible internal structure, and proved that bFDRP is unaffected by structural atrophy and independent of normal resting state networks loss.
AB - Behavioral variant of frontotemporal dementia (bvFTD) is common among young-onset dementia patients. While bvFTD-specific multivariate metabolic brain pattern (bFDRP) has been identified previously, little is known about its temporal evolution, internal structure, effect of atrophy, and its relationship with nonspecific resting-state networks such as default mode network (DMN). In this multicenter study, we explored FDG-PET brain scans of 111 bvFTD, 26 Alzheimer's disease, 16 Creutzfeldt-Jakob's disease, 24 semantic variant primary progressive aphasia (PPA), 18 nonfluent variant PPA and 77 healthy control subjects (HC) from Slovenia, USA, and Germany. bFDRP was identified in a cohort of 20 bvFTD patients and age-matched HC using scaled subprofile model/principle component analysis and validated in three independent cohorts. It was characterized by hypometabolism in frontal cortex, insula, anterior/middle cingulate, caudate, thalamus, and temporal poles. Its expression in bvFTD patients was significantly higher compared to HC and other dementia syndromes (p <.0004), correlated with cognitive decline (p =.0001), and increased over time in longitudinal cohort (p =.0007). Analysis of internal network organization by graph-theory methods revealed prominent network disruption in bvFTD patients. We have further found a specific atrophy-related pattern grossly corresponding to bFDRP; however, its contribution to the metabolic pattern was minimal. Finally, despite the overlap between bFDRP and FDG-PET-derived DMN, we demonstrated a predominant role of the specific bFDRP. Taken together, we validated the bFDRP network as a diagnostic/prognostic biomarker specific for bvFTD, provided a unique insight into its highly reproducible internal structure, and proved that bFDRP is unaffected by structural atrophy and independent of normal resting state networks loss.
KW - FDG-PET
KW - SSM/PCA
KW - behavioral variant of frontotemporal dementia
KW - default mode network
KW - functional connectivity
KW - network analysis
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U2 - 10.1002/hbm.26140
DO - 10.1002/hbm.26140
M3 - Article
C2 - 36334269
AN - SCOPUS:85141530637
SN - 1065-9471
VL - 44
SP - 1079
EP - 1093
JO - Human Brain Mapping
JF - Human Brain Mapping
IS - 3
ER -