TY - JOUR
T1 - Differential trajectories of hypometabolism across cognitively-defined Alzheimer's disease subgroups
AU - Groot, Colin
AU - Risacher, Shannon L.
AU - Chen, J. Q. Alida
AU - Dicks, Ellen
AU - Saykin, Andrew J.
AU - Mac Donald, Christine L.
AU - Mez, Jesse
AU - Trittschuh, Emily H.
AU - Mukherjee, Shubhabrata
AU - Barkhof, Frederik
AU - Scheltens, Philip
AU - van der Flier, Wiesje M.
AU - Alzheimer's Disease Neuroimaging Initiative (ADNI)
AU - Ossenkoppele, Rik
AU - Crane, Paul K.
N1 - Funding Information: This work was supported by R01 AG 029672 (Paul K Crane, PI). Wiesje van der Flier is recipient of JPND-funded E-DADS (ZonMW project #733051106). Frederik Barkhof is supported by the NIHR biomedical research center at UCLH. Jesse Mez is supported by P30AG13846 and K23AG046377. Research of Alzheimer center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. Wiesje van der Flier holds the Pasman chair. The clinical database structure was developed with funding from Stichting Dioraphte. The sponsors had no role in the writing of the report and in the decision to submit the article for publication. Funding Information: This work was supported by R01 AG 029672 (Paul K Crane, PI). Wiesje van der Flier is recipient of JPND-funded E-DADS (ZonMW project #733051106). Frederik Barkhof is supported by the NIHR biomedical research center at UCLH. Jesse Mez is supported by P30AG13846 and K23AG046377. Research of Alzheimer center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. Wiesje van der Flier holds the Pasman chair. The clinical database structure was developed with funding from Stichting Dioraphte. The sponsors had no role in the writing of the report and in the decision to submit the article for publication. Publisher Copyright: © 2021 The Author(s) Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - Disentangling biologically distinct subgroups of Alzheimer's disease (AD) may facilitate a deeper understanding of the neurobiology underlying clinical heterogeneity. We employed longitudinal [18F]FDG-PET standardized uptake value ratios (SUVRs) to map hypometabolism across cognitively-defined AD subgroups. Participants were 384 amyloid-positive individuals with an AD dementia diagnosis from ADNI who had a total of 1028 FDG-scans (mean time between first and last scan: 1.6 ± 1.8 years). These participants were categorized into subgroups on the basis of substantial impairment at time of dementia diagnosis in a specific cognitive domain relative to the average across domains. This approach resulted in groups of AD-Memory (n = 135), AD-Executive (n = 8), AD-Language (n = 22), AD-Visuospatial (n = 44), AD-Multiple Domains (n = 15) and AD-No Domains (for whom no domain showed substantial relative impairment; n = 160). Voxelwise contrasts against controls revealed that all AD-subgroups showed progressive hypometabolism compared to controls across temporoparietal regions at time of AD diagnosis. Voxelwise and regions-of-interest (ROI)-based linear mixed model analyses revealed there were also subgroup-specific hypometabolism patterns and trajectories. The AD-Memory group had more pronounced hypometabolism compared to all other groups in the medial temporal lobe and posterior cingulate, and faster decline in metabolism in the medial temporal lobe compared to AD-Visuospatial. The AD-Language group had pronounced lateral temporal hypometabolism compared to all other groups, and the pattern of metabolism was also more asymmetrical (left < right) than all other groups. The AD-Visuospatial group had faster decline in metabolism in parietal regions compared to all other groups, as well as faster decline in the precuneus compared to AD-Memory and AD-No Domains. Taken together, in addition to a common pattern, cognitively-defined subgroups of people with AD dementia show subgroup-specific hypometabolism patterns, as well as differences in trajectories of metabolism over time. These findings provide support to the notion that cognitively-defined subgroups are biologically distinct.
AB - Disentangling biologically distinct subgroups of Alzheimer's disease (AD) may facilitate a deeper understanding of the neurobiology underlying clinical heterogeneity. We employed longitudinal [18F]FDG-PET standardized uptake value ratios (SUVRs) to map hypometabolism across cognitively-defined AD subgroups. Participants were 384 amyloid-positive individuals with an AD dementia diagnosis from ADNI who had a total of 1028 FDG-scans (mean time between first and last scan: 1.6 ± 1.8 years). These participants were categorized into subgroups on the basis of substantial impairment at time of dementia diagnosis in a specific cognitive domain relative to the average across domains. This approach resulted in groups of AD-Memory (n = 135), AD-Executive (n = 8), AD-Language (n = 22), AD-Visuospatial (n = 44), AD-Multiple Domains (n = 15) and AD-No Domains (for whom no domain showed substantial relative impairment; n = 160). Voxelwise contrasts against controls revealed that all AD-subgroups showed progressive hypometabolism compared to controls across temporoparietal regions at time of AD diagnosis. Voxelwise and regions-of-interest (ROI)-based linear mixed model analyses revealed there were also subgroup-specific hypometabolism patterns and trajectories. The AD-Memory group had more pronounced hypometabolism compared to all other groups in the medial temporal lobe and posterior cingulate, and faster decline in metabolism in the medial temporal lobe compared to AD-Visuospatial. The AD-Language group had pronounced lateral temporal hypometabolism compared to all other groups, and the pattern of metabolism was also more asymmetrical (left < right) than all other groups. The AD-Visuospatial group had faster decline in metabolism in parietal regions compared to all other groups, as well as faster decline in the precuneus compared to AD-Memory and AD-No Domains. Taken together, in addition to a common pattern, cognitively-defined subgroups of people with AD dementia show subgroup-specific hypometabolism patterns, as well as differences in trajectories of metabolism over time. These findings provide support to the notion that cognitively-defined subgroups are biologically distinct.
KW - Alzheimer's disease
KW - FDG-PET
KW - Heterogeneity
KW - Psychometrics
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85111149597&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/34153688
UR - http://www.scopus.com/inward/record.url?scp=85111149597&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.nicl.2021.102725
DO - https://doi.org/10.1016/j.nicl.2021.102725
M3 - Article
C2 - 34153688
SN - 2213-1582
VL - 31
JO - NeuroImage: Clinical
JF - NeuroImage: Clinical
M1 - 102725
ER -