PMID- 33189136
OWN - NLM
STAT- MEDLINE
DCOM- 20210624
LR  - 20240430
IS  - 1758-9193 (Electronic)
VI  - 12
IP  - 1
DP  - 2020 Nov 14
TI  - Investigating the clinico-anatomical dissociation in the behavioral variant of 
      Alzheimer disease.
PG  - 148
LID - 10.1186/s13195-020-00717-z [doi]
LID - 148
AB  - BACKGROUND: We previously found temporoparietal-predominant atrophy patterns in 
      the behavioral variant of Alzheimer's disease (bvAD), with relative sparing of 
      frontal regions. Here, we aimed to understand the clinico-anatomical dissociation 
      in bvAD based on alternative neuroimaging markers. METHODS: We retrospectively 
      included 150 participants, including 29 bvAD, 28 "typical" amnestic-predominant 
      AD (tAD), 28 behavioral variant of frontotemporal dementia (bvFTD), and 65 
      cognitively normal participants. Patients with bvAD were compared with other 
      diagnostic groups on glucose metabolism and metabolic connectivity measured by 
      [(18)F]FDG-PET, and on subcortical gray matter and white matter hyperintensity 
      (WMH) volumes measured by MRI. A receiver-operating-characteristic-analysis was 
      performed to determine the neuroimaging measures with highest diagnostic 
      accuracy. RESULTS: bvAD and tAD showed predominant temporoparietal hypometabolism 
      compared to controls, and did not differ in direct contrasts. However, overlaying 
      statistical maps from contrasts between patients and controls revealed broader 
      frontoinsular hypometabolism in bvAD than tAD, partially overlapping with bvFTD. 
      bvAD showed greater anterior default mode network (DMN) involvement than tAD, 
      mimicking bvFTD, and reduced connectivity of the posterior cingulate cortex with 
      prefrontal regions. Analyses of WMH and subcortical volume showed closer 
      resemblance of bvAD to tAD than to bvFTD, and larger amygdalar volumes in bvAD 
      than tAD respectively. The top-3 discriminators for bvAD vs. bvFTD were FDG 
      posterior-DMN-ratios (bvAD<bvFTD), MRI posterior-DMN-ratios (bvAD<bvFTD), MRI 
      salience-network-ratios (bvAD>bvFTD, area under the curve [AUC] range 0.85-0.91, 
      all p < 0.001). The top-3 for bvAD vs. tAD were amygdalar volume (bvAD>tAD), MRI 
      anterior-DMN-ratios (bvAD<tAD), FDG anterior-DMN-ratios (bvAD<tAD, AUC range 
      0.71-0.84, all p < 0.05). CONCLUSIONS: Subtle frontoinsular hypometabolism and 
      anterior DMN involvement may underlie the prominent behavioral phenotype in bvAD.
FAU - Singleton, Ellen H
AU  - Singleton EH
AUID- ORCID: 0000-0002-6034-8688
AD  - Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, 
      Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands. 
      e.singleton@amsterdamumc.nl.
FAU - Pijnenburg, Yolande A L
AU  - Pijnenburg YAL
AD  - Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, 
      Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
FAU - Sudre, Carole H
AU  - Sudre CH
AD  - School of Biomedical Engineering and Imaging Sciences, King's College London, 
      London, UK.
FAU - Groot, Colin
AU  - Groot C
AD  - Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, 
      Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
FAU - Kochova, Elena
AU  - Kochova E
AD  - Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, 
      Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
FAU - Barkhof, Frederik
AU  - Barkhof F
AD  - Department of Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, 
      Amsterdam UMC, Amsterdam, the Netherlands.
AD  - Center for Medical Image Computing, Department of Medical Physics and Biomedical 
      Engineering, University College London, London, UK.
FAU - La Joie, Renaud
AU  - La Joie R
AD  - Department of Neurology, Memory and Aging Center, University of California San 
      Francisco, San Francisco, USA.
FAU - Rosen, Howard J
AU  - Rosen HJ
AD  - Department of Neurology, Memory and Aging Center, University of California San 
      Francisco, San Francisco, USA.
FAU - Seeley, William W
AU  - Seeley WW
AD  - Department of Neurology, Memory and Aging Center, University of California San 
      Francisco, San Francisco, USA.
FAU - Miller, Bruce
AU  - Miller B
AD  - Department of Neurology, Memory and Aging Center, University of California San 
      Francisco, San Francisco, USA.
FAU - Cardoso, M Jorge
AU  - Cardoso MJ
AD  - School of Biomedical Engineering and Imaging Sciences, King's College London, 
      London, UK.
AD  - Translational Imaging Group, CMIC, Department of Medical Physics and Biomedical 
      Engineering, University College London, London, UK.
FAU - Papma, Janne
AU  - Papma J
AD  - Department of Neurology, Erasmus University Medical Center, Rotterdam, the 
      Netherlands.
AD  - Department of Radiology, Erasmus University Medical Center, Rotterdam, the 
      Netherlands.
FAU - Scheltens, Philip
AU  - Scheltens P
AD  - Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, 
      Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
FAU - Rabinovici, Gil D
AU  - Rabinovici GD
AD  - Department of Neurology, Memory and Aging Center, University of California San 
      Francisco, San Francisco, USA.
AD  - Department of Radiology and Biomedical Imaging, University of California San 
      Francisco, San Francisco, USA.
AD  - Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley 
      National Laboratory, Berkeley, CA, USA.
AD  - Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, 
      USA.
FAU - Ossenkoppele, Rik
AU  - Ossenkoppele R
AD  - Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, 
      Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
AD  - Clinical Memory Research Unit, Lund University, Lund, Sweden.
LA  - eng
GR  - R01-AG045611/AG/NIA NIH HHS/United States
GR  - K24 AG045333/AG/NIA NIH HHS/United States
GR  - P01 AG003991/AG/NIA NIH HHS/United States
GR  - P30 AG062422/AG/NIA NIH HHS/United States
GR  - P01 AG019724/AG/NIA NIH HHS/United States
GR  - R01 AG045611/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20201114
PL  - England
TA  - Alzheimers Res Ther
JT  - Alzheimer's research & therapy
JID - 101511643
SB  - IM
MH  - *Alzheimer Disease/diagnostic imaging
MH  - *Frontotemporal Dementia/diagnostic imaging
MH  - Gray Matter
MH  - Humans
MH  - Magnetic Resonance Imaging
MH  - Retrospective Studies
PMC - PMC7666520
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Behavior
OT  - Frontotemporal dementia
OT  - MRI
OT  - PET
COIS- The authors declare that they have no competing interests.
EDAT- 2020/11/16 06:00
MHDA- 2021/06/25 06:00
PMCR- 2020/11/14
CRDT- 2020/11/15 20:18
PHST- 2020/08/04 00:00 [received]
PHST- 2020/10/26 00:00 [accepted]
PHST- 2020/11/15 20:18 [entrez]
PHST- 2020/11/16 06:00 [pubmed]
PHST- 2021/06/25 06:00 [medline]
PHST- 2020/11/14 00:00 [pmc-release]
AID - 10.1186/s13195-020-00717-z [pii]
AID - 717 [pii]
AID - 10.1186/s13195-020-00717-z [doi]
PST - epublish
SO  - Alzheimers Res Ther. 2020 Nov 14;12(1):148. doi: 10.1186/s13195-020-00717-z.