PMID- 26260856
OWN - NLM
STAT- MEDLINE
DCOM- 20160809
LR  - 20220409
IS  - 1097-0193 (Electronic)
IS  - 1065-9471 (Print)
IS  - 1065-9471 (Linking)
VI  - 36
IP  - 11
DP  - 2015 Nov
TI  - Atrophy patterns in early clinical stages across distinct phenotypes of 
      Alzheimer's disease.
PG  - 4421-37
LID - 10.1002/hbm.22927 [doi]
AB  - Alzheimer's disease (AD) can present with distinct clinical variants. Identifying 
      the earliest neurodegenerative changes associated with each variant has 
      implications for early diagnosis, and for understanding the mechanisms that 
      underlie regional vulnerability and disease progression in AD. We performed 
      voxel-based morphometry to detect atrophy patterns in early clinical stages of 
      four AD phenotypes: Posterior cortical atrophy (PCA, "visual variant," n=93), 
      logopenic variant primary progressive aphasia (lvPPA, "language variant," n=74), 
      and memory-predominant AD categorized as early age-of-onset (EOAD, <65 years, 
      n=114) and late age-of-onset (LOAD, >65 years, n=114). Patients with each 
      syndrome were stratified based on: (1) degree of functional impairment, as 
      measured by the clinical dementia rating (CDR) scale, and (2) overall extent of 
      brain atrophy, as measured by a neuroimaging approach that sums the number of 
      brain voxels showing significantly lower gray matter volume than cognitively 
      normal controls (n=80). Even at the earliest clinical stage (CDR=0.5 or bottom 
      quartile of overall atrophy), patients with each syndrome showed both common and 
      variant-specific atrophy. Common atrophy across variants was found in 
      temporoparietal regions that comprise the posterior default mode network (DMN). 
      Early syndrome-specific atrophy mirrored functional brain networks underlying 
      functions that are uniquely affected in each variant: Language network in lvPPA, 
      posterior cingulate cortex-hippocampal circuit in amnestic EOAD and LOAD, and 
      visual networks in PCA. At more advanced stages, atrophy patterns largely 
      converged across AD variants. These findings support a model in which 
      neurodegeneration selectively targets both the DMN and syndrome-specific 
      vulnerable networks at the earliest clinical stages of AD.
CI  - (c) 2015 Wiley Periodicals, Inc.
FAU - Ossenkoppele, Rik
AU  - Ossenkoppele R
AD  - Department of Neurology, Memory and Aging Center, University of California San 
      Francisco, San Francisco, California.
AD  - Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, 
      California.
AD  - Department of Neurology & Alzheimer Center, Neuroscience Campus Amsterdam, VU 
      University Medical Center, Amsterdam, The Netherlands.
AD  - Department of Radiology & Nuclear Medicine, VU University Medical Center, 
      Amsterdam, The Netherlands.
FAU - Cohn-Sheehy, Brendan I
AU  - Cohn-Sheehy BI
AD  - Department of Neurology, Memory and Aging Center, University of California San 
      Francisco, San Francisco, California.
FAU - La Joie, Renaud
AU  - La Joie R
AD  - Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, 
      California.
FAU - Vogel, Jacob W
AU  - Vogel JW
AD  - Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, 
      California.
FAU - Moller, Christiane
AU  - Moller C
AD  - Department of Neurology & Alzheimer Center, Neuroscience Campus Amsterdam, VU 
      University Medical Center, Amsterdam, The Netherlands.
FAU - Lehmann, Manja
AU  - Lehmann M
AD  - Department of Neurology, Memory and Aging Center, University of California San 
      Francisco, San Francisco, California.
AD  - Dementia Research Centre, UCL Institute of Neurology, University College London, 
      London, United Kingdom.
FAU - van Berckel, Bart N M
AU  - van Berckel BN
AD  - Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, 
      California.
FAU - Seeley, William W
AU  - Seeley WW
AD  - Department of Neurology, Memory and Aging Center, University of California San 
      Francisco, San Francisco, California.
FAU - Pijnenburg, Yolande A
AU  - Pijnenburg YA
AD  - Department of Neurology & Alzheimer Center, Neuroscience Campus Amsterdam, VU 
      University Medical Center, Amsterdam, The Netherlands.
FAU - Gorno-Tempini, Maria L
AU  - Gorno-Tempini ML
AD  - Department of Neurology, Memory and Aging Center, University of California San 
      Francisco, San Francisco, California.
FAU - Kramer, Joel H
AU  - Kramer JH
AD  - Department of Neurology, Memory and Aging Center, University of California San 
      Francisco, San Francisco, California.
FAU - Barkhof, Frederik
AU  - Barkhof F
AD  - Department of Radiology & Nuclear Medicine, VU University Medical Center, 
      Amsterdam, The Netherlands.
FAU - Rosen, Howard J
AU  - Rosen HJ
AD  - Department of Neurology, Memory and Aging Center, University of California San 
      Francisco, San Francisco, California.
FAU - van der Flier, Wiesje M
AU  - van der Flier WM
AD  - Department of Neurology & Alzheimer Center, Neuroscience Campus Amsterdam, VU 
      University Medical Center, Amsterdam, The Netherlands.
AD  - Department of Epidemiology & Biostatistics, VU University Medical Center, 
      Amsterdam, The Netherlands.
FAU - Jagust, William J
AU  - Jagust WJ
AD  - Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, 
      California.
FAU - Miller, Bruce L
AU  - Miller BL
AD  - Department of Neurology, Memory and Aging Center, University of California San 
      Francisco, San Francisco, California.
FAU - Scheltens, Philip
AU  - Scheltens P
AD  - Department of Neurology & Alzheimer Center, Neuroscience Campus Amsterdam, VU 
      University Medical Center, 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, California.
AD  - Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, 
      California.
LA  - eng
GR  - R01 AG034570/AG/NIA NIH HHS/United States
GR  - P50 AG023501/AG/NIA NIH HHS/United States
GR  - P50-AG023501/AG/NIA NIH HHS/United States
GR  - P01-AG1792403/AG/NIA NIH HHS/United States
GR  - R01-AG034570/AG/NIA NIH HHS/United States
GR  - R01 AG045611/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 - 20150811
PL  - United States
TA  - Hum Brain Mapp
JT  - Human brain mapping
JID - 9419065
SB  - IM
MH  - Age of Onset
MH  - Aged
MH  - Alzheimer Disease/classification/*pathology/physiopathology
MH  - Animals
MH  - Aphasia, Primary Progressive/*pathology/physiopathology
MH  - Atrophy/pathology
MH  - Cerebral Cortex/*pathology/physiopathology
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Nerve Net/*pathology/physiopathology
MH  - Phenotype
MH  - Syndrome
PMC - PMC4692964
MID - NIHMS744750
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - atrophy
OT  - default mode network
OT  - early-onset dementia
OT  - language
OT  - logopenic variant primary progressive aphasia
OT  - magnetic resonance imaging (MRI)
OT  - memory
OT  - posterior cortical atrophy
OT  - vision
OT  - voxel-based morphometry
EDAT- 2015/08/12 06:00
MHDA- 2016/08/10 06:00
PMCR- 2015/08/11
CRDT- 2015/08/12 06:00
PHST- 2015/04/02 00:00 [received]
PHST- 2015/06/29 00:00 [revised]
PHST- 2015/07/27 00:00 [accepted]
PHST- 2015/08/12 06:00 [entrez]
PHST- 2015/08/12 06:00 [pubmed]
PHST- 2016/08/10 06:00 [medline]
PHST- 2015/08/11 00:00 [pmc-release]
AID - HBM22927 [pii]
AID - 10.1002/hbm.22927 [doi]
PST - ppublish
SO  - Hum Brain Mapp. 2015 Nov;36(11):4421-37. doi: 10.1002/hbm.22927. Epub 2015 Aug 
      11.