PMID- 33949799
OWN - NLM
STAT- MEDLINE
DCOM- 20220112
LR  - 20240402
IS  - 2328-9503 (Electronic)
IS  - 2328-9503 (Linking)
VI  - 8
IP  - 6
DP  - 2021 Jun
TI  - Selective vulnerability to atrophy in sporadic Creutzfeldt-Jakob disease.
PG  - 1183-1199
LID - 10.1002/acn3.51290 [doi]
AB  - OBJECTIVE: Identification of brain regions susceptible to quantifiable atrophy in 
      sporadic Creutzfeldt-Jakob disease (sCJD) should allow for improved understanding 
      of disease pathophysiology and development of structural biomarkers that might be 
      useful in future treatment trials. Although brain atrophy is not usually present 
      by visual assessment of MRIs in sCJD, we assessed whether using voxel-based 
      morphometry (VBM) can detect group-wise brain atrophy in sCJD. METHODS: 3T brain 
      MRI data were analyzed with VBM in 22 sCJD participants and 26 age-matched 
      controls. Analyses included relationships of regional brain volumes with major 
      clinical variables and dichotomization of the cohort according to expected 
      disease duration based on prion molecular classification (i.e., 
      short-duration/Fast-progressors (MM1, MV1, and VV2) vs. 
      long-duration/Slow-progressors (MV2, VV1, and MM2)). Structural equation modeling 
      (SEM) was used to assess network-level interactions of atrophy between specific 
      brain regions. RESULTS: sCJD showed selective atrophy in cortical and subcortical 
      regions overlapping with all but one region of the default mode network (DMN) and 
      the insulae, thalami, and right occipital lobe. SEM showed that the effective 
      connectivity model fit in sCJD but not controls. The presence of visual 
      hallucinations correlated with right fusiform, bilateral thalami, and medial 
      orbitofrontal atrophy. Interestingly, brain atrophy was present in both Fast- and 
      Slow-progressors. Worse cognition was associated with bilateral mesial frontal, 
      insular, temporal pole, thalamus, and cerebellum atrophy. INTERPRETATION: Brain 
      atrophy in sCJD preferentially affects specific cortical and subcortical regions, 
      with an effective connectivity model showing strength and directionality between 
      regions. Brain atrophy is present in Fast- and Slow-progressors, correlates with 
      clinical findings, and is a potential biomarker in sCJD.
CI  - (c) 2021 The Authors. Annals of Clinical and Translational Neurology published by 
      Wiley Periodicals LLC on behalf of American Neurological Association.
FAU - Younes, Kyan
AU  - Younes K
AUID- ORCID: 0000-0002-9912-1616
AD  - Department of Neurology, Weill Institute for Neurosciences, Memory and Aging 
      Center, University of California, San Francisco (UCSF), San Francisco, 
      California.
FAU - Rojas, Julio C
AU  - Rojas JC
AUID- ORCID: 0000-0002-1308-646X
AD  - Department of Neurology, Weill Institute for Neurosciences, Memory and Aging 
      Center, University of California, San Francisco (UCSF), San Francisco, 
      California.
FAU - Wolf, Amy
AU  - Wolf A
AD  - Department of Neurology, Weill Institute for Neurosciences, Memory and Aging 
      Center, University of California, San Francisco (UCSF), San Francisco, 
      California.
FAU - Sheng-Yang, Goh M
AU  - Sheng-Yang GM
AD  - Department of Neurology, Weill Institute for Neurosciences, Memory and Aging 
      Center, University of California, San Francisco (UCSF), San Francisco, 
      California.
FAU - Paoletti, Matteo
AU  - Paoletti M
AUID- ORCID: 0000-0002-1221-7747
AD  - Department of Neurology, Weill Institute for Neurosciences, Memory and Aging 
      Center, University of California, San Francisco (UCSF), San Francisco, 
      California.
AD  - Advanced Imaging and Radiomics Center, Neuroradiology Department, IRCCS Mondino 
      Foundation, Pavia, Italy.
FAU - Toller, Gianina
AU  - Toller G
AUID- ORCID: 0000-0002-0200-7949
AD  - Department of Neurology, Weill Institute for Neurosciences, Memory and Aging 
      Center, University of California, San Francisco (UCSF), San Francisco, 
      California.
FAU - Caverzasi, Eduardo
AU  - Caverzasi E
AUID- ORCID: 0000-0002-0350-0460
AD  - Department of Neurology, University of California, San Francisco (UCSF), San 
      Francisco, California.
FAU - Luisa Mandelli, Maria
AU  - Luisa Mandelli M
AUID- ORCID: 0000-0002-2518-2520
AD  - Department of Neurology, Weill Institute for Neurosciences, Memory and Aging 
      Center, University of California, San Francisco (UCSF), San Francisco, 
      California.
FAU - Illan-Gala, Ignacio
AU  - Illan-Gala I
AUID- ORCID: 0000-0002-5418-2052
AD  - Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat 
      Autonoma de Barcelona, Barcelona, Spain.
FAU - Kramer, Joel H
AU  - Kramer JH
AUID- ORCID: 0000-0002-2917-8297
AD  - Department of Neurology, Weill Institute for Neurosciences, Memory and Aging 
      Center, University of California, San Francisco (UCSF), San Francisco, 
      California.
FAU - Cobigo, Yann
AU  - Cobigo Y
AUID- ORCID: 0000-0002-0354-4092
AD  - Department of Neurology, Weill Institute for Neurosciences, Memory and Aging 
      Center, University of California, San Francisco (UCSF), San Francisco, 
      California.
FAU - Miller, Bruce L
AU  - Miller BL
AUID- ORCID: 0000-0002-2152-4220
AD  - Department of Neurology, Weill Institute for Neurosciences, Memory and Aging 
      Center, University of California, San Francisco (UCSF), San Francisco, 
      California.
FAU - Rosen, Howard J
AU  - Rosen HJ
AUID- ORCID: 0000-0001-9281-7402
AD  - Department of Neurology, Weill Institute for Neurosciences, Memory and Aging 
      Center, University of California, San Francisco (UCSF), San Francisco, 
      California.
FAU - Geschwind, Michael D
AU  - Geschwind MD
AUID- ORCID: 0000-0003-2861-3776
AD  - Department of Neurology, Weill Institute for Neurosciences, Memory and Aging 
      Center, University of California, San Francisco (UCSF), San Francisco, 
      California.
LA  - eng
GR  - P50 AG023501/AG/NIA NIH HHS/United States
GR  - K24 AG045333/AG/NIA NIH HHS/United States
GR  - UL1 RR024131/RR/NCRR NIH HHS/United States
GR  - RF1 AG032289/AG/NIA NIH HHS/United States
GR  - T32 AG023481/AG/NIA NIH HHS/United States
GR  - P01 AG019724/AG/NIA NIH HHS/United States
GR  - R01 AG031189/AG/NIA NIH HHS/United States
GR  - K23 AG059888/AG/NIA NIH HHS/United States
GR  - R01 AG032289/AG/NIA NIH HHS/United States
GR  - R01 AG062562/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 - 20210505
PL  - United States
TA  - Ann Clin Transl Neurol
JT  - Annals of clinical and translational neurology
JID - 101623278
RN  - Creutzfeldt-Jakob Disease, Sporadic
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Atrophy/pathology
MH  - Cerebellum/diagnostic imaging/*pathology
MH  - Cerebral Cortex/diagnostic imaging/*pathology
MH  - Cohort Studies
MH  - Creutzfeldt-Jakob Syndrome/diagnostic imaging/*pathology/physiopathology
MH  - Default Mode Network/diagnostic imaging/*pathology
MH  - *Disease Progression
MH  - Female
MH  - Humans
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Middle Aged
MH  - Nerve Net/diagnostic imaging/*pathology
MH  - Thalamus/diagnostic imaging/*pathology
PMC - PMC8164858
COIS- MDG receives/received research support on prion disease from the NIH/NIA 
      (R01-AG031189; R56-AG055619; R01AG062562), the Michael J. Homer Family Fund and 
      Alliance Biosecure. He has consulted for Adept Field Consulting (Backbay 
      consulting), Advanced Medical Inc., Anderson Boutwell Traylor, Acsel Health LLC, 
      Best Doctors Inc., Blade Therapeutics, Biohaven Pharmaceuticals, Bioscience 
      Pharma Partners, LLC (BPP), ClearView HealthCare Partners, Grand Rounds 
      Inc./Second Opinion Inc., Gerson Lehrman Group (GLG) Inc., Guidepoint Global LLC, 
      Market Plus, InThought Consulting, LifeSci Capital LLC, Maupin Cox Legoy, 
      MEDACorp, Quest Diagnostics, 3M Communications (Microvention Terumo), Smith & 
      Hennessey LLC, TeleDoc Health Inc., and Trinity Partners LLC. He has received 
      speaking honoraria for various medical center lectures and from Oakstone 
      Publishing. He has received past research support from CurePSP, the Tau 
      Consortium, Quest Diagnostics, and NIH. Dr. Geschwind serves on the board of 
      directors for San Francisco Bay Area Physicians for Social Responsibility and on 
      the editorial board of Dementia & Neuropsychologia. JCR is a site PI for clinical 
      trials supported by Eli Lilly and receives support from NIH. IIG is supported by 
      the Rio Hortega grant (CM17/00074) from "Accion Estrategica en Salud 2013-2016" 
      and the Global Brain Health Institute.
EDAT- 2021/05/06 06:00
MHDA- 2022/01/13 06:00
PMCR- 2021/05/05
CRDT- 2021/05/05 09:21
PHST- 2020/11/16 00:00 [revised]
PHST- 2020/09/18 00:00 [received]
PHST- 2020/12/04 00:00 [accepted]
PHST- 2021/05/06 06:00 [pubmed]
PHST- 2022/01/13 06:00 [medline]
PHST- 2021/05/05 09:21 [entrez]
PHST- 2021/05/05 00:00 [pmc-release]
AID - ACN351290 [pii]
AID - 10.1002/acn3.51290 [doi]
PST - ppublish
SO  - Ann Clin Transl Neurol. 2021 Jun;8(6):1183-1199. doi: 10.1002/acn3.51290. Epub 
      2021 May 5.