PMID- 30894627
OWN - NLM
STAT- MEDLINE
DCOM- 20201104
LR  - 20210109
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Mar 18
TI  - White matter microstructural abnormalities and default network degeneration are 
      associated with early memory deficit in Alzheimer's disease continuum.
PG  - 4749
LID - 10.1038/s41598-019-41363-2 [doi]
LID - 4749
AB  - Instead of assuming a constant relationship between brain abnormalities and 
      memory impairment, we aimed to examine the stage-dependent contributions of 
      multimodal brain structural and functional deterioration to memory impairment in 
      the Alzheimer's disease (AD) continuum. We assessed grey matter volume, white 
      matter (WM) microstructural measures (free-water (FW) and FW-corrected fractional 
      anisotropy), and functional connectivity of the default mode network (DMN) in 54 
      amnestic mild cognitive impairment (aMCI) and 46 AD. We employed a novel sparse 
      varying coefficient model to investigate how the associations between abnormal 
      brain measures and memory impairment varied throughout disease continuum. We 
      found lower functional connectivity in the DMN was related to worse memory across 
      AD continuum. Higher widespread white matter FW and lower fractional anisotropy 
      in the fornix showed a stronger association with memory impairment in the early 
      aMCI stage; such WM-memory associations then decreased with increased dementia 
      severity. Notably, the effect of the DMN atrophy occurred in early aMCI stage, 
      while the effect of the medial temporal atrophy occurred in the AD stage. Our 
      study provided evidence to support the hypothetical progression models underlying 
      memory dysfunction in AD cascade and underscored the importance of FW increases 
      and DMN degeneration in early stage of memory deficit.
FAU - Ji, Fang
AU  - Ji F
AD  - Center for Cognitive Neuroscience, Neuroscience and Behavioural Disorders 
      Program, Duke-National University of Singapore Medical School, Singapore, 
      Singapore.
FAU - Pasternak, Ofer
AU  - Pasternak O
AD  - Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard 
      Medical School, Boston, USA.
FAU - Ng, Kwun Kei
AU  - Ng KK
AD  - Center for Cognitive Neuroscience, Neuroscience and Behavioural Disorders 
      Program, Duke-National University of Singapore Medical School, Singapore, 
      Singapore.
FAU - Chong, Joanna Su Xian
AU  - Chong JSX
AD  - Center for Cognitive Neuroscience, Neuroscience and Behavioural Disorders 
      Program, Duke-National University of Singapore Medical School, Singapore, 
      Singapore.
FAU - Liu, Siwei
AU  - Liu S
AD  - Center for Cognitive Neuroscience, Neuroscience and Behavioural Disorders 
      Program, Duke-National University of Singapore Medical School, Singapore, 
      Singapore.
FAU - Zhang, Liwen
AU  - Zhang L
AD  - Center for Cognitive Neuroscience, Neuroscience and Behavioural Disorders 
      Program, Duke-National University of Singapore Medical School, Singapore, 
      Singapore.
FAU - Shim, Hee Youn
AU  - Shim HY
AD  - Center for Cognitive Neuroscience, Neuroscience and Behavioural Disorders 
      Program, Duke-National University of Singapore Medical School, Singapore, 
      Singapore.
FAU - Loke, Yng Miin
AU  - Loke YM
AD  - Center for Cognitive Neuroscience, Neuroscience and Behavioural Disorders 
      Program, Duke-National University of Singapore Medical School, Singapore, 
      Singapore.
FAU - Tan, Boon Yeow
AU  - Tan BY
AD  - St Luke's Hospital, Singapore, Singapore.
FAU - Venketasubramanian, Narayanaswamy
AU  - Venketasubramanian N
AD  - Raffles Neuroscience Centre, Raffles Hospital, Singapore, Singapore.
FAU - Chen, Christopher Li-Hsian
AU  - Chen CL
AD  - Department of Pharmacology, National University Health System, Clinical Research 
      Centre, Singapore, Singapore.
AD  - Memory, Aging & Cognition Centre, National University Health System, National 
      University of Singapore, Singapore, Singapore.
FAU - Zhou, Juan Helen
AU  - Zhou JH
AUID- ORCID: 0000-0002-0180-8648
AD  - Center for Cognitive Neuroscience, Neuroscience and Behavioural Disorders 
      Program, Duke-National University of Singapore Medical School, Singapore, 
      Singapore. helen.zhou@duke-nus.edu.sg.
AD  - Clinical Imaging Research Centre, the Agency for Science, Technology and 
      Research, Singapore, Singapore. helen.zhou@duke-nus.edu.sg.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190318
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
SB  - IM
MH  - Aged
MH  - Alzheimer Disease/*physiopathology
MH  - Cognitive Dysfunction/physiopathology
MH  - Disease Progression
MH  - Gray Matter/pathology
MH  - Humans
MH  - Memory Disorders/*physiopathology
MH  - Nerve Net/physiopathology
MH  - White Matter/*abnormalities/physiopathology/ultrastructure
PMC - PMC6426923
COIS- The authors declare no competing interests.
EDAT- 2019/03/22 06:00
MHDA- 2020/11/05 06:00
PMCR- 2019/03/18
CRDT- 2019/03/22 06:00
PHST- 2018/11/19 00:00 [received]
PHST- 2019/03/07 00:00 [accepted]
PHST- 2019/03/22 06:00 [entrez]
PHST- 2019/03/22 06:00 [pubmed]
PHST- 2020/11/05 06:00 [medline]
PHST- 2019/03/18 00:00 [pmc-release]
AID - 10.1038/s41598-019-41363-2 [pii]
AID - 41363 [pii]
AID - 10.1038/s41598-019-41363-2 [doi]
PST - epublish
SO  - Sci Rep. 2019 Mar 18;9(1):4749. doi: 10.1038/s41598-019-41363-2.