PMID- 28035927
OWN - NLM
STAT- MEDLINE
DCOM- 20180223
LR  - 20180605
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Linking)
VI  - 56
IP  - 2
DP  - 2017
TI  - Integration of Multilocus Genetic Risk into the Default Mode Network Longitudinal 
      Trajectory during the Alzheimer's Disease Process.
PG  - 491-507
LID - 10.3233/JAD-160787 [doi]
AB  - The aim of the study was to investigate the cognitive significance of the changes 
      in default mode network (DMN) during the process of Alzheimer's disease (AD) and 
      the genetic basis that drives the alteration. Eighty-seven subjects with mild 
      cognitive impairment (MCI) and 131 healthy controls (HC) were employed at 
      baseline, and they had the genetic risk scores (GRS) based on the GWAS-validated 
      AD-related top loci. Eleven MCIs who converted to AD (c-MCIs), 32 subjects who 
      remained stable (nc-MCIs), and 56 HCs participated in the follow-up analyses 
      after an average of 35 months. Decreased functional connectivity (FC) within 
      temporal cortex was identified for MCIs at baseline, which was partially 
      determined by the GRS; moreover, compensations may occur within the 
      frontal-parietal brain to maintain relatively intact cognition. During the 
      follow-ups, c-MCIs exhibited more FC declines within the prefrontal-parietal 
      lobes and parahippocampal gyrus/hippocampus than the HCs and nc-MCIs. The GRS did 
      not significantly vary among the three groups, whereas associations were 
      identified at risky alleles and FC declines in all AD spectra. Interestingly, the 
      influence of APOEvarepsilon4 varied as the disease progressed; APOEvarepsilon4 was associated with 
      longitudinal FC decreases only for HCs in the single variance-based analyses and 
      deteriorated DMN integration in nc-MCIs by combining the effects of other loci. 
      However, the GRS without APOEvarepsilon4 predicted FC decline for converters. It is 
      suggested that the integration of multilocus genetic risk predicted the 
      longitudinal trajectory of DMN and may be used as a clinical strategy to track AD 
      progression.
FAU - Su, Fan
AU  - Su F
AD  - Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, 
      Southeast University, Nanjing, Jiangsu, China.
FAU - Shu, Hao
AU  - Shu H
AD  - Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, 
      Southeast University, Nanjing, Jiangsu, China.
AD  - Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA.
FAU - Ye, Qing
AU  - Ye Q
AD  - Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, 
      Southeast University, Nanjing, Jiangsu, China.
FAU - Xie, Chunming
AU  - Xie C
AD  - Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, 
      Southeast University, Nanjing, Jiangsu, China.
FAU - Yuan, Baoyu
AU  - Yuan B
AD  - Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, 
      Southeast University, Nanjing, Jiangsu, China.
FAU - Zhang, Zhijun
AU  - Zhang Z
AD  - Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, 
      Southeast University, Nanjing, Jiangsu, China.
FAU - Bai, Feng
AU  - Bai F
AD  - Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, 
      Southeast University, Nanjing, Jiangsu, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (Apolipoprotein E4)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Alzheimer Disease/diagnostic imaging/*genetics/*physiopathology
MH  - Apolipoprotein E4/genetics
MH  - Brain/diagnostic imaging/*physiopathology
MH  - Brain Mapping
MH  - Cognition
MH  - Cognitive Dysfunction/diagnostic imaging/*genetics/*physiopathology
MH  - Disease Progression
MH  - Female
MH  - Follow-Up Studies
MH  - *Genetic Testing
MH  - Humans
MH  - Longitudinal Studies
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Middle Aged
MH  - Neural Pathways/diagnostic imaging/physiopathology
MH  - Polymorphism, Single Nucleotide
MH  - Rest
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - default mode network
OT  - functional MRI
OT  - genetic polymorphism
OT  - longitudinal investigation
OT  - mild cognitive impairment
EDAT- 2016/12/31 06:00
MHDA- 2018/02/24 06:00
CRDT- 2016/12/31 06:00
PHST- 2016/12/31 06:00 [pubmed]
PHST- 2018/02/24 06:00 [medline]
PHST- 2016/12/31 06:00 [entrez]
AID - JAD160787 [pii]
AID - 10.3233/JAD-160787 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2017;56(2):491-507. doi: 10.3233/JAD-160787.