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Family history and APOE4 risk for Alzheimer's disease impact the neural correlates of episodic memory by early midlife.

Abstract Episodic memory impairment is a consistent, pronounced deficit in pre-clinical stages of late-onset Alzheimer's disease (AD). Individuals with risk factors for AD exhibit altered brain function several decades prior to the onset of AD-related symptoms. In the current event-related fMRI study of spatial context memory we tested the hypothesis that middle-aged adults (MA; 40-58 yrs) with a family history of late onset AD (MA+ FH), or a combined + FH and apolipoprotein E ε4 allele risk factors for AD (MA+ FH + APOE4), will exhibit differences in encoding and retrieval-related brain activity, compared to - FH - APOE4 MA controls. We also hypothesized that the two at-risk MA groups will exhibit distinct patterns of correlation between brain activity and memory performance, compared to controls. To test these hypotheses we conducted multivariate task, and behavior, partial least squares analysis of fMRI data obtained during successful context encoding and retrieval. Our results indicate that even though there were no significant group differences in context memory performance, there were significant differences in brain activity and brain-behavior correlations involving the hippocampus, inferior parietal cortex, cingulate, and precuneus cortex in MA with AD risk factors, compared to controls. In addition, we observed that brain activity and brain-behavior correlations in anterior-medial PFC and in ventral visual cortex differentiated the two MA risk groups from each other, and from MAcontrols. Our results indicate that functional differences in episodic memory-related regions are present by early midlife in adults with + FH and + APOE-4 risk factors for late onset AD, compared to middle-aged controls.
PMID
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Authors

Mayor MeshTerms

Alzheimer Disease

Family Health

Memory, Episodic

Keywords
Journal Title neuroimage. clinical
Publication Year Start




PMID- 28413778
OWN - NLM
STAT- MEDLINE
DA  - 20170417
DCOM- 20170420
LR  - 20170420
IS  - 2213-1582 (Electronic)
IS  - 2213-1582 (Linking)
VI  - 14
DP  - 2017
TI  - Family history and APOE4 risk for Alzheimer's disease impact the neural
      correlates of episodic memory by early midlife.
PG  - 760-774
LID - 10.1016/j.nicl.2017.03.016 [doi]
AB  - Episodic memory impairment is a consistent, pronounced deficit in pre-clinical
      stages of late-onset Alzheimer's disease (AD). Individuals with risk factors for 
      AD exhibit altered brain function several decades prior to the onset of
      AD-related symptoms. In the current event-related fMRI study of spatial context
      memory we tested the hypothesis that middle-aged adults (MA; 40-58 yrs) with a
      family history of late onset AD (MA+ FH), or a combined + FH and apolipoprotein E
      epsilon4 allele risk factors for AD (MA+ FH + APOE4), will exhibit differences in
      encoding and retrieval-related brain activity, compared to - FH - APOE4 MA
      controls. We also hypothesized that the two at-risk MA groups will exhibit
      distinct patterns of correlation between brain activity and memory performance,
      compared to controls. To test these hypotheses we conducted multivariate task,
      and behavior, partial least squares analysis of fMRI data obtained during
      successful context encoding and retrieval. Our results indicate that even though 
      there were no significant group differences in context memory performance, there 
      were significant differences in brain activity and brain-behavior correlations
      involving the hippocampus, inferior parietal cortex, cingulate, and precuneus
      cortex in MA with AD risk factors, compared to controls. In addition, we observed
      that brain activity and brain-behavior correlations in anterior-medial PFC and in
      ventral visual cortex differentiated the two MA risk groups from each other, and 
      from MAcontrols. Our results indicate that functional differences in episodic
      memory-related regions are present by early midlife in adults with + FH and +
      APOE-4 risk factors for late onset AD, compared to middle-aged controls.
FAU - Rajah, M N
AU  - Rajah MN
AD  - Department of Psychiatry, McGill University, Canada.
AD  - Brain Imaging Centre, Douglas Mental Health University Institute, Canada.
FAU - Wallace, L M K
AU  - Wallace LMK
AD  - Brain Imaging Centre, Douglas Mental Health University Institute, Canada.
AD  - Integrated Program in Neuroscience, McGill University, Canada.
FAU - Ankudowich, E
AU  - Ankudowich E
AD  - Brain Imaging Centre, Douglas Mental Health University Institute, Canada.
AD  - Integrated Program in Neuroscience, McGill University, Canada.
FAU - Yu, E H
AU  - Yu EH
AD  - Brain Imaging Centre, Douglas Mental Health University Institute, Canada.
AD  - Integrated Program in Neuroscience, McGill University, Canada.
FAU - Swierkot, A
AU  - Swierkot A
AD  - Brain Imaging Centre, Douglas Mental Health University Institute, Canada.
AD  - Integrated Program in Neuroscience, McGill University, Canada.
FAU - Patel, R
AU  - Patel R
AD  - Brain Imaging Centre, Douglas Mental Health University Institute, Canada.
AD  - Department of Biological and Biomedical Engineering, McGill University, Canada.
FAU - Chakravarty, M M
AU  - Chakravarty MM
AD  - Department of Psychiatry, McGill University, Canada.
AD  - Brain Imaging Centre, Douglas Mental Health University Institute, Canada.
AD  - Department of Biological and Biomedical Engineering, McGill University, Canada.
FAU - Naumova, D
AU  - Naumova D
AD  - Department of Psychiatry, McGill University, Canada.
AD  - Integrated Program in Neuroscience, McGill University, Canada.
FAU - Pruessner, J
AU  - Pruessner J
AD  - Department of Psychiatry, McGill University, Canada.
AD  - Brain Imaging Centre, Douglas Mental Health University Institute, Canada.
FAU - Joober, R
AU  - Joober R
AD  - Department of Psychiatry, McGill University, Canada.
FAU - Gauthier, S
AU  - Gauthier S
AD  - Department of Neurology and Neurosurgery, McGill University, Canada.
FAU - Pasvanis, S
AU  - Pasvanis S
AD  - Brain Imaging Centre, Douglas Mental Health University Institute, Canada.
LA  - eng
PT  - Journal Article
DEP - 20170331
PL  - Netherlands
TA  - Neuroimage Clin
JT  - NeuroImage. Clinical
JID - 101597070
RN  - 0 (Apolipoprotein E4)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Adult
MH  - *Alzheimer Disease/diagnostic imaging/genetics/physiopathology
MH  - Analysis of Variance
MH  - Apolipoprotein E4/*genetics
MH  - Brain/*diagnostic imaging
MH  - *Family Health
MH  - Female
MH  - Humans
MH  - Image Processing, Computer-Assisted
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Memory Disorders/*etiology
MH  - *Memory, Episodic
MH  - Mental Recall/physiology
MH  - Mental Status Schedule
MH  - Middle Aged
MH  - Neuropsychological Tests
MH  - Oxygen/blood
PMC - PMC5385589
EDAT- 2017/04/18 06:00
MHDA- 2017/04/21 06:00
CRDT- 2017/04/18 06:00
PHST- 2016/11/21 [received]
PHST- 2017/03/29 [revised]
PHST- 2017/03/30 [accepted]
AID - 10.1016/j.nicl.2017.03.016 [doi]
AID - S2213-1582(17)30075-X [pii]
PST - epublish
SO  - Neuroimage Clin. 2017 Mar 31;14:760-774. doi: 10.1016/j.nicl.2017.03.016.
      eCollection 2017.

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