PMID- 25107496
OWN - NLM
STAT- MEDLINE
DCOM- 20150921
LR  - 20211021
IS  - 1558-1497 (Electronic)
IS  - 0197-4580 (Print)
IS  - 0197-4580 (Linking)
VI  - 36
IP  - 1
DP  - 2015 Jan
TI  - Synergistic associations of catechol-O-methyltransferase and brain-derived 
      neurotrophic factor with executive function in aging are selective and modified 
      by apolipoprotein E.
PG  - 249-56
LID - S0197-4580(14)00439-4 [pii]
LID - 10.1016/j.neurobiolaging.2014.06.020 [doi]
AB  - Genetic polymorphisms of catechol-O-methyltransferase (COMT) and brain-derived 
      neurotrophic factor (BDNF) have shown promising but inconsistent linkages with 
      executive function (EF) in normal aging. We tested (1) independent contributions 
      of COMT and BDNF risk; (2) potential magnification by risk-related interactions 
      or additive effects with age; and (3) effect modification through stratification 
      by apolipoprotein E (APOE) (risk: epsilon4+). Multiple linear regression models were 
      applied with nondemented older adults (N = 634; range: 53-95 years) for an EF 
      latent variable. No independent effects of BDNF or COMT on EF were observed. 
      Additive (but not interactive) effects of COMT, BDNF, and age showed that older 
      adults with a high-risk allelic combination performed differentially worse. Of 2 
      tested models of synergistic effects, the additive approach selectively supported 
      a magnification hypothesis, which was qualified by the presence or the absence of 
      APOE epsilon4.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Sapkota, Shraddha
AU  - Sapkota S
AD  - Neuroscience and Mental Health Institute, University of Alberta, Edmonton, 
      Alberta, Canada.
FAU - Vergote, David
AU  - Vergote D
AD  - Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, 
      Alberta, Canada.
FAU - Westaway, David
AU  - Westaway D
AD  - Neuroscience and Mental Health Institute, University of Alberta, Edmonton, 
      Alberta, Canada; Centre for Prions and Protein Folding Diseases, University of 
      Alberta, Edmonton, Alberta, Canada.
FAU - Jhamandas, Jack
AU  - Jhamandas J
AD  - Neuroscience and Mental Health Institute, University of Alberta, Edmonton, 
      Alberta, Canada; Division of Neurology, Department of Medicine, University of 
      Alberta, Edmonton, Alberta, Canada.
FAU - Dixon, Roger A
AU  - Dixon RA
AD  - Neuroscience and Mental Health Institute, University of Alberta, Edmonton, 
      Alberta, Canada; Department of Psychology, University of Alberta, Edmonton, 
      Alberta, Canada. Electronic address: rdixon@ualberta.ca.
LA  - eng
GR  - R01 AG008235/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 - 20140620
PL  - United States
TA  - Neurobiol Aging
JT  - Neurobiology of aging
JID - 8100437
RN  - 0 (Apolipoproteins E)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - EC 2.1.1.6 (COMT protein, human)
RN  - EC 2.1.1.6 (Catechol O-Methyltransferase)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Aging/*genetics/*physiology
MH  - Apolipoproteins E/*physiology
MH  - Brain-Derived Neurotrophic Factor/*genetics/*physiology
MH  - Catechol O-Methyltransferase/*genetics/*physiology
MH  - Epistasis, Genetic/*genetics
MH  - Executive Function/*physiology
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Genetic
MH  - Risk
PMC - PMC4268316
MID - NIHMS607160
OTO - NOTNLM
OT  - Aging
OT  - Apolipoprotein E
OT  - Brain-derived neurotrophic factor
OT  - Catechol-O-methyltransferase
OT  - Executive function
OT  - Victoria longitudinal study
COIS- Disclosure Statement All authors confirm that there is no actual or potential 
      conflict of interest. All research has been approved continuously by relevant 
      institutional review boards. Certificates are available and on file in the 
      University of Alberta Research Services Office and the US National Institutes of 
      Health. All participants have completed and signed informed consent forms.
EDAT- 2014/08/12 06:00
MHDA- 2015/09/22 06:00
PMCR- 2016/01/01
CRDT- 2014/08/10 06:00
PHST- 2014/01/25 00:00 [received]
PHST- 2014/06/16 00:00 [revised]
PHST- 2014/06/16 00:00 [accepted]
PHST- 2014/08/10 06:00 [entrez]
PHST- 2014/08/12 06:00 [pubmed]
PHST- 2015/09/22 06:00 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - S0197-4580(14)00439-4 [pii]
AID - 10.1016/j.neurobiolaging.2014.06.020 [doi]
PST - ppublish
SO  - Neurobiol Aging. 2015 Jan;36(1):249-56. doi: 
      10.1016/j.neurobiolaging.2014.06.020. Epub 2014 Jun 20.