COMT val158met is not associated with Aβ-amyloid and APOE ε4 related cognitive decline in cognitively normal older adults

Tenielle Porter; Samantha C. Burnham; Lidija Milicic; Greg Savage; Paul Maruff; Hamid R. Sohrabi; Madeline Peretti; Yen Ying Lim; Michael Weinborn; David Ames; Colin L. Masters; Ralph N. Martins; Stephanie Rainey-Smith; Christopher C. Rowe; Olivier Salvado; David Groth; Giuseppe Verdile; Victor L. Villemagne; Simon M. Laws

doi:10.1016/j.ibror.2019.05.001

COMT val158met is not associated with Aβ-amyloid and APOE ε4 related cognitive decline in cognitively normal older adults

Tenielle Porter, Samantha C. Burnham, Lidija Milicic, Greg Savage, Paul Maruff, Hamid R. Sohrabi, Madeline Peretti, Yen Ying Lim, Michael Weinborn, David Ames, Colin L. Masters, Ralph N. Martins, Stephanie Rainey-Smith, Christopher C. Rowe, Olivier Salvado, David Groth, Giuseppe Verdile, Victor L. Villemagne, Simon M. Laws^*

^*Corresponding author for this work

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Abstract

The non-synonymous single nucleotide polymorphism (SNP), Val158Met within the Catechol-O-methyltransferase (COMT) gene has been associated with altered levels of cognition and memory performance in cognitively normal adults. This study aimed to investigate the independent and interactional effects of COMT Val158Met on cognitive performance. In particular, it was hypothesised that COMT Val158Met would modify the effect of neocortical Aβ-amyloid (Aβ) accumulation and carriage of the apolipoprotein E (APOE) ε4 allele on cognition in preclinical Alzheimer's disease (AD). In 598 cognitively normal older adults with known neocortical Aβ levels, linear mixed modelling revealed no significant independent or interactional associations between COMT Val158Met and cognitive decline. These findings do not support previous associations between COMT Val158Met and cognitive performance and suggest this variant does not influence Aβ-amyloid or APOE ε4 driven cognitive decline in a well characterised cohort of cognitively normal older adults.

Original language	English
Pages (from-to)	147-152
Number of pages	6
Journal	IBRO Reports
Volume	6
DOIs	https://doi.org/10.1016/j.ibror.2019.05.001
Publication status	Published - 1 Jun 2019

Bibliographical note

Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

Aβ-amyloid
Catechol-O-methyltransferase
Cognitive decline
COMT
Episodic memory

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10.1016/j.ibror.2019.05.001

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Porter, T., Burnham, S. C., Milicic, L., Savage, G., Maruff, P., Sohrabi, H. R., Peretti, M., Lim, Y. Y., Weinborn, M., Ames, D., Masters, C. L., Martins, R. N., Rainey-Smith, S., Rowe, C. C., Salvado, O., Groth, D., Verdile, G., Villemagne, V. L., & Laws, S. M. (2019). COMT val158met is not associated with Aβ-amyloid and APOE ε4 related cognitive decline in cognitively normal older adults. IBRO Reports, 6, 147-152. https://doi.org/10.1016/j.ibror.2019.05.001

@article{36a13d6c4f8243ba94ecdd12d920a46b,

title = "COMT val158met is not associated with Aβ-amyloid and APOE ε4 related cognitive decline in cognitively normal older adults",

abstract = "The non-synonymous single nucleotide polymorphism (SNP), Val158Met within the Catechol-O-methyltransferase (COMT) gene has been associated with altered levels of cognition and memory performance in cognitively normal adults. This study aimed to investigate the independent and interactional effects of COMT Val158Met on cognitive performance. In particular, it was hypothesised that COMT Val158Met would modify the effect of neocortical Aβ-amyloid (Aβ) accumulation and carriage of the apolipoprotein E (APOE) ε4 allele on cognition in preclinical Alzheimer's disease (AD). In 598 cognitively normal older adults with known neocortical Aβ levels, linear mixed modelling revealed no significant independent or interactional associations between COMT Val158Met and cognitive decline. These findings do not support previous associations between COMT Val158Met and cognitive performance and suggest this variant does not influence Aβ-amyloid or APOE ε4 driven cognitive decline in a well characterised cohort of cognitively normal older adults.",

keywords = "Aβ-amyloid, Catechol-O-methyltransferase, Cognitive decline, COMT, Episodic memory",

author = "Tenielle Porter and Burnham, {Samantha C.} and Lidija Milicic and Greg Savage and Paul Maruff and Sohrabi, {Hamid R.} and Madeline Peretti and Lim, {Yen Ying} and Michael Weinborn and David Ames and Masters, {Colin L.} and Martins, {Ralph N.} and Stephanie Rainey-Smith and Rowe, {Christopher C.} and Olivier Salvado and David Groth and Giuseppe Verdile and Villemagne, {Victor L.} and Laws, {Simon M.}",

note = "Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

year = "2019",

month = jun,

day = "1",

doi = "10.1016/j.ibror.2019.05.001",

language = "English",

volume = "6",

pages = "147--152",

journal = "IBRO Reports",

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Porter, T, Burnham, SC, Milicic, L, Savage, G, Maruff, P, Sohrabi, HR, Peretti, M, Lim, YY, Weinborn, M, Ames, D, Masters, CL, Martins, RN, Rainey-Smith, S, Rowe, CC, Salvado, O, Groth, D, Verdile, G, Villemagne, VL & Laws, SM 2019, 'COMT val158met is not associated with Aβ-amyloid and APOE ε4 related cognitive decline in cognitively normal older adults', IBRO Reports, vol. 6, pp. 147-152. https://doi.org/10.1016/j.ibror.2019.05.001

TY - JOUR

T1 - COMT val158met is not associated with Aβ-amyloid and APOE ε4 related cognitive decline in cognitively normal older adults

AU - Porter, Tenielle

AU - Burnham, Samantha C.

AU - Milicic, Lidija

AU - Savage, Greg

AU - Maruff, Paul

AU - Sohrabi, Hamid R.

AU - Peretti, Madeline

AU - Lim, Yen Ying

AU - Weinborn, Michael

AU - Ames, David

AU - Masters, Colin L.

AU - Martins, Ralph N.

AU - Rainey-Smith, Stephanie

AU - Rowe, Christopher C.

AU - Salvado, Olivier

AU - Groth, David

AU - Verdile, Giuseppe

AU - Villemagne, Victor L.

AU - Laws, Simon M.

N1 - Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2019/6/1

Y1 - 2019/6/1

N2 - The non-synonymous single nucleotide polymorphism (SNP), Val158Met within the Catechol-O-methyltransferase (COMT) gene has been associated with altered levels of cognition and memory performance in cognitively normal adults. This study aimed to investigate the independent and interactional effects of COMT Val158Met on cognitive performance. In particular, it was hypothesised that COMT Val158Met would modify the effect of neocortical Aβ-amyloid (Aβ) accumulation and carriage of the apolipoprotein E (APOE) ε4 allele on cognition in preclinical Alzheimer's disease (AD). In 598 cognitively normal older adults with known neocortical Aβ levels, linear mixed modelling revealed no significant independent or interactional associations between COMT Val158Met and cognitive decline. These findings do not support previous associations between COMT Val158Met and cognitive performance and suggest this variant does not influence Aβ-amyloid or APOE ε4 driven cognitive decline in a well characterised cohort of cognitively normal older adults.

AB - The non-synonymous single nucleotide polymorphism (SNP), Val158Met within the Catechol-O-methyltransferase (COMT) gene has been associated with altered levels of cognition and memory performance in cognitively normal adults. This study aimed to investigate the independent and interactional effects of COMT Val158Met on cognitive performance. In particular, it was hypothesised that COMT Val158Met would modify the effect of neocortical Aβ-amyloid (Aβ) accumulation and carriage of the apolipoprotein E (APOE) ε4 allele on cognition in preclinical Alzheimer's disease (AD). In 598 cognitively normal older adults with known neocortical Aβ levels, linear mixed modelling revealed no significant independent or interactional associations between COMT Val158Met and cognitive decline. These findings do not support previous associations between COMT Val158Met and cognitive performance and suggest this variant does not influence Aβ-amyloid or APOE ε4 driven cognitive decline in a well characterised cohort of cognitively normal older adults.

KW - Aβ-amyloid

KW - Catechol-O-methyltransferase

KW - Cognitive decline

KW - COMT

KW - Episodic memory

UR - http://www.scopus.com/inward/record.url?scp=85065198554&partnerID=8YFLogxK

U2 - 10.1016/j.ibror.2019.05.001

DO - 10.1016/j.ibror.2019.05.001

M3 - Article

C2 - 31080907

AN - SCOPUS:85065198554

SN - 2451-8301

VL - 6

SP - 147

EP - 152

JO - IBRO Reports

JF - IBRO Reports

ER -

COMT val158met is not associated with Aβ-amyloid and APOE ε4 related cognitive decline in cognitively normal older adults

Abstract

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Keywords

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