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
Affiliations
Tenielle Porter
Collaborative Genomics Group, Centre of Excellence for Alzheimer’s Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup 6027, Western Australia, Australia; Cooperative Research Centre for Mental Health, Australia1
Samantha C. Burnham
CSIRO Health and Biosecurity, Parkville 3052, Victoria, Australia; Centre of Excellence for Alzheimer’s Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup 6027, Western Australia, Australia
Lidija Milicic
Collaborative Genomics Group, Centre of Excellence for Alzheimer’s Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup 6027, Western Australia, Australia; Cooperative Research Centre for Mental Health, Australia1
Greg Savage
ARC Centre of Excellence in Cognition and its Disorders, Department of Psychology, Macquarie University, North Ryde 2113, NSW, Australia
Paul Maruff
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville 3052, Victoria, Australia; CogState Ltd., Melbourne 3000, Victoria, Australia
Hamid R. Sohrabi
Centre of Excellence for Alzheimer’s Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup 6027, Western Australia, Australia
Madeline Peretti
Collaborative Genomics Group, Centre of Excellence for Alzheimer’s Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup 6027, Western Australia, Australia; Cooperative Research Centre for Mental Health, Australia1
Yen Ying Lim
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville 3052, Victoria, Australia
Michael Weinborn
Centre of Excellence for Alzheimer’s Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup 6027, Western Australia, Australia; School of Psychology, University of Western Australia, Crawley 6009, Western Australia, Australia
David Ames
Academic Unit for Psychiatry of Old Age, St. Vincent’s Health, The University of Melbourne, Kew 3101, Victoria, Australia; National Ageing Research Institute, Parkville 3052, Victoria, Australia
Colin L. Masters
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville 3052, Victoria, Australia
Ralph N. Martins
Centre of Excellence for Alzheimer’s Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup 6027, Western Australia, Australia
Stephanie Rainey-Smith
Centre of Excellence for Alzheimer’s Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup 6027, Western Australia, Australia
Christopher C. Rowe
Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg 3084, Victoria, Australia; Department of Medicine, Austin Health, The University of Melbourne, Heidelberg 3084, Victoria, Australia
Olivier Salvado
CSIRO Health and Biosecurity/Australian e-Health Research Centre, Herston 4029, Queensland, Australia
David Groth
School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley 6102, Western Australia, Australia
Giuseppe Verdile
Centre of Excellence for Alzheimer’s Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup 6027, Western Australia, Australia; School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley 6102, Western Australia, Australia
Victor L. Villemagne
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville 3052, Victoria, Australia; Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg 3084, Victoria, Australia; Department of Medicine, Austin Health, The University of Melbourne, Heidelberg 3084, Victoria, Australia
Simon M. Laws
Collaborative Genomics Group, Centre of Excellence for Alzheimer’s Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup 6027, Western Australia, Australia; Cooperative Research Centre for Mental Health, Australia1; School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley 6102, Western Australia, Australia; Corresponding author at: Collaborative Genomics Group, School of Medical and Health Sciences, Edith Cowan University, 270 Joondalup Drive, Joondalup 6027, Western Australia, Australia.
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: Catechol-O-methyltransferase, COMT, Cognitive decline, Episodic memory, Aβ-amyloid
