| 1. |
- de Frias, Cindy M., et al.
(author)
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Catechol O-Methyltransferase Val¹-sup-5-sup-8 Met Polymorphism is Associated with Cognitive Performance in Nondemented Adults.
- 2005
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In: Journal of Cognitive Neuroscience. - : MIT Press - Journals. - 0898-929X .- 1530-8898. ; 17:7, s. 1018-1025
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Journal article (peer-reviewed)abstract
- The catechol O-methyltransferase (COMT) gene is essential in the metabolic degradation of dopamine in the prefrontal cortex. In the present study, we examined the effect of a Val¹-sup-5-sup-8Met polymorphism in the COMT gene on individual differences and changes in cognition (executive functions and visuospatial ability) in adulthood and old age. The participants were 292 nondemented men (initially aged 35-85 years) from a random sample of the population (i.e., the Betula study) tested at two occasions with a 5-year interval. Confirmatory factor analyses were used to test the underlying structure of three indicators of executive functions (verbal fluency, working memory, and Tower of Hanoi). Associations between COMT, age, executive functioning, and visuospatial (block design) tasks were examined using repeated-measures analyses of variance. Carriers of the Val allele (with higher enzyme activity) compared with carriers of the Met/Met genotype (with low enzyme activity) performed worse on executive functioning and visuospatial tasks. Individuals with the /Val genotype declined in executive functioning over the 5-year period, whereas carriers of the Met allele remained stable in performance. An Age × COMT interaction for visuospatial ability located the effect for middle-aged men only. This COMT polymorphism is a plausible candidate gene for executive functioning and fluid intelligence in nondemented middle-aged and older adults.
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| 2. |
- de Frias, Cindy M., et al.
(author)
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Cholesterol and triglycerides moderate the effect of apolipoprotein E on memory functioning in older adults.
- 2007
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In: Journal of Gerontology: Psychological Sciences. - Washington : The gerontological society of America. - 1079-5014 .- 1758-5368. ; 62B:2, s. P112-P118
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Journal article (peer-reviewed)abstract
- We used data from the Betula Study to examine associations between total cholesterol, triglycerides, and apolipoprotein E on 10-year changes in cognitive performance. Tests assessing episodic memory (recall and recognition), semantic memory (knowledge and fluency), and visuospatial ability (block design) were administered to 524 nondemented adults (initial age of 55-80 years); multilevel modeling was applied to the data. Higher triglyceride levels were associated with a decline in verbal knowledge. Lipid levels moderated the influence of apolipoprotein E on episodic memory, such that among epsilon 4 allele carriers, decline in recognition was noted for individuals with higher cholesterol levels. Cholesterol and triglyceride levels are pharmacologically modifiable risk factors that account for variation In normal cognitive aging.
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| 3. |
- de Frias, Cindy M, et al.
(author)
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COMT gene polymorphism is associated with declarative memory in adulthood and old age.
- 2004
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In: Behavior genetics. - New York : Kluwer Academic Publishers. - 0001-8244 .- 1573-3297. ; 34:5, s. 533-9
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Journal article (peer-reviewed)abstract
- Variation in memory performance is to a large extent explained by genes. In the prefrontal cortex, the catechol O-methyltransferase (COMT) gene is essential in the metabolic degradation of dopamine, a neurotransmitter implicated in cognitive functions. The present study examined the effect of a polymorphism in the COMT gene on individual differences and changes in memory in adulthood and old age. Tests assessing episodic and semantic memory were administered to 286 men (initially aged 35-85 years) from a random sample of the population (i.e., the Betula prospective cohort study) at two occasions followed over a 5-year period. Carriers of the Met/Met genotype (with low enzyme activity) performed better on episodic and semantic memory, as compared to carriers of the Val allele (with higher enzyme activity). Division of episodic memory into its recall and recognition components showed that the difference was specific to episodic recall, not recognition tasks; an effect that was observed across three age groups (middle-age, young-old, and old-old adults) and over a 5-year period. The COMT gene is a plausible candidate gene for memory functioning in adulthood and old age.
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| 4. |
- de Frias, Cindy M., et al.
(author)
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Influence of COMT Gene Polymorphism on fMRI-assessed Sustained and Transient Activity during a Working Memory Task
- 2010
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In: Journal of cognitive neuroscience. - Cambridge, Mass. : MIT Press. - 0898-929X .- 1530-8898. ; 22:7, s. 1614-1622
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Journal article (peer-reviewed)abstract
- The catechol O-methyltransferase (COMT) gene-encoding an enzyme that is essential for the degradation of dopamine (DA) in prefrontal cortex (PFC)-contains a single nucleotide polymorphism (val/met) important for cognition. According to the tonic-phasic hypothesis, individuals carrying the low-enzyme- activity allele (met) are characterized by enhanced tonic DA activity in PFC, promoting sustained cognitive representations in working memory. Val carriers have reduced tonic but enhanced phasic dopaminergic activity in subcortical regions, enhancing cognitive flexibility. We tested the tonic-phasic DA hypothesis by dissociating sustained and transient brain activity during performance on a 2-back working memory test using mixed blocked/event-related functional magnetic resonance imaging. Participants were men recruited from a random sample of the population (the Betula study) and consisted of 11 met/met and 11 val/val carriers aged 50 to 65 years, matched on age, education, and cognitive performance. There were no differences in 2-back performance between genotype groups. Met carriers displayed a greater transient medial temporal lobe response in the updating phase of working memory, whereas val carriers showed a greater sustained PFC activation in the maintenance phase. These results support the tonic-phasic theory of DA function in elucidating the specific phenotypic influence of the COMT val(158)met polymorphism on different components of working memory.
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| 5. |
- Nilsson, Lars-Göran, et al.
(author)
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Betula : a prospective cohort study on memory, health and aging
- 2004
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In: Aging, Neuropsychology and Cognition. - Hove : Psychology Press. - 1382-5585 .- 1744-4128. ; 11:2-3, s. 134-148
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Journal article (peer-reviewed)abstract
- This article describes the Betula Study with respect to objectives, design, participants, and assessment instruments for health and cognition. Three waves of data collection have been completed in 5-year intervals since 1988-1990. A fourth wave started in 2003 and will be completed in 2005. An overview of Betula research is presented under the headings of memory and cognition and cognitive neuroscience. Health-related issues and sex differences as well as comparisons between cross-sectional and longitudinal studies are discussed in the first section. The influence of different genes and of some brain abnormalities for memory functioning in adulthood and old age constitute main topics in the second section. New data are presented on the association between blood pressure and dementia. We demonstrated that a demented group of participants had higher levels of systolic blood pressure and pulse pressure than non-dementia controls 10 years before diagnosis. The new fourth wave of data collection will, in addition to enriching the Betula database, permit revisiting and reanalyzing the existing data from new perspectives.
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| 6. |
- Nilsson, Lars-Göran, et al.
(author)
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The effect of genetics and vascular health on memory functioning: The Betula Study.
- 2006
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In: Proceedings of the 28th International Congress of Psychology.. ; , s. 113-128
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Conference paper (other academic/artistic)abstract
- This chapter presents a review of the role of different genes and vascular health factors in understanding normal and pathological human memory. Recent results are presented from a large-scale prospective cohort study on memory, health, and aging. The Betula project. Possible mechanisms for the genetic and vascular influences on individual differences and changes in memory in adulthood and old age are discussed. It is proposed taht multiple genes, each with specific functions, impact different memory systems and at specific points in the adult lifespan. It is also suggested that a combination of experimental methods in cognitive psychology, genetics, and brain imaging may be the ultimate recipe for the detection of early signs of neurodegenerative diseases.
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