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| 2. |
- 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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| 3. |
- Duarte Fernandes, Carla Patricia, et al.
(author)
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Lack of association of the rs1344706 ZNF804A variant with cognitive functions and DTI indices of white matter microstructure in two independent healthy populations
- 2014
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In: Psychiatry Research. - : Elsevier BV. - 0925-4927 .- 1872-7506. ; 222:1-2, s. 60-66
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Journal article (peer-reviewed)abstract
- The rs1344706 single nucleotide polymorphism with in intron 2 of the ZNF804A gene is strongly associated with schizophrenia and bipolar disorder. This variant has also been associated in some studies with a range of cognitive and neuro imaging phenotypes, but several studies have reported no effect on the same phenotypes in other samples. Here, we genotyped 670 healthy adult Norwegian subjects and 1753 healthy adult Swedish subjects for rs1344706, and tested for associations with cognitive phenotypes including general intellectual abilities, memory functions and cognitive inhibition. We also tested whether rs1344706 is associated with white matter microstructural properties using diffusion tensor imaging (DTI) data from 250 to 340 of the Norwegian and Swedish subjects, respectively. Whole-brain voxel-wise statistical modeling of the effect of the ZNF804A variant on two DTI indices, fractional anisotropy (FA) and radial diffusivity (RD), was performed using tract-based spatial statistics (TBSS), and commonly reported effect sizes were calculated within several large-scale white matter pathways based on neuroanatomic atlases. No significant associations were found between rs1344706 and the cognitive traits or white matter microstructure. We conclude that the rs1344706 SNP has no significant effect on these phenotypes in our two reasonably powered samples.
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| 4. |
- Thompson, Paul M., et al.
(author)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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In: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Journal article (peer-reviewed)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 5. |
- Wikgren, Mikael, 1981-, et al.
(author)
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APOE ε4 is associated with longer telomeres, and longer telomeres among ε4 carriers predicts worse episodic memory
- 2012
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In: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 33:2, s. 335-344
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Journal article (peer-reviewed)abstract
- Both leukocyte telomere length and the apolipoprotein ε4 allele have been associated with mortality, cardiovascular disease, cognition, and dementia. The authors investigated whether leukocyte telomere length was associated with APOE genotype or cognitive abilities in the context of APOE genotype. The setting for this cross-sectional study was 427 nondemented individuals aged 41–81 yr. The authors found that ε4 carriers overall exhibited significantly longer telomeres compared with non-carriers (difference of 268 bp, p = 0.001). This difference was greatest at the lower limit of the age span and nonsignificant at the upper limit, which translated into a significantly higher telomere attrition rate (p = 0.049) among ε4 carriers (37 bp/years) compared with non-carriers (21 bp/year). Further, longer telomeres among ε4 carriers significantly predicted worse performance on episodic memory tasks. No significant associations were found on tasks tapping semantic and visuospatial ability, or among ε3/ε3 carriers. In conclusion, APOE ε4 carriers had longer telomeres compared with non-carriers, but higher rate of attrition. Among them, longer telomeres predicted worse performance on episodic memory tasks. These observations suggest that the ε4 allele is associated with abnormal cell turnover of functional and possibly clinical significance.
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| 6. |
- Wikgren, Mikael, et al.
(author)
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Longer Leukocyte Telomere Length Is Associated with Smaller Hippocampal Volume among Non-Demented APOE epsilon 3/epsilon 3 Subjects
- 2012
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In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 7:4
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Journal article (peer-reviewed)abstract
- Telomere length shortens with cellular division, and leukocyte telomere length is used as a marker for systemic telomere length. The hippocampus hosts adult neurogenesis and is an important structure for episodic memory, and carriers of the apolipoprotein E epsilon 4 allele exhibit higher hippocampal atrophy rates and differing telomere dynamics compared with non-carriers. The authors investigated whether leukocyte telomere length was associated with hippocampal volume in 57 cognitively intact subjects (29 epsilon 3/epsilon 3 carriers; 28 epsilon 4 carriers) aged 49-79 yr. Leukocyte telomere length correlated inversely with left (r(s) = -0.465; p = 0.011), right (r(s) = -0.414; p = 0.025), and total hippocampus volume (r(s) = -0.519; p = 0.004) among APOE epsilon 3/epsilon 3 carriers, but not among epsilon 4 carriers. However, the epsilon 4 carriers fit with the general correlation pattern exhibited by the epsilon 3/epsilon 3 carriers, as epsilon 4 carriers on average had longer telomeres and smaller hippocampi compared with epsilon 3/epsilon 3 carriers. The relationship observed can be interpreted as long telomeres representing a history of relatively low cellular proliferation, reflected in smaller hippocampal volumes. The results support the potential of leukocyte telomere length being used as a biomarker for tapping functional and structural processes of the aging brain.
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| 8. |
- Backeström, A., et al.
(author)
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Glucose metabolism and cognitive dysfunction
- 2010
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In: Abstracts of the EASD, Stockholm 2010. - : Springer Science and Business Media LLC. ; , s. S292-S292
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Conference paper (peer-reviewed)abstract
- Background and aims: The association between type 2 diabetes and different forms of cognitive impairment is well established. The mechanism behind the association is however still unrevealed. We have recently reported that raised blood glucose levels were associated to impairment in episodic memory, the memory function first affected in the progress to dementia. However, patients with type 2 diabetes have not only elevated levels of blood glucose, but also increased levels of insulin because of insulin resistance. It has been suggested that insulin itself might have a negative effect on cognitive function and memory. Diabetes is associated with a long standing hyperglycaemia but also with hypertension and hyperlipideima, leading to micro and macro vascular disease. Thus, our aim was to study whether insulin affects episodic memory independently of glucose in a nondiabetic adult population. Materials and methods: We linked and matched two large population based data sets in Sweden, the Betula study and the Västerbotten Intervention Program. We identified 364 (F/M 207/157, mean age 50.5 ±8.0 years) nondiabetic subjects, free from dementia, who had participated in the two surveys within six months. The memory test included testing of episodic memory. We transformed the results using the mean values and standard deviation from the youngest age group to compute a composite z-score (subjects’ value minus mean score in the 40-year-old group divided by SD). Fasting plasma insulin (FPI) and glucose (FPG) were analyzed with standard methods. Results: Women had higher levels of episodic memory (mean z-score -0.06, SD 0.54) compared to men (mean z-score -0.36, SD 0.51, p<0.001). Given the sex difference in the outcome variable we stratified for sex. In a univariate linear regression both FPG (B -0.274, SE 0.068, Beta -0.271, p<0.001) and FPI (B -0.389, SE 0.131, Beta -0.204, p=0.003) were significantly associated with episodic memory in women but not in men. FPG, but not FPI, remained significantly associated with episodic memory after adjustment for hypertension, total P-cholesterol, bodymass index, educational level, depression, smoking and cardiovascular disease ( FPG: B -0.218, SE 0.070, Beta -0.220, p=0.002; FPI: B -0.232, SE 0.149, Beta -0.127, p=n.s.), when FPG and FPI were analyzed separately. Entering both FPG and FPI into the regression model did not attenuate the association between FPG and episodic memory (FPG: B -0.204, SE 0.071, Beta -0.206, p=0.005). Conclusion: We conclude that an increase in plasma glucose, but not plasma insulin, is associated with impairment in episodic memory in women. This could be explained by a negative effect on the hippocampus caused by raised plasma glucose levels.
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| 9. |
- Bergman, Olle, 1978, et al.
(author)
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Preliminary evidence that polymorphisms in dopamine-related transcription factors LMX1A, LMX1B and PITX3 are associated with schizophrenia
- 2010
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In: Progress in Neuro-psychopharmacology and Biological Psychiatry. - : Elsevier. - 0278-5846 .- 1878-4216. ; 34:6, s. 1094-1097
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Journal article (peer-reviewed)abstract
- The early development of dopaminergic pathways has been attributed importance for the aetiology of schizophrenia. Several transcription factors are involved in the survival and maturation of dopamine neurons, including LMX1A, LMX1B and PITX3. The possibility that polymorphisms in these genes may influence the development and/or the maintenance of dopaminergic neurons prompted us to investigate if five single nucleotide polymorphisms (SNPs) previously linked to Parkinson's disease are associated with this disorder. Preliminary evidence that genetic variation in LMX1A (rs6668493, rs4657411), LMX1B (rs10987386) and PITX3 (rs4919621) may increase the risk of developing schizophrenia is presented.
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| 10. |
- Hansson, Patrik, et al.
(author)
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Relationship between natural teeth and memory in a healthy elderly population
- 2013
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In: European Journal of Oral Sciences. - : Wiley. - 0909-8836 .- 1600-0722. ; 121:4, s. 333-340
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Journal article (peer-reviewed)abstract
- The relationship between mastication and cognitive function remains unclear, but both animal and experimental human studies suggest a possible causal relationship. In the present study it was hypothesized that natural teeth are of importance for hippocampus-based cognitive processes, such as episodic long-term memory. A population-based sample of 273 participants (55-80yr of age; 145 women) was investigated in a cross-sectional study. The participants underwent health assessment, completed a battery of cognitive tests, and took part in an extensive clinical oral examination. The number of natural teeth contributed uniquely and significantly to explaining variance (3-4%) in performance on measures of episodic memory and semantic memory over and above individual differences in age, years of education, gender, occupation, living conditions, and medical history. The number of natural teeth did not have an influence on the performance of measures of working memory, visuospatial ability, or processing speed. Within the limitations of the current study, a small, but significant, relationship between episodic memory and number of natural teeth is evident.
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