| 1. |
- Duarte Fernandes, Carla Patricia, et al.
(författare)
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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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Ingår i: Psychiatry Research. - : Elsevier BV. - 0925-4927 .- 1872-7506. ; 222:1-2, s. 60-66
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Giddaluru, Sudheer, et al.
(författare)
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Genetics of structural connectivity and information processing in the brain
- 2016
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Ingår i: Brain Structure and Function. - : Springer Science and Business Media LLC. - 1863-2653 .- 1863-2661. ; 221:9, s. 4643-4661
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the genetic factors underlying brain structural connectivity is a major challenge in imaging genetics. Here, we present results from genome-wide association studies (GWASs) of whole-brain white matter (WM) fractional anisotropy (FA), an index of microstructural coherence measured using diffusion tensor imaging. Data from independent GWASs of 355 Swedish and 250 Norwegian healthy adults were integrated by meta-analysis to enhance power. Complementary GWASs on behavioral data reflecting processing speed, which is related to microstructural properties of WM pathways, were performed and integrated with WM FA results via multimodal analysis to identify shared genetic associations. One locus on chromosome 17 (rs145994492) showed genome-wide significant association with WM FA (meta P value = 1.87 × 10(-08)). Suggestive associations (Meta P value <1 × 10(-06)) were observed for 12 loci, including one containing ZFPM2 (lowest meta P value = 7.44 × 10(-08)). This locus was also implicated in multimodal analysis of WM FA and processing speed (lowest Fisher P value = 8.56 × 10(-07)). ZFPM2 is relevant in specification of corticothalamic neurons during brain development. Analysis of SNPs associated with processing speed revealed association with a locus that included SSPO (lowest meta P value = 4.37 × 10(-08)), which has been linked to commissural axon growth. An intergenic SNP (rs183854424) 14 kb downstream of CSMD1, which is implicated in schizophrenia, showed suggestive evidence of association in the WM FA meta-analysis (meta P value = 1.43 × 10(-07)) and the multimodal analysis (Fisher P value = 1 × 10(-07)). These findings provide novel data on the genetics of WM pathways and processing speed, and highlight a role of ZFPM2 and CSMD1 in information processing in the brain.
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| 3. |
- Hessen, Erik, et al.
(författare)
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Subjective Cognitive Impairment Is a Predominantly Benign Condition in Memory Clinic Patients Followed for 6 Years: The Gothenburg-Oslo MCI Study.
- 2017
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Ingår i: Dementia and geriatric cognitive disorders extra. - : S. Karger AG. - 1664-5464. ; 7:1, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- In the quest for prevention or treatment, there is a need to find early markers for preclinical dementia. This study observed memory clinic patients with subjective cognitive impairment (SCI) and normal cognitive function at baseline. The primary aim was to address SCI as a potential risk factor for cognitive decline. The secondary aim was to address a potential relation between (1) baseline cerebrospinal fluid biomarkers and (2) a decline in memory performance over the first 2 years of follow-up, with a possible cognitive decline after 6 years.Eighty-one patients (mean age 61 years) were recruited from university memory clinics and followed up for 6 years.Eighty-six percent of the cohort remained cognitively stable or improved, 9% developed mild cognitive impairment, and only 5% (n = 4) developed dementia. Regression analysis revealed that low levels of Aβ42 at baseline and memory decline during the first 2 years predicted dementia. When combined, these variables were associated with a 50% risk of developing dementia.Cognitive stability for 86% of the cohort suggests that SCI is predominantly a benign condition with regard to neuropathology. The low number of individuals who developed dementia limits the generalizability of the results and discussion of progression factors.
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| 4. |
- Myrum, Craig, et al.
(författare)
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Common variants in the ARC gene are not associated withcognitive abilities
- 2015
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Ingår i: Brain and Behavior. - : Wiley. - 2162-3279 .- 2162-3279. ; 5:10
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The Activity-Regulated Cytoskeleton-associated (ARC) gene encodes a protein that is critical for the consolidation of synaptic plasticity and long-term memory formation. Given ARC's key role in synaptic plasticity, we hypothesized that genetic variations in ARC may contribute to interindividual variability in human cognitive abilities or to attention-deficit hyperactivity disorder (ADHD) susceptibility, where cognitive impairment often accompanies the disorder. Methods: We tested whether ARC variants are associated with six measures of cognitive functioning in 670 healthy subjects in the Norwegian Cognitive NeuroGenetics (NCNG) by extracting data from its Genome-Wide Association Study (GWAS). In addition, the Swedish Betula sample of 1800 healthy subjects who underwent similar cognitive testing was also tested for association with 19 tag SNPs. Results: No ARC variants show association at the study-wide level, but several markers show a trend toward association with human cognitive functions. We also tested for association between ARCSNPs and ADHD in a Norwegian sample of cases and controls, but found no significant associations. Conclusion: This study suggests that common genetic variants located in ARC do not account for variance in human cognitive abilities, though small effects cannot be ruled out.
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| 7. |
- Thorvaldsson, Valgeir, 1976, et al.
(författare)
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Memory in individuals with mild cognitive impairment in relation to APOE and CSF Abeta42.
- 2010
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Ingår i: International psychogeriatrics / IPA. - 1741-203X. ; 22:4, s. 598-606
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The epsilon4 allele of the apolipoprotein E (APOE) gene and low levels of cerebrospinal fluid (CSF) amyloid beta-proteins 42 (Abeta) have previously been associated with increased risk of cognitive decline in old age. In this study we examine the interaction of these markers with episodic memory in a sample identified as having mild cognitive impairment (MCI). METHODS: The sample (N = 149) was drawn from the Gothenburg MCI study and measured according to three free recall tests on three occasions spanning over four years. Second-order Latent Curve Models (LCM) were fitted to the data. RESULTS: Analyses accounting for age, gender, education, APOE, Abeta42, and interaction between APOE and Abeta42 revealed that the epsilon4 allele was significantly associated with level of memory performance in the presence of low Abeta42 values (< or = 452 ng/L). Associations between memory performance and Abeta42 were significant among the epsilon4 carriers but not among the non-carriers. The Abeta42 marker was, however, significantly associated with changes in memory over the study time period in the total sample. CONCLUSION: The findings support the hypothesis of an interactive effect of APOE and Abeta42 for memory decline in MCI patients.
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| 8. |
- Wehling, Eike, et al.
(författare)
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Even cognitively well-functioning adults are unaware of their olfactory dysfunction : Implications for ENT clinicians and researchers
- 2015
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Ingår i: Rhinology. - Utrecht, Netherlands : International Rhinologic Society. - 0300-0729 .- 1996-8604. ; 53:1, s. 89-94
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Tidskriftsartikel (refereegranskat)abstract
- Background: Past findings of an impact of cognitive impairment on awareness of olfactory dysfunction, and high prevalence of age-associated cognitive impairment motivated the present study of whether middle-aged and elderly adults are unaware of an olfactory dysfunction despite being carefully screened for cognitive impairment. Methodology: The sample included 203 Norwegian participants, aged 46-79 years, 134 women and 69 men, who underwent comprehensive neuropsychological assessment for screening of cognitive impairment. Subjective assessment of olfactory function ("How would you estimate your sense of smell?") was compared with outcome on objective assessment of olfactory function with the Scandinavian Odor Identification Test, which in the present study was shown to be valid for use on Norwegian populations. Results: We found that 79% of this cognitively healthy sample with objectively assessed olfactory dysfunction reported normal olfactory function (57% of functionally anosmics reported normal function). In contrast, only 9% with objectively assessed normal olfactory function reported olfactory dysfunction. Conclusion: A large proportion of cognitively well-functioning middle-aged and elderly adults with an olfactory dysfunction are unaware of their dysfunction.The ENT physician who suspects that the sense of smell may be compromised should, in addition to an anamnesis, assess the patient's olfactory function objectively.
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| 9. |
- Wehling, Eike Ines, et al.
(författare)
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Familiarity, cued and free odoridentification and their association with cognitive functioning in middleaged and older adults
- 2010
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Ingår i: Aging, Neuropsychology and Cognition. - : Psychology Press, Taylor and Francis Group. - 1382-5585 .- 1744-4128. ; 17:2, s. 205-219
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to examine the association between familiarity of odors, cued and free odor identification performance and cognitive function in elderly adults. It was further investigated how age affects performance on the various odor tasks. A third aim was to investigate the role of familiarity in explaining performance on the free identification task. One hundred and thirty-six participants (aged 45–79 years) with normal olfactory sensitivity were assessed with the Scandinavian Odor Identification Test (SOIT) and standardized tests of cognitive function. Familiarity did not correlate with any measure of cognitive function, while verbal identification performance was associated with several cognitive measures, although correlations were modest. In this sample, free odor identification was affected by increasing age to a marginally larger extent than cued identification performance and familiarity ratings. The results suggest that the different olfactory tasks involve different levels of cognitive processing.
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| 10. |
- Wehling, Eike, et al.
(författare)
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Unawareness of olfactory dysfunction and its association with cognitive functioning in middle aged and old adults
- 2011
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Ingår i: Archives of clinical neuropsychology. - : Oxford University Press. - 0887-6177 .- 1873-5843. ; 26:3, s. 260-269
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was (a) to investigate the accordance of self-reported and objectively assessed olfactory functioning and (b) to compare performance on cognitive tests of individuals unaware of their olfactory dysfunction with individuals aware of their olfactory status. Two hundred forty participants, constituting two age groups, were evaluated with the Scandinavian Odor Identification Test, a question of self-evaluated olfactory function, tests of cognitive function, and a memory questionnaire. The proportion of individuals being unaware of an olfactory dysfunction was high in both middle aged (86%) and old (78%) participants. Performance on neuropsychological tests showed that persons unaware of their olfactory dysfunction performed poorer on tests of verbal learning and memory and attention/processing speed compared to individuals aware of a normal olfactory status as well as individuals aware of their olfactory dysfunction. The clinical relevance of unawareness of olfactory dysfunction, as suggested earlier, needs further investigation and stresses the need of an extensive multi-modal and longitudinal assessment of unawareness of sensory and cognitive function to learn more about the facets of the concept of unawareness.
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