| 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. |
- Lind, Johanna, et al.
(författare)
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Reduced functional brain activity response in cognitively intact apolipoprotein E ε4 carriers
- 2006
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Ingår i: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 129:5, s. 1240-1248
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Tidskriftsartikel (refereegranskat)abstract
- The apolipoprotein E epsilon4 (APOE epsilon4) is the main known genetic risk factor for Alzheimer's disease. Genetic assessments in combination with other diagnostic tools, such as neuroimaging, have the potential to facilitate early diagnosis. In this large-scale functional MRI (fMRI) study, we have contrasted 30 APOE epsilon4 carriers (age range: 49-74 years; 19 females), of which 10 were homozygous for the epsilon4 allele, and 30 non-carriers with regard to brain activity during a semantic categorization task. Test groups were closely matched for sex, age and education. Critically, both groups were cognitively intact and thus symptom-free of Alzheimer's disease. APOE epsilon4 carriers showed reduced task-related responses in the left inferior parietal cortex, and bilaterally in the anterior cingulate region. A dose-related response was observed in the parietal area such that diminution was most pronounced in homozygous compared with heterozygous carriers. In addition, contrasts of processing novel versus familiar items revealed an abnormal response in the right hippocampus in the APOE epsilon4 group, mainly expressed as diminished sensitivity to the relative novelty of stimuli. Collectively, these findings indicate that genetic risk translates into reduced functional brain activity, in regions pertinent to Alzheimer's disease, well before alterations can be detected at the behavioural level.
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| 4. |
- Lind, Johanna, et al.
(författare)
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Reduced hippocampal volume in non-demented carriers fo the apolipoprotein E ε4 : Relation to chronological age and recognition memory
- 2006
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 396:1, s. 23-27
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein E ε4 (APOE ε4) is the main known genetic risk factor for Alzheimer's disease (AD). Some previous studies have reported structural brain changes as well as cognitive deficits in non-demented APOE ε4 carriers, but the pattern of results is inconsistent and studies with larger sample sizes have been called for. Here we compared hippocampal volume and recognition–memory performance between AD-symptom-free carriers (N = 30) and non-carriers (N = 30) of the APOE ε4 (age range: 49–79 years). We observed reduced right hippocampal volume in APOE ε4 carriers, and found that the difference was most pronounced before the age of 65. Further, the APOE ε4 carriers made significantly more false alarms in the recognition–memory test, and the number of false alarms correlated significantly with right hippocampus volume. These results indicate that relatively young individuals at genetic risk for AD have smaller hippocampal volume and lower performance on hippocampal-dependent cognitive tasks. A question for the future is whether smaller hippocampal volume represents early-onset hippocampal volume reduction or an inherent trait.
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| 5. |
- Maitland, Scott B., et al.
(författare)
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On the structure of personality : Are there separate temperament and character factors?
- 2009
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Ingår i: Personality and Individual Differences. - : Elsevier. - 0191-8869 .- 1873-3549. ; 47:3, s. 180-184
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Tidskriftsartikel (refereegranskat)abstract
- The Temperament and Character Inventory (TCI) is a widely used measure of psychobiological aspects of personality. Theoretically, the TCI is defined as comprising four temperament and three character factors. Most previous examinations of the factor structure have used exploratory factor methods with mixed results. We used confirmatory factor analyses (CFA) to examine the TCI in a sample of 2423 adults aged 35–90 years (1093 women, 1330 men) from the Betula study. Support for the seven TCI factors was mixed. Models including second-order factors provided no evidence that the seven first-order TCI factors reflect higher-order temperament and character constructs. Our findings provide no support that individual differences on the seven first-order TCI factors reflect distinct temperament or character dimensions of personality. Whereas more complex modeling strategies rejected separate character and temperament models, the simultaneous (seven-factor) model, and the use of second-order factors; the harm avoidance, self-directedness, and cooperativeness factors were acceptable examined individually. Results for novelty seeking were marginal and self-transcendence, reward dependence and/or persistence factors were not acceptable.
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| 6. |
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| 7. |
- Nilsson, Lars-Göran, et al.
(författare)
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Betula : a prospective cohort study on memory, health and aging
- 2004
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Ingår i: Aging, Neuropsychology and Cognition. - Hove : Psychology Press. - 1382-5585 .- 1744-4128. ; 11:2-3, s. 134-148
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Tidskriftsartikel (refereegranskat)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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| 8. |
- Nilsson, Lars-Göran, et al.
(författare)
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The influence of APOE status on episodic and semantic memory : data from a population-based study
- 2006
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Ingår i: Neuropsychology. - Washington : American Psychological Association. - 0894-4105 .- 1931-1559. ; 20:6, s. 645-57
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Tidskriftsartikel (refereegranskat)abstract
- In a prospective cohort study, the authors demonstrated a more pronounced epsilon4-related deficit for participants 70 years of age and older in tasks assessing episodic recall. Apolipoprotein E (APOE) and age interacted for episodic memory tasks, whereas the interaction for semantic memory tasks was between APOE and test wave. Heterozygotes of epsilon4 between middle-age and young-old participants performed at a higher level than noncarriers of this allele in recall tasks. A dose effect was found such that carriers of 2 epsilon4 alleles failed more profoundly in acquiring and recollecting episodic information than carriers of 1 epsilon4 allele, who in turn failed more than carriers of non-epsilon4 alleles. The pattern of findings observed for older epsilon4 carriers suggests that these individuals have particular difficulty when the executive task demands are high. Several factors (e.g., smaller hippocampal volumes, less effective neural repair mechanisms) may account for these findings. On the basis of the data obtained, the authors argue that analyses of the effect of specific genes in cognition should be accompanied by assessment of performance at a specific level, with due attention to the individual's age.
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| 9. |
- Olofsson, Jonas K., et al.
(författare)
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Long-term episodic memory decline is associated with olfactory deficits only in carriers of ApoE-є4
- 2016
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Ingår i: Neuropsychologia. - : Elsevier BV. - 0028-3932 .- 1873-3514. ; 85, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- The ɛ4 allele of the Apolipoprotein E gene is a genetic risk factor for late-onset dementia of the Alzheimers' type (DAT), which is characterized by loss of both episodic memoryand olfactory functions. Little is known about the possible role of ɛ4 in the association between ongoing episodic memory decline and olfactory deficits in the general population, but such information is relevant in determining the relevance of olfaction as a marker of DAT risk. The present study was based on a large, population-based sample (n=1087, aged 45–90 years, of which 324 were ɛ4-carriers). Episodic memory change rates were established using data collected every 5 years for a 10–20 year interval leading up to an olfactory assessment using the Scandinavian Odor Identification Test at the last wave of data collection. Participants were classified according to whether or not their episodic memory ability declined more rapidly than the age-typical norm (by >1SD). Our main result is that only in ɛ4-carriers was episodic memory decline associated with odor identification impairment. In individuals without ɛ4, odor identification was unrelated to episodic memory decline status. Follow-up analyses indicated that this moderation by ɛ4 was due to the olfactory nature of the identification test, and that the effect was not caused by 63 individuals with dementia. Our results suggest that the ɛ4 determines the functional association between ongoing episodic memory decline and olfaction. These findings are consistent with the notion that ɛ4-carriers with DAT, compared to non-carriers, display a cortical atrophy pattern that is more focused on mediotemporal lobe regions supporting olfactory and episodic memory functions. Olfactory and memory assessments might provide complementary information on mediotemporal atrophy prior to clinical dementia onset, but the ɛ4 should be considered when using olfactory assessment as an early-stage indicator.
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| 10. |
- Oudin, Anna, et al.
(författare)
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Traffic-Related Air Pollution and Dementia Incidence in Northern Sweden : A Longitudinal Study
- 2016
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 124:3, s. 306-312
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Exposure to ambient air pollution is suspected to cause cognitive effects, but a prospective cohort is needed to study exposure to air pollution at the home address and the incidence of dementia.OBJECTIVES: We aimed to assess the association between long-term exposure to traffic-related air pollution and dementia incidence in a major city in northern Sweden.METHODS: Data on dementia incidence over a 15-year period were obtained from the longitudinal Betula study. Traffic air pollution exposure was assessed with a Land Use Regression Model with a spatial resolution of 50 m x 50 m. Annual mean nitrogen oxide levels at the residential address of the participants at baseline (the start of follow-up) was used as a marker for long-term exposure to air pollution.RESULTS: Out of 1806 participants at baseline, 191 were diagnosed with Alzheimer's disease during follow-up, and 111 were diagnosed with vascular dementia. Participants in the highest exposure group were more likely to be diagnosed with dementia (Alzheimer's disease or vascular dementia), with a Hazard Ratio (HR) of 1.43 (95% Confidence Interval (CI): 0.998, 2.05 for the highest versus lowest quartile). The estimates were similar for Alzheimer's disease (HR 1.38) and vascular dementia (HR 1.47). The HR for dementia associated for the third quartile versus the lowest quartile was 1.48 (95% CI: 1.03, 2.11). A sub-analysis that excluded a younger sample that had been re-tested after only 5 years of follow-up suggested stronger associations with exposure than in the full cohort (HR = 1.71; 95% CI: 1.08, 2.73 for the highest versus lowest quartile).CONCLUSIONS: If the associations we observed are causal, then air pollution from traffic might be an important risk factor for vascular dementia and Alzheimer's disease.
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| 11. |
- Stomby, Andreas, et al.
(författare)
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Higher diurnal salivary cortisol levels are related to smaller prefrontal cortex surface area in elderly men and women
- 2016
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 175:2, s. 117-126
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Elevated cortisol levels with aging have been associated with atrophy of the hippocampus and prefrontal cortex (PFC), as well as with impaired cognitive functions in men. However, coexisting diseases have confounded many studies examining these relationships. Studies in women are lacking. Our objective was to test whether salivary cortisol levels were related to morphology of the hippocampus and the PFC, and to cognitive performance.Design: A cross-sectional study including 200 elderly (55-80 years old) men and women.Method: We used magnetic resonance imaging, tests of episodic-, semantic-, and working memory, visuospatial ability, and cortisol levels in four saliva samples collected during 1 day.Results: Area under the curve (AUC) for cortisol levels was negatively related to cortical surface area of the left anterior cingulate gyrus (caudal P < 0.001; rostral P = 0.006), right lateral orbitofrontal cortex (P = 0.004), and right rostral middle frontal gyrus (P = 0.003). In women, there was also a negative relationship with cortical surface area in the left rostral middle frontal gyrus (P = 0.006). No relationship was found between cortisol levels and hippocampal volume.Conclusion: This study suggests that the structure of the medial PFC is related to cortisol levels in both elderly women and men.
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| 12. |
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| 13. |
- Athanasiu, L., et al.
(författare)
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A genetic association study of CSMD1 and CSMD2 with cognitive function
- 2017
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Ingår i: Brain Behavior and Immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 61, s. 209-216
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Tidskriftsartikel (refereegranskat)abstract
- The complement cascade plays a role in synaptic pruning and synaptic plasticity, which seem to be involved in cognitive functions and psychiatric disorders. Genetic variants in the closely related CSMD1 and CSMD2 genes, which are implicated in complement regulation, are associated with schizophrenia. Since patients with schizophrenia often show cognitive impairments, we tested whether variants in CSMD1 and CSMD2 are also associated with cognitive functions per se. We took a discovery-replication approach, using well-characterized Scandinavian cohorts. A total of 1637 SNPs in CSMD1 and 206 SNPs in CSMD2 were tested for association with cognitive functions in the NCNG sample (Norwegian Cognitive NeuroGenetics; n = 670). Replication testing of SNPs with p-value < 0.001 (7 in CSMD1 and 3 in CSMD2) was carried out in the TOP sample (Thematically Organized Psychosis; n =1025) and the BETULA sample (Betula Longitudinal Study on aging, memory and dementia; n = 1742). Finally, we conducted a meta-analysis of these SNPs using all three samples. The previously identified schizophrenia marker in CSMD1 (SNP rs10503253) was also included. The strongest association was observed between the CSMDI SNP rs2740931 and performance in immediate episodic memory (p-value = 5 Chi 10(-6), minor allele A, MAF 0.48-0.49, negative direction of effect). This association reached the study-wide significance level (p <= 1.2 Chi 10(-5)). SNP rs10503253 was not significantly associated with cognitive functions in our samples. In conclusion, we studied n = 3437 individuals and found evidence that a variant in CSMD1 is associated with cognitive function. Additional studies of larger samples with cognitive phenotypes will be needed to further clarify the role of CSMD1 in cognitive phenotypes in health and disease. (C) 2016 The Authors. Published by Elsevier Inc.
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| 14. |
- Bergman, Olle, 1978, et al.
(författare)
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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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Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - : Elsevier. - 0278-5846 .- 1878-4216. ; 34:6, s. 1094-1097
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Tidskriftsartikel (refereegranskat)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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| 15. |
- Boraxbekk, Carl-Johan, 1980-, et al.
(författare)
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Free Recall Episodic Memory Performance Predicts Dementia Ten Years prior to Clinical Diagnosis : Findings from the Betula Longitudinal Study
- 2015
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Ingår i: Dementia and Geriatric Cognitive Disorders Extra. - : S. Karger AG. - 1664-5464. ; 5:2, s. 191-202
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Early dementia diagnosis is a considerable challenge. The present study examined the predictive value of cognitive performance for a future clinical diagnosis of late-onset Alzheimer's disease or vascular dementia in a random population sample. Methods: Cognitive performance was retrospectively compared between three groups of participants from the Betula longitudinal cohort. Group 1 developed dementia 11-22 years after baseline testing (n = 111) and group 2 after 1-10 years (n = 280); group 3 showed no deterioration towards dementia during the study period (n = 2,855). Multinomial logistic regression analysis was used to investigate the predictive value of tests reflecting episodic memory performance, semantic memory performance, visuospatial ability, and prospective memory performance. Results: Age-and education-corrected performance on two free recall episodic memory tests significantly predicted dementia 10 years prior to clinical diagnosis. Free recall performance also predicted dementia 11-22 years prior to diagnosis when controlling for education, but not when age was added to the model. Conclusion: The present results support the suggestion that two free recall-based tests of episodic memory function may be useful for detecting individuals at risk of developing dementia 10 years prior to clinical diagnosis.
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| 16. |
- Danielsson, Pär, 1958-, et al.
(författare)
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Different effect on axonal outgrowth of application of nonabsorbable or absorbable tubes around a nerve repair
- 2001
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Ingår i: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery. - : Informa UK Limited. - 1651-2073 .- 0284-4311. ; 35:4, s. 347-353
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Tidskriftsartikel (refereegranskat)abstract
- We studied regeneration distance of rat sciatic nerve, with the sensory pinch reflex test and immunocytochemical staining for neurofilaments, four to 21 days after transsection, repair, and enclosure of the repair site in either a non-absorbable silicone tube or an absorbable polyglycolic acid (PGA) tube. The size of both tube-types was carefully selected so that they did not compress the repaired nerve. The opposite nerve was repaired and not inserted in a tube (control). The regeneration distances in repaired nerves enclosed in silicone tube were significantly longer than the control side at all time points, a result not seen when PGA tube was used. The number of proliferating non-neuronal cells (incorporation of 5-bromodeoxyuridine (BrdU)) was studied just proximal to the site of nerve repair after six days. Numerous stained cells were seen, but there where no significant differences between the groups. We conclude that outgrowth of sensory axons after transsection and repair of rat sciatic nerve with sutures can be increased by enclosing the site of repair in a silicone tube but not in a PGA tube. The effect is probably not related to the number of proliferative non-neuronal cells.
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| 17. |
- de Frias, Cindy M., et al.
(författare)
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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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Ingår i: Journal of Cognitive Neuroscience. - : MIT Press - Journals. - 0898-929X .- 1530-8898. ; 17:7, s. 1018-1025
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Tidskriftsartikel (refereegranskat)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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| 18. |
- de Frias, Cindy M, et al.
(författare)
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Catechol O-methyltransferase Val158Met polymorphism is associated with cognitive performance in nondemented adults.
- 2005
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Ingår i: Journal of cognitive neuroscience. - Cambridge : MIT Press - Journals. - 0898-929X .- 1530-8898. ; 17:7, s. 1018-25
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Tidskriftsartikel (refereegranskat)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 Val158Met 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/Val genotype declined in executive functioning over the 5-year period, whereas carriers of the Met allele remained stable in performance. An Age x 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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| 19. |
- de Frias, Cindy M, et al.
(författare)
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COMT gene polymorphism is associated with declarative memory in adulthood and old age.
- 2004
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Ingår i: Behavior genetics. - New York : Kluwer Academic Publishers. - 0001-8244 .- 1573-3297. ; 34:5, s. 533-9
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Tidskriftsartikel (refereegranskat)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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| 20. |
- Degerman, Sofie, et al.
(författare)
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Maintained memory in aging is associated with young epigenetic age
- 2017
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Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 55, s. 167-171
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetic alterations during aging have been proposed to contribute to decline in physical and cognitive functions, and accelerated epigenetic aging has been associated with disease and all-cause mortality later in life. In this study, we estimated epigenetic age dynamics in groups with different memory trajectories (maintained high performance, average decline, and accelerated decline) over a 15-year period. Epigenetic (DNA-methylation [DNAm]) age was assessed, and delta age (DNAm age - chronological age) was calculated in blood samples at baseline (age: 55-65 years) and 15 years later in 52 age- and gender-matched individuals from the Betula study in Sweden. A lower delta DNAm age was observed for those with maintained memory functions compared with those with average (p = 0.035) or accelerated decline (p = 0.037). Moreover, separate analyses revealed that DNAm age at follow-up, but not chronologic age, was a significant predictor of dementia (p = 0.019). Our findings suggest that young epigenetic age contributes to maintained memory in aging.
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| 21. |
- Ekström, Ingrid, et al.
(författare)
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Smell Loss Predicts Mortality Risk Regardless of Dementia Conversion
- 2017
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Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 65:6, s. 1238-1243
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo determine whether dementia could explain the association between poor olfactory performance and mortality risk within a decade-long follow-up period.DesignProspective cohort study.SettingBetula Study, Umeå, Sweden.ParticipantsA population-based sample of adult participants without dementia at baseline aged 40 to 90 (N = 1,774).MeasurementsOlfactory performance using the Scandinavian Odor-Identification Test (SOIT) and self-reported olfactory function; several social, cognitive, and medical risk factors at baseline; and incident dementia during the following decade.ResultsWithin the 10-year follow-up, 411 of 1,774 (23.2%) participants had died. In a Cox model, the association between higher SOIT score and lower mortality was significant (hazard ratio (HR) = 0.74 per point interval, 95% confidence interval (CI) = 0.71-0.77, P < .001). The effect was attenuated, but remained significant, after controlling for age, sex, education, and health-related and cognitive variables (HR = 0.92, 95% CI = 0.87-0.97, P = .001). The association between SOIT score and mortality was retained after controlling for dementia conversion before death (HR = 0.92, 95% CI = 0.87-0.97, P = .001). Similar results were obtained for self-reported olfactory dysfunction.ConclusionPoor odor identification and poor self-reported olfactory function are associated with greater likelihood of future mortality. Dementia does not attenuate the association between olfactory loss and mortality, suggesting that olfactory loss might mark deteriorating health, irrespective of dementia.
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| 22. |
- Figueira, Joao, et al.
(författare)
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NMR analysis of the human saliva metabolome distinguishes dementia patients from matched controls
- 2016
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Ingår i: Molecular Biosystems. - : Royal Society of Chemistry (RSC). - 1742-206X .- 1742-2051. ; 12:8, s. 2562-2571
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Tidskriftsartikel (refereegranskat)abstract
- Saliva is a biofluid that is sensitive to metabolic changes and is straightforward to collect in a non-invasive manner, but it is seldom used for metabolite analysis when studying neurodegenerative disorders. We present a procedure for both an untargeted and targeted analysis of the saliva metabolome in which nuclear magnetic resonance (NMR) spectroscopy is used in combination with multivariate data analysis. The applicability of this approach is demonstrated on saliva samples selected from the 25 year prospective Betula study, including samples from dementia subjects with either Alzheimer's disease (AD) or vascular dementia at the time of sampling or who developed it by the next sampling/assessment occasion five years later, and age-, gender-, and education-matched control individuals without dementia. Statistically significant multivariate models were obtained that separated patients with dementia from controls and revealed seven discriminatory metabolites. Dementia patients showed significantly increased concentrations of acetic acid (fold change (fc) = 1.25, p = 2 x 10(-5)), histamine (fc = 1.26, p = 0.019), and propionate (fc = 1.35, p = 0.002), while significantly decreased levels were observed for dimethyl sulfone (fc = 0.81, p = 0.005), glycerol (fc = 0.79, p = 0.04), taurine (fc = 0.70, p = 0.007), and succinate (fc = 0.62, p = 0.008). Histamine, succinate, and taurine are known to be important in AD, and acetic acid and glycerol are involved in related pathways. Dimethyl sulfone and propionate originate from the diet and bacterial flora and might reflect poorer periodontal status in the dementia patients. For these seven metabolites, a weak but statistically significant pre-diagnostic value was observed. Taken together, we present a robust and general NMR analysis approach for studying the saliva metabolome that has potential use for screening and early detection of dementia.
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| 23. |
- Figueira, Joao, et al.
(författare)
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Serum Metabolite Markers of Dementia Through Quantitative NMR Analysis : The Importance of Threonine-Linked Metabolic Pathways
- 2019
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 69:3, s. 763-774
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Tidskriftsartikel (refereegranskat)abstract
- There is a great need for diagnostic biomarkers of impending dementia. Metabolite markers in blood have been investigated in several studies, but inconclusive findings encourage further investigation, particularly in the pre-diagnostic phase. In the present study, the serum metabolomes of 110 dementia or pre-diagnostic dementia individuals and 201 healthy individuals matched for age, gender, and education were analyzed by nuclear magnetic resonance spectroscopy in combination with multivariate data analysis. 58 metabolites were quantified in each of the 311 samples. Individuals with dementia were discriminated from controls using a panel of seven metabolites, while the pre-diagnostic dementia subjects were distinguished from controls using a separate set of seven metabolites, where threonine was a common significant metabolite in both panels. Metabolite and pathway alterations specific for dementia and pre-diagnostic dementia were identified, in particular a disturbed threonine catabolism at the pre-diagnostic stage that extends to several threonine-linked pathways at the dementia stage.
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| 24. |
- Hagg, S, et al.
(författare)
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Short telomere length is associated with impaired cognitive performance in European ancestry cohorts
- 2017
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 7:4, s. e1100-
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Tidskriftsartikel (refereegranskat)abstract
- The association between telomere length (TL) dynamics on cognitive performance over the life-course is not well understood. This study meta-analyses observational and causal associations between TL and six cognitive traits, with stratifications on APOE genotype, in a Mendelian Randomization (MR) framework. Twelve European cohorts (N=17 052; mean age=59.2±8.8 years) provided results for associations between qPCR-measured TL (T/S-ratio scale) and general cognitive function, mini-mental state exam (MMSE), processing speed by digit symbol substitution test (DSST), visuospatial functioning, memory and executive functioning (STROOP). In addition, a genetic risk score (GRS) for TL including seven known genetic variants for TL was calculated, and used in associations with cognitive traits as outcomes in all cohorts. Observational analyses showed that longer telomeres were associated with better scores on DSST (β=0.051 per s.d.-increase of TL; 95% confidence interval (CI): 0.024, 0.077; P=0.0002), and MMSE (β=0.025; 95% CI: 0.002, 0.047; P=0.03), and faster STROOP (β=−0.053; 95% CI: −0.087, −0.018; P=0.003). Effects for DSST were stronger in APOE ɛ4 non-carriers (β=0.081; 95% CI: 0.045, 0.117; P=1.0 × 10−5), whereas carriers performed better in STROOP (β=−0.074; 95% CI: −0.140, −0.009; P=0.03). Causal associations were found for STROOP only (β=−0.598 per s.d.-increase of TL; 95% CI: −1.125, −0.072; P=0.026), with a larger effect in ɛ4-carriers (β=−0.699; 95% CI: −1.330, −0.069; P=0.03). Two-sample replication analyses using CHARGE summary statistics showed causal effects between TL and general cognitive function and DSST, but not with STROOP. In conclusion, we suggest causal effects from longer TL on better cognitive performance, where APOE ɛ4-carriers might be at differential risk.
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| 25. |
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| 26. |
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| 27. |
- Husdal, Rebecka, et al.
(författare)
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Associations between quality of work features in primary health care and glycaemic control in people with Type 2 diabetes mellitus: A nationwide survey.
- 2019
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Ingår i: Primary care diabetes. - : Elsevier BV. - 1878-0210 .- 1751-9918. ; 13:2, s. 176-186
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Tidskriftsartikel (refereegranskat)abstract
- To describe and analyse the associations between primary health care centres' (PHCCs') quality of work (QOW) and individual HbA1c levels in people with Type 2 diabetes mellitus (T2DM).This cross-sectional study invited all 1152 Swedish PHCCs to answer a questionnaire addressing QOW conditions. Clinical, socio-economic and comorbidity data for 230,958 people with T2DM were linked to data on QOW conditions for 846 (73.4%) PHCCs.Of the participants, 56% had controlled (≤52mmol/mol), 31.9% intermediate (53-69mmol/mol), and 12.1% uncontrolled (≥70mmol/mol) HbA1c. An explanatory factor analysis identified seven QOW features. The features having a call-recall system, having individualized treatment plans, PHCCs' results always on the agenda, and having a follow-up strategy combined with taking responsibility of outcomes/results were associated with lower HbA1c levels in the controlled group (all p<0.05). For people with intermediate or uncontrolled HbA1c, having individualized treatment plans was the only QOW feature that was significantly associated with a lower HbA1c level (p<0.05).This nationwide study adds important knowledge regarding associations between QOW in real life clinical practice and HbA1c levels. PHCCs' QOW may mainly only benefit people with controlled HbA1c and more effective QOW strategies are needed to support people with uncontrolled HbA1c.
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| 28. |
- Husdal, Rebecka, et al.
(författare)
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Resource allocation and organisational features in Swedish primary diabetes care : Changes from 2006 to 2013
- 2017
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Ingår i: Primary Care Diabetes. - : Elsevier. - 1751-9918 .- 1878-0210. ; 11:1, s. 20-28
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To compare the resource allocation and organisational features in Swedish primary diabetes care for patients with type 2 diabetes mellitus (T2DM) between 2006 and 2013.Methods: Using a repeated cross-sectional study design, questionnaires covering personnel resources and organisational features for patients with T2DM in 2006 and 2013 were sent to all Swedish primary health care centres (PHCCs) during the following year. In total, 684 (74.3%) PHCCs responded in 2006 and 880 (76.4%) in 2013.Results: Compared with 2006, the median list size had decreased in 2013 (p<0.001), whereas the median number of listed patients with T2DM had increased (p<0.001). Time devoted to patients with T2DM and diabetes-specific education levels for registered nurses (RNs) had increased, and more PHCCs had in-house psychologists (all p<0.001). The use of follow-up systems and medical check-ups had increased (all p<0.05). Individual counselling was more often based on patients' needs, while arrangement of group-based education remained low. Patient participation in setting treatment targets mainly remained low.Conclusions: Even though the diabetes-specific educational level among RNs increased, the arrangement of group-based education and patient participation in setting treatment targets remained low. These results are of concern and should be prioritised as key features in the care of patients with T2DM. (C) 2016 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.
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| 29. |
- Husdal, Rebecka, et al.
(författare)
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Resources and organisation in primary health care are associated with HbA(1c) level : A nationwide study of 230 958 people with Type 2 diabetes mellitus
- 2018
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Ingår i: Primary Care Diabetes. - : Elsevier. - 1751-9918 .- 1878-0210. ; 12:1, s. 23-33
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To examine the association between personnel resources and organisational features of primary health care centres (PHCCs) and individual HbAic level in people with Type 2 diabetes mellitus (T2DM).Methods: People with T2DM attending 846 PHCCs (n =230 958) were included in this crosssectional study based on PHCC-level data from a questionnaire sent to PHCCs in 2013 and individual-level clinical data from 2013 for people with T2DM reported in the Swedish National Diabetes Register, linked to individual-level data on socio-economic status and comorbidities. Data were analysed using a generalized estimating equations linear regression models.Results: After adjusting for PHCC- and individual-level confounding factors, personnel resources associated with lower individual HbAi, level were mean credits of diabetes specific education among registered nurses (RNs) (-0.02 mmol/mol for each additional credit; P < 0.001) and length of regular visits to RNs (-0.19 mmol/mol for each additional 15 min; P < 0.001). Organisational features associated with HbAie level were having a diabetes team (-0.18 mmol/mol; P <0.01) and providing group education (-0.20 mmol/mol; P < 0.01).Conclusions: In this large sample, PHCC personnel resources and organisational features were associated with lower HbA(1c), level in people with T2DM.
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| 30. |
- Johansson, Lars-Åke, 1950, et al.
(författare)
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Bone Regeneration Using a Hollow Hydroxyapatite Space-Maintaining Device for Maxillary Sinus Floor Augmentation – A Clinical Pilot Study
- 2012
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Ingår i: Clinical implant dentistry and related research. - : Wiley. - 1708-8208 .- 1523-0899. ; 14:4, s. 575-584
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT Background: The mere lifting of the maxillary sinus membrane by implants protruding into the sinus cavity allows the establishment of a void space for blood clot and new bone formation. Purpose: To evaluate bone formation by using a spherical, hollow, and perforated hydroxyapatite space-maintaining device (HSMD) in a two-stage sinus lift procedure where residual alveolar bone height was
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| 31. |
- Josefsson, Maria, 1979-, et al.
(författare)
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Memory profiles predict dementia over 23–28 years in normal but not successful aging
- 2023
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Ingår i: International psychogeriatrics. - : Cambridge University Press. - 1041-6102 .- 1741-203X. ; 35:7, s. 351-359
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Prospective studies suggest that memory deficits are detectable decades before clinical symptoms of dementia emerge. However, individual differences in long-term memory trajectories prior to diagnosis need to be further elucidated. The aim of the current study was to investigate long-term dementia and mortality risk for individuals with different memory trajectory profiles in a well-characterized population-based sample.Methods: 1062 adults (aged 45–80 years) who were non-demented at baseline were followed over 23–28 years. Dementia and mortality risk were studied for three previously classified episodic memory trajectory groups: maintained high performance (Maintainers; 26%), average decline (Averages; 64%), and accelerated decline (Decliners; 12%), using multistate modeling to characterize individuals’ transitions from an initial non-demented state, possibly to a state of dementia and/or death.Results: The memory groups showed considerable intergroup variability in memory profiles, starting 10–15 years prior to dementia diagnosis, and prior to death. A strong relationship between memory trajectory group and dementia risk was found. Specifically, Decliners had more than a fourfold risk of developing dementia compared to Averages. In contrast, Maintainers had a 2.6 times decreased dementia risk compared to Averages, and in addition showed no detectable memory decline prior to dementia diagnosis. A similar pattern of association was found for the memory groups and mortality risk, although only among non-demented.Conclusion: There was a strong relationship between accelerated memory decline and dementia, further supporting the prognostic value of memory decline. The intergroup differences, however, suggest that mechanisms involved in successful memory aging may delay symptom onset.
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| 32. |
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| 33. |
- Kauppi, Karolina, et al.
(författare)
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Combined gene effects on hippocampal mnemonic processing : a large-scale imaging-genetics study of APOE, BDNF, KIBRA, and CLSTN2
- 2013
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Ingår i: Journal of cognitive neuroscience. - 0898-929X .- 1530-8898. ; 25:Suppl., s. S140-S141
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Twin studies have revealed that memory and relatedbrain functions are highly heritable traits, but putative candidate geneshave shown small and inconsistent effects -referred to as "the missing heritability". Little is known about the combined effect of several genes onbrain function: whether the presence of one "risk" variant hides the effect ofanother, interacts with it, or increases the risk in an additive -or even multiplicative -way. In a large fMRI sample we explored the combined effect ofpolymorphisms with documented impact on brain activation in the medialtemporal lobe (MTL) during episodic memory encoding or retrieval. Analyses of the effects of individual genes revealed decreased MTL activationfor ApoE £4 and BDNF Met alíeles during encoding, and for Kibra CCand the CLSTN2 T alíele during retrieval. Analyses of combined effectsrevealed that, during encoding, carriers of both the ApoE £4 and the BDNFMet alíele had lowest MTL activation, whereas non
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| 34. |
- Kauppi, Karolina, 1985-, et al.
(författare)
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Decreased medial temporal lobe activation in BDNF 66Met allele carriers during memory encoding
- 2013
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Ingår i: Neuropsychologia. - : Elsevier. - 0028-3932 .- 1873-3514. ; 51:12, s. 2462-2468
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Tidskriftsartikel (refereegranskat)abstract
- The Met allele of the Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with impaired activity-dependent secretion of BDNF protein and decreased memory performance. Results from imaging studies relating Val66Met to brain activation during memory processing have been inconsistent, with reports of both increased and decreased activation in the Medial Temporal Lobe (MTL) in Met carriers relative to Val homozygotes. Here, we extensively studied BDNF Val66Met in relation to brain activation and white matter integrity as well as memory performance in a large imaging (n=194) and behavioral (n=2229) sample, respectively. Functional magnetic resonance imaging (fMRI) was used to investigate MTL activation in healthy participants in the age of 55–75 years during a face-name episodic encoding and retrieval task. White matter integrity was measured using diffusion tensor imaging.BDNF Met allele carriers had significantly decreased activation in the MTL during encoding processes, but not during retrieval processes. In contrast to previous proposals, the effect was not modulated by age and the polymorphism was not related to white matter integrity. Met carriers had lower memory performance than Val homozygotes, but differences were subtle and not significant. In conclusion, the BDNF Met allele has a negative influence on MTL functioning, preferentially during encoding processes, which might translate into impaired episodic memory function.
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| 35. |
- Kauppi, Karolina, et al.
(författare)
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KIBRA polymorphism is related to enhanced memory and elevated hippocampal processing.
- 2011
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Ingår i: The Journal of neuroscience : the official journal of the Society for Neuroscience. - : Society for Neuroscience. - 1529-2401 .- 0270-6474. ; 31:40, s. 14218-22
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have linked the KIBRA rs17070145 T polymorphism to superior episodic memory in healthy humans. One study investigated the effect of KIBRA on brain activation patterns (Papassotiropoulos et al., 2006) and observed increased hippocampal activation in noncarriers of the T allele during retrieval. Noncarriers were interpreted to need more hippocampal activation to reach the same performance level as T carriers. Using large behavioral (N = 2230) and fMRI (N = 83) samples, we replicated the KIBRA effect on episodic memory performance, but found increased hippocampal activation in T carriers during episodic retrieval. There was no evidence of compensatory brain activation in noncarriers within the hippocampal region. In the main fMRI sample, T carriers performed better than noncarriers during scanning but, importantly, the difference in hippocampus activation remained after post hoc matching according to performance, sex, and age (N = 64). These findings link enhanced memory performance in KIBRA T allele carriers to elevated hippocampal functioning, rather than to neural compensation in noncarriers.
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| 36. |
- Larsson, Maria, et al.
(författare)
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Loss of Olfactory Function Predicts Mortality Irrespective of Dementia Conversion : 10-year follow-up of an age-varied sample
- 2016
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Ingår i: Chemical Senses. - : Oxford University Press (OUP). - 0379-864X .- 1464-3553. ; 41:9, s. e111-e288
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to examine the association between performance in odor identification and future mortality in a community cohort of adults aged between 40 and 90 years. We assessed olfactory performance with a 13-item-version of the Scandinavian Odor Identification Test (SOIT). The results showed that during follow-up (mean=9.4 years, standard deviation=2.23), 411 of 1774 (23.2%) participants died. In a Cox model, the association between higher SOIT score and mortality was highly significant (hazard ratio [HR]=0.74, per point interval, 95% confidence interval [CI]=0.71–0.77, p<0.001). The effect was attenuated, but remained significant after controlling for age, sex, education, and health and cognitive variables that were also associated with an increased risk of mortality (HR=0.92, 95% CI=0.87–0.97, p=0.001). Controlling for dementia conversion prior to death did not attenuate the association between SOIT score and mortality (HR=0.92, 95% CI=0.87–0.97, p=0.001). Similar results were obtained for olfactory sensitivity as assessed by self-report. Overall, the present findings show that poor odor identification performance is associated with an increased likelihood of future mortality in middle-aged and older adults, after controlling for social, cognitive, and medical risk factors. Most importantly, controlling for the development of dementia did not attenuate the association between odor identification and mortality, suggesting that olfactory decline might mark deteriorating health also irrespective of dementia.
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| 37. |
- Lind, Johanna, et al.
(författare)
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Parietal cortex activation predicts memory decline in apolipoprotein E-epsilon 4 carriers
- 2006
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Ingår i: NeuroReport. - Oxford : Rapid Communications of Oxford. - 0959-4965 .- 1473-558X. ; 17:16, s. 1683-1686
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein E-[varepsilon]4 is the main known genetic risk factor for Alzheimer's disease. Functional abnormalities in the parietal cortex have been reported for Alzheimer's disease patients and also for those at risk. Hence, a critical question is whether measurements of parietal cortex integrity may predict negative outcome among at-risk persons. We studied nondementedapolipoprotein E-[varepsilon]4 carriers and found a significant relationship between parietal blood-oxygen-level-dependent functional magnetic resonance imaging response during a word categorization task and subsequent episodic memory performance. Thus, the results show that parietal cortex alterations predict memory decline in nondemented apolipoprotein E-[varepsilon]4 carriers, and hence likely progression to Alzheimer's disease.
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| 38. |
- Lövdén, Martin, et al.
(författare)
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Studying Individual Aging in an Interindividual Context : Typical Paths of Age-Related, Dementia-Related, and Mortality-Related Cognitive Development in Old Age
- 2005
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Ingår i: Psychology and Aging. - Washington : American Psychological Association (APA). - 0882-7974 .- 1939-1498. ; 20:2, s. 303-316
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Tidskriftsartikel (refereegranskat)abstract
- This study has 2 objectives: (a) to explore typical paths of cognitive development associated with aging, terminal decline, and dementia and (b) to promote and illustrate an individual-oriented approach to the study of cognitive aging based on longitudinal panel data from a population-based sample (N = 500; age range-sub(T1)= 60-80, where T refers to time) tested at 3 occasions 5 years apart. Results document interindividual differences in multivariate patterns of change. Although cognitive changes generally covary, the present study indicates that subgroups of individuals develop along different paths characterized by selective changes in subsets of cognitive functions. Typical progression of dementia followed a developmental cascade from low declarative memory, via low functioning across all observed cognitive measures, to dementia diagnosis, and finally, death.
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| 39. |
- Melke, Jonas, 1971, et al.
(författare)
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A polymorphism in the serotonin receptor 3A (HTR3A) gene and its association with harm avoidance in women.
- 2003
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Ingår i: Archives of general psychiatry. - : American Medical Association (AMA). - 0003-990X. ; 60:10, s. 1017-23
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The brain neurotransmitter serotonin is known to affect various aspects of human behavior, including personality traits. Serotonin receptor type 3 is a ligand-gated channel encoded by 2 different subunit genes, HTR3A and HTR3B. A polymorphism (C178T) in the 5' region of the HTR3A gene has recently been identified and suggested to be of functional importance. OBJECTIVE: To elucidate the possible association between the C178T polymorphism in the HTR3A gene and personality traits in women. DESIGN: Two independent samples of 35- to 45-year-old Swedish women were recruited using the population register. Sample 1 (n = 195) was assessed via the Karolinska Scales of Personality and the Temperament and Character Inventory; sample 2 (n = 175) was assessed using the latter only. Both samples were genotyped with respect to the C178T polymorphism in the HTR3A gene. The A1596G polymorphism in the same gene was also investigated. RESULTS: A significant association between C178T genotype and the Temperament and Character Inventory factor harm avoidance was observed in sample 1 (corrected for multiple comparisons P =.04); this finding was subsequently replicated in sample 2 (P =.004) (pooled populations: P<.001). In the pooled sample, all harm avoidance subscales were found to be significantly associated with the C178T polymorphism: anticipatory worry (P =.001), fear of uncertainty (P<.001), shyness (P<.001), and fatigability and asthenia (P =.008). In addition, a significant association was found in sample 1 between the C178T polymorphism and the Karolinska Scales of Personality nonconformity factor (corrected P =.002), including the subscales of social desirability (P<.001), indirect aggression (P =.002), verbal aggression (P =.05), and irritability (P<.001). Participants homozygous for the less common T allele (<4%) differed from the remaining women by displaying lower ratings on harm avoidance and nonconformity. CONCLUSION: The C178T polymorphism in the HTR3A gene may affect the personality trait of harm avoidance in women.
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| 40. |
- Mousavi, Malahat, et al.
(författare)
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Serum metabolomic biomarkers of dementia
- 2014
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Ingår i: Dementia and Geriatric Cognitive Disorders Extra. - : S. Karger AG. - 1664-5464. ; 4:2, s. 252-62
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Tidskriftsartikel (refereegranskat)abstract
- Aims: This study compared serum metabolites of demented patients (Alzheimer's disease and vascular dementia) and controls, and explored serum metabolite profiles of nondemented individuals 5 years preceding the diagnosis. Methods: Cognitively healthy participants were followed up for 5-20 years. Cognitive assessment, serum sampling, and diagnosis were completed every 5 years. Multivariate analyses were conducted on the metabolite profiles generated by gas chromatography/time-of-flight mass spectrometry. Results: A significant group separation was found between demented patients and controls, and between incident cases and controls. Metabolites that contributed in both analyses were 3,4-dihydroxybutanoic acid, docosapentaenoic acid, and uric acid. Conclusions: Serum metabolite profiles are altered in demented patients, and detectable up to 5 years preceding the diagnosis. Blood sampling can make an important contribution to the early prediction of conversion to dementia.
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| 41. |
- Naghavi, Hamid Reza, et al.
(författare)
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Personality traits predict response to novel and familiar stimuli in the hippocampal region
- 2009
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Ingår i: Psychiatry Research. - : Elsevier. - 0165-1781 .- 1872-7123 .- 0925-4927 .- 1872-7506. ; 173:2, s. 94-99
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Tidskriftsartikel (refereegranskat)abstract
- Current evidence from genetic, neurochemical, and clinical research supports the notion that a combination of high novelty seeking and low harm avoidance traits (NS-ha) is reliably dissociable from the opposite personality profile (i.e., low novelty seeking and high harm avoidance, ns-HA). Little is known, however, about how the differences between these two types of personality are regulated by brain function. Here we used functional magnetic resonance imaging (fMRI) and recruited two groups of individuals, one group with the NS-ha profile and the other group with the ns-HA profile, to examine whether there is a difference between the two groups in their brain response to novel versus familiar word stimuli. Results revealed a differential pattern of response in an area in the hippocampal region, with the NS-ha group showing a greater sensitivity to novel stimuli and the ns-HA group demonstrating a greater response to familiar stimuli. We conclude that the response pattern to novel and familiar stimuli in the hippocampal region has a role in mediating differences between the NS-ha and ns-HA temperamental profiles.
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| 42. |
- Nyberg, Lars, 1966-, et al.
(författare)
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Biological and environmental predictors of heterogeneity in neurocognitive ageing : Evidence from Betula and other longitudinal studies
- 2020
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Ingår i: Ageing Research Reviews. - : Elsevier. - 1568-1637 .- 1872-9649. ; 64
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Forskningsöversikt (refereegranskat)abstract
- Individual differences in cognitive performance increase with advancing age, reflecting marked cognitive changes in some individuals along with little or no change in others. Genetic and lifestyle factors are assumed to influence cognitive performance in aging by affecting the magnitude and extent of age-related brain changes (i.e., brain maintenance or atrophy), as well as the ability to recruit compensatory processes. The purpose of this review is to present findings from the Betula study and other longitudinal studies, with a focus on clarifying the role of key biological and environmental factors assumed to underlie individual differences in brain and cognitive aging. We discuss the vital importance of sampling, analytic methods, consideration of non-ignorable dropout, and related issues for valid conclusions on factors that influence healthy neurocognitive aging.
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| 43. |
- Nyberg, Lars, 1966-, et al.
(författare)
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Elevated plasma neurofilament light in aging reflects brain white-matter alterations but does not predict cognitive decline or Alzheimer's disease
- 2020
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionWe investigated neurofilament light (NFL) accumulation in normal aging as well as in preclinical and clinical Alzheimer's disease (AD) and assessed individual differences in NFL load in relation to cognition and brain white-matter integrity. MethodsWe analyzed longitudinal data covering 30 years (1988-2017). Cognitive testing was done up to six times. Plasma NFL was quantified for controls and 142 cases who developed AD over time, and longitudinal changes in NFL were quantified for 100 individuals with three brain-imaging sessions. ResultsLongitudinal analyses revealed age-related NFL increases with marked variability. AD cases had elevated NFL levels, while no significant group differences were seen in the preclinical phase. Variability in NFL levels showed non-significant correlations with cognition but was associated with brain white matter. DiscussionOur findings suggest that elevated blood NFL, likely reflecting brain white-matter alterations, characterizes clinical AD, while NFL levels do not predict age-related cognitive impairment or impending AD.
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| 44. |
- Persson, Jonas, 1971-, et al.
(författare)
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Altered brain white matter integrity in healthy carriers of the APOE epsilon4 allele : A risk for AD?
- 2006
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 66, s. 1029-1033
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previous research has shown that polymorphisms of apolipoprotein E (APOE) represent genetic risk factors for dementia and for cognitive impairment in the elderly. The neural mechanisms by which these genetic variations influence behavioral performance or clinical severity are not well understood.METHODS: The authors used diffusion tensor imaging to investigate ultrastructural properties in brain white matter to detect pathologic processes that modify tissue integrity. Sixty participants were included in the study of which 30 were homozygous for the APOE epsilon3 allele, 10 were homozygous for the APOE epsilon4 allele, and 20 had the APOE epsilon34 allele combination. All individuals were non-demented, and the groups were matched on demographic variables and cognitive performance.RESULTS: The results showed a decline in fractional anisotropy, a marker for white matter integrity, in the posterior corpus callosum of epsilon4 carriers compared to non-carriers. Additional sites of altered white matter integrity included the medial temporal lobe.CONCLUSIONS: Although the mechanism underlying vulnerability of white matter tracts in APOE epsilon4 carriers is still unknown, these findings suggest that increased genetic risk for developing Alzheimer disease is associated with changes in microscopic white matter integrity well before the onset of dementia.
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| 45. |
- Persson, Jonas, et al.
(författare)
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Altered deactivation in individuals with genetic risk for Alzheimer's disease
- 2008
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Ingår i: Neuropsychologia. - : Elsevier BV. - 0028-3932 .- 1873-3514. ; 46:6, s. 1679-1687
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Tidskriftsartikel (refereegranskat)abstract
- Regions that show task-induced deactivations may be part of a default-mode network related to processes that are more engaged during passive than active task conditions. Alteration of task-induced deactivations with age and dementia is indicated by atypical engagement of default-mode network regions. Genetic studies show a relation between the apolipoprotein E4 (APOE4) allele and the common form of Alzheimer’s disease (AD), and altered functional brain activation has been observed in non-demented APOE4 carriers compared to non-carriers. Here we investigate the hypothesis of altered default-mode network brain responses in individuals with genetic risk for AD. Functional MRI was used to assess task-induced deactivation in 60 subjects of which 30 carried at least one copy of the APOE4 allele, and 30 non-carriers. Subjects were scanned while performing a semantic categorization task shown to promote episodic memory encoding. The results show patterns of deactivation consistent with the default-mode network. We also found reduced deactivation in non-demented APOE4 carriers compared to non-carriers, suggesting alterations in the default-mode network in the absence of dementia. These results implicate possibilities for investigatin altered properties of task-induced deactivations in individuals with genetic risk for AD, and may prove useful for pre-clinical identification of individuals susceptible to memory problems and AD.
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| 46. |
- Salami, Alireza, et al.
(författare)
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Association of APOE ɛ4 and Plasma p-tau181 with Preclinical Alzheimer’s Disease and Longitudinal Change in Hippocampus Function
- 2022
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 85:3, s. 1309-1320
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Apolipoprotein E (APOE) ɛ4 allele has been linked to increased tau phosphorylation and tangle formation. APOE ɛ4 carriers with elevated tau might be at the higher risk for Alzheimer’s disease (AD) progression. Previous studies showed that tau pathology begins early in areas of the medial temporal lobe. Similarly, APOE ɛ4 carriers showed altered hippocampal functional integrity. However, it remains unknown whether the influence of elevated tau accumulation on hippocampal functional changes would be more pronounced for APOE ɛ4 carriers.Objective: We related ɛ4 carriage to levels of plasma phosphorylated tau (p-tau181) up to 15 years prior to AD onset. Furthermore, elevated p-tau181 was explored in relation to longitudinal changes in hippocampal function and connectivity.Methods: Plasma p-tau181 was analyzed in 142 clinically defined AD cases and 126 matched controls. The longitudinal analysis involved 87 non-demented individuals (from population-based study) with two waves of plasma samples and three waves of functional magnetic resonance imaging during rest and memory encoding.Results: Increased p-tau181 was observed for both ɛ4 carriers and non-carriers close to AD onset, but exclusively for ɛ4 carriers in the early preclinical groups (7- and 13-years pre-AD). In ɛ4 carriers, longitudinal p-tau181 increase was paralleled by elevated local hippocampal connectivity at rest and subsequent reduction of hippocampus encoding-related activity.Conclusion: Our findings support an association of APOE ɛ4 and p-tau181 with preclinical AD and hippocampus functioning.
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| 47. |
- Sundström, Anna, 1969-, et al.
(författare)
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APOE influences on neurosychological function after mild head injury : within-person comparisons
- 2004
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Ingår i: Neurology. - Minneapolis, Minn : Lancet Publications Inc.. - 0028-3878 .- 1526-632X. ; 62:11, s. 1963-1966
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the relationship between neuropsychological outcome following mild head injury (MHI) and APOE genotype. Methods: Data from a population-based longitudinal study (n = 3,500) were used to identify 34 adults who experienced MHI during the course of the study. Their pre- and postinjury performances on a battery of nine neuropsychological tests were compared within person, and the postinjury performance was compared with that of age- and gender-matched control subjects. Results: The within-person comparisons showed that participants with at least oneAPOE ε4 allele (n = 11) had a significantly decreased postinjury performance on three of the tests, whereas the postinjury performance for APOE ε4-negative participants (n = 23) was unchanged. There was no significant difference in postinjury performance between participants with/without the ε4 allele, and neither group was impaired relative to controls. Conclusions: APOE genotype may influence the outcome following an MHI. Pre/postinjury within-person comparisons seem more sensitive than control group comparisons for detecting injury-related effects.
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| 48. |
- Sundström, Anna, 1969-, et al.
(författare)
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Fatigue before and after mild traumatic brain injury: Pre- and post-comparisons in relation to ApolipoproteinE
- 2007
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Ingår i: Brain Injury. - London : Informa UK Limited. - 0269-9052 .- 1362-301X. ; 21:10, s. 1049-1054
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Tidskriftsartikel (refereegranskat)abstract
- Primary objective: To assess the incidence of fatigue for persons following a mild traumatic brain injury (MTBI) and to evaluate the relationship between fatigue and APOE genotype. As fatigue is often found to be influenced by anxiety, depression and sleep disturbance, these factors were also measured. Methods and procedures: Thirty-one persons who sustained a MTBI were drawn from a population-based longitudinal study. Each person who sustained a MTBI was matched by age, gender, education and APOE genotype with two non-head injury controls. Self-reported pre- and post-injury incidence of fatigue, anxiety, depression and sleep disturbance was compared within-group and between groups. Results: For the MTBI group, incidence of fatigue was almost twice as common post- than pre-injury, whereas there was no corresponding change in a non-injured control group. Within the MTBI-group, post-injury fatigue was particularly common for carriers of the APOE ε4 allele. Conclusions: Fatigue is common sequela after a MTBI and especially pronounced for carriers of the APOE ε4 allele.
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| 49. |
- Sundström, Anna, et al.
(författare)
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Increased risk of dementia following mild head injury for carriers but not for non-carriers of the APOE ε4 allele.
- 2007
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Ingår i: International Psychgeriatrics. ; 19
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Background: The є4-allele of Apolipoprotein-E (APOE) and head injury are risk factors for dementia diseases, and these factors may act synergistically to further increase the risk. The aim of the present study was to examine the association between mild head injury, APOE, and dementia.Methods: Data were obtained from the Betula prospective population-based study of aging, memory, and health. The study included 543 participants in the age range 40-85 years, free of dementia at baseline, who were followed-up within a 5-year interval. Dementia was classified using the Diagnostic and Statistical Manual of Mental Disorders Criteria. Information of previous head injury was done through screening of the participants’ answers to health questionnaires both at baseline and at following test occasions.Results: We found that subjects with head injury but without APOE є4 had no increased risk of dementia. Subjects with APOE є4 had elevated risk and those with both APOE є4 and head injury had the highest risk (OR = 5.2).Conclusions: This study confirms that APOE ε4 constitutes a risk factor of dementia, that mild injury in isolation does not increase the risk, but that head injury in combination with the APOE ε4 lead to increased risk of dementia.
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| 50. |
- Sundström, Anna, 1969-, et al.
(författare)
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Increased risk of dementia following mild head injury for carriers but not for non-carriers of the APOE ε4 allele
- 2007
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Ingår i: International psychogeriatrics. - New York : Springer. - 1041-6102 .- 1741-203X. ; 19:1, s. 159-165
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Tidskriftsartikel (refereegranskat)abstract
- Background: The ε4 allele of apolipoprotein E (APOE) and head injury are risk factors for dementia diseases, and may act synergistically to further increase the risk. The aim of this study was to examine the association between mild head injury, APOE and dementia.Methods: Data were obtained from the Betula prospective population-based study of aging, memory, and health. The study included 543 participants in the age range 40–85 years, free of dementia at baseline, who were followed up within a 5-year interval. Dementia was classified using DSM-IV criteria. Information on previous head injury was obtained through screening of the participants' answers to health questionnaires at baseline and at follow-up.Results: Subjects with head injury but without APOE ε4 had no increased risk of dementia. Subjects with APOE ε4 had an increased risk and those with both APOE ε4 and head injury had the highest risk of dementia (odds ratio = 5.2).Conclusions: APOE ε4 constitutes a risk factor for dementia, mild injury in isolation does not increase the risk, but head injury in combination with the APOE ε4 leads to increased risk of dementia.
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