| 1. |
- de Frias, Cindy M., et al.
(författare)
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Cholesterol and triglycerides moderate the effect of apolipoprotein E on memory functioning in older adults.
- 2007
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Ingår i: Journal of Gerontology: Psychological Sciences. - Washington : The gerontological society of America. - 1079-5014 .- 1758-5368. ; 62B:2, s. P112-P118
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Tidskriftsartikel (refereegranskat)abstract
- We used data from the Betula Study to examine associations between total cholesterol, triglycerides, and apolipoprotein E on 10-year changes in cognitive performance. Tests assessing episodic memory (recall and recognition), semantic memory (knowledge and fluency), and visuospatial ability (block design) were administered to 524 nondemented adults (initial age of 55-80 years); multilevel modeling was applied to the data. Higher triglyceride levels were associated with a decline in verbal knowledge. Lipid levels moderated the influence of apolipoprotein E on episodic memory, such that among epsilon 4 allele carriers, decline in recognition was noted for individuals with higher cholesterol levels. Cholesterol and triglyceride levels are pharmacologically modifiable risk factors that account for variation In normal cognitive aging.
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| 2. |
- 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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| 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. |
- Massat, Isabelle, et al.
(författare)
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Positive association of dopamine D2 receptor polymorphism with bipolar affective disorder in a European Multicenter Association Study of affective disorders
- 2002
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Ingår i: American Journal of Medical Genetics. - : Wiley. - 0148-7299 .- 1096-8628. ; 114:2, s. 177-85
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Tidskriftsartikel (refereegranskat)abstract
- Convincing evidence for a genetic component in the etiology of affective disorders (AD), including bipolar affective disorder (BPAD) and unipolar affective disorder (UPAD), is supported by traditional and molecular genetic studies. Most arguments lead to the complex inheritance hypothesis, suggesting that the mode of inheritance is probably not Mendelian but most likely oligogenic (or polygenic) and that the contribution of genes could be moderate or weak. The purpose of the present European multicenter study (13 centers) was to test the potential role in BPAD and UPAD of two candidate dopaminergic markers, DRD2 and DRD3, using a case-control association design. The following samples were analyzed for DRD2: 358 BPAD/358 control (C) and 133 UPAD/ 133 C subjects, and for DRD3: 325 BPAD/ 325 C and 136 UPAD/136 C subjects. Patients and controls were individually matched for sex, age ( plus minus five years) and geographical origin. Evidence for significant association between BPAD and DRD2 emerged, with an over-representation of genotype 5-5 (P=0.004) and allele 5 (P=0.002) in BPAD cases compared to controls. No association was found for DRD2 in UPAD, and for DRD3 neither in BPAD or UPAD. Our results suggest that the DRD2 microsatellite may be in linkage disequilibrium with a nearby genetic variant involved in the susceptibility to BPAD. Our large European sample allowed for replicating of some previous reported positive findings obtained in other study populations.
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| 6. |
- Mendlewicz, Julien, et al.
(författare)
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Expanded RED products and loci containing CAG/CTG repeats on chromosome 17 (ERDA1) and chromosome 18 (CTG18.1) in trans-generational pairs with bipolar affective disorder
- 2004
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Ingår i: American Journal of Medical Genetics. - Hoboken : John Wiley & Sons. - 0148-7299 .- 1096-8628. ; 128B:1, s. 71-75
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the present study was to further test if expanded CAG repeats detected by the repeat expansion detection (RED) method in bipolar affective disorder (BPAD) are correlated with ERDA1 (17q21.3) and/or CTG18.1 (18q21.1) loci expansions, and changes of phenotype severity in successive generations (anticipation). The sample was designed to analyze ERDA1 and CTG18.1 expansions in trans-generational pairs of affected individuals (parent-offspring pairs: G1 and G2). Clinical and genetic information was available on 95 two-generations pairs. We found in our sample no one patient.
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| 7. |
- 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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| 8. |
- Sternäng, Ola, et al.
(författare)
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APOE and lipid level synergy effects on declarative memory functioning in adulthood
- 2009
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Ingår i: European Psychologist. - : Hogrefe Publishing Group. - 1016-9040 .- 1878-531X. ; 14:4, s. 268-278
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Tidskriftsartikel (refereegranskat)abstract
- This study of the general population examined interactions of the gene Apolipoprotein E (APOE) and/or lipid levels, and their effects on cognitive change. A MANCOVA model based on longitudinal data (with a 5 year follow-up) obtained from the Betula study (n = 1777; age 35–85 years) was used. The significant two-way and three-way interaction effects detected were equally frequent in tests of episodic and semantic memory. A difference in the distribution of interaction effects on episodic and semantic memory decline was also found. Men demonstrated the worst cognitive development as shown by significant two-way interaction effects on episodic memory whereas two-way interaction effects among women resulted in the worst semantic memory development. This result is discussed from the viewpoint that tests of episodic and semantic memory have different cognitive demands. This study focuses on how interaction effects of the gene APOE and vascular risk factors (such as lipid levels) affect cognitive abilities and also whether the interaction effects vary across age and sex. In this study, the main focus is on interaction effects as a phenomenon in itself.
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| 9. |
- 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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| 10. |
- 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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