| 1. |
- 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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| 2. |
- 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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| 3. |
- Habib, Reza, et al.
(författare)
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Cognitive and non-cognitive factors contributing to the longitudinal identification of successful older adults in the Betula study.
- 2007
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Ingår i: Aging, Neuropsychology and Cognition.. - Lisse : Swets & Zeitlinger. ; 14:3, s. 257-273
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Tidskriftsartikel (refereegranskat)abstract
- Studies of successful aging have typically defined elderly who fall in the upper end of a distribution of test scores as successful. A different definition of successful aging requires that older adults fall at or above the mean level of younger adults and maintain this level over time. Here we examined this definition of successful aging in a sample of 1463 individuals between 50 to 85 years of age. Based on principal coordinate analysis of cognitive and non-cognitive variables, we identified a group of 55 (8.3%) 70-85 years olds that were high functioning. This group of elderly showed elevated performance on a range of cognitive tasks. Non-cognitive factors that characterized this group included education and subjective health. The participants were re-tested 5 years later and the same type of analysis was repeated. Of the remaining individuals who initially were classified as high functioning, 18 (35%) remained high functioning and thus met the definition for successful aging. Years of education was a significant predictor of who remained successful over time.
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| 4. |
- Hedner, Margareta, et al.
(författare)
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Age-Related Olfactory Decline is Associated with the BDNF Val66met Polymorphism : Evidence from a Population-Based Study
- 2010
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 2:7, s. 24-
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Tidskriftsartikel (refereegranskat)abstract
- The present study investigates the effect of the brain-derived neurotrophic factor (BDNF) val66met polymorphism on change in olfactory function in a large scale, longitudinal population-based sample (n = 836). The subjects were tested on a 13 item force-choice odor identification test on two test occasions over a 5-year-interval. Sex, education, health-related factors, and semantic ability were controlled for in the statistical analyses. Results showed an interaction effect of age and BDNF val66met on olfactory change, such that the magnitude of olfactory decline in the older age cohort (70–90years old at baseline) was larger for the val homozygote carriers than for the met carriers. The older met carriers did not display larger age-related decline in olfactory function compared to the younger group. The BDNF val66met polymorphism did not affect the rate of decline in the younger age cohort (45–65years). The findings are discussed in the light of the proposed roles of BDNF in neural development and maintenance.
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| 5. |
- Josefsson, Maria, 1979-, et al.
(författare)
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Genetic and Lifestyle Predictors of 15-Year Longitudinal Change in Episodic Memory
- 2012
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Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 60:12, s. 2308-2312
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To reveal distinct longitudinal trajectories in episodic memory over 15 years and to identify demographic, lifestyle, health-related, and genetic predictors of stability or decline. Design: Prospective cohort study. Setting: The Betula Project, Umeå, Sweden. Participants: One thousand nine hundred fifty-four healthy participants aged 35 to 85 at baseline. Measurements: Memory was assessed according to validated episodic memory tasks in participants from a large population-based sample. Data were analyzed using a random-effects pattern-mixture model that considered the effect of attrition over two to four longitudinal sessions. Logistic regression was used to determine significant predictors of stability or decline relative to average change in episodic memory. Results: Of 1,558 participants with two or more test sessions, 18% were classified as maintainers and 13% as decliners, and 68% showed age-typical average change. More educated and more physically active participants, women, and those living with someone were more likely to be classified as maintainers, as were carriers of the met allele of the catechol-O-methyltransferase gene. Less educated participants, those not active in the labor force, and men were more likely to be classified as decliners, and the apolipoprotein E ɛ4 allele was more frequent in decliners. Conclusion: Quantitative, attrition-corrected assessment of longitudinal changes in memory can reveal substantial heterogeneity in aging trajectories, and genetic and lifestyle factors predict such heterogeneity.
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| 6. |
- 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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| 7. |
- 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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| 8. |
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| 9. |
- Olofsson, Jonas K., et al.
(författare)
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Odor Identification Deficit as a Predictor of Five-Year Global Cognitive Change : Interactive Effects with Age and ApoE-ε4
- 2009
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Ingår i: Behavior Genetics. - : Springer Netherlands. - 0001-8244 .- 1573-3297. ; 39:5, s. 496-503
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Tidskriftsartikel (refereegranskat)abstract
- Olfactory impairments are present in common neurodegenerative disorders and predict conversion to dementia in non-demented individuals with cognitive impairment. In cognitively intact elderly, evidence is sparse regarding the role of olfactory deficits in predicting cognitive impairment. The present study investigated predictors of 5-year prospective decline in the Mini-Mental State Examination (MMSE) in a large (n = 501), population-based sample of elderly (65–90 years) individuals. All participants were genotyped for the ApoE gene, assessed for health factors, and were non-demented at the baseline assessment. After partialling out the influences of demographic and health-factors at baseline and dementia at follow-up, poor odor identification ability in combination with older age and the ApoE-ε4 allele predicted larger prospective global cognitive decline. This effect could not be produced by a vocabulary test. In sum, the findings suggest that an olfactory deficit can dissociate between benign and malign global cognitive development in non-demented, very old ε4-carriers, who are at high risk of developing dementia.
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| 10. |
- 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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