| 1. |
- Pedersen, N. L., et al.
(författare)
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IGEMS: The Consortium on Interplay of Genes and Environment Across Multiple Studies
- 2013
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Ingår i: Twin Research and Human Genetics. - : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 16:1, s. 481-489
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Tidskriftsartikel (refereegranskat)abstract
- The Interplay of Genes and Environment across Multiple Studies (IGEMS) group is a consortium of eight longitudinal twin studies established to explore the nature of social context effects and gene-environment interplay in late-life functioning. The resulting analysis of the combined data from over 17,500 participants aged 25–102 at baseline (including nearly 2,600 monogygotic and 4,300 dizygotic twin pairs and over 1,700 family members) aims to understand why early life adversity, and social factors such as isolation and loneliness, are associated with diverse outcomes including mortality, physical functioning (health, functional ability), and psychological functioning (well-being, cognition), particularly in later life.
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| 2. |
- Jansson, M, et al.
(författare)
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Gender differences in heritability of depressive symptoms in the elderly
- 2004
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Ingår i: PSYCHOLOGICAL MEDICINE. - 0033-2917 .- 1469-8978. ; 34:3, s. 471-479
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The present study aimed to investigate the relative importance of genetic and environmental influences on depressive symptoms in the elderly. METHOD: Depressive symptoms were assessed through the Center for Epidemiological Studies-Depression (CES-D) scale. The CES-D scale was administered to 959 twin pairs (123 female MZs, 90 male MZs, 207 same-sex female DZs, 109 same-sex male DZs and 430 opposite-sex DZs) aged 50 years or older (mean age 72 years). A dichotomous depressed state variable was constructed based on CES-D cut-offs and self-reported use of antidepressant medication. Structural equation models were fitted to the data to dissect genetic and environmental variance components. RESULTS: The sex-specific heritability estimates for depressive symptoms were 14% for males and 29% for females and 23% when constrained to be equal for men and women. The prevalence of clinically significant depressive symptoms was 16% for men and 24% for women. Heritability estimates for the dichotomous depressed state measure were 7% for males and 49% for females in the full model and 33% when constrained to be equal. CONCLUSION: Our results suggest that depressive symptoms in the elderly are moderately heritable, with a higher heritability for women than men, although differences in heritability estimates were not statistically significant.
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| 3. |
- Andel, R, et al.
(författare)
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Physical exercise at midlife and risk of dementia three decades later: a population-based study of Swedish twins.
- 2008
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Ingår i: J Gerontol A Biol Sci Med Sci. ; 63:1, s. 62-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: With the number of people with dementia increasing, identifying potential protective factors has become more important. We explored the association between physical exercise at midlife and subsequent risk of dementia among members of the HARMONY study. METHODS: Measures of exercise were obtained by the Swedish Twin Registry an average of 31 years prior to dementia assessment. Dementia was diagnosed using a two-stage procedure--screening for cognitive impairment followed by full clinical evaluation. We used two study designs: case-control analyses included 264 cases with dementia (176 had Alzheimer's disease) and 2870 controls; co-twin control analyses included 90 twin pairs discordant for dementia. RESULTS: In case-control analyses, controlling for age, sex, education, diet (eating fruits and vegetables), smoking, drinking alcohol, body mass index, and angina, light exercise such as gardening or walking and regular exercise involving sports were associated with reduced odds of dementia compared to hardly any exercise (odds ratio [OR] = 0.63, 95% confidence interval [CI], 0.43-0.91 for light exercise; OR = 0.34, 95% CI, 0.16-0.72 for regular exercise). Findings were similar for Alzheimer's disease alone. In co-twin control analyses, controlling for education, the association between higher levels of exercise and lower odds of dementia approached significance (OR = 0.50, 95% CI, 0.23-1.06; p =.072). CONCLUSIONS: Exercise at midlife may reduce the odds of dementia in older adulthood, suggesting that exercise interventions should be explored as a potential strategy for delaying disease onset
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| 4. |
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| 5. |
- Gatz, M, et al.
(författare)
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Accounting for the relationship between low education and dementia: a twin study.
- 2007
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Ingår i: Physiol Behav. ; , s. 232-237
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated whether the association between low education and greater risk of dementia is explained by genetic influences, using three different types of analyses. The HARMONY study (Swedish for "health" (Hälsa), "genes" (ARv), "environment" (Miljö), "and" (Och), and "new" (NY)) includes members of the Swedish Twin Registry who were aged 65 and older and alive in 1998, and who were screened and clinically assessed for dementia. There were 394 cases with dementia and 7786 unrelated controls. Analyses included co-twin control, tests for association between education and a measured genotype, and bivariate twin modeling. Low education was a significant risk factor for dementia both in case-control analyses (odds ratio=1.77, 95% confidence interval 1.38 to 2.28) and co-twin control analyses with monozygotic twin pairs (odds ratio=3.17, 95% confidence interval 1.26 to 7.93). Apolipoprotein E genotype was not associated with education and did not account for the relationship between education and dementia. Bivariate twin modeling showed that the association between education and dementia was not mediated by genetic influences in common between education and dementia. The association was mediated by shared environmental influences that were related to both dementia and to education. Low education is confirmed as a risk factor for dementia. Findings from three different analytic approaches showed that genetic influences did not explain this association.
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| 6. |
- Johansson, Boo, et al.
(författare)
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Complexity of work and risk of Alzheimer's disease: a population-based study of Swedish twins.
- 2005
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Ingår i: J Gerontology: Psychological Science. ; , s. 251-8
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Tidskriftsartikel (refereegranskat)abstract
- We examined the association between risk of dementia or Alzheimer's disease (AD) and occupation by using measures of complexity of work with data, people, and things. The study included 10,079 members of the population-based Swedish Twin Registry who were participants in the HARMONY study. We diagnosed dementia by means of a two-stage procedure--cognitive impairment screening fol-lowed by full clinical evaluation. We analyzed data with case-control and cotwin control designs. The cotwin control design provides control over genetic and fa-milial factors. In the case-control study, controlling for age, gender, and level of education, we found that more complex work with people was associated with re-duced risk of AD. Greater complexity of work with people and data was protective in twin pairs discordant for AD. Findings suggest that greater complexity of work, and particularly complex work with people, may reduce the risk of AD.
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| 7. |
- Bennet, Anna M, et al.
(författare)
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Genetic association of sequence variants near AGER/NOTCH4 and dementia.
- 2011
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 24:3, s. 475-84
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Tidskriftsartikel (refereegranskat)abstract
- We performed a survey of sequence variation in a series of 20 genes involved in inflammation-related pathways for association with dementia risk in twin and unrelated case-control samples consisting in total of 1462 Swedish dementia casesand 1929 controls. For a total of 218 tested genetic markers, strong evidence was obtained implicating a region near AGER and NOTCH4 on chromosome 6p with replication across both samples and maximum combined significance at marker rs1800625 (OR = 1.37, 95% CI 1.19–1.56, p = 1.36×10(–6)). Imputation of the associated genomic interval provided an improved signal atrs8365, near the 3UTR of AGER (p = 7.34×10(–7)). The associated region extends 120 kb encompassing 11 candidate genes.While AGER encodes a key receptor for amyloid-β protein, an analysis of network context based upon genes now confirmed to contribute to dementia risk (AβPP, PSEN1, PSEN2, CR1, CLU, PICALM, and APOE) suggested strong functional coupling to NOTCH4, with no significant coupling to the remaining candidates. The implicated region occurs in the broad HLA locus on chromosome 6p, but associated markers were not in strong LD with known variants that regulate HLA gene function, suggesting that this may represent a signal distinct from immune-system pathways.
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| 8. |
- Bennet, Anna M, et al.
(författare)
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Pleiotropy in the Presence of Allelic Heterogeneity: Alternative Genetic Models for the Influence of APOE on Serum LDL, CSF Amyloid-β42, and Dementia.
- 2010
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 22:1, s. 129-134
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Tidskriftsartikel (refereegranskat)abstract
- The two genetic polymorphisms, rs7412 and rs429358, that collectively form the ε2, ε3, and ε4 alleles of apolipoprotein E (APOE) are among the most widely studied sequence variants in the genome. The predominant model for testing APOE involves the haplotype combinations of ε2, ε3, and ε4 and has been basis of associations with dementia, atherosclerosis, and serum lipid levels. Here, we demonstrate the functional independence of these two component sites, with rs7412 contributing to the majority of variance in serum LDL (p=10-20), whereas rs429358 alone influences variance in CSF amyloid-β42 (Aβ42) (p=10-17). This latter relationship is also reflected in the association of APOE with dementia, where rs429358 strongly influences disease (p=10-67), but rs7412 does not. Models based upon ε2, ε3, and ε4 explained less variance for both dementia risk and CSF Aβ42 than did rs429358 alone. When adjusted for CSF Aβ42, the association of rs429358 with dementia is greatly reduced but remains significant indicating that APOE polymorphism influences disease by additional mechanisms distinct from Aβ42 metabolism. We reach four principal conclusion from this study: 1) rs429358 alone is responsible for the association of APOE with dementia; 2) The association of APOE with dementia is substantially mediated by its effect on CNS Aβ42 levels; 3) The association of APOE with dementia is not mediated by its impact on peripheral lipid metabolism; and 4) The dichotomy of effects of rs429358 and rs7412 represents one of the best examples of genetic pleiotropy for complex traits known and illustrates the importance of allelic heterogeneity in APOE.
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| 9. |
- Dahl, Anna, et al.
(författare)
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BODY MASS INDEX IN EARLY AND LATE MIDLIFE AND COGNITIVE ABILITIES IN LATE LIFE
- 2011
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Ingår i: Gerontologist. - : Oxford University Press (OUP). - 0016-9013. ; 51:Supplement 2
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Konferensbidrag (refereegranskat)abstract
- The aims of this study were to study the association between early and late midlife body mass index (BMI), change in BMI, and late life cognitive abilities in a dementia free sample. BMI was calculated from self-reported height and weight in early midlife (mean age 39.9 years, range 25-50) (1963 or 1973) and from assessed weight and height in late midlife (mean age 61.1 years, range 50-75). Starting in 1986 participants were assessed five times at three year intervals on a cognitive test battery in the longitudinal Swedish doption/Twin Study of Aging (N=657). Latent growth curve models, adjusting for pairness, showed that persons with higher BMI in early midlife had significantly lower cognitive performance across domains in late life. Moreover, obesity was significantly associated with a steeper decline in perceptual speed and non-significantly associated with steeper decline in verbal and spatial abilities. Both being underweight and overweight/obese in late life were associated with an increased risk of lower cognitive abilities across domains. However, when decline in BMI was controlled for, underweight in late midlife was no longer associated with lower cognitive ability in any domain. Further, being underweight across midlife, and weight loss between early and late midlife, were each associated with lower mean level cognitive abilities in late life (centered at age 65). In conclusion, several different weight patterns were associated with lower cognitive abilities in late life. Weight patterns may be an important clue to understand the association between weight and cognitive health in late life.
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| 10. |
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