| 61. |
- Fall, Tove, 1979-, et al.
(författare)
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Non-targeted metabolomics combined with genetic analyses identifies bile acid synthesis and phospholipid metabolism as being associated with incident type 2 diabetes
- 2016
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 59:10, s. 2114-2124
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesisIdentification of novel biomarkers for type 2 diabetes and their genetic determinants could lead to improved understanding of causal pathways and improve risk prediction.MethodsIn this study, we used data from non-targeted metabolomics performed using liquid chromatography coupled with tandem mass spectrometry in three Swedish cohorts (Uppsala Longitudinal Study of Adult Men [ULSAM], n = 1138; Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS], n = 970; TwinGene, n = 1630). Metabolites associated with impaired fasting glucose (IFG) and/or prevalent type 2 diabetes were assessed for associations with incident type 2 diabetes in the three cohorts followed by replication attempts in the Cooperative Health Research in the Region of Augsburg (KORA) S4 cohort (n = 855). Assessment of the association of metabolite-regulating genetic variants with type 2 diabetes was done using data from a meta-analysis of genome-wide association studies.ResultsOut of 5961 investigated metabolic features, 1120 were associated with prevalent type 2 diabetes and IFG and 70 were annotated to metabolites and replicated in the three cohorts. Fifteen metabolites were associated with incident type 2 diabetes in the four cohorts combined (358 events) following adjustment for age, sex, BMI, waist circumference and fasting glucose. Novel findings included associations of higher values of the bile acid deoxycholic acid and monoacylglyceride 18:2 and lower concentrations of cortisol with type 2 diabetes risk. However, adding metabolites to an existing risk score improved model fit only marginally. A genetic variant within the CYP7A1 locus, encoding the rate-limiting enzyme in bile acid synthesis, was found to be associated with lower concentrations of deoxycholic acid, higher concentrations of LDL-cholesterol and lower type 2 diabetes risk. Variants in or near SGPP1, GCKR and FADS1/2 were associated with diabetes-associated phospholipids and type 2 diabetes.Conclusions/interpretationWe found evidence that the metabolism of bile acids and phospholipids shares some common genetic origin with type 2 diabetes.Access to research materialsMetabolomics data have been deposited in the Metabolights database, with accession numbers MTBLS93 (TwinGene), MTBLS124 (ULSAM) and MTBLS90 (PIVUS).
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| 62. |
- Finkel, Deborah, et al.
(författare)
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Financial strain moderates genetic influences on self-reported health : Support for social compensation model
- 2018
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Konferensbidrag (refereegranskat)abstract
- The existence of genetic influences on both health and SES attainment suggests that GE interplay plays a role in SES-health associations. Adverse environments raise the risk of disease for everyone, but various models of GE interplay predict that some genotypes are more vulnerable to adversity than others (diathesis-stress), enriched environments prevent the expression of an underlying genetic vulnerability (social compensation), or genetic factors are minimized in adverse environments and maximized in favorable ones (social enhancement). Differential susceptibility models propose that specific genotypes might be more responsive to the social environment at both positive and negative extremes. Nine of the 15 twin studies of adult development and aging that are part of the IGEMS consortium included items assessing financial strain as well as subjective health, representing 10,756 individuals. The sample was 55% women, included 3185 MZ twins and 5228 DZ twins, and age ranged from 24 to 98. A factor model was used to create a harmonized measure of financial strain across studies and items: extent to which money covers needs, difficulty in paying monthly bills, economic situation compared to others, and whether there is money for extras. Twin analysis of genetic and environmental variance for self-rated health incorporating age and financial strain as continuous moderators and sex as a dichotomous moderator indicated significant financial strain moderation of genetic influences on self-rated health. Genetic variance increased as financial strain increased, matching the predictions of the diathesis-stress and social comparison models for components of variance.
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| 63. |
- Finkel, Deborah, et al.
(författare)
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Functional Aging Index Complements Frailty in Prediction of Entry into Care and Mortality.
- 2019
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press. - 1079-5006 .- 1758-535X. ; 74:12, s. 1980-1986
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim was to develop a functional aging index (FAI) that taps four body systems: sensory (vision and hearing), pulmonary, strength (grip strength), and movement/balance (gait speed) and to test the predictive value of FAI for entry into care and mortality.METHOD: Growth curve models and cox regression models were applied to data from 1695 individuals from three Swedish longitudinal studies of aging. Participants were aged 45 to 93 at intake and data from up to 8 follow-up waves were available.RESULTS: The rate of change in FAI was twice as fast after age 75 as before, women demonstrated higher mean FAI, but no sex differences in rates of change with chronological age were identified. FAI predicted entry into care and mortality, even when chronological age and a frailty index were included in the models. Hazard ratios indicated FAI was a more important predictor of entry into care for men than women; whereas it was a stronger predictor of mortality for men than women.CONCLUSIONS: Measures of biological aging and functional aging differ in their predictive value for entry into care and mortality for men and women, suggesting that both are necessary for a complete picture of the aging process across genders.
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| 64. |
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| 65. |
- Finkel, Deborah, et al.
(författare)
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Gender Differences in Longitudinal Trajectories of Change in Physical, Social, and Cognitive/Sedentary Leisure Activities
- 2018
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Ingår i: The journals of gerontology. Series B, Psychological sciences and social sciences. - : Oxford University Press. - 1079-5014 .- 1758-5368. ; 73:8, s. 1491-1500
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We examined changes in participation in cognitive, social, and physical leisure activities across middle and older adulthood and tested moderation of trajectories of change in participation by gender.Method: In all, 1,398 participants in the Swedish Adoption/Twin Study of Aging (SATSA) completed a 7-item leisure activity questionnaire up to 4 times over 17 years. Mean baseline age was 64.9 years (range = 36-91); 59% were women. Factor analysis identifed physical, social, and cognitive/sedentary leisure activity participation factors. Age-based latent growth curve models adjusted for marital status, gender, education, depressive symptoms, and physical health were used.Results: Overall, results indicated stability in social activities, increase in cognitive/sedentary activities, and decrease in physical activities, as well as accelerated decline in all three types of activities after about the age of 70 years. Social activity remained mostly stable for women and declined for men. Women reported higher levels of cognitive/sedentary leisure activity across the study. Both men and women declined in physical leisure activity. Variance in leisure activities increased with age; men demonstrated more variance in social activities and women in physical activities.Conclusions: Understanding change in leisure activities with age and by gender can have important implications for interventions and for use of leisure activity data in epidemiological research.
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| 66. |
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| 67. |
- Finkel, Deborah, et al.
(författare)
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Sex differences in genetic and environmental influences on longitudinal change in functional ability in late adulthood
- 2015
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Ingår i: The journals of gerontology. Series B, Psychological sciences and social sciences. - : Oxford University Press (OUP). - 1079-5014 .- 1758-5368. ; 70:5, s. 709-717
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To determine the extent to which genetic and environmental factors contribute to individual and gender differences in aging of functional ability.Method. Twenty assessments of functional ability are collected as part of the longitudinal Swedish Adoption/Twin Study of Aging from 859 twins aged 50–88 at the first wave. Participants completed up to 6 assessments covering a 19-year period. Factor analysis was used to create 3 factors: flexibility, fine motor skills, and balance.Results. Latent growth curve analysis demonstrated increasing disability and variability after age 70. For flexibility, results indicated significant sex differences in mean change trajectories but no sex differences in components of variance. No sex differences were found for fine motor movement. For balance, there were no sex differences in mean change trajectories; however, there was significant genetic variance for changes in balance in women after age 70 but not for men.Discussion. Although idiosyncratic environmental influences account for a large part of increasing variance, correlated and shared rearing environmental effects were also evident. Thus, both microenvironmental (individual) and macroenvironmental (family and cultural) effects, as well as genetic factors, affect maintenance of functional ability in late adulthood.
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| 68. |
- Finkel, Deborah, et al.
(författare)
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Temporal dynamics of motor functioning and cognitive aging
- 2016
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 71:1, s. 109-116
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Tidskriftsartikel (refereegranskat)abstract
- Background. Because of the possible implications for intervention and thus successful aging, researchers have striven to determine whether the age changes in physical and cognitive functioning are coincident or does functioning in one domain change before, and possibly contribute to, functioning in the other.Methods. Bivariate dual change score models were applied to four cognitive factors and three motor functioning factors available from 813 adults who participated in the Swedish Adoption/Twin Study of Aging. Participants were aged 50–88 at the first of six waves of testing covering a 19-year follow-up period; 68% participated in at least three waves.Results. Model comparisons indicated dynamic coupling relationships between Balance and Fine Motor factors and the Speed cognitive factor. Decline in motor function precedes decline in performance on processing speed tasks, even though the motor function tasks were not timed. Results indicated possible bidirectional coupling between Fine Motor and Speed.Conclusions. Combined with other dual change score model analyses of cognition and physical function, a picture is beginning to emerge of the cascade of events that may lead to cognitive aging.
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| 69. |
- Gerritsen, Lotte, et al.
(författare)
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Influence of Negative Life Events and Widowhood on Risk for Dementia
- 2017
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Ingår i: The American journal of geriatric psychiatry. - : Elsevier BV. - 1064-7481 .- 1545-7214. ; 25:7, s. 766-778
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of the current study was to examine the effect of negative life events and widowhood on the incidence of dementia. Methods: Data were from four Swedish longitudinal cohort studies with a total of nearly 2,000 participants and 8-25 years of follow-up. Seven stressful events were examined for which data were available in all cohorts. Clinical dementia diagnoses were made through medical and psychological examinations. Cox proportional hazards models were used to estimate the association between life events and dementia, adjusting for lifestyle and cardiovascular risk factors. Results: The experience of one stressful life event was not associated with dementia incidence, but two or more negative life events at baseline predicted higher risk for dementia (pooled HR:2.00). This was most apparent for the incidence of vascular dementia (pooled HR: 3.60) but not for Alzheimer disease (pooled HR: 1.29). Moreover, persons who were widowed and had experienced one or more negative life events were found to have a threefold risk for dementia. Conclusion: Widowhood augments the effect of negative life events on dementia incidence and negative life events specifically increase the risk for vascular dementia.
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| 70. |
- Hallgren, Jenny, 1978-, et al.
(författare)
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Cognitive trajectories in relation to hospitalization among older Swedish adults
- 2018
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Ingår i: Archives of gerontology and geriatrics (Print). - : Elsevier. - 0167-4943 .- 1872-6976. ; 74, s. 9-14
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionResearch indicate that cognitive impairment might be related to hospitalization, but little is known about these effects over time.ObjectiveTo assess cognitive change before and after hospitalization among older adults in a population-based longitudinal study with up to 25 years of follow-up.MethodA longitudinal study on 828 community living men and women aged 50–86 from the Swedish Adoption/Twin Study of Ageing (SATSA) were linked to The Swedish National Inpatient Register. Up to 8 assessments of cognitive performance (general cognitive ability, verbal, spatial/fluid, memory, and processing speed) from 1986 to 2010 were available. Latent growth curve modelling was used to assess the association between cognitive performance and hospitalization including spline models to analyse cognitive trajectories pre- and post-hospitalization.ResultsA total of 735 persons (89%) had at least one hospital admission during the follow-up. Mean age at first hospitalization was 70.2 (±9.3) years. Persons who were hospitalized exhibited a lower mean level of cognitive performance in general ability, processing speed and spatial/fluid ability compared with those who were not hospitalized. The two-slope models revealed steeper cognitive decline before hospitalization than after among those with at least one hospitalization event, as compared to non-hospitalized persons who showed steeper cognitive decline after the centering age of 70 years.ConclusionsPersons being hospitalized in late life have lower cognitive performance across all assessed domains. The results indicate that the main decline occurs before the hospitalization, and not after. This might indicate that when you get treatment you also benefit cognitively.
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