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- Bannon, Brittany L., et al.
(författare)
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Confirmatory factor analysis of illness behavior in the Swedish Adoption/Twin Study of Aging (SATSA)
- 2017
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Ingår i: Annals of Behavioral Medicine. - : Springer. - 0883-6612 .- 1532-4796. ; 51:Suppl. 1, s. S2654-S2655
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Tidskriftsartikel (refereegranskat)abstract
- Background: Illness behaviors—or affective, cognitive, and behavioral responses to symptoms of illness—predict patient outcomes, including symptom exacerbation and functional recovery, and they account for a large proportion of U.S. healthcare costs. Although priorcross-sectional work has examined illness behaviors like symptom reporting in isolation, the measurement of illness behavior using a longitudinal, multi-indicator approach has yet to be explored.Aim: We evaluated illness behavior as a latent, developmental construct in the Swedish Adoption/Twin Study of Aging (SATSA).Method: Participants were up to 1,886 individuals (from 1,223 twin pairs) ages 29 to 102 years (Mage baseline = 62.32 years; SD =13.69; 59% Female). Illness behavior indicators included somatic complaints, non-prescription medication use, pain-related disability and perceived illness complications. The psychomotor retardation subscale of the CES-D was used to index somatic complaints, and medication use was a simple composite of 9 dichotomous items on participants’ use of non-prescription medications, such as over-the-counter analgesics, in the previous month. Pain-related disability included a simple composite of three dichotomous items on the presence of neck,back, or shoulder pain that prevented participants from performing daily tasks or activities. Perceived illness disability was a composite of difference scores, calculated from subtracting a physician panel’s objective ratings of disability for each of 35 medical conditions (on a 3-pointscale; 1= Little or no disability; 3= Severe disability) from participants’ self-ratings of how much each of the same endorsed medical conditions interfered with their daily lives (on the same 3-point scale; 1= Not at all; 3= A lot). Positive composite scores reflected higher perceived disability relative to what was expected from the objective ratings, whereas a composite score of zero reflected “accuracy” or agreement in perceived illness complications. Confirmatory Factor Analysis (CFA) was used to evaluate invariance in the loadings of these four indicatorson a latent illness behavior factor across four questionnaire waves (1987-2004).Findings: Confirmatory factor analyses revealed moderate factor loadings of the four indicators (standardized loadings ranged from .49 to .52, all ps < .0001). Also, practical fit indices from the nested model comparisons suggested strong factorial invariance in the loadings across time (CFI = .96; TLI = .95, RMSEA= .03, 90% CI: [.026, .035]).Conclusion: Illness behavior as a latent, multi-indicator construct represents a promising focus for longitudinal work on behavior change and maintenance.
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| 4. |
- Hong, Mun-Gwan, et al.
(författare)
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Genome-wide and gene-based association implicates FRMD6 in Alzheimer disease
- 2012
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 33:3, s. 521-529
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) that allow for allelic heterogeneity may facilitate the discovery of novel genes not detectable by models that require replication of a single variant site. One strategy to accomplish this is to focus on genes rather than markers as units of association, and so potentially capture a spectrum of causal alleles that differ across populations. Here, we conducted a GWAS of Alzheimer disease (AD) in 2,586 Swedes and performed gene-based meta-analysis with three additional studies from France, Canada, and the United States, in total encompassing 4,259 cases and 8,284 controls. Implementing a newly designed gene-based algorithm, we identified two loci apart from the region around APOE that achieved study-wide significance in combined samples, the strongest finding being for FRMD6 on chromosome 14q (P = 2.6 × 10(-14)) and a weaker signal for NARS2 that is immediately adjacent to GAB2 on chromosome 11q (P = 7.8 × 10(-9)). Ontology-based pathway analyses revealed significant enrichment of genes involved in glycosylation. Results suggest that gene-based approaches that accommodate allelic heterogeneity in GWAS can provide a complementary avenue for gene discovery and may help to explain a portion of the missing heritability not detectable with single nucleotide polymorphisms (SNPs) derived from marker-specific meta-analysis.
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| 5. |
- Karlsson, Ida K., et al.
(författare)
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Apolipoprotein E ε4 genotype and the temporal relationship between depression and dementia
- 2015
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Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 36:4, s. 1751-1756
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Tidskriftsartikel (refereegranskat)abstract
- To investigate how apolipoprotein E (. APOE) affects the temporal relationship between depression and dementia, we conducted a nested case-control study with longitudinal depression and dementia evaluations from several population studies by using 804 dementia cases and 1600 matched controls, totaling 1519 unique individuals. Depression within 10 years of onset of dementia was strongly associated with dementia diagnosis regardless of APOE status (incidence rate ratio [IRR] 5.25, 95% confidence interval [95% CI] 3.32-8.31 for ε4 carriers, IRR 4.40, 95%CI 3.23-5.99 for noncarriers). However, we found a significant interaction between depression more than 10 years before the onset of dementia and APOE (. p= 0.01), with depression more distal to dementia being a risk factor only in ε4 carriers (IRR 3.39, 95% CI 1.69-6.78 for carriers, IRR 1.01, 95% CI 0.60-1.70 for noncarriers). Thus, depression with onset close in time to dementia onset is associated with disease irrespective of APOE genotype, whereas depression more distal to dementia onset is a risk factor only in ε4-carriers. This is the first study to show the interaction between APOE and depression to be dependent on timing of depression onset.
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| 6. |
- Mak, Jonathan K L, et al.
(författare)
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Genetic and environmental influences on longitudinal frailty trajectories from adulthood into old age.
- 2023
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1758-535X. ; 78:2
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Tidskriftsartikel (refereegranskat)abstract
- Frailty is a complex, dynamic geriatric condition, but limited evidence has shown how genes and environment may contribute to its longitudinal changes. We sought to investigate sources of individual differences in the longitudinal trajectories of frailty, considering potential selection bias when including a sample of oldest-old twins.Data were from two Swedish twin cohort studies: a younger cohort comprising 1,842 adults aged 29-96 years followed up to 15 waves, and an older cohort comprising 654 adults aged ≥79 years followed up to five waves. Frailty was measured using the frailty index (FI). Age-based latent growth curve models were used to examine longitudinal trajectories, and extended to a biometric analysis to decompose variability into genetic and environmental etiologies.A bilinear model with an inflection point at age 75 best described the data, indicating a four- to five-fold faster FI increase after 75 years. Twins from the older cohort had significantly higher mean FI at baseline but slower rate of increase afterwards. FI level at age 75 was moderately heritable in both men (42%) and women (55%). Genetic influences were relatively stable across age for men and increasing for women, although the most salient amplification in FI variability after age 75 was due to individual-specific environmental influences for both men and women; conclusions were largely consistent when excluding the older cohort.Increased heterogeneity of frailty in late life is mainly attributable to environmental influences, highlighting the importance of targeting environmental risk factors to mitigate frailty in older adults.
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| 7. |
- Beam, Christopher R., et al.
(författare)
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Estimating Likelihood of Dementia in the Absence of Diagnostic Data : A Latent Dementia Index in 10 Genetically Informed Studies
- 2022
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 90:3, s. 1187-1201
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Epidemiological research on dementia is hampered by differences across studies in how dementia is classified, especially where clinical diagnoses of dementia may not be available. OBJECTIVE: We apply structural equation modeling to estimate dementia likelihood across heterogeneous samples within a multi-study consortium and use the twin design of the sample to validate the results. METHODS: Using 10 twin studies, we implement a latent variable approach that aligns different tests available in each study to assess cognitive, memory, and functional ability. The model separates general cognitive ability from components indicative of dementia. We examine the validity of this continuous latent dementia index (LDI). We then identify cut-off points along the LDI distributions in each study and align them across studies to distinguish individuals with and without probable dementia. Finally, we validate the LDI by determining its heritability and estimating genetic and environmental correlations between the LDI and clinically diagnosed dementia where available. RESULTS: Results indicate that coordinated estimation of LDI across 10 studies has validity against clinically diagnosed dementia. The LDI can be fit to heterogeneous sets of memory, other cognitive, and functional ability variables to extract a score reflective of likelihood of dementia that can be interpreted similarly across studies despite diverse study designs and sampling characteristics. Finally, the same genetic sources of variance strongly contribute to both the LDI and clinical diagnosis. CONCLUSION: This latent dementia indicator approach may serve as a model for other research consortia confronted with similar data integration challenges.
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| 8. |
- 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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| 9. |
- 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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| 10. |
- Dahl, Anna, et al.
(författare)
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Being overweight in midlife is associated with lower cognitive ability and steeper cognitive decline in late life.
- 2010
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1758-535X .- 1079-5006. ; 65:1, s. 57-62
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although an increasing body of evidence links being overweight in midlife with an increased risk for dementia in late life, no studies have examined the association between being overweight in midlife and cognitive ability in late life. Our aim was to examine the association between being overweight in midlife as measured by body mass index (BMI) and cognitive ability assessed over time. METHODS: Participants in the Swedish Adoption/Twin Study Aging were derived from a population-based sample. The participants completed baseline surveys in 1963 or 1973 (mean age 41.6 years, range 25-63 years). The surveys included questions about height, weight, diseases, and lifestyle factors. Beginning in 1986, the same individuals were assessed on neuropsychological tests every 3 years (except in 1995) until 2002. During the study period, 781 individuals who were 50 years and older (60% women) had at least one complete neuropsychological assessment. A composite score of general cognitive ability was derived from the cognitive test battery for each measurement occasion. RESULTS: Latent growth curve models adjusted for twinness showed that persons with higher midlife BMI scores had significantly lower general cognitive ability and significantly steeper longitudinal decline than their thinner counterparts. The association did not change substantially when persons who developed dementia during the study period were excluded from the analysis. CONCLUSIONS: Higher midlife BMI scores precede lower general cognitive ability and steeper cognitive decline in both men and women. The association does not seem to be mediated by an increased risk for dementia.
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