| 31. |
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| 32. |
- Hefling, L A, et al.
(författare)
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Cancer as a risk factor for long-term cognitive deficits and dementia.
- 2005
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 97:11, s. 854-856
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have shown that cancer survivors frequently experience short-term cognitive deficits, but it is unknown how long these deficits last or whether they worsen over time. Using a co-twin control design, the cognitive function of 702 cancer survivors aged 65 years and older was compared with that of their cancer-free twins. Dementia rates were also compared in 486 of the twin pairs discordant for cancer. Cancer survivors overall, as well as individuals who had survived cancer for 5 or more years before cognitive testing, were more likely than their co-twins to have cognitive dysfunction (odds ratio [OR] = 2.10, 95% confidence interval [CI] = 1.36 to 3.24; P<.001; and OR = 2.71, 95% CI = 1.47 to 5.01; P<.001, respectively). Cancer survivors were also twice as likely to be diag-nosed with dementia as their co-twins, but this odds ratio did not reach statisti-cal significance (OR = 2.0, 95% CI = 0.86 to 4.67; P = .10). These results suggest that cancer patients are at increased risk for long-term cognitive dysfunction compared with individuals who have never had cancer, even after controlling for the influence of genetic factors and rearing environment.
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| 33. |
- Hernandez, Raymond, et al.
(författare)
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Visual-Motor Integration (VMI) Is Also Relevant for Computer, Smartphone, and Tablet Use by Adults : Introducing the Brief Box Clicking Test
- 2024
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Ingår i: American Journal of Occupational Therapy. - : American Occupational Therapy Association. - 0272-9490 .- 1943-7676. ; 78:5
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Visual-motor integration (VMI) is typically examined in children to promote handwriting, but it may also be relevant for adults' capacity for technology use.OBJECTIVE: To examine the reliability and validity of speed of completion of the box clicking test, a web-based test of VMI.DESIGN: Participants in the Understanding America Study completed online surveys on a regular basis, including a very brief (less than 30 s) self-administered box clicking test. For validity testing, we examined whether box clicking speed was associated with constructs relevant to visual-perceptual skills and motor coordination, the skills underlying VMI. Test-retest reliability was examined by computation of intraclass correlation coefficients.PARTICIPANTS: A total of 11,114 adults. MEASURES: Measures included the completion time for the box clicking task and measures relevant to visual perception (e.g., perceptual speed) and motor coordination (e.g., self-reported functional limitation).RESULTS: Results suggested that the box clicking test was a VMI task. Slower test performance was associated with lower visual-perceptual speed and a greater likelihood of reporting difficulties with dressing, a motor coordination relevant task. Box clicking tests taken within at least 2 yr of one another had moderate test-retest stability, but future studies are needed to examine test-retest reliabilities over brief (e.g., 2-wk) time intervals.CONCLUSIONS AND RELEVANCE: The box clicking test may serve both as a tool for research and to clinically observe whether clients have VMI difficulties that interfere with computer, smartphone, or tablet use.Plain-Language Summary: Use of devices such as smartphones and computers is increasingly becoming integral for daily functioning. Visual-motor integration (VMI) has often been addressed by occupational therapists to support handwriting of children, but it may also be important for technology use by adults. Prior literature supports the relevance of VMI to technology use, and adults with various chronic conditions have been found to have decrements in VMI. We tested the psychometric properties of a brief box clicking test of VMI that could be used to examine VMI underlying technology use among adults. Overall, results suggested that the box clicking test was a VMI task. Just as speed of gait has been used as an index of functional mobility, speed on the box clicking task seemed serviceable as an index of VMI ability. The box clicking test may also be used for clinical observation of whether VMI interferes with technology use.
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| 34. |
- Hong, Mun-Gwan, et al.
(författare)
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Evidence that the gene encoding insulin degrading enzyme influences human lifespan.
- 2008
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 17:15, s. 2370-8
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Tidskriftsartikel (refereegranskat)abstract
- Studies in model organisms have demonstrated that components of insulin and insulin-like signaling pathways are involved in the regulation of lifespan but the relevance of those findings to humans has remained obscure. Here we provide evidence suggesting that variants of the gene encoding insulin-degrading enzyme (IDE) may be influencing human lifespan. We have employed a variety of models and diverse samples that reproducibly indicate the relative change in IDE genotype frequency across the age spectrum as well as allow the detection of association with age-at-death. A tenable molecular basis of this is suggested by the observation of genetic association with both fasting plasma insulin levels and IDE mRNA expression. Across populations the emergent genetic model is indicative of over-dominance, where heterozygotes of critical markers have increased IDE mRNA expression and insulin levels, and this is reflected in diminished heterozygosity at advanced age. A critical and replicating feature of this study is that change in IDE genotype frequency with advancing age appears to be occurring only in men, and this is supported in that insulin levels are only associated with IDE in men. Results suggest a relationship between a gene that is intimately involved in insulin metabolism and the determination of lifespan in humans, but over-dominance and gender specificity will be important parameters to consider clarifying the biological importance of these findings.
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| 35. |
- Hughes, Tiffany F, et al.
(författare)
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Midlife fruit and vegetable consumption and risk of dementia in later life in Swedish twins.
- 2010
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Ingår i: The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. - 1545-7214 .- 1064-7481. ; 18:5, s. 413-20
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Diet may be associated with risk of dementia and Alzheimer disease (AD). The authors examined the association between fruit and vegetable consumption in midlife and risk for all types of dementia and AD. METHODS: Participants were 3,779 members of the Swedish Twin Registry who completed a diet questionnaire approximately 30 years before cognitive screening and full clinical evaluation for dementia as part of the study of dementia in Swedish Twins (HARMONY) study. Among the participants, 355 twins were diagnosed with dementia. Among these, 81 twin pairs were discordant for dementia (50 discordant for AD). Data were analyzed with logistic regression for the entire sample using generalized estimating equations to adjust for relatedness of twins and with conditional logistic regression for the co-twin control design. RESULTS: In fully adjusted models, a medium or great proportion of fruits and vegetables in the diet, compared with no or small, was associated with a decreased risk of dementia and AD. This effect was observed among women and those with angina. Similar, but nonsignificant, odds ratios were found in the co-twin control analyses. CONCLUSION: The findings suggest that higher fruit and vegetable consumption may reduce the risk of dementia, especially among women and those with angina pectoris in midlife.
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| 36. |
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| 37. |
- Jelenkovic, Aline, et al.
(författare)
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Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age : A Study of the CODATwins Project
- 2015
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Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:5, s. 557-570
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Tidskriftsartikel (refereegranskat)abstract
- A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m(2) in childhood and adolescence and up to 0.2 kg/m(2) in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
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| 38. |
- Karlsson, Ida K., et al.
(författare)
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Adiposity and the risk of dementia : mediating effects from inflammation and lipid levels
- 2022
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Ingår i: European Journal of Epidemiology. - : Springer Nature Switzerland AG.. - 0393-2990 .- 1573-7284. ; 37:12, s. 1261-1271
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Tidskriftsartikel (refereegranskat)abstract
- While midlife adiposity is a risk factor for dementia, adiposity in late-life appears to be associated with lower risk. What drives the associations is poorly understood, especially the inverse association in late-life. Using results from genome-wide association studies, we identified inflammation and lipid metabolism as biological pathways involved in both adiposity and dementia. To test if these factors mediate the effect of midlife and/or late-life adiposity on dementia, we then used cohort data from the Swedish Twin Registry, with measures of adiposity and potential mediators taken in midlife (age 40–64, n = 5999) or late-life (age 65–90, n = 7257). Associations between body-mass index (BMI), waist-hip ratio (WHR), C-reactive protein (CRP), lipid levels, and dementia were tested in survival and mediation analyses. Age was used as the underlying time scale, and sex and education included as covariates in all models. Fasting status was included as a covariate in models of lipids. One standard deviation (SD) higher WHR in midlife was associated with 25% (95% CI 2–52%) higher dementia risk, with slight attenuation when adjusting for BMI. No evidence of mediation through CRP or lipid levels was present. After age 65, one SD higher BMI, but not WHR, was associated with 8% (95% CI 1–14%) lower dementia risk. The association was partly mediated by higher CRP, and suppressed when high-density lipoprotein levels were low. In conclusion, the negative effects of midlife adiposity on dementia risk were driven directly by factors associated with body fat distribution, with no evidence of mediation through inflammation or lipid levels. There was an inverse association between late-life adiposity and dementia risk, especially where the body’s inflammatory response and lipid homeostasis is intact.
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| 39. |
- Karlsson, Ida K., et al.
(författare)
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Age-dependent effects of body mass index across the adult life span on the risk of dementia : A cohort study with a genetic approach
- 2020
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Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: While a high body mass index (BMI) in midlife is associated with higher risk of dementia, high BMI in late-life may be associated with lower risk. This study combined genetic designs with longitudinal data to achieve a better understanding of this paradox. Methods: We used longitudinal data from 22,156 individuals in the Swedish Twin Registry (STR) and 25,698 from the Health and Retirement Study (HRS). The STR sample had information about BMI from early adulthood through late-life, and the HRS sample from age 50 through late-life. Survival analysis was applied to investigate age-specific associations between BMI and dementia risk. To examine if the associations are influenced by genetic susceptibility to higher BMI, an interaction between BMI and a polygenic score for BMI (PGSBMI) was included in the models and results stratified into those with genetic predisposition to low, medium, and higher BMI. In the STR, co-twin control models were applied to adjust for familial factors beyond those captured by the PGSBMI. Results: At age 35-49, 5 units higher BMI was associated with 15% (95% CI 7-24%) higher risk of dementia in the STR. There was a significant interaction (p = 0.04) between BMI and the PGSBMI, and the association present only among those with genetic predisposition to low BMI (HR 1.38, 95% CI 1.08-1.78). Co-twin control analyses indicated genetic influences. After age 80, 5 units higher BMI was associated with 10-11% lower risk of dementia in both samples. There was a significant interaction between late-life BMI and the PGSBMI in the STR (p = 0.01), but not the HRS, with the inverse association present only among those with a high PGSBMI (HR 0.70, 95% CI 0.52-0.94). No genetic influences were evident from co-twin control models of late-life BMI. Conclusions: Not only does the association between BMI and dementia differ depending on age at BMI measurement, but also the effect of genetic influences. In STR, the associations were only present among those with a BMI in opposite direction of their genetic predisposition, indicating that the association between BMI and dementia across the life course might be driven by environmental factors and hence likely modifiable. © 2020 The Author(s).
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| 40. |
- Karlsson, Ida K., et al.
(författare)
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Apolipoprotein E DNA methylation and late-life disease
- 2018
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 47:3, s. 899-907
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study aims to investigate if DNA methylation of the apolipoprotein E (APOE) locus affects the risks of dementia, Alzheimers disease (AD) or cardiovascular disease (CVD).Methods: DNA methylation across the APOE gene has previously been categorized into three distinct regions: a hypermethylated region in the promoter, a hypomethylated region in the first two introns and exons and a hypermethylated region in the 3'exon that also harbours the APOE epsilon 2 and epsilon 4 alleles. DNA methylation levels in leukocytes were measured using the Illumina 450K array in 447 Swedish twins (mean age 78.1 years). We used logistic regression to investigate whether methylation levels in those regions affect the odds of disease.Results: We found that methylation levels in the promoter region were associated with dementia and AD after adjusting for sex, age at blood draw, education, smoking and relatedness among twins [odds ratio (OR) 1.32 per standard deviation increase in methylation levels, 95% confidence interval (CI) 1.08-1.62 for dementia; OR 1.38, 95% CI 1.07-1.78 for AD). We did not detect any difference in methylation levels between CVD cases and controls. Results were similar when comparing within discordant twin pairs, and did not differ as a function of APOE genotype.Conclusions: We found that higher DNA methylation levels in the promoter region of APOE increase the odds of dementia and AD, but not CVD. The effect was independent of APOE genotype, indicating that allelic variation and methylation variation in APOE may act independently to increase the risk of dementia.
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