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Biomedical subjects

Nancy L Pedersen

Publications and source records attributed to Nancy L Pedersen.

At least 37 records · Page 2Linked to original sources

A twin study on the heritability of walking ability among older women.

BACKGROUND: This study examined the role of genetic and environmental factors explaining individual differences in women's walking ability in old age. METHODS: A maximal walking speed test over 10 meters and a 6-minute walking endurance test were done under standard conditions among 92 monozygotic and 105 dizygotic pairs of twin sisters reared together, aged 63-75 years. RESULTS: The mean maximum walking speed was 1.73 +/- 0.32 m/s and the mean distance covered in the 6-minute walking test was 525.6 +/- 77.3 m. Multivariate genetic modeling showed that a minor part of the variances in walking speed (16%, 95% confidence interval [CI]: 0%-54%) and endurance (20%, 95% CI: 0%-56%) were accounted for by genetic influences, and that the genetic influences were common to both traits. The corresponding proportions for common environmental factors were 37% (95% CI: 4%-58%) and 26% (95% CI: 0%-52%), and for individual environmental factors 46% (95% CI: 35%-59%) and 54% (95% CI 42%-68%), respectively. The environmental effects were partially common to both traits. CONCLUSIONS: Among relatively healthy older women, a modest portion of the variances of walking speed and endurance were accounted for by genetic factors, whereas shared and individual environmental factors explained most of the variance in both traits.

Aged↗

Sex differences after all those years? Heritability of cognitive abilities in old age.

We investigated sex differences in genetic and environmental effects on cognitive abilities among older adult twins. We drew participants from the Swedish Twin Registry; our sample included 647 twin pairs. Our cognitive measures included Synonyms, Block Design, Digit Span, Thurstone's Picture Memory, Symbol Digit, and general cognitive ability tests. Higher age was related to lower performance in all cognitive measures, except synonyms. For digit span forward, symbol digit, and general cognitive ability tasks, there was a Sex x Age interaction, with greater deficits in the performance of women compared with those of men at higher ages. We found no sex-specific genetic influences. In other words, the same genetic effects were operating for men and women. Furthermore, the magnitude of genetic effect was similar for men and women.

Adoption↗

Cigarettes and oral snuff use in Sweden: Prevalence and transitions.

AIMS: To investigate the prevalence and patterns of transitions between cigarette and snus use. DESIGN: Cross-sectional study within the population-based Swedish Twin Registry. SETTING AND PARTICIPANTS: A total of 31 213 male and female twins 42-64 years old. MEASUREMENTS: Age-adjusted prevalence odds ratios (POR) and 95% confidence intervals (CIs) described the association between gender and tobacco use, while Kaplan-Meier survival methods produced cumulative incidence curves of age at onset of tobacco use. Life-time tobacco use histories were constructed using ages at onset of tobacco use and current tobacco use status. FINDINGS: Although more males reported ever smoking (64.4%) than females (61.7%), more males were former smokers (POR: 1.33, 95% CI: 1.27-1.39). Males were far more likely to use snus than females (POR: 18.0, 95% CI: 16.17-20.04). Age at onset of cigarette smoking occurred almost entirely before age 25, while the age at onset of snus use among males occurred over a longer time period. Most men began using cigarettes first, nearly one-third of whom switched to using cigarettes and snus in combination. While 30.6% of these combined users quit tobacco completely, only 7.4% quit snus and currently use cigarettes, while 47.7% quit cigarettes and currently use snus. CONCLUSIONS: Current cigarette smoking is more prevalent among Swedish women than men, while snus use is more prevalent among men. Among men who reported using both cigarettes and snus during their life-time, it was more common to quit cigarettes and currently use snus than to quit snus and currently use cigarettes. Once snus use was initiated, more men continued using snus rather than quit tobacco completely.

Adult↗

A Swedish national twin study of lifetime major depression.

OBJECTIVE: Substantial evidence supports the heritability of lifetime major depression. Less clear is whether genetic influences in major depression are more important in women than in men and whether genetic risk factors are the same in the two sexes. It is not known whether genetic effects on major depression are constant across historical cohorts. METHOD: Lifetime major depression was assessed at personal interview by modified DSM-IV criteria in 42,161 twins, including 15,493 complete pairs, from the national Swedish Twin Registry. Twin models were evaluated by using the program Mx. RESULTS: Model fitting indicated that the heritability of liability to major depression was significantly higher in women (42%) than men (29%) and the genetic risk factors for major depression were moderately correlated in men and women. No significant differences were seen in the etiologic roles of genetic and environmental factors in major depression in three cohorts spanning birth years 1900-1958. CONCLUSIONS: In the largest sample to date, lifetime major depression was moderately heritable, with estimates similar to those in prior studies. In accord with some but not other previous investigations, this study suggests both that the heritability of major depression is higher in women than in men and that some genetic risk factors for major depression are sex-specific in their effect. No evidence was found for differences in the roles of genetic and environmental risk factors in major depression in birth cohorts spanning nearly six decades.

Cohort Studies↗

Bias in variance components due to nonresponse in twin studies.

Incomplete data on trait values may bias estimates of genetic and environmental variance components obtained from twin analyses. If the nonresponse mechanism is 'ignorable' then methods such as full information maximum likelihood estimation will produce consistent variance component estimates. If, however, nonresponse is 'nonignorable', then the situation is more complicated. We demonstrate that a within-pair correlation of nonresponse, possibly different for monozygotic (MZ) and dizygotic (DZ) twins, may well be compatible with 'ignorability'. By means of Monte Carlo simulation, we assess the potential bias in variance component estimates for different types of nonresponse mechanisms. The simulation results guide the interpretation of analyses of data on perceptual speed from the Swedish Adoption/Twin Study of Aging. The results suggest that the dramatic decrease in genetic influences on perceptual speed observed after 13 years of follow-up is not attributable solely to dropout from the study, and thus support the hypothesis that genetic influences on some cognitive abilities decrease with age in late life.

Aging↗

A twin study of lifetime Generalized Anxiety Disorder (GAD) in older adults: genetic and environmental influences shared by neuroticism and GAD.

The nature of Generalized Anxiety Disorder (GAD) and worry across the lifespan remains incompletely understood. We investigated genetic and environmental influences on GAD and the proportion of genetic and environmental variation in GAD that is shared with neuroticism in older adult twins. Participants included 1618 monozygotic and 2291 same-sexed dizygotic twin pairs from the Swedish Twin Registry aged 55 to 74. Participants provided personality information in 1973 and also participated in a telephone screening between 1998 and 2002 that included an assessment for lifetime GAD. Univariate biometric models indicated that both GAD and neuroticism were moderately heritable (.27 and .47, respectively), while the balance of variation reflected environmental factors unique to the individual. Bivariate analyses indicated that approximately one third of the genetic influences on GAD were in common with genetic influences on neuroticism, while individual specific environmental influences were virtually unshared between GAD and neuroticism. Analyses of sex effects suggested that men and women differed in the frequency of lifetime GAD and level of neuroticism; however, no sex differences for genetic and environmental influences for either trait were identified.

Anxiety Disorders↗

Heritability of an age-dependent categorical phenotype: cognitive dysfunction.

We investigated the extent to which cognitive dysfunction is shaped by genetic or environmental influences, and whether these factors differ in women and men. All members of the Swedish Twin Registry aged 65 and older were screened by telephone using the TELE, a brief cognitive assessment instrument (Gatz et al., 2002), and the Blessed Dementia Rating Scale (Blessed et al., 1968) from relatives of those who scored poorly on the TELE. Data were available for 4308 pairs where both members responded and 5070 pairs where only one member was alive and participated. To analyze all available data, we used a raw data method extended to ordinal data. As the prevalence of cognitive dysfunction increases with age, we incorporated age-adjusted thresholds. The best fitting model from biometric analyses indicated 35% of the variation in liability to cognitive dysfunction could be explained by heritable influences and the remaining 65% by nonfamilial environmental influences. Differences by gender were not significant. As this is a normative population including cognitively intact individuals, preclinical dementia cases and demented individuals, the relative magnitude of genetic and environmental effects is of particular interest in light of high heritabilities found for dementias such as Alzheimer's disease. The findings emphasize the extent to which research is needed to uncover nonfamilial environmental influences on cognitive dysfunction in later life.

Age of Onset↗

Surprising lack of sex differences in normal cognitive aging in twins.

Sex differences in the etiology of normal cognitive functioning in aging remain largely unexplored. We conducted an investigation of genetic and environmental contributions to sex differences in level of cognitive performance and rate of decline in the Swedish Adoption/Twin Study of Aging (SATSA) (Finkel & Pedersen, 2004) data set. Behavioral genetic parameterizations of a latent growth curve model were fit to longitudinal data on 11 cognitive measures. Seven hundred and ninety-eight non-demented individuals had cognitive data across four waves of measurement covering 13 years. Participants ranged in age from 44 to 88 at first testing wave; 60% were female. Results indicated sex differences in mean performance for five cognitive measures and in rates of decline for Information and Card Rotations. Only Synonyms demonstrated sex differences in genetic and environmental contributions to mean performance: heritability was higher in men than women. Despite differential longevity and susceptibility to disease, there are no consistent indications that men and women show different patterns of cognitive aging.

Adult↗

MAOA haplotypes associated with thrombocyte-MAO activity.

BACKGROUND: The aim was to ascertain whether thrombocyte MAO (trbc-MAO) activity and depressed state are genetically associated with the MAO locus on chromosome X (Xp11.3 - 11.4). We performed novel sequencing of the MAO locus and validated genetic variants found in public databases prior to constructing haplotypes of the MAO locus in a Swedish sample (N = 573 individuals). RESULTS: Our results reveal a profound SNP desert in the MAOB gene. Both the MAOA and MAOB genes segregate as two distinct LD blocks. We found a significant association between two MAOA gene haplotypes and reduced trbc-MAO activity, but no association with depressed state. CONCLUSION: The MAO locus seems to have an effect on trbc-MAO activity in the study population. The findings suggest incomplete X-chromosome inactivation at this locus. It is plausible that a gene-dosage effect can provide some insight into the greater prevalence of depressed state in females than males.

Blood Platelets↗

Genetic liability to fractures in the elderly.

BACKGROUND: The genetic impact on the causation of osteoporotic fractures is unclear. A large twin study is ideally suited to determine the genetic liability to categories of fracture at various ages. METHODS: A cohort of all 33 432 Swedish twins born from 1896 to 1944 was used to evaluate the genetic liability to fracture occurrence in the elderly. The Swedish Inpatient Registry and computer-assisted telephone interviews enabled us to identify 6021 twins with any fracture, 3599 with an osteoporotic fracture, and 1055 with a hip fracture after the age of 50 years. RESULTS: Genetic variation in liability to fracture differed considerably by type of fracture and age. Less than 20% of the overall age-adjusted fracture variance was explained by genetic variation. The age-adjusted heritability of any osteoporotic fracture was slightly greater (0.27; 95% confidence interval [CI], 0.09-0.28), and for hip fracture alone, it was 0.48 (95% CI, 0.28-0.57). Heritability was not attenuated after further adjustment for several known osteoporotic covariates but was considerably greater for first hip fractures before the age of 69 years (0.68; 95% CI, 0.41-0.78) and between 69 and 79 years (0.47; 95% CI, 0.04-0.62) than for hip fractures after 79 years of age (0.03; 95% CI, 0.00-0.26). CONCLUSIONS: The importance of genetic factors in propensity to fractures depends on fracture site and age. The search for susceptibility genes and environmental factors that may modulate expression of these genes in younger elderly patients with hip fracture, the most devastating osteoporotic fracture, should be encouraged. Prevention of fractures in the oldest elderly should focus on lifestyle interventions.

Age Factors↗

Cancer as a risk factor for long-term cognitive deficits and dementia.

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 diagnosed with dementia as their co-twins, but this odds ratio did not reach statistical 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.

Aged↗

Risk and protective factors for Parkinson's disease: a study in Swedish twins.

Many studies have shown a protective effect of cigarette smoking on Parkinson's disease. However, criticism has been raised concerning confounding by genetic factors. We investigated the associations between Parkinson's disease and smoking, alcohol, coffee, area of living, and education in a co-twin control study. Because twins are matched for genetic and familial environmental factors, this design controls for confounding by these factors. We also examined control subjects unrelated to cases. Exposure information was taken from questionnaires answered in the 1960s and 1970s. Parkinson's disease cases were identified through the Swedish Inpatient Discharge Register (IDR) and the Cause of Death Register. In the unrelated control subject comparison, 476 Parkinson's disease cases and 2,380 control subjects were included. In the co-twin control comparison, 415 same-sex twin pairs were included. There was an inverse association between smoking and Parkinson's disease using unrelated control subjects and co-twin control cases. There was no association between Parkinson's disease and alcohol, coffee, or area of living. High educational level was associated with Parkinson's disease in the unrelated control subject comparison but not in the co-twin control comparison. We confirm the protective effect of smoking on Parkinson's disease and establish that the association is only partially explained by genetic and familial environmental factors.

Activities of Daily Living↗

Personality and coping: a study of twins reared apart and twins reared together.

The relative importance of genetic and environmental factors for stress coping styles, age and gender differences, and the relationship between coping styles and personality traits were assessed in middle-aged and older adult twins reared apart and reared together, as part of the ongoing Swedish Adoption/Twin Study of Aging (SATSA). The Billings and Moos Coping Measure was administered to 1339 individual twins (in 446 intact pairs). The mean age was 58.0+/-12.8. Moderate genetic influences and significant gender differences in variance estimates were found for the three coping scales (Problem Solving, Turning to Others, and Avoidance). Turning to Others and Avoidance in women also showed shared rearing environmental influences. In contrast, no age differences in variance estimates were found in this sample. Multivariate model fitting indicated that genetic influences on adults' coping differentially reflect genetic factors in common with personality traits. The sources of covariation also showed significant gender differences.

Adaptation, Psychological↗

The longitudinal relationship between processing speed and cognitive ability: genetic and environmental influences.

Goals of the present study were to investigate the relationship between age changes in speed and cognition and the genetic and environmental influences on that relationship. Latent growth models and quantitative genetic methods were applied to data from the Swedish Adoption/Twin Study of Aging. The sample included 778 individuals from both complete and incomplete twin pairs who participated in at least 1 of 4 testing occasions over a 13-year-period. Four factors were constructed from 11 cognitive measures: verbal, spatial, memory, and processing speed. Results indicate that for measures of fluid abilities, the explanatory value of processing speed is paramount for both mean cognitive performance and acceleration with age. A significant proportion of the genetic influences on cognitive ability arose from genetic factors affecting processing speed. For measures of fluid abilities, it is not the linear age changes but the accelerating age changes in cognition that share genetic variance with processing speed.

Aged↗

Complete ascertainment of dementia in the Swedish Twin Registry: the HARMONY study.

The purpose of this report is to describe the Study of Dementia in Swedish Twins (known as HARMONY), including procedures for complete ascertainment of all cases of Alzheimer's disease (AD) and other dementias in 14,435 individuals aged 65 and older from the national Swedish twin registry. Telephone cognitive screening identified 11.5% as positive for cognitive dysfunction. Clinical diagnoses were completed for 1557 individuals, including individuals who screened positive, their twin partners, and a sample of normal controls. Estimated prevalence of dementia ranged from 1.4% for age 65-69 to 29.2% for age 90 and older. Concordance rates for Alzheimer's disease were 59% for monozygotic twins, 32% for like-sexed, and 24% for unlike-sexed dizygotic twins. Among monozygotic twins where both twins had Alzheimer's disease, the within pair difference in age of onset ranged from both becoming demented in the same year to 7 years difference in onset.

Age Factors↗

Endogenous and exogenous hormone exposure and risk of cognitive impairment in Swedish twins: a preliminary study.

PURPOSE: To analyze the risk of cognitive impairment among female Swedish Twins with regard to endogenous and exogenous hormone exposure. DESIGN AND SETTING: A cross-sectional analysis of data from the HARMONY Study, a population-based cohort study of cognitive impairment in the Swedish Twin Registry. METHODS: Information regarding age at menarche and menopause, parity, and length and type of hormone therapy (HT) was collected via a telephone interview from 6604 women, aged 65-84. Cognitive impairment was assessed with the TELE, a brief telephone cognitive screen. RESULTS: Length of reproductive period was inversely associated with risk of cognitive impairment (p<0.01). The OR was 1.15 (CI 95% 0.96-1.36) for women with reproductive periods <35 years and 0.82 (CI 95% 0.66-1.00) for women with reproductive periods >39 years. Age at menopause was inversely associated with risk of cognitive impairment. Use of HT was associated with average 40% decline in the risk of cognitive impairment, independent of type and timing of treatment. CONCLUSION: Our results suggest that both increased length of reproductive period and HT are associated with reduced risk of cognitive impairment.

Age Factors↗

The epidemiology of chronic fatigue in the Swedish Twin Registry.

BACKGROUND: Chronic fatigue syndrome (CFS) remains an idiopathic and controversial entity. METHOD: We screened 31405 individual members of the Swedish Twin Registry (aged 42-64 years) for the symptoms of fatiguing illness via a telephone questionnaire. We refined self-reported symptoms via data from several national registries and from physician review of all available medical records in order to approximate closely the dominant case definition of CFS. FINDINGS: The 6-month prevalence of CFS-like illness was 2.36% (95% CI 2.19-2.53) and was markedly higher in women than men, odds ratio 3.92 (95% CI 3.24-4.72) with no significant association with age or years of education. There was a highly significant association with occupation that disappeared after accounting for gender. INTERPRETATION: CFS-like illness may be more common that previously acknowledged. There is a marked increase in risk by gender. Previous reports that CFS is more prevalent in individuals in certain occupational categories were not confirmed and may have been due to confounding by gender.

Adult↗