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Biomedical subjects

Henrik Frederiksen

Publications and source records attributed to Henrik Frederiksen.

At least 19 recordsLinked to original sources

Physical and mental function and incident low back pain in seniors: a population-based two-year prospective study of 1387 Danish Twins aged 70 to 100 years.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: To investigate whether physical performance, grip strength, cognitive function, and depression symptomatology are risk factors for incident low back pain (LBP) over a 2-year period in seniors. SUMMARY OF BACKGROUND DATA: LBP is common in the older age groups, but little is known about predictors of LBP in this age group. METHODS: Data from the 2001 and 2003 data collection from the population-based Longitudinal Study of Aging Danish Twins formed the basis of this analysis. Participants free from LBP at baseline (no LBP during the past month, N = 1387) were included and interview data on overall physical function, and assessment of grip strength, overall cognitive function, and depression at baseline were obtained. LBP status at follow-up was assessed using a modified version of the Standardized Nordic Questionnaire. Logistic regression was used to assess the associations between the baseline risk factors and LBP at follow-up. RESULTS: A total of 1387 persons 70 to 100 years of age at baseline were included in the analyses. Of the initially LBP-free individuals, 7% had experienced LBP more than 30 days out of the past year, 7% had altered or decreased their physical activities due to LBP, and 11% had received treatment for LBP at follow-up. Good overall physical function (being among the top 50%) at baseline was protective for LBP of more than 30 days duration and for diminishing physical activities due to LBP and for care seeking due to LBP. High depression scores (being among the top 25%) were strongly associated with altering or decreasing daily activities because of LBP. Grip strength and overall cognitive performance at baseline were associated with lower incidence of LBP and decreasing activities due to LBP at follow-up; however, these associations were not statistically significant. CONCLUSION: Poor overall physical function and depression symptomatology are associated with LBP and consequences of LBP in persons 70 years of age and older.

Activities of Daily Living↗

Age trajectories of grip strength: cross-sectional and longitudinal data among 8,342 Danes aged 46 to 102.

PURPOSE: The purpose is to study the age trajectory of hand-grip strength after the age of 45 years. METHODS: In this study, we use data from three large nationwide population-based surveys of Danes aged 45 to 102 years with a total of 8342 participants with grip-strength measurements and up to 4 years of follow-up. Grip strength was measured by using a portable hand dynamometer. RESULTS: Grip strength declines throughout life for both males and females, but among the oldest women, the longitudinal curve reaches a horizontal plateau. The course of the decline is estimated by using full information in the longitudinal data and is found to be almost linear in the age span of 50 to 85 years. In this age span, mean annual grip-strength loss is estimated to be 0.59 (0.02) (SE) kg for men and 0.31 (0.01) kg for women. CONCLUSION: This study confirms the previously reported grip-strength decline with increasing age. Estimates were obtained by using full-information methods from large population-representative studies. Equations of expected grip strength, as well as tables with sex-, age-, and height-stratified reference data, provide an opportunity to include grip-strength measurement in clinical care in similar populations.

Aged↗

Possible associations between successful aging and polymorphic markers in the Werner gene region.

Werner syndrome (WS) is an autosomal recessive segmental progeroid syndrome caused by mutations in the Werner (WRN) gene leading to the early onset of many (but not all) aspects of normal aging. To investigate whether the WRN gene affects the course of aging in non-Werner syndrome individuals, we performed association studies analyzing several single nucleotide polymorphisms (SNPs) in the WRN locus. We found certain close-set SNPs in the 5' flanking region and 5' UTR to be significantly associated with the cognitive functioning level in old age.

5' Flanking Region↗

Back and neck pain in seniors-prevalence and impact.

Neck pain (NP) and back pain (BP) are common complaints in seniors yet specific information on these complaints is lacking in the scientific literature. We present cross-sectional interview data from the 2003 data collection within the population based Longitudinal Study of Aging Danish Twins dealing with the 1-month prevalence of NP and BP and the intensity of possible pain. Further, we present the 1-year prevalence of NP and BP, duration of pain, influence of NP and BP on daily activities and care seeking for NP and BP. 84.4% of invited twins aged 70-102 years participated in the study. The 1-month prevalence of NP and BP was similar to previously reported results. 7% of men and 13% of women reported moderate or severe NP and 12% of men and 19% of women reported moderate or severe BP on a monthly basis. 10% of men and 12% of women reported more than 30 days of NP within the past year and 13% of men and 21% of women reported more than 30 days of BP within the past year. 5% of men and 8% of women had altered or diminished their physical activities due to NP and 9% of men and 16% of women had diminished their physical activities due to BP within the past year. 10% of men and 12% of women had had treatment for NP within the past year and 13% of men and 19% of women had had treatment for BP within the past year, most commonly from general medical practitioners and physical therapists. Altering or diminishing physical activities and care seeking were associated with both pain intensity and duration of pain. NP and BP of longer duration were associated with significantly lower physical performance scores when compared to no NP or BP during the past year. NP and BP in seniors are probably associated with difficulty but not inability to perform daily activities.

Activities of Daily Living↗

Genetic dissection of gene expression observed in whole blood samples of elderly Danish twins.

The microarray technique is an important tool in gene expression analysis to study the activities of thousands of genes measured by their transcript levels under disease or laboratory controlled experimental conditions. Recent studies have suggested a genetic component in the variations of gene expression thus indicating the important role of genetic control over gene activities. In this study, we analyze and report the twin correlation on gene expression in whole blood samples of six female Danish twin pairs aged from 81 to 85 years. We studied the expression phenotype by treating the measured gene expression as a quantitative trait and introducing analytical approaches including the traditional twin methods in population genetics and the multivariate statistical methods. Using this combinatory approach, we were able to estimate and compare the twin correlation on the expression phenotype while accounting for systematic influence in microarray experiments. Analyses on our twin data detected a significant correlation on the expression levels of the actively regulated genes in both monozygotic and dizygotic twins, which is more pronounced in monozygotic twins. Gene ontology analysis has shown that these actively regulated genes are predominantly involved in defense and immune responses against antigenic stimulus. In conclusion, the correlation patterns revealed in our twin data provide evidence of the existence of a heritable mechanism in gene expression regulation persistently functioning even in aged subjects.

Aged↗

Small effect of genetic factors on neck pain in old age: a study of 2,108 Danish twins 70 years of age and older.

STUDY DESIGN: Classic twin study. OBJECTIVES: To determine the heritability of neck pain in persons 70 years of age and older. SUMMARY OF BACKGROUND DATA: Previous studies have shown a moderate effect of genetic factors on back pain in the elderly. Genetic influence on neck pain in old age is unknown. METHODS: Data on the 1-month prevalence of neck pain from twin pairs participating in the population based Longitudinal Study of Aging Danish Twins formed the basis of this analysis. To assess twin similarity, probandwise concordance rates, odds ratios, and tetrachoric correlations were calculated and compared for monozygotic and dizygotic twins. Further, heritability estimates were calculated using bivariate probit estimation. RESULTS: A total of 2,108 twin individuals, including 1,054 complete twin pairs, answered the question related to neck pain at intake into the Longitudinal Study of Aging Danish Twins study. Low and nonsignificant probandwise concordance rates, odds ratios, and tetrachoric correlations were found for both men and women in monozygotic and dizygotic twin pairs, indicating small or negligible genetic effects. Heritability estimates adjusted for age and significant environmental risk factors (rheumatoid arthritis, osteoarthritis, disc prolapse, and coronary heart disease) showed no significant additive genetic, dominant genetic, or common environmental effects. CONCLUSION: Genetic factors do not play an important role in the liability to neck pain in persons 70 years of age or older.

Aged↗

Genetic and environmental contributions to back pain in old age: a study of 2,108 danish twins aged 70 and older.

STUDY DESIGN: Self-reported 1-month prevalence of back pain in older twins assessed at intake in a population-based longitudinal survey. OBJECTIVES: To determine the relative contribution of genetic and environmental factors to back pain in old age. SUMMARY OF BACKGROUND DATA: To date, genetic contributions to back pain in old age have not been assessed, to the authors' best knowledge. METHODS: Interview data given at entry into a nationwide cohort-sequential population-based survey of Danish twins aged 70 years and older in 1995, 1997, 1999, and 2001 form the basis of this analysis. Analysis of twin similarity was estimated using probandwise concordance rates, odds ratios, and tetrachoric correlations for back pain. Heritability (proportion of the population variance attributable to genetic variation) was estimated by bivariate probit estimation and adjusted for known significant environmental factors. Odds ratios for known environmental effects were estimated after controlling for age, sex, and genetic effects. RESULTS: Modest and nonsignificant differences between monozygotic and dizygotic twin pairs were found for probandwise concordance rates, odds ratios, and tet-rachoric correlations for both men and women. In the bivariate probit estimation, a current or previous diagnosis of osteoporosis, degenerative joint disease, or lumbar disc prolapse was found to significantly affect the risk of back pain. Additive genetic effects explained approximately one fourth of the liability to report back pain in men and none of the occurrence in women. Individual environmental effects were found to explain roughly 75% of the occurrence of back pain in men and 100% in women. CONCLUSIONS: Additive genetic effects are modest contributors to back pain in older men but not in women. A current or previous medical diagnosis of osteoporosis, degenerative joint disease, or lumbar disc prolapse is-strongly associated with back pain, also when genetic factors are controlled for. Because of inherent methodologic issues, this estimate of the genetic influence on back pain in old age is probably conservative.

Age Distribution↗

Back and neck pain exhibit many common features in old age: a population-based study of 4,486 Danish twins 70-102 years of age.

STUDY DESIGN: Cross-sectional and longitudinal analysis of data comprising 4486 Danish twins 70-102 years of age. OBJECTIVES: To describe the 1-month prevalence of back pain, neck pain, and concurrent back and neck pain and the development of these over time, associations with other health problems, education, smoking, and physical, and mental functioning. SUMMARY OF BACKGROUND DATA: Back pain and neck pain are prevalent symptoms in the population; however, there is little research addressing these conditions in older age groups. METHODS: Extensive interview data on health, lifestyle, social, and educational factors were collected in a nationwide cohort-sequential study of 70+-year-old Danish twins. Data for back pain, neck pain, lifetime prevalence of a comprehensive list of diseases, education, and self-rated health were based on self-report. Physical and mental functioning were measured using validated performance tests. Data including associated factors were analyzed in a cross-sectional analysis for answers given at entry into the study, and longitudinal analysis was performed for participants in all four surveys. RESULTS: The overall 1-month prevalence for back pain only was 15%, for neck pain only 11%, and for concurrent back and neck pain 11%. The prevalence varied negligibly over time and between the age groups, and 63% of participants in all surveys had no episodes or only one episode of back or neck pain. Back pain and neck pain were associated with a number of other diseases and with poorer self-rated health. Back and neck pain sufferers had significantly lower scores on physical but not cognitive functioning. CONCLUSIONS: Back pain and neck pain are common, intermittent symptoms in old age. Back pain and neck pain are associated with general poor physical health in old age.

Aged↗

A polymorphic marker in the first intron of the Werner gene associates with cognitive function in aged Danish twins.

Werner's syndrome is a premature aging syndrome with many features common to normal aging. The possible association between phenotypic markers for normal aging and SNP's in the WRN gene was investigated in 426 dizygotic, Danish twins age 70-90 years. All participants were scored every second year using a number of physical and cognitive tests. In addition their self-rated health was registered as well as self reported status with regards to nine diseases. Blood was drawn from all participants and purified DNA was typed for four SNP's in the WRN gene. The four SNP's were located in intron 1, exon 6, exon 9 and exon 34. In an unpaired analysis of this material a significant association between the intron 1 SNP and cognitive function was demonstrated. Our finding, which will need corroboration in independent samples, therefore may suggest that the t-allele of the intron 1 SNP is beneficial to cognitive function. However, since the t-allele of this SNP is very rare, we did not encounter any tt-homozygous individuals for this allele.

Activities of Daily Living↗

Association between low self-rated health and heterozygosity for -110A > C polymorphism in the promoter region of HSP70-1 in aged Danish twins.

We have studied the possible association between the -110A > C polymorphism in the promoter region of one of the heat shock protein genes HSP70-1 with human longevity in a cohort of aged Danish twins. This cohort includes individuals aged between 70 and 91 years (mean = 75.6 years), who are categorized according to the presence or absence of various diseases and according to the various, age-related parameters for which a genetic component has already been defined. Four hundred DNA samples from the cohort were genotyped using real-time PCR. Aging phenotypes (diseases, physical and cognitive functioning) were compared with regard to genotype. Of all the aging phenotypes studied, self-rated health and relative self-rated health, which represent an individual's overall sense of physical well-being and which have been shown to be both predictors of survival at older ages and better indicators of future survival than objectively measured health status, were associated with the polymorphism. An association was found between low self-rated health and heterozygosity for -110A > C polymorphism in the promoter region of HSP70-1 in aged Danish twins.

Aged↗

The catalase -262C/T promoter polymorphism and aging phenotypes.

A low level of the central antioxidant enzyme catalase has been suggested to be a risk factor for diseases influenced by oxidative stress. In this study, we investigated the possible association of the catalase -262C/T polymorphism with survival, physical and cognitive functioning, and a number of oxidative stress-mediated disorders. The study population was 2223 Danish individuals, aged 45-93 years, drawn from three population-based surveys. The results suggest that the catalase -262C/T polymorphism is not associated with either survival, or the majority of the age-related phenotypes investigated. However, our data indicate a statistical significant association of TT homozygosity with improved physical functioning as well as a trend of the T allele conferring an improved general cognitive functioning, although these results did not remain significant after correcting for multiple testing. The results raise the hypothesis that the catalase -262T allele serves as protection against neurodegenerative and physical decline, although replication in other studies is warranted for confirmation of these findings.

Aged↗

Back pain remains a common symptom in old age. a population-based study of 4486 Danish twins aged 70-102.

Back pain (BP) has been rated among the most important factors affecting physical health status in old age. Yet there is an under-representation of the older population in the BP literature. We present extensive interview data from the Longitudinal Study of Aging Danish Twins, dealing with a population-based sample of Danish twins aged 70-102, and describing the 1-month prevalence of BP and the development of BP over time. The associations between BP and education, self-rated health, other health problems, lifestyle factors, and physical and mental function were also investigated. Data were analysed in a cross-sectional analysis for all answers given at entry into the study and in a longitudinal analysis for participants in all four surveys. Associated factors were analysed for the cross-sectional sample using univariate and multivariate analysis accounting for the non-independence of twins in complete pairs. The overall 1-month prevalence of BP was 25% and differed significantly between men and women. The variations in prevalence between the age groups and over time were negligible. The majority of participants in all four surveys had either not experienced BP during the previous month or had done so on one occasion only. Education was not associated with BP. Self-rated health was associated with BP in a significant "dose-response" like pattern. BP was associated with bone and joint disorders, migraine headaches, lung disease, cardiovascular disorders and gastric ulcer, but not neurologic or endocrinologic diseases. BP sufferers had significantly lower scores on physical but not on mental functioning. We conclude that BP is a common symptom in old age; however, the prevalence does not change with increasing age. BP may be part of a more general syndrome of poor health among the old.

Aged↗

ACE genotype and physical training effects: a randomized study among elderly Danes.

BACKGROUND AND AIMS: The level of physical functioning (PF) late in life has, in recent years, been shown to be influenced by genetic factors. One of the most extensively studied genetic variants associated with PF and trainability is insertion/deletion (I/D) polymorphism in the gene encoding Angiotensin Converting Enzyme (ACE). However, ACE studies have mainly been conducted among younger persons in excellent physical shape. In this study, we examine whether the level of PF, trainability, or rate-of-change are associated with the ACE genotype among the elderly. METHODS: We used data from 4 randomized training studies of elderly Danes (N = 203). The measures of PF were self-report, maximal oxygen uptake, muscle strength, walking speed, and body composition. RESULTS: Overall, a favorable change in the measures of PF was observed in training groups compared with control groups. However, within groups, neither pre- or post-training/control period levels of PF nor differences in pre- and post-levels were associated with the ACE genotype. CONCLUSIONS: On the basis of our randomized studies, we could not detect any association between the ACE genotype and the level of PF or change, regardless of whether response to physical training or spontaneous changes was studied.

Aged↗

Angiotensin I-converting enzyme (ACE) gene polymorphism in relation to physical performance, cognition and survival--a follow-up study of elderly Danish twins.

PURPOSE: Studies of younger individuals have suggested an association between ACE genotype and physical and cognitive performance. Using a longitudinal study of elderly twins we studied the association between ACE genotype and physical and cognitive functioning and survival in old age. METHODS: Participants were 684 twins aged 73+ years from the 1997 and 1999 surveys of the Longitudinal Study of Aging Danish Twins. Cognitive skills were assessed by the MMSE, while physical abilities were determined through self-report in 1997 and through both self-report and measurement of performance in two physical tasks in 1999. Survival status was obtained through linkage with a national death register. RESULTS: Neither physical nor cognitive performance was associated with ACE genotype at baseline in 1997, or at follow-up in 1999. For participants in both surveys longitudinal changes in these skills did not depend on ACE genotype. The relative risk of dying was increased in II compared with the DI and DD genotype with relative risks of 1.6 (95 percent confidence intervals 1.1-2.5) and 1.3 (0.8-2.1), respectively. CONCLUSION: We found no substantial effects of ACE genotype on physical and cognitive performance, or rate of change among elderly. Persons with the D allele may have a lower mortality at older ages.

Aged↗

Age trajectories of genetic variance in physical functioning: a longitudinal study of Danish twins aged 70 years and older.

Genetic-evolutionary theories of aging predict that the genetic variance for fitness traits increases with age, while epidemiological-gerontological theories predict an increase in the environmental variance for most traits. In this study we examine the age trajectories of the genetic and environmental variance in physical functioning in a sample of 4731 Danish twins aged 70+ who are being followed longitudinally every second year with up to four assessments completed. A biometric growth model (Neale and McArdle, 2000) was applied to a validated physical ability score. The model included an overall level effect, a rate of linear change effect, and residual effects. The best-fitting model was a sex-specific model including additive genetic and nonshared environmental factors affecting level and rate of change and only nonshared environmental factors affecting the wave-specific levels. For both sexes there is an approximate doubling of both the total variance and the genetic variance in the physical ability score over the four waves and, hence, a rather stable heritability. However, the heritability is approximately.10 for males and.30 for females in all four waves. The heritability of level and slope showed a similar pattern:.11-14 in males and.35-.39 in females. The increase in both additive genetic variance and environmental variance is in agreement with genetic-evolutionary and epidemiological-gerontological theories of aging, respectively. The present study suggests that overall level of strength may be a better phenotype for future molecular genetic studies on physical functioning in the elderly than rate of change, because rate of change is vulnerable to sample attrition due to mortality and dropout and because four waves were needed to be able to detect a heritability for rate of change of the same magnitude as the heritability for level of physical functioning.

Age Factors↗