Biomedical subjects

D Carmelli

Publications and source records attributed to D Carmelli.

At least 55 records · Page 3Linked to original sources

PubMed1995

Performance on the digit symbol substitution test and 5-year mortality in the Western Collaborative Group Study.

The relation between performance on the digit symbol substitution test and subsequent 5-year mortality was examined in 1,118 male participants in the Western Collaborative Group Study (mean age at time of examination = 70.6 years). Cox regression analyses revealed that the unadjusted relative risk from all-cause mortality was 1.79 (95% confidence interval 1.45-2.21) for subjects who scored 10 points (1 standard deviation) lower on the digit symbol substitution test. The relative risk remained significant at 1.44 (95% confidence interval 1.12-1.86) after adjustment for age, education, baseline serum cholesterol, and systolic blood pressure levels and for the prevalence of cancer, cardiovascular/cerebrovascular disease, and ever smoking. Tree-structured survival analysis revealed the presence of a subgroup of subjects (n = 130) with low digit symbol substitution performance (mean = 26.3) who experienced a mortality rate of 34.9 deaths per 1,000 person-years. This mortality rate was not significantly different from that encountered by another subgroup of subjects with a history of cancer (n = 128; 45.7 deaths per 1,000 person-years). If age-related slowing of information processing is a marker for aging of the central nervous system, then people with lower digit symbol scores may be "older" physiologically than similarly aged persons with higher digit symbol scores. Aging of the central nervous system might be expected to reduce adaptive capacity in a general way, thereby increasing susceptibility to death from a variety of causes.

Aged↗

PubMed1995

Cognition and depression in a cohort of aging men: results from the Western Collaborative Group Study.

Relationships between cognitive performance and self-ratings of depression on the Center for Epidemiologic Studies Depression scale (CES-D; L.S. Radloff, 1977) were examined for 1,217 older men. After controlling for demographic variables and both objective and subjective measures of health, significant associations were observed between several CES-D variables and measures of cognitive mental status, memory, and psychomotor speed. The Well-Being factor of the CES-D was the most robust predictor of cognitive scores. Therefore, for older adults with generally favorable health and socioeconomic resources, there may be a link between positive affect and maintenance of cognitive effectiveness.

Aged↗

PubMed1995

Genetic mediation in the relationship of education to cognitive function in older people.

We used data from 136 monozygotic and 125 dizygotic human, male twin pairs (M age = 64 years, range = 59 to 70 years) to test whether the previously observed association (r = .30, p < .01) between cognitive performance and education in this sample is genetically mediated. Biometric genetic modeling found that a common genetic latent variable accounted for 44% of the total variance in the Mini-Mental State Exam (MMSE: M. F. Folstein, S. E. Folstein, & P. R. McHugh, 1975), 40% of the variance in the Iowa Screening Battery for Mental Decline (P. J. Eslinger, A. R. Damasio, & A. L. Benton, 1984), and 21% of the variance in educational attainment. In addition, specific genetic and environmental variables contributed significantly to individual differences in education and cognitive performance of the participants.

Aged↗

PubMed1995

Self-reported alcohol intake and cognition in aging twins.

OBJECTIVE: To determine the relationship between long-term alcohol intake and cognitive functioning in aging Caucasian men. METHOD: A retrospective cohort and co-twin-control study of self-reported alcohol intake and cognitive testing using the National Academy of Sciences-National Research Council (NAS-NRC) Twin Panel of U.S. veterans (born between 1917 and 1927). The study included 4,739 twins with two self-reported drinking histories (1970s and 1980s) and a telephone mental status interview (1990 and 1991) that also included 145 individuals with a diagnosis of alcoholism. RESULTS: Age and education adjusted cognitive scores were lower (p < .05) in diagnosed alcoholics than in the remainder of the subjects. To compare age and education adjusted cognitive scores in alcohol intake, the 4,739 twins were divided, based upon questionnaire data, into nondrinkers and 5 quintiles of drinkers by average reported drinks of alcohol weekly (< 1.0, 1-3.3, 3.4-8.1, 8.2-16.0, > 16.0). Past drinkers had scores lower (p < .05) than nondrinkers and all but quintiles 1 and 5 of the drinkers. The light drinkers in quintile 1 and the heavy drinkers in quintile 5 scored lower (p < .05) than the moderate drinkers in quintile 4. Monozygotic twins in quintile 4 scored higher (p < .05) than their co-twins in quintiles 1-3. CONCLUSIONS: No evidence was found to indicate an association between moderate long-term alcohol intake and lower cognitive scores in aging individuals. There was a suggestion of a small protective effect of past moderate alcohol intake on cognitive function with aging.

Aged↗

PubMed1995

Characteristics associated with excessive weight gain after smoking cessation in men.

OBJECTIVES: Data from two surveys of the National Academy of Sciences-National Research Council Twin Registry, conducted 16 years apart, were used to determine characteristics of individuals that were predictive of excessive weight gain after smoking cessation. METHODS: Over the follow-up, 2179 men quit smoking and averaged a weight gain of 3.5 kg. Quitters were grouped into four categories of weight change: lost weight, no change, gained weight, and excessive weight gain ("super-gainers"). RESULTS: In comparison with quitters reporting no change in weight, super-gainers were younger, were of lower socioeconomic status, and differed on a number of health habits before quitting (all Ps < .05). At follow-up, super-gainers reported changes in health habits that were significantly different from those seen in quitters reporting stable weight (all Ps < .05). Pairwise concordance for weight change in 146 monozygotic and 111 dizygotic twin pairs in which both twins quit smoking was significantly greater in monozygotic than dizygotic pairs (P < .01). CONCLUSIONS: These results indicate that super-gainers differ in important ways from those who do not gain weight after smoking cessation and that these weight changes may be influenced by underlying genetic factors.

Humans↗

PubMed1995

World War II-veteran male twins who are discordant for alcohol consumption: 24-year mortality.

The role of genetic and shared environmental influences in the association of alcohol with mortality was studied by using the National Academy of Sciences-National Research Council World War II-veteran male twin registry. An epidemiologic questionnaire administered from 1967 through 1969 permitted identification of twin pairs discordant for alcohol consumption. The subsequent 24 years of mortality follow-up yielded data on time and cause of death. Analyzing the first or only death in drinking-discordant pairs, we observed 27 deaths in abstainer twins and 14 deaths in their light- to moderate-drinker cotwins (relative risk [RR] = 1.93). Excess mortality in twin abstainers was also indicated for deaths from cardiovascular diseases (RR = 2.0) and other causes of death excluding cancers (RR = 3.2). The protective effect, however, of light to moderate drinking did not persist in twins who were smokers at baseline.

Alcohol Drinking↗

PubMed1995

Evidence for a major gene influencing 7-year increases in diastolic blood pressure with age.

The contribution of genetic factors to blood pressure levels is well established. The contribution of genes to the longitudinal change in blood pressure has been less well studied, because of the lack of longitudinal family data. The present study investigated a possible major-gene effect on the observed increase with age in diastolic blood pressure (DBP) levels. Subjects included 965 unmedicated adults (age > or = 18 years) in 73 pedigrees collected in Utah as part of a longitudinal cardiovascular family study. Segregation analysis of DBP change over 7.2 years of follow-up identified a recessive major-gene effect with a gene frequency of p = .23. There was also a significant age effect on the genotypic means, which decreased expression of the major gene at older ages. For those inferred to have the genotype responsible for large DBP increases, DBP increased 32.3%, compared with a 1.5% increase in the nonsusceptible group (P < .0001). The relative risk of developing hypertension between the susceptible and nonsusceptible groups after 7.2 years was 2.4 (P = .006). Baseline DBP reactivities to mental arithmetic (P < .0001), and isometric handgrip (P < .0001) stress tests were greatest in those assigned to the susceptible genotype. We conclude that age-related changes in DBP are influenced by a major gene. Characteristics of this major-gene effect for greater age-related blood pressure increases include greater reactivity to mental and physical stressors. The present study thus provides evidence for genetic control of changes in blood pressure, in addition to the previously suggested genetic control of absolute blood pressure level.

Adult↗

PubMed1994

Genetic influences on adult weight gain and maximum body mass index in male twins.

The National Heart, Lung, and Blood Institute Twin Study is a multicenter, longitudinal study of 514 white, male twin pairs examined during military induction at the mean age of 20 years (1943) and by the National Heart, Lung, and Blood Institute Twin Study at mean ages 48 (1971), 58 (1981), and 63 years (1986). Of these, 121 of 254 monozygotic pairs and 113 of 260 dizygotic pairs had complete data for all examinations. Using these data, genetic influences on maximum body mass index (BMI) and changes in BMI during this 43-year interval were estimated. BMI (kg/m2) was calculated for each examination and for the maximum weight as recalled by the participant at the last examination. Regression equations were fitted to each person's four-examination measurements to estimate the trend in weight change over adulthood. Twins gained an average of 0.11 kg/m2 per year from mean ages 20-63 years. Maximum BMI averaged 28.4 kg/m2 for monozygotic twins and 28.3 kg/m2 for dizygotic twins. The distribution of the ages at maximum BMI appeared to be bimodal for each zygosity, with modes around ages 20 and 60 years. Heritability (variation attributable to genetic factors) was estimated to be 0.71 (95% confidence interval 0.55-0.87) for maximum BMI and 0.70 (95% confidence interval 0.55-0.84) for trend in adult weight gain. In contrast, variability of BMI around the trend line showed no evidence of significant genetic determination.

Adolescent↗

PubMed1994

Lower cognitive performance in normal older adult male twins carrying the apolipoprotein E epsilon 4 allele.

OBJECTIVE: Given the strong association of the apolipoprotein E (apoE) allele epsilon 4 with late-onset Alzheimer dementia or multi-infarct dementia, we tested whether normal older adult men with at least one epsilon 4 allele demonstrate subclinical changes in cognition and perform more poorly on tests of cognitive function compared with subjects without the epsilon 4 allele. DESIGN: Matched-pair design of normal adult male (average age, 63 years) fraternal twins. SETTING: Subjects voluntarily participated on an outpatient basis at a research or medical center facility. PARTICIPANTS: Members of the National Heart, Lung, and Blood Institute twin panel third examination previously genotyped for apoE. MAIN OUTCOME MEASURE: Education-adjusted scores on several neuropsychological tests were compared in twins discordant for the apoE epsilon 4 allele. Subjects with documented cerebrovascular disease were excluded. RESULTS: Among 20 fraternal twin pairs discordant for the presence of epsilon 4, twins with the epsilon 4 allele demonstrated poorer mean performance than their co-twins without the epsilon 4 allele. This relationship was also noted cross-sectionally where age- and education-adjusted scores of 50 individual twin subjects with at least one epsilon 4 allele demonstrated poorer performance compared with 138 individual twins without an epsilon 4 allele. CONCLUSIONS: The apoE epsilon 4 allele may be associated with decreased cognitive function in discordant twin pairs. Our results suggest that epsilon 4 may represent a potential marker for accelerated cognitive aging and such individuals may be at greater risk for development of late-onset Alzheimer dementia or multi-infarct dementia.

Alleles↗

PubMed1994

16-year incidence of ischemic heart disease in the NHLBI twin study. A classification of subjects into high- and low-risk groups.

Prospective data from the National Heart, Lung, and Blood Institute (NHLBI) Twin Study were used to investigate the relationship of risk factors measured in 1970 to 1971 to 16-year incidence of ischemic heart disease (IHD) in 905 males born between 1917 and 1927. A newly developed methodology, tree-structured survival analysis (TSSA), was used to classify subjects into discrete subgroups that differed significantly in profiles of risk factors and incidence of IHD. On the basis of five characteristics--systolic blood pressure (SBP), high-density-lipoprotein cholesterol (HDL-C), 1-hour postload glucose levels, forced expiratory volume in 1 second (FEV1), and a family history score for heart disease--the TSSA algorithm partitioned the cohort into six discrete subgroups that formed three clusters of individuals with distinct IHD experience. Highest IHD incidence rates were experienced by a subgroup of 56 men with baseline SBP above 134 mm Hg and HDL-C levels lower than 33 mg/dL. No IHD events were observed in a subgroup of 117 men who had low SBP, high FEV1, and a negative family history of heart disease. Relationships to the twinning condition showed that for both zygosities, cotwin-pair members were in the same risk subgroup more often than expected; however, the overall difference between the frequency of monozygotic (MZ) and dizygotic (DZ) cotwins was relatively small. The highest MZ/DZ ratios of observed to expected cotwin-pair membership occurred in subgroups with the highest and lowest incidences of IHD, suggesting that these extremes of incidence are most likely to be genetically determined.

Aged↗

PubMed1994

Correlations of alcohol consumption with related covariates and heritability estimates in older adult males over a 14- to 18-year period: the NHLBI Twin Study.

Consistent maximum-likelihood heritability estimates of consumption of alcoholic beverages were observed at three separate times during a 14- to 18-year period in adult twin males initially aged 42-56 years in 1969-1973. Log transformation of the average number of drinks/week of the returnees to all three examinations was examined relative to potential covariates representing both antecedents of drinking alcohol and consequences of alcohol consumption. Significant relationships were noted for 38 of the covariates at one or more of the separate examinations, including positive correlations with smoking, coffee consumption, high-density lipoprotein cholesterol, mean corpuscular volume, systolic blood pressure, uric acid and behavioral measures, and negative correlations with blood urea nitrogen, red blood cell count, tea consumption, and tricep skinfolds. Analysis of the average alcohol consumption adjusted for nine independent covariates selected from multiple stepwise regression resulted in a modest decline in maximum-likelihood heritability estimates compared with unadjusted data, but little difference from heritability estimates obtained when abstainers from alcohol (no alcoholic beverages consumed at all three examinations) were excluded. The most striking effect of omitting abstainers from alcohol was the decline in the intraclass correlations in dizygotic twins. Bivariate analyses of alcohol and individual covariates revealed the phenotypic correlation between alcohol consumption and a measure of hostility was primarily environmental, that for high-density lipoprotein, smoking and coffee drinking with alcohol was primarily genetic, and the phenotypic correlation between alcohol consumption and mean corpuscular volume had both significant genetic and environmental correlations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Concordance, discordance and prevalence of hypertension in World War II male veteran twins.

OBJECTIVE: To determine concordance for hypertension in adult male twins and to examine individual environmental factors associated with the manifestation of the disease in one member but not both members of a twin pair. METHODS: The subjects were 1003 monozygotic and 858 dizygotic Caucasian, male, World War II veteran twins born in the USA between 1917 and 1927, who were aged 56-66 years when surveyed by the National Heart, Lung, and Blood Institute for health behaviors and cardiovascular disease status. Hypertensive status was determined by the subjects' diagnostic reports from physicians and the subjects' past or current use of antihypertensive medications. Self-reports were validated in a subsample of 675 individual twins who were participants in a series of cardiovascular examinations and for whom blood pressure measurements were available. RESULTS: The data analyses indicate that in this cohort of adult male twins, 62% of monozygotic and 48% of dizygotic cotwins of the hypertensive twins were hypertensives, compared with a prevalence of 36% in the whole cohort. Among the 281 monozygotic twins discordant for hypertension, hypertensive twins differed significantly from their non-hypertensive cotwins in the weight gain throughout adulthood and in alcohol consumption. They did not differ in weight at induction into the military, or according to smoking, physical activity or demographics. Those pairs that were concordant for hypertension gained significantly more weight throughout adulthood, consumed more alcohol, and were physically less active than concordant-negative pairs. CONCLUSIONS: The findings from this study suggest that although genetic factors influence the development of hypertension, non-genetic and potentially modifiable lifestyle behaviors, including adult weight gain, alcohol consumption and physical activity, are closely related to the clinical manifestation of the disease.

Aged↗

PubMed1994

Genetic and environmental correlations between obesity and body fat distribution in adult male twins.

Genetic and environmental correlations between measures of obesity [body mass index (BMI)] and body fat distribution [waist/hip ratio (WHR) and subscapular/triceps ratio (SSTR)] were examined in 133 monozygotic and 129 dizygotic pairs of elderly white male twins, age 59 to 70 years, participating in the third cardiovascular examination of the National Heart, Lung, and Blood Institute Twin Study. The BMI, WHR, and SSTR fat measures were significantly correlated in these twins, with BMI more closely related to WHR (r = 0.52) than to SSTR (r = 0.18), and the WHR-SSTR association intermediate (r = 0.27). Multivariate genetic analyses of the three indexes using the LISREL modeling approach indicated a significant heritable component for each fatness variable, h2 = 0.66, 0.46, and 0.25 for BMI, WHR, and SSTR, respectively, and a significant correlation between genetic influences on BMI and WHR (genetic r = 0.51). The common genetic component accounted for 54% of the observed BMI-WHR correlation, suggesting that overall obesity and abdominal adiposity distribution are mediated to some extent by similar genetic influences. The genetic correlations between SSTR and BMI and between SSTR and WHR were not significantly different from zero, suggesting that genetic influences on skinfold distribution are independent of those on abdominal body fat and overall obesity. The genetic findings support the hypothesis that the WHR and SSTR indexes do not assess the same dimensions of fat patterning.

Adipose Tissue↗

PubMed1994

Clustering of hypertension, diabetes, and obesity in adult male twins: same genes or same environments?

We investigated the mediating role of genetic factors in the clustering of hypertension, diabetes, and obesity, using the twin registry maintained by the National Academy of Sciences--National Research Council. The study sample included 2,508 male twin pairs born between 1917 and 1927 who responded to a mailed questionnaire that covered demographic variables, cardiovascular risk factors, and health behaviors. The incidence of hypertension and diabetes in this cohort was ascertained from subjects' self-report of a physician diagnosis and/or the use of prescription medications. The body-mass index calculated from self-reports of height and weight was used as a measure of obesity. Descriptive analyses indicated probandwise concordance rates of 34.0%, 31.2%, and 32.7%, respectively, for the joint occurrences of hypertension and diabetes, hypertension and obesity, and diabetes and obesity in MZ twin pairs. Corresponding concordance rates in DZ twin pairs were 8.1%, 14.9%, and 2.8%. The probandwise concordance for the clustering of all three conditions in the same individuals was 31.6% in MZ pairs and 6.3% in DZ pairs (relative risk 5.0; X2(1) = 2.6; P < .15). Multivariate genetic modeling of the correlation in liabilities to develop these conditions suggested the presence of a common latent factor mediating the clustering of hypertension, diabetes, and obesity in this twin sample. This common factor was influenced by both genetic and environmental effects (59% 8 genetic, 41% environmental). The genetic influences on the common latent factor were due to dominant rather than additive sources; the environmental influences appeared to be specific rather than shared by co-twins.

Aged↗

PubMed1993

Genetic analysis of drinking behavior in World War II veteran twins.

The objective of the present study was to investigate longitudinal changes in drinking behaviors of adult male twins and model these changes as a function of genetic and environmental influences. Alcohol data available for World War II veteran twins, first surveyed in 1967-69 and followed up during 1983-85, were used to examine components of variability in measures of alcohol consumption. Multivariate biometric analysis of these data indicated 1) longitudinal stability of drinking behaviors in this cohort, 2) a significant contribution of genetic factors to the observed stability that accounted for more than 80% of the stable variation in frequency and in quantity of alcohol consumed per drinking occasion, and 3) evidence for a significant contribution of shared environmental influences to drinking of specific beverages (e.g., wine). The implications of these results for issues of health in the elderly are considered.

Aging↗

PubMed1993

The NHLBI male veteran twin study data.

The National Heart, Lung and Blood Institute (NHLBI) twin study is a collaborative, longitudinal study of the role of genetic risk factors on subsequent cardiovascular disease processes in 514 pairs of white, male World War II and Korean veteran twins born between 1917 and 1927. This paper describes the sampling procedures and zygosity determination at the initial examination, participation by the cohort members at later examinations, and a summary of the variables provided for Genetic Analysis Workshop 8 (GAW8).

Aged↗

PubMed1993

Differential rates of relapse in subgroups of male and female smokers.

Subjects for this study were 265 participants of stop-smoking clinics (mean age = 42.6 years; average number of cigarettes smoked daily = 26.0) who were examined before and immediately after cessation and then followed for 1 year. The objective of this study was to identify subgroups of smokers with different rates of relapse using tree-structured survival analysis, a multivariate approach to classification. Five distinct subgroups that differed with respect to the rate of relapse were identified: (I) subjects (n = 15) with very low precessation cotinine levels (< or = 129 ng/ml), who had an exceptionally low rate of relapse (mean abstinence time = 270 days); (II) women 32 years old and younger (n = 24), who had a very high rate of relapse (mean abstinence time = 30.5 days); (III) women over 32 years old (n = 121), with the next highest rate of relapse (mean abstinence time = 98.9 days); (IV) men 36 years old and younger (n = 31), who had a mean abstinence time of 196.7 days; and (V) men over 36 years old (n = 74), who abstained an average of 130.2 days before relapsing. Relapse curves for all groups (except III vs V) differed significantly from each other, p < 0.05. Results indicate that this approach can identify interactions among individual differences that are variably associated with relapse rates. Identification of relapse subgroups may have important implications for both theories and treatment of smoking relapse.

Adult↗

PubMed1993

The relationship between quitting smoking and changes in drinking in World War II veteran twins.

Smoking has been associated with the intake of alcohol, and abstinence from tobacco has been hypothesized to increase alcohol intake. There is no consensus, however, on the extent of changes in alcohol intake following withdrawal from nicotine. The current study of a large cohort (n = 5,510) of World War II male veteran twins examined, prospectively, changes in drinking in relation to changes in smoking over a 16-year time period in late adulthood. Self-reported histories of smoking habits obtained from two surveys, administered in 1967-1969 and in 1983-1985, allowed the classification of subjects into continuing smokers (n = 1,441), quitters (n = 1,760), and continuing nonsmokers (n = 2,309). Analyses of the change in alcohol consumption over the period of follow-up, after adjustment for baseline consumption, socioeconomic variables, and health status, found: (1) a significant but moderate increase in alcohol consumption in quitters, due to an increase in wine consumption; (2) a significant marked increase in alcohol consumption in continuing smokers due to an increase in consumption of spirits; and (3) no significant change in alcohol consumption in continuing nonsmokers. These findings indicate that smoking cessation, a behavior change that promotes health, is associated with an increase in alcohol consumption, which may have other adverse long-term effects on health in this cohort.

Adult↗