Biomedical subjects

A B Zonderman

Publications and source records attributed to A B Zonderman.

At least 19 recordsLinked to original sources

PubMed2001

Coordinately up-regulated genes in ovarian cancer.

A better understanding of the molecular circuitry in normal ovarian tissues and in ovarian cancer will likely provide new targets for diagnosis and therapy. Recently, much has been learned about the genes expressed in ovarian cancer through studies with cDNA arrays and serial analysis of gene expression. However, these methods do not allow highly quantitative analysis of gene expression on a large number of specimens. Here, we have used quantitative real-time RT-PCR in a panel of 39 microdissected ovarian carcinomas of various subtypes to systematically analyze the expression of 13 genes, many of which were previously identified as up-regulated in a subset of ovarian cancers by serial analyses of gene expression. The genes analyzed are glutathione peroxidase 3 (GPX3), apolipoprotein J/clusterin, insulin-like growth factor-binding protein 2, epithelial cell adhesion molecule/GA733-2, Kop protease inhibitor, matrix gla protein, tissue inhibitor of metalloproteinase 3, folate receptor 1, S100A2, signal transducer and activator of transcription 1, secretory leukocyte protease inhibitor, apolipoprotein E, and ceruloplasmin. All of the genes were found overexpressed, some at extremely high levels, in the vast majority of ovarian carcinomas irrespective of the subtype. Interestingly, GPX3 was found at much higher levels in tumors with clear cell histology and may represent a biomarker for this subtype. Some of the genes studied here may thus represent targets for early detection ovarian cancer. The gene expression patterns were not associated with age at diagnosis, stage, or K-ras mutation status in ovarian cancer. We find that several genes are coordinately regulated in ovarian cancer, likely representing the fact that many genes are activated as part of common signaling pathways or that extensive cross-talk exists between several pathways in ovarian cancer. A statistical analysis shows that genes commonly up-regulated in ovarian cancer may result from the aberrant activation of a limited number of pathways, providing promising targets for novel therapeutic strategies.

Biomarkers, Tumor↗

PubMed2001

Is the apoE4 allele an independent predictor of coronary events?

PURPOSE: Although the apolipoprotein E genotype epsilon4 (apoE4) has been associated with high cholesterol levels, whether it is an independent predictor of coronary events is not certain. SUBJECTS AND METHODS: We measured apoE genotypes in 730 participants in the Baltimore Longitudinal Study of Aging (421 men and 309 women, mean [+/- SD] age of 52+/-17 years) who were free of preexisting coronary heart disease. A proportional hazards regression model was used to study the association between risk factors and the occurrence of coronary events, defined as angina pectoris, documented myocardial infarction by history or major Q waves on the electrocardiogram (Minnesota Code 1:1 or 1:2), or coronary death, adjusted for other risk factors, including total plasma cholesterol level. RESULTS: The apoE4 allele was observed in 200 subjects (27%), including 183 heterozygotes and 17 homozygotes. Coronary risk factor profiles were similar in those with and without apoE4. Coronary events developed in 104 (14%) of the 730 subjects, including 77 (18%) of the 421 men during a mean follow-up of 20 years and 27 (9%) of the 309 women during a mean follow-up of 13 years. Coronary events occurred significantly more frequently in subjects with apoE4 (n = 40, 20%) than in those without this allele (64, 12%, P <0.05). In a multivariate model, apoE4 was an independent predictor of coronary events in men (risk ratio [RR]= 2.9, 95% confidence interval [CI]: 1.8 to 4.5, P<0.0001) but not in women (RR = 0.9, 95% CI: 0.4 to 1.9, P = 0.62). CONCLUSION: The apoE4 genotype is a strong independent risk factor for coronary events in men, but not women. The association does not appear to be mediated by differences in total cholesterol levels.

Adult↗

PubMed2001

Enhanced verbal memory in nondemented elderly women receiving hormone-replacement therapy.

OBJECTIVE: This study examined the effects of hormone-replacement therapy on memory and other cognitive abilities in cognitively intact older women. METHOD: This prospective observational study in nondemented postmenopausal women aged 50-89 from the Baltimore Longitudinal Study of Aging involved study groups consisting of 103 women who were receiving oral or transdermal estrogen-replacement therapy (44 of whom were receiving adjuvant progesterone) and 81 women who had never received such therapy. Groups were naturally matched on education, health status, depressive symptoms, annual income, and general verbal ability. To restrict the study group to cognitively healthy women, prospective clinical data were used to exclude women who developed dementia up to 5 years after assessment. Data were cross-sectional. Multivariate analysis of variance and follow-up univariate analyses of variance were performed to compare those women who were receiving and those who had never received hormone-replacement therapy on measures of verbal memory, figural memory, mental rotations, attention, and working memory. RESULTS: The women receiving hormone-replacement therapy performed significantly better on measures of verbal learning and memory than did those who had never received hormones, but there were no significant differences in scores on other cognitive tests. Specific aspects of memory performance, including encoding and retrieval, were superior among the women receiving hormone therapy. CONCLUSIONS: These findings, based on groups of women who were receiving and had never received hormone-replacement therapy and who were naturally matched on health and cognitive status, suggest that hormone-replacement therapy may have a selective beneficial effect on verbal memory in older nondemented women.

Aged↗

PubMed2000

The relationship between longitudinal declines in dehydroepiandrosterone sulfate concentrations and cognitive performance in older men.

BACKGROUND: The observation that dehydroepiandrosterone (DHEA) concentrations decrease markedly with age has led to the hypothesis that declining DHEA concentrations may contribute to age-related changes in cognition. In the United States, DHEA is widely available as an over-the-counter supplement that individuals are using in an effort to ameliorate age-related cognitive and physical changes. OBJECTIVE: To investigate the relationship between age-associated decreases in endogenous DHEA sulfate (DHEA-S) concentrations and declines in neuropsychological performance in a prospective, longitudinal study. METHODS: The subjects were 883 men from a community-dwelling volunteer sample in the Baltimore Longitudinal Study of Aging. The men were aged 22 to 91 years at the initial visit, and they were followed up for as long as 31 years (mean, 11. 55 years), with biennial reassessments of multiple cognitive domains and contemporaneous measurement of serum DHEA-S concentrations. Outcome measures were the results of cognitive tests of verbal and visual memory, 2 tests of mental status, phonemic and semantic word fluency tests, and measures of visuomotor scanning and attention. Serum DHEA-S concentrations were determined by standard radioimmunoassay. RESULTS: Neither the rates of decline in mean DHEA-S concentrations nor the mean DHEA-S concentrations within individuals were related to cognitive status or cognitive decline. A comparison between the highest and lowest DHEA-S quartiles revealed no cognitive differences, despite the fact that these groups differed in endogenous DHEA-S concentration by more than a factor of 4 for a mean duration of 12 years. CONCLUSION: Our longitudinal results augment those of previous prospective studies by suggesting that the decline in endogenous DHEA-S concentration is independent of cognitive status and cognitive decline in healthy aging men.

Adult↗

PubMed2000

Longitudinal change in hippocampal volume as a function of apolipoprotein E genotype.

The epsilon4 allele of the apolipoprotein E (APOE) gene confers an increased risk for the development of AD. The authors compared longitudinal rates of change in hippocampal volume as a function of APOE genotype in nondemented elderly individuals. Rate of volumetric loss was significantly greater among epsilon4+ compared with epsilon4- individuals. These results indicate that individuals positive for the APOE epsilon4 allele may show a greater rate of hippocampal atrophy than their epsilon4- counterparts, even in the absence of a diagnosis of AD.

Age Factors↗

PubMed2000

One-year age changes in MRI brain volumes in older adults.

Longitudinal studies indicate that declines in cognition and memory accelerate after age 70 years. The neuroanatomic and neurophysiologic underpinnings of cognitive change are unclear, as there is little information on longitudinal brain changes. We are conducting a longitudinal neuroimaging study of nondemented older participants in the Baltimore Longitudinal Study of Aging. This report focuses on age and sex differences in brain structure measured by magnetic resonance imaging during the first two annual evaluations. Cross-sectional results from 116 participants aged 59-85 years reveal significantly larger ventricular volumes and smaller gray and white matter volumes in older compared with younger participants and in men compared with women. Regional brain volumes show that the effects of age and sex are not uniform across brain regions. Age differences are greatest for the parietal region. Sex differences tend to be larger for frontal and temporal than parietal and occipital regions. Longitudinal analysis demonstrates an increase of 1526 mm(3) in ventricular volume over 1 year, but no detectable change in total or regional brain volumes. Definition of the pattern and rate of longitudinal brain changes will facilitate the detection of pathological brain changes, which may be predictors of dementia.

Age Factors↗

PubMed2000

Do the dimensions of the temperament and character inventory map a simple genetic architecture? Evidence from molecular genetics and factor analysis.

OBJECTIVE: It has been reported that the human temperament dimensions of novelty seeking and harm avoidance are associated with polymorphisms in the D(4) dopamine receptor gene (D4DR) and the serotonin-transporter-linked promoter region (5-HTTLPR), respectively. Although these findings are consistent with Cloninger's hypothesized psychobiological model of temperament and character, many studies failed to replicate these findings. In the present study the authors tested whether the psychobiological model taps the genetic architecture of personality by exploring associations between these candidate genes and the dimensions of the Temperament and Character Inventory and by examining its phenotypic structure. METHOD: Of the 946 male and female participants in the Baltimore Longitudinal Study of Aging to whom the Temperament and Character Inventory was administered, 587 were genotyped for a polymorphism with a 48-base-pair repeat in the D4DR gene and 425 were genotyped for a 44-base-pair insertion or deletion in the 5-HTTLPR polymorphism. RESULTS: There was no significant association between D4DR polymorphisms and novelty seeking. The authors also failed to find an association between 5-HTTLPR polymorphisms and harm avoidance. The factor structure of the Temperament and Character Inventory did not reveal the hypothesized phenotypic structure. CONCLUSIONS: This investigation produced no support for the temperament-character model at either the biological or psychological level.

Adult↗

PubMed1999

Age differences in implicit memory: fragmented object identification and category exemplar generation.

In a cross-sectional study of 164 participants aged 21 to 91, the authors examined age differences on two implicit tests, fragmented object identification (FOI) and category exemplar generation (CEG), and on tests of explicit memory, attention, and verbal fluency. FOI results revealed impaired perceptual skill learning in those over 60 and a decrease in perceptual priming across young, middle-aged, and older groups. CEG priming was impaired in those over 80. Regression analysis revealed explicit contamination of priming on both the FOI and CEG tests. Across the three implicit measures, age accounted for 4 to 13% of the variance when explicit memory was controlled. Semantic fluency predicted CEG priming, suggesting possible frontal lobe involvement on the test. Altogether, results indicate that age has a small but reliable influence on implicit memory.

Adult↗

PubMed1998

Effects of estrogen replacement therapy on PET cerebral blood flow and neuropsychological performance.

Reports that estrogen may protect against age-associated memory decline and Alzheimer's Disease have kindled interest in the effects of estrogen replacement therapy (ERT) on cognition and brain function. As part of a 9-year study in the Baltimore Longitudinal Study of Aging, we are performing annual magnetic resonance imaging, positron emission tomography (PET), and neuropsychological assessments to examine brain structure and function in individuals aged 55 and older. PET measurements of regional cerebral blood flow (rCBF) are obtained under 3 conditions: rest and verbal and figural delayed recognition memory tasks. Fifteen women receiving ERT (with or without the addition of progesterone) were compared with a matched sample of 17 untreated women. There were no significant differences between groups in regional brain volumes or ventricular size. However, ERT users and nonusers showed significant differences in PET-rCBF relative activation patterns during the memory tasks. During verbal memory processing, there were significant interactions in rCBF activations for the right parahippocampal gyrus, right precuneus, right frontal regions, and left hypothalamus. During figural memory processing, significant interactions were observed for right parahippocampal and inferior parietal regions and for left visual association and anterior thalamic regions. ERT users also showed better performance on neuropsychological tests of figural and verbal memory and on some aspects of the PET activation tests, although the two groups did not differ in education, overall verbal ability, or performance on other neuropsychological tests. These findings confirm our previous observation of the beneficial effects of ERT on figural memory. Moreover, differences in rCBF activation patterns between ERT users and nonusers suggest an area for future research to examine mechanisms through which ERT may influence memory and other cognitive abilities.

Aged↗

PubMed1997

No association between novelty seeking and dopamine D4 receptor (D4DR) exon III seven repeat alleles in Baltimore Longitudinal Study of Aging participants.

Recent studies by Ebstein et al and Benjamin et al found associations between long repeat polymorphisms in the D4 dopamine receptor gene (D4DR) and individual variation in a human personality trait, identified as 'Novelty Seeking' (NS). Ebstein et al used the Tridimensional Personality Questionnaire (TPQ) to measure NS scores; Benjamin et al used the Revised NEO Personality Inventory (NEO-PI-R) to estimate NS scores. However, Malhotra et al failed to replicate the association between the direct measure of NS using the TPQ and the long alleles of the D4DR genotypes in two Finnish samples. In an attempt to confirm the association found by Benjamin et al using NEO-PI-R estimated NS, the present study used an alternative design extreme groups strategy to select high and low novelty seeking research volunteers from the Baltimore Longitudinal Study of Aging (BLSA). There were no significant associations between long alleles (7-repeat allele) and high novelty seeking groups. The findings of Ebstein and colleagues and those of Benjamin and colleagues do not generalize to this American middle-aged, mixed-gender sample, a conclusion also consistent with the findings of a recent Swedish study. Demographic factors such as the age and gender composition of the samples are important sources of variation in allelic association studies and future research must carefully address whether the D4DR genetic polymorphisms vary substantially across demographic groups.

Adult↗

PubMed1997

Estrogen replacement therapy and longitudinal decline in visual memory. A possible protective effect?

Estrogen replacement therapy (ERT) is increasingly recommended for postmenopausal women due to its beneficial effects on physical health in older women. Recent studies have suggested that ERT may have a protective effect on cognitive function and may reduce the risk of Alzheimer's disease. In the present study we test the hypothesis that ERT may have a protective effect on memory in nondemented women. Data on hormonal status and memory were examined in 288 postmenopausal women in the Baltimore Longitudinal Study of Aging. One hundred sixteen women who reported that they were receiving ERT during a cognitive assessment were compared with 172 women who had never received ERT. Women who were receiving ERT had fewer errors on the Benton Visual Retention Test (BVRT), a measure of short-term visual memory, visual perception, and constructional skills. Furthermore, ERT appeared to protect against age changes in BVRT performance in a subgroup of 18 women for whom BVRT data were available before and during treatment with ERT. These findings suggest that ERT may protect against memory decline in nondemented postmenopausal women and offer further support for a beneficial role of estrogen on cognitive function in aging women.

Aged↗

PubMed1995

Adult life span changes in immediate visual memory and verbal intelligence.

A sample of 558 women and 1,163 men 17 to 102 years old, screened for neurodegenerative and neuropsychiatric disease, was administered tests of immediate visual memory (Benton Visual Retention Test) and crystallized intelligence (Wechsler Adult Intelligence Scale Vocabulary subtest) from 1 to 5 times over 27.7 years. Cross-sectional and longitudinal evidence led to the conclusion that the 65-74-year decade was a watershed for decremental changes in immediate visual memory and verbal intelligence. Age accounted for considerably less variance in vocabulary than in immediate memory. The proportion of individuals whose longitudinal trajectories were contrary to group trends decreased substantially with increased age; observed age changes remained when analyses were restricted to individuals who had perfect or near-perfect mental status scores. Selected neuronal loss and slower reproduction times were considered as possible causes.

Adolescent↗

PubMed1995

Age-associated changes in specific errors on the Benton Visual Retention Test.

While total errors on the Benton Visual Retention Test (BVRT) are known to increase in normal aging, there is little information on changes for specific error types. We examined the differential increase in seven specific error categories for 2,000 participants in the Baltimore Longitudinal Study of Aging. Cross-sectional analyses indicated that all errors increased with age, but differences between age groups in error profiles suggested relatively greater age effects for distortions, omissions, and rotations. There were also significant gender differences in error profiles, reflecting increased rotation and omission errors in females. Longitudinal analyses of age changes for a subset of 673 participants with three BVRT assessments were consistent with the cross-sectional data and indicated intra-individual increases with age in distortions, omissions, and rotations. While women made more omission errors, men showed steeper increases in omission errors with age. These findings suggest that cerebral aging impacts all categories of BVRT errors but has differential effects on particular error types.

Adult↗

PubMed1993

Depressive symptoms as a nonspecific, graded risk for psychiatric diagnoses.

Using data from a 16-year follow-up of a nationally representative sample of 6,913 adults, measures of depressive symptoms were used to predict psychiatric diagnoses taken from hospitalization records. In proportional hazards analyses, two measures of depression were significantly associated with subsequent diagnoses of depression and other psychiatric disorders after statistical control for demographic variables and previous history of psychological problems. Depressive symptoms predicted late as well as early occurrence of psychiatric diagnoses and showed a pattern of increasing risk with increasing scores, even below clinical cutoffs. This pattern of results is consistent with the view that depressive symptoms predict future psychiatric disorders largely because they serve as proxy measures of some chronic vulnerability, such as the normal personality dimension of neuroticism.

Adult↗

PubMed1990

Prevalence and prognostic significance of exercise-induced silent myocardial ischemia detected by thallium scintigraphy and electrocardiography in asymptomatic volunteers.

Although a silent ischemic electrocardiographic response to treadmill exercise in clinically healthy populations is associated with an increased likelihood of future coronary events (i.e., angina pectoris, myocardial infarction, or cardiac death), such a response has a low predictive value for future events because of the low prevalence of disease in asymptomatic populations. To examine whether detection of reduced regional perfusion by thallium scintigraphy improved the predictive value of exercise-induced ST segment depression, we performed maximal treadmill exercise electrocardiography (ECG) and thallium scintigraphy (201Tl) in 407 asymptomatic volunteers 40-96 years of age (mean = 60) from the Baltimore Longitudinal Study on Aging. The prevalence of exercise-induced silent ischemia, defined by concordant ST segment depression and a thallium perfusion defect, increased more than sevenfold from 2% in the fifth and sixth decades to 15% in the ninth decade. Over a mean follow-up period of 4.6 years, cardiac events developed in 9.8% of subjects and consisted of 20 cases of new angina pectoris, 13 myocardial infarctions, and seven deaths. Events occurred in 7% of individuals with both negative 201Tl and ECG, 8% of those with either test positive, and 48% of those in whom both tests were positive (p less than 0.001). By proportional hazards analysis, age, hypertension, exercise duration, and a concordant positive ECG and 201Tl result were independent predictors of coronary events. Furthermore, those with positive ECG and 201Tl had a 3.6-fold relative risk for subsequent coronary events, independent of conventional risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Depression as a risk for cancer morbidity and mortality in a nationally representative sample.

The relative risks for cancer morbidity and mortality associated with depressive symptoms were examined using data from the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study. The Center for Epidemiologic Studies Depression scale and the depression subscale from the General Well-being Schedule were used as predictors in this 10-year follow-up study of a nationally representative sample. No significant risk for cancer morbidity or mortality was associated with depressive symptoms with or without adjustment for age, sex, marital status, smoking, family history of cancer, hypertension, and serum cholesterol level. These data were also reanalyzed for subjects aged 55 years or older who were retraced by a second follow-up. Neither measure of depressive symptoms was a significant risk for cancer death during the 15-year follow-up interval. These results call into question the causal connection between depressive symptoms and cancer morbidity and mortality.

Age Factors↗

PubMed1988

Symptoms of psychologic distress associated with irritable bowel syndrome. Comparison of community and medical clinic samples.

Women with symptoms indicative of irritable bowel syndrome who had not consulted a physician were compared with female patients at a gastroenterology clinic to investigate whether self-selection for treatment accounts for psychologic abnormalities in clinic patients' with irritable bowel syndrome. Two sets of diagnostic criteria were compared: restrictive criteria based on the work of Manning and conventional criteria (abdominal pain plus altered bowel habits). Lactose malabsorbers were included as a control group because they have medically explained bowel symptoms similar to those that define irritable bowel syndrome. Thus they control for the causative effects of chronic bowel symptoms on psychologic distress. Women who met restrictive criteria for irritable bowel syndrome but had not consulted a physician had no more symptoms of psychologic distress on the Hopkins Symptom Checklist than asymptomatic controls. However, medical clinic patients with both irritable bowel syndrome and lactose malabsorption had significantly more psychologic symptoms than asymptomatic controls or nonconsulters with the same diagnoses. Individuals who met only the conventional criteria for irritable bowel syndrome reported more psychologic distress than controls, whether or not they consulted a physician. These results suggest that (a) symptoms of psychologic distress are unrelated to irritable bowel syndrome but influence which patients consult a doctor and (b) conventional diagnostic criteria identify more psychologically distressed individuals than do restrictive criteria.

Adolescent↗

PubMed1987

A comparison of the symptoms of medical and psychiatric patients matched on the Beck Depression Inventory.

The goals of this study were to examine, in greater detail, the experience of depression in the medically ill, and to compare their experience with that of depressed psychiatric patients. Medical and psychiatric inpatients were matched in terms of total scores on the Beck Depression Inventory (BDI). In addition to the BDI, all patients completed a self-report symptom battery. No difference was found between the two groups in terms of total BDI scores, but psychiatric patients scored significantly higher on the affective BDI items, and medical patients scored significantly higher on the somatic BDI items. Discriminant analysis was used to compare their responses to the symptom battery. Depression in the psychiatric patients was characterized primarily by suicidal ideation and loss of interest, whereas in medical patients a lack of energy and worry were the predominant symptoms. The implications of these findings for assessing depression in the medically ill are discussed.

Adult↗