Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is growing evidence that post menopausal use of estrogen may have a beneficial effect on cognition and may reduce the risk of dementia. In a vast majority of studies, the use of estrogen replacement in the postmenopausal period was associated with a reduced risk of dementia. Meta-analyses of both retrospective case controlled and prospective studies indicate a 30% reduction in the risk of dementia, with larger effect sizes (50% reduction) reported in the latter. Some, but not all, large epidemiological studies indicate that estrogen use is associated with better performance on both verbal and visual memory testing in later life. However, studies of the effect of estrogen on patients with Alzheimer's disease are less convincing with minimal effects reported in open trials and following brief exposure. Biological mechanisms, which could be responsible for some of these effects, include activation of the cholinergic system, anti-oxidant action, neurotrophic stimulation and anti-amyloidogenic properties. Beneficial effects of estrogen in primary prevention but not secondary prevention of heart disease indicates that the ability to observe beneficial effects may depend on the point at which intervention occurs. Ongoing double-blind randomized clinical trial to determine if estrogen is a safe and effective treatment for the prevention of memory loss and Alzheimer's disease will be described. Future work will undoubtedly include the identification of specific estrogenic receptors in the central nervous system that can be selectively activated without adverse involvement of other biologic systems.
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PMID:Understanding the role of estrogen on cognition and dementia. 1096 33

PURPOSE: The purpose of this study is to examine the relation between hip fractures and Alzheimer's disease in institutionalized men and women who participated in the 1994-1995 Canadian National Population Health Survey (NPHS).METHODS: Participants in the institutional component of NPHS were randomly chosen from selected health care institutions from all provinces in Canada. A questionnaire, which assessed health, demographic and socio-economic status, risk factors, medication use, and falls, was administered by an interviewer. Proxy respondents were sought for residents who were ill or incapacitated. Logistic regression was used to examine the association between hip fractures and Alzheimer's disease in 408 men and 1105 women >/=65 years. Models were examined with either hip fracture or Alzheimer's disease as the dependent variable. Covariates that were assessed included osteoporosis, age group, sex, medications, reported falls and comorbid conditions.RESULTS: All hip fractures reported in this survey were the result of a fall, however only 3.7% of falls resulted in a hip fracture. Those who had sustained a hip fracture were more likely to have Alzheimer's disease (OR 2.0, 95% CI 1.1-3.5), osteoporosis (OR 4.3, 95% CI 2.5-7.4) and heart disease (OR 2.4, 95% CI 1.1-5.0). Respondents who had Alzheimer's disease were more likely to have sustained a hip fracture (OR 2.1 95% CI 1.2-3.6), to have osteoporosis (OR 1.9, 95% CI 1.5-2.5), and to have fallen (OR 1.4, 95% CI 1.1-1.8) and were less likely to be taking anti-psychotic medication (OR 0.4, 95% CI 0.3-0.6) than those with no diagnosis of Alzheimer's disease.CONCLUSIONS: There is an association between Alzheimer's disease and hip fractures that is independent of other covariates in this representative sample of institutionalized elderly Canadians.
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PMID:The relation between hip fracture and alzheimer's disease in the canadian national population health survey health institutions data, 1994-1995. A cross-sectional study. 1101 77

HRT provides both prevention and treatment of osteoporosis. HRT is most likely beneficial in primary prevention of heart disease, and may have a role in preventing Alzheimer's disease and colon cancer. Prospective trials, such as the Women's Health Initiative, are needed to substantiate both benefits and risks. Decisions regarding HRT, as well as nonhormonal regimens, should be individualized.
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PMID:Benefits and challenges of hormone replacement therapy. 1102 58

Apolipoprotein E (apoE) is an important lipid-transport protein in human plasma and brain. It has three common isoforms (apoE2, apoE3, and apoE4). ApoE is a major genetic risk factor in heart disease and in neurodegenerative disease, including Alzheimer's disease. The interaction of apoE with heparan sulfate proteoglycans plays an important role in lipoprotein remnant uptake and likely in atherogenesis and Alzheimer's disease. Here we report our studies of the interaction of the N-terminal domain of apoE4 (residues 1-191), which contains the major heparin-binding site, with an enzymatically prepared heparin oligosaccharide. Identified by its high affinity for the N-terminal domain of apoE4, this oligosaccharide was determined to be an octasaccharide of the structure DeltaUAp2S(1-->[4)-alpha-D-GlcNpS6S(1-->4)-alpha-L-IdoAp2S(1-->](3)4)-alpha-D-GlcNpS6S by nuclear magnetic resonance spectroscopy, capillary electrophoresis, and polyacrylamide gel electrophoresis. Kinetic analysis of the interaction between the N-terminal apoE4 fragment and immobilized heparin by surface plasmon resonance yielded a K(d) of 150 nM. A similar binding constant (K(d) = 140 nM) was observed for the interaction between immobilized N-terminal apoE4 and the octasaccharide. Isothermal titration calorimetry revealed a K(d) of 75 nM for the interaction of the N-terminal apoE fragment and the octasaccharide with a binding stoichiometry of approximately 1:1. Using previous studies and molecular modeling, we propose a binding site for this octasaccharide in a basic residue-rich region of helix 4 of the N-terminal fragment. From the X-ray crystal structure of the N-terminal apoE4, we predicted that binding of the octasaccharide at this site would result in a change in intrinsic fluorescence. This prediction was confirmed experimentally by an observed increase in fluorescence intensity with octasaccharide binding corresponding to a K(d) of approximately 1 microM.
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PMID:Interaction of the N-terminal domain of apolipoprotein E4 with heparin. 1125 93

Hormone replacement therapy (HRT) has been proposed for the prevention and treatment of many chronic conditions, ranging from osteoporosis, heart disease, urinary incontinence, and Alzheimer's disease. With the exception of osteoporosis, however, many of the suggested benefits remain controversial. Part of the controversy stems from the relative absence of randomized controlled trials, particularly those enrolling sufficient numbers of elderly women. We propose that another factor may also contribute, one that has been overlooked - failure to consider the variable endogenous estrogen status of elderly women. Highly variable levels of estrogens are present in nearly all postmenopausal women, even at advanced ages. Similar to other endocrine systems, estrogen deficiency and the need for its replacement are, therefore, likely to be relative rather than absolute. Recent studies indicate that elderly women who are less able to compensate for declining ovarian 17beta-estradiol production by adipose synthesis of estrone (E1) may be at greater risk for certain chronic conditions associated with relative estrogen deficiency. Because many markers of estrogen deficiency exhibit overlap between risk groups, their clinical usefulness as predictors of frailty, disability, and response to HRT has been limited. Future studies will need to focus not only on the use of highly variable circulating serum estrogen levels but also on markers of overall estrogenic effects at the level of individual target tissues (i.e., markers of bone turnover, karyopyknotic index on a vaginal wall smear). We propose that a clinical approach that takes into consideration the remarkable heterogeneity (physiological as well as psychological) of elderly women will enable us to approach the decision about HRT in a more individualized and possibly better targeted fashion.
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PMID:Can variability in the hormonal status of elderly women assist in the decision to administer estrogens? 1126 96

Menopause marks the end of menstruation, once generally accepted as the closure of women's reproductive lives. The current medical view of menopause, however, is as a pathological event with its own distinct set of symptoms and diseases. Researchers have described women as facing a dramatic increase in the risk of heart disease, osteoporosis, stroke, and Alzheimer's, all as the result of the impact of changing hormone levels, particularly the decline in estrogen. The clinical literature has interpreted these findings in terms of the absolute necessity of replacing these lost hormones for all women who are menopausal regardless of any other physiological, social, or cultural characteristic they might possess. Using research done in Japan, Canada, and the United States, this paper challenges the notion of a universal menopause by showing that both the symptoms reported at menopause and the post-menopause disease profiles vary from one study population to the next. For most of the symptoms commonly associated with menopause in the medical literature, rates are much lower for Japanese women than for women in the United States and Canada, although they are comparable to rates reported from studies in Thailand and China. Mortality and morbidity data from these same societies are used to show that post-menopausal women are also not equally at risk for heart disease, breast cancer, or osteoporosis. Rather than universality, the paper suggests that it is important to think in terms of "local biologies", which reflect the very different social and physical conditions of women's lives from one society to another.
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PMID:Menopause, local biologies, and cultures of aging. 1140 Feb 20

Dehydroepiandrosterone (DHEA) is a steroid hormone secreted primarily by the adrenal glands and to a lesser extent by the brain, skin, testes, and ovaries. It is the most abundant circulating steroid in humans and can be converted into other hormones, including estrogen and testosterone. It has been characterized as a pleiotropic "buffer hormone," with receptor sites in the liver, kidney, and testes, and has a key role in a wide range of physiological responses. Circulating levels of DHEA decline with age and a relationship has been suggested between lower DHEA levels and heart disease, cancer, diabetes, obesity, chronic fatigue syndrome, AIDS, and Alzheimer's disease. Other research suggests that autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, and multiple sclerosis might be associated with declining DHEA levels.
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PMID:DHEA. Monograph. 1141 76

The term "cardiogenic dementia" was introduced a few decades ago to indicate an alteration of consciousness and cognition due to heart disease. Although this term is now disused, the relationship between cardiovascular disease and cognitive impairment is currently of great interest, not only for its potential therapeutic implications. but also for the recently recognized important role that vascular factors appear to play in Alzheimer's disease. The aims of this review are therefore 1) to show data supporting the role of cardiac disease--namely congestive heart failure, myocardial infarction and atrial fibrillation--and other vascular risk factors--i.e., hypertension and diabetes--in the development or worsening of cognitive impairment; 2) to highlight recent observations on the relationship between presence and severity of congestive heart failure/ myocardial infarction/atrial fibrillation and Alzheimer's disease: and 3) to uncover the type of studies needed in this field in order to facilitate a more precise algorithm of dementia prevention as well as intervention in demented patients with cardiovascular disease.
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PMID:Heart disease and vascular risk factors in the cognitively impaired elderly: implications for Alzheimer's dementia. 1144 5

To identify neuropsychiatric and somatic factors related to survival in early-onset Alzheimer's disease, we longitudinally studied 108 patients (35 male, 73 female) with early-onset Alzheimer's disease who were 46 to 64 years old at onset and 50 to 69 years old when diagnosed at our institution. A five-year follow-up, 30 patients had died. Pneumonia was the most common cause (73%), followed by malignancy (20%) and heart disease (7%). Kaplan-Meier survival curves showed a lower survival rate in patients with early-onset Alzheimer's disease than in age- and sex-matched life-table data in Japan. In Cox proportional hazards analysis, male gender, early disease onset, concurrent physical illness at time of diagnosis, and a low mini-mental state examination score increased the likelihood of death in patients with early-onset Alzheimer's disease. Our study confirmed that these patients have considerable excess mortality and a different pattern of cause of death than in the general population. Gender, age at onset, physical illness, and cognitive function strongly influenced survival. These factors may be predictors of mortality in patients with early-onset Alzheimer's disease that are useful in counseling patients and their families.
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PMID:Factors associated with mortality in patients with early-onset Alzheimer's disease: a five-year longitudinal study. 1153 48

Nearly all of the literature on the ethical, legal, or social issues surrounding genetic tests has proceeded on the assumption that any particular test for a gene mutation yields information about only one disease condition. Even though the phenomenon of pleiotropy, where a single gene has multiple, apparently unrelated phenotypic effects, is widely recognized in genetics, it has not had much significance for genetic testing until recently. In this article, I examine a moral dilemma created by one sort of pleiotropic testing, APOE genotyping, which can yield information about the risk of two different conditions -- coronary heart disease and Alzheimer's disease. A physician administering APOE testing for the beneficial purpose of assessing the risk of heart disease may discover medically useless and socially harmful information about the patient's risk of Alzheimer's disease. I explore how much providers should disclose to patients about pleiotropic test results and whether patients are obligated to know as much about their genetic condition as possible.
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PMID:The question not asked: the challenge of pleiotropic genetic tests. 1165 25


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