Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular risk factors increase the risk of developing Alzheimer's disease. Increased concentrations of circulating homocysteine are associated with an increased risk of both vascular disease and Alzheimer's disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase. There is an increase in the concentration of ADMA in the circulation in vascular disease. We measured the concentrations of homocysteine, ADMA and nitric oxide (as nitrate and nitrite) in the plasma of 25 patients with Alzheimer's disease and 25 control subjects. There was a highly significant increase in the plasma concentration of homocysteine (P<0.001) and ADMA (P<0.0001) and a highly significant decrease in the plasma concentration of nitric oxide (P<0.0001) among the Alzheimer's patients. In the combined patient and control groups a highly significant positive correlation was found between the plasma concentrations of homocysteine and ADMA (r=0.782, P<0.0001). In addition, significant negative correlations were detected between the plasma concentration of nitric oxide and the plasma concentration of homocysteine (r=-0.592, P<0.0001) and ADMA (r=-0.789, P<0.0001). These significant correlations were found to persist, even when they were restricted to the Alzheimer's patients. The inhibition of endothelial nitric oxide synthesis by ADMA impairs cerebral blood flow, which may contribute to the development of Alzheimer's disease. Endothelial dysfunction is also associated with atherosclerosis and stroke, which are important risk factors for Alzheimer's disease. Inflammation plays an important role in Alzheimer's disease and the inhibition of endothelial nitric oxide by ADMA may increase the concentration of inflammatory mediators in the brain. The inhibition of neuronal nitric oxide synthesis by ADMA may cause cognitive dysfunction in Alzheimer's disease.
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PMID:Increased concentrations of homocysteine and asymmetric dimethylarginine and decreased concentrations of nitric oxide in the plasma of patients with Alzheimer's disease. 1292 48

Initially used to treat the vasomotor and vaginal symptoms of menopause, hormone replacement therapy (HRT) appeared to have many unexpected beneficial effects in early observational trials. It was hailed as a deterrent of atherosclerosis, osteoporosis, cognitive impairment, and Alzheimer disease. While its salutary effects on bone mass were substantiated, randomized clinical trials noted an increased risk of breast cancer, coronary artery disease, and thromboembolism, and raised doubts about the efficacy of HRT in improving quality of life. This article summarizes the literature and discusses current recommendations on the use of HRT.
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PMID:Current issues in hormone replacement therapy. 1504

Renal impairment is associated with an increased risk of carotid atherosclerosis and stroke, determinants of cognitive dysfunction and dementia. The purpose of this study was to determine whether moderate renal impairment is associated with incident dementia among community-dwelling older adults. Participants in the Cardiovascular Health Cognition Study without prevalent dementia (n = 3349) were included in the analysis. Incident dementia was confirmed through neurologic testing. Renal function at baseline was estimated by the inverse of serum creatinine (1/SCr); moderate renal impairment was defined as SCr > or = 1.3 mg/dl for women and > or = 1.5 mg/dl for men. Cox regression models were used to estimate the association of renal impairment with incident dementia. Because SCr is also a function of muscle mass, the authors determined whether the relationship between SCr and dementia was particularly strong among individuals without severe co-morbidity at baseline, as reflected by self-reported general health status. There were 477 incident dementia cases over a median 6 yr follow-up. After adjustment for potential confounders, moderate renal insufficiency was associated with a 37% increased risk of dementia (95% CI = 1.06 to 1.78). Similarly, a 0.5-unit decrement in 1/SCr (equivalent to an increase in SCr from 1.0 to 2.0 mg/dl) was associated with a 26% increased risk (95% CI = 1.02 to 1.60). These associations were present only among the 84% of older adults who reported good-excellent health. Among those in good-excellent health, higher SCr was associated with vascular-type dementia but not Alzheimer-type dementia. Moderate renal impairment, reflected by a higher SCr, is associated with an excess risk of incident dementia among individuals in good-excellent health. Strategies to prevent or delay the onset of dementia in patients with moderate renal impairment are needed.
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PMID:Moderate renal impairment and risk of dementia among older adults: the Cardiovascular Health Cognition Study. 1521 80

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory deficit, cognitive impairment, and personality changes accompanied by specific structural abnormalities in the brain. Deposition of amyloid-beta (Abeta) peptide into senile plaques is a consistent feature of the brains of patients affected by AD. Studies with both animal and cellular models of AD have shown that cholesterol homeostasis and distribution regulate Abeta generation. We have provided genetic, biochemical, and metabolic evidence that implicates intracellular cholesterol distribution, rather than total cholesterol levels, in the regulation of Abeta generation. This minireview focuses on the role of acyl-coenzyme A: cholesterol acyltransferase activity (ACAT) in Abeta generation. In genetically mutant cell lines that overproduce cholesterol but cannot synthesize cholesteryl esters (CEs) because of deficient ACAT activity, Abeta production is almost completely inhibited. Acyl-coenzyme A: cholesterol acyltransferase activity (ACAT) inhibitors, currently being developed for the treatment and prevention of atherosclerosis, reduce CE levels and Abeta generation by up to 50% in cell culture models of AD. Future mechanistic and transgenic animal studies are needed to evaluate the potential use of ACAT inhibitors in the therapeutic treatment or prevention of AD.
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PMID:Role of acyl-coenzyme a: cholesterol acyltransferase activity in the processing of the amyloid precursor protein. 1531 56

Obstructive sleep apnea (OSA) occurs commonly in the U.S. population and is seen in both obese as well as non-obese individuals. OSA is a disease characterized by periodic upper airway collapse during sleep, which then results in either apnea, hypopnea, or both. The disorder leads to a variety of medical complications. Neuropsychiatric complications include daytime somnolence, cognitive dysfunction, and depression. Increased incidence of motor vehicle accidents has been documented in these patients and probably reflects disordered reflex mechanisms or excessive somnolence. More importantly, vascular disorders such as hypertension, stroke, congestive cardiac failure, arrhythmias, and atherosclerosis occur frequently in these patients. The lungs may be affected by pulmonary hypertension and worsening of asthma. Recent data from several laboratories demonstrate that obstructive sleep apnea is characterized by an inflammatory response. Cytokines are elaborated during the hypoxemic episodes leading to inflammatory responses as marked clinically by elevated C-reactive protein (CRP). As elevated CRP levels are considered markers of the acute phase response and characterize progression of vascular injury in coronary artery disease, it is likely that obstructive sleep apnea could lead to worsening of vasculopathy. Moreover, as inflammatory mechanisms regulate bronchial asthma, it is also likely that cytokines and superoxide radicals generated during hypoxemic episodes could exacerbate reactive airway disease. Patients with Cough, Obstructive sleep apnea, Rhinosinusitis, and Esophageal reflux clustered together can be categorized by the acronym, "CORE", syndrome. The purpose of this manuscript is to review the inflammatory responses that occur in patients with obstructive sleep apnea and relate them to the occurrence of cardiopulmonary disease.
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PMID:Obstructive sleep apnea, inflammation, and cardiopulmonary disease. 1535 23

Cerebrovascular disease is highly heterogeneous but can culminate in vascular cognitive impairment or vascular dementia (VaD). As much as the clinical diagnosis warrants scrutiny, the neuropathological substrates of VaD also need to be better defined. Atherosclerosis and small vessel disease are the main causes of brain infarction. Lacunar infarcts or multiple microinfarcts in the basal ganglia, thalamus, brainstem and white matter are associated with more than half of VaD cases consistent with subcortical ischaemic VaD. White matter changes including regions of incomplete infarction are usually widespread in VaD, but their contribution to impairment is not explicit. Other pathologies including hippocampal injury and Alzheimer type of lesions may also modify the course of dementia. Similar to other common dementias consensus criteria for VaD need unambiguous definition to impact on preventative and treatment strategies and are critical for selective recruitment to clinical trials.
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PMID:Towards defining the neuropathological substrates of vascular dementia. 1553 25

Using analyses of the large cohort (n=5732) from the prospective study of pravastatin in the elderly at risk (PROSPER), we tested the hypothesis that Lp(a) concentration is an independent predictor of major vascular events and cognitive impairment in the elderly. Baseline Lp(a) levels were measured on fresh samples from 5732 subjects aged 70-82, who were followed for 3.2 years on average. Lp(a) levels were not significantly different across the age range in PROSPER, but were significantly higher in women (geometric mean 14.8 versus 12.4 mg/dl, P<0.0001). Those with a history of vascular disease had significantly higher Lp(a) levels, which remained after adjustment (P<0.0001). There was no statistically significant association between baseline Lp(a) and the risk of the primary endpoint (CHD death, non-fatal MI and fatal or non-fatal stroke) (hazard ratio 1.05, 95% CI 1.00-1.11, P=0.077), but after adjustment for baseline risk factors this did achieve statistical significance (1.06, 1.005-1.12, P=0.032). Finally, there was no statistically or clinically significant association between any adjusted baseline or dynamic cognition variables and Lp(a), and nor was there any significant association between Lp(a) and indices of disability throughout the study. This is the first study of the association between Lp(a) and a range of cardiovascular endpoints including cognitive and disability indices in the elderly. The main finding is that Lp(a) level, while influenced by a number of baseline characteristics, is not a significant predictor of cognitive function or levels of disability, but is a predictor of combined cardiovascular events over an average 3.2 year follow-up.
Atherosclerosis 2005 Jun
PMID:Plasma lipoprotein(a) [Lp(a)] concentrations and cardiovascular events in the elderly: evidence from the prospective study of pravastatin in the elderly at risk (PROSPER). 1591 Aug 66

This review gives a brief overview of the main types of dementia and summarizes current thinking on the relationship between nutritional-related factors and disorders, and dementia. Dementia is a multi-factor pathological condition, and nutrition is one factor that may play a role on its onset and progression. An optimal intake of nutrients doesn't protect people from dementia. However, studies in this area show that inadequate dietary habits, which are of particular concern in elderly populations, may increase the risk of developing a number of age-related diseases, including disorders of impaired cognitive function. They show that a deficiency in essential nutrients, such as certain B complex vitamins, can result in hyperhomocysteinemia, a well-known risk factor for atherosclerosis and recently associated with cognitive impairment in old age. A deficiency of antioxidants such as vitamins C and E, and beta-carotene, as well as nutrition-related disorders like hypercholesterolemia, hypertension, and diabetes, may also have some role in cognitive impairment. These factors can be present for a long time before cognitive impairment becomes evident, therefore they could be potentially detected and corrected in a timely manner.
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PMID:Relationship between dementia and nutrition-related factors and disorders: an overview. 1592 30

Reducing sugars can react non-enzymatically with amino groups of protein to form Amadori products. These early glycation products undergo further complex reaction such as rearrangement, dehydration, and condensation to become irreversibly cross-linked, heterogeneous fluorescent derivatives, termed advanced glycation end products (AGEs). The formation and accumulation of AGEs in various tissues has been known to progress at an accelerated rate under hyperglycemic conditions in diabetes. Recent understanding of this process has revealed that AGEs have been implicated in the development of many of the pathological sequelae of diabetes and aging, such as atherosclerosis and diabetic microangiopathy. Furthermore, recently, AGE-their receptor (RAGE) interaction was also involved in neurodegenerative diseases, melanoma growth, expansion and metastasis. These observations suggest that blockade of AGE formation may be a novel promising target for therapeutic intervention in these devastating AGE-related disorders. We have recently found that unicellular green alga Chlorella inhibited the formation of AGEs in vitro. Since several lines of evidence have shown anti-atherogenic effects of Chlorella on animal models, we hypothesize here that the beneficial aspects of Chlorella on atherosclerosis could be ascribed, at least in part, to its AGE inhibitory property and that Chlorella may have therapeutic potentials in treatment of patients with other AGE-related disorders such as diabetic microangiopathy and Alzheimer's disease. In this paper, we would like to propose the possible ways of testing our hypotheses. Does daily intake of Chlorella reduce the risk of the incidence and progression of diabetic vascular complications including atherosclerosis? Does Chlorella treatment prevent the development of Alzheimer's disease and/or improve the cognitive impairment of patients with this disorder? If the answers are yes, are plasma or tissue levels of AGE in these patients actually suppressed by Chlorella treatment? And, does the extent of the AGE reduction by Chlorella predict the beneficial effects of Chlorella on these disorders? These prospective studies will provide further valuable information whether blockade by Chlorella of the AGE formation could be clinically relevant.
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PMID:Therapeutic potentials of unicellular green alga Chlorella in advanced glycation end product (AGE)-related disorders. 1599 28

With increasing emphasis on early diagnosis of Alzheimer disease (AD), clinical research has focused on the identification of risk factors that may be modified at a preclinical and early clinical stage of dementing disorders. Prevalence and incidence of different predementia syndromes vary as a result of different diagnostic criteria, as well as different sampling and assessment procedures. Particular interest in mild cognitive impairment (MCI) arises from the fact that MCI is thought to be a prodromal phase and therefore highly predictive of subsequent AD. Furthermore, many of the risk factors for cerebrovascular disease (CVD) and vascular dementia (VaD), including serum total cholesterol, hypertension, atherosclerosis, and apolipoprotein E (APOE) genotype have also been shown to increase the risk of AD. Both vascular factors and APOE epsilon4 allele have been associated with higher risk of AD. Some recent studies suggested further that CVD or vascular factors increased the risk of conversion of MCI to dementia. This review will focus on the possible role of vascular risk factors in modulating the risk of age-related cognitive decline, and the progression of predementia syndrome such as MCI to dementia.
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PMID:Cognitive frailty: Predementia syndrome and vascular risk factors. 1602 66


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