Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent epidemiological evidence suggests that some antihypertensive medications may reduce the risk for Alzheimer disease (AD). We screened 55 clinically prescribed antihypertensive medications for AD-modifying activity using primary cortico-hippocampal neuron cultures generated from the Tg2576 AD mouse model. These agents represent all drug classes used for hypertension pharmacotherapy. We identified 7 candidate antihypertensive agents that significantly reduced AD-type beta-amyloid protein (Abeta) accumulation. Through in vitro studies, we found that only 1 of the candidate drugs, valsartan, was capable of attenuating oligomerization of Abeta peptides into high-molecular-weight (HMW) oligomeric peptides, known to be involved in cognitive deterioration. We found that preventive treatment of Tg2576 mice with valsartan significantly reduced AD-type neuropathology and the content of soluble HMW extracellular oligomeric Abeta peptides in the brain. Most importantly, valsartan administration also attenuated the development of Abeta-mediated cognitive deterioration, even when delivered at a dose about 2-fold lower than that used for hypertension treatment in humans. These preclinical studies suggest that certain antihypertensive drugs may have AD-modifying activity and may protect against progressive Abeta-related memory deficits in subjects with AD or in those at high risk of developing AD.
 ...
PMID:Valsartan lowers brain beta-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease. 1796 77

Hypertension in an 83-year-old woman with early Alzheimer disease was treated with a calcium channel blocker, nilvadipine, for 3 months. Before and after nilvadipine treatment, global and regional cerebral blood flow (gCBF and rCBF) were measured using Tc-99m ethyl cysteinate dimer SPECT. This treatment elevated both the Mini-Mental State Examination score from 23 to 27 and gCBF from 37.6 to 42.0 mL/100 g/min. This treatment also elevated rCBF prominently in the bilateral frontal cortex, right parietal cortex, and posterior cingulate cortex. These areas with rCBF increase generated by subtraction of pretreatment SPECT from post-treatment SPECT were demonstrated on a coregistered MRI.
 ...
PMID:Effect of nilvadipine on regional cerebral blood flow in a patient with early Alzheimer disease. 1809 55

Physiologically, the cerebral autoregulation system allows maintenance of constant cerebral blood flow over a wide range of blood pressure. In old people, there is a progressive reshape of cerebral autoregulation from a sigmoid curve to a straight line. This implies that any abrupt change in blood pressure will result in a rapid and significant change in cerebral blood flow. Hypertension has often been observed to be a risk factor for vascular dementia (VaD) and sometimes for Alzheimer disease although not always. Indeed, high blood pressure may accelerate cerebral white matter lesions, but white matter lesions have been found to be facilitated by excessive fall in blood pressure, including orthostatic dysregulation and postprandial hypotension. Many recent studies observed among other data, that there was a correlation between systolic pressure reduction and cognitive decline in women, which was not accounted for by other factors. Baseline blood pressure level was not significantly related to cognitive decline with initial good cognition. Some researchers speculate that blood pressure reduction might be an early change of the dementing process. The most confounding factor is that low pressure by itself might be a predictor of death; nevertheless, the effect of low blood pressure on cognition is underestimated because of a survival bias. Another explanation is that clinically unrecognized vascular lesions in the brain or atherosclerosis are responsible for both cognitive decline and blood pressure reduction. We discuss the entire process, and try to define a possible mechanism that is able to explain the dynamic by which hypotension might be related to dementia.
 ...
PMID:Risk factors for vascular dementia: hypotension as a key point. 1856 14

Neonatal brain iron deficiency occurs after insufficient maternal dietary iron intake, maternal hypertension, and maternal diabetes mellitus and results in short and long-term neurologic and behavioral deficits. Early iron deficiency affects the genomic profile of the developing hippocampus that persists despite iron repletion. The purpose of the present study was threefold: 1) quantitative PCR confirmation of our previous microarray results, demonstrating upregulation of a network of genes leading to beta-amyloid production and implicated in Alzheimer disease etiology in iron-deficient anemic rat pups at the time of hippocampal differentiation; 2) investigation of the potential contributions of iron deficiency anemia and iron treatment to this differential gene expression in the hippocampus; and 3) investigation of these genes over a developmental time course in a mouse model where iron deficiency is limited to hippocampus, is not accompanied by anemia and is not repletable. Quantitative PCR confirmed altered regulation in 6 of 7 Alzheimer-related genes (Apbb1, C1qa, Clu, App, Cst3, Fn1, Htatip) in iron-deficient rats relative to iron-sufficient controls at P15. Comparison of untreated to treated iron-deficient animals at this age suggested the strong role of iron deficiency, not treatment, in the upregulation of this gene network. The non-anemic hippocampal iron-deficient mouse demonstrated upregulation of all 7 genes in this pathway from P5 to P25. Our results suggest a role for neonatal iron deficiency in dysregulation of genes that may set the stage for long-term neurodegenerative disease and that this may occur through a histone modification mechanism.
 ...
PMID:Iron deficiency alters expression of genes implicated in Alzheimer disease pathogenesis. 1872 4

Aging, Alzheimer disease, and hypertension, major determinants of cognitive dysfunction, are associated with profound alterations in the structure and function of cerebral blood vessels. These vascular alterations may impair the delivery of energy substrates and nutrients to the active brain, and impede the clearance of potentially toxic metabolic byproducts. Reactive oxygen species derived form the enzyme NADPH oxidase are key pathogenic effectors of the cerebrovascular dysregulation. The resulting alterations in the homeostasis of the cerebral microenvironment may lead to cellular dysfunction and death and to cognitive impairment. The prominent role that cerebrovascular oxidative stress plays in conditions associated with cognitive impairment suggests new therapeutic opportunities to counteract and, possibly, reverse the devastating effects of cerebrovascular dysfunction on the brain.
 ...
PMID:Threats to the mind: aging, amyloid, and hypertension. 1906 85

The accumulation of the amyloid beta-protein (Abeta), the main constituent of the 'amyloid plaque', is widely considered to be the key pathological event in Alzheimer's disease (AD). In particular, the accumulation of Abeta42 is the central event triggering neurodegeneration. Reduction of Abeta is now a major therapeutic strategy. However, only a few patients show evidence of increased Abeta production. Thus, defects in proteases that degrade Abeta could underlie some or many cases of familial and sporadic AD. Among the Abeta degrading enzymes, namely, neprilysin (NEP), insulin-degrading enzyme (IDE), endothelin-converting enzyme (ECE) and angiotensin-converting enzyme (ACE), ACE is the most commonly targeted enzyme by inhibitors in elderly populations because it plays a central role in the regulation of blood pressure and hypertension. Genetic, pathological and biochemical studies have associated ACE with AD. This review discusses genetic, molecular and clinical studies that might help explain the relationship between ACE, hypertension, Abeta degradation and AD.
 ...
PMID:Angiotensin-converting enzyme as a potential target for treatment of Alzheimer's disease: inhibition or activation? 1914 83

Aging is often associated with some cognitive impairment. Greater population life expectancy is one explanation for increased incidence of cognitive impairment cases. Large number of people with cognitive impairment and dementia is becoming one of the most important medical and social problems worldwide. Therefore, prevention of Alzheimer disease is becoming an imperative. Dementia includes a heterogeneous group of disorders, the most common being Alzheimer dementia (AD) and vascular dementia (VD). Most cardiovascular risk factors, such as hypertension, diabetes mellitus, hypercholsterolemia, atrial fibrillation, and smoking are not exclusively risk factors for VD, but also for AD. Intracranial hemodynamics of the aging brain can be assessed by Transcranial Doppler Sonography (TCD), functional TCD with various functional tests, and TCD detection of cerebral emboli. Extracranial circulation can be assessed by means of color Doppler flow imaging (CDFI). New neurosonology techniques and possibilities provide information necessary to closer determine the relation between cognitive deterioration and vascular risk factors, so that the evolution towards dementia could be prevented or at least postponed.
 ...
PMID:Evaluation of aging vs dementia by means of neurosonology. 1926 5

In recent years a rapidly increasing number of studies has focused on the relationship between dementia and metabolic disorders such as diabetes, obesity, hypertension, and dyslipidemia. Etiological heterogeneity and comorbidity pose challenges for determining relationships among metabolic disorders. The independent and interactive effects of brain vascular injury and classic pathological agents such as beta-amyloid have also proved difficult to distinguish in human patients, blurring the lines between Alzheimer disease and vascular dementia. This review highlights recent work aimed at identifying convergent mechanisms such as insulin resistance that may underlie comorbid metabolic disorders and thereby increase dementia risk. Identification of such convergent factors will not only provide important insight into the causes and interdependencies of late-life dementias but will also inspire novel strategies for treating and preventing these disorders.
 ...
PMID:The role of metabolic disorders in Alzheimer disease and vascular dementia: two roads converged. 1927 47

There is a cluster of risk factors for Type 2 diabetes and vascular disease that include high blood glucose, obesity, high blood pressure, increased blood triacylglycerols and insulin resistance. All of these factors, both individually and collectively, increase the risk of Alzheimer's disease (AD) and vascular dementia. Alterations in insulin signaling, glucose and fatty acid metabolism, as well as the accumulation of oxidatively modified and glycated proteins, are associated with both diabetes and the dementias. Data from animal and cell culture models have shown that there is a synergistic interaction between most of these stresses in both AD and diabetes, and with the elevated beta-amyloid peptide levels that are also linked to AD. Some of these parameters can be modified by diet and others may require novel drugs. However, because of the multiplicity of physiological pathways involved, conventional drug therapies directed against a single target are not going to be effective in treating AD or the complications of diabetes. It is therefore likely that the only successful therapy will involve the use of drugs with multiple targets in concert with changes in diet and lifestyle.
 ...
PMID:Metabolic links between diabetes and Alzheimer's disease. 1940 68

Cumulative evidence implicates hypertension in the pathogenesis of Alzheimer disease. Although it may not presently be possible to completely differentiate the effects of treatment and control of hypertension itself from those of the medication used to achieve such treatment goals, efforts directed at the treatment and control of hypertension can have significant public health impact.
 ...
PMID:Hypertension and cognitive function. 1955 72


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>