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

Mutations in the amyloid precursor protein (APP) gene cause one form of early onset familial Alzheimer's disease (AD). One such family has been studied genetically and neuropathologically and represents the basis of the present report. Four siblings with the APP717 Val to Ile mutation, aged 59, 65, 61 and 64 years, apolipoprotein E (APOE) genotyped 2,4 (first three) and 2,3 respectively, had severe AD, Braak stage VI with frequent neurofibrillary tangles in the primary visual cortex, Brodmann area 17. The first one also met McKeith criteria for the limbic stage of dementia with Lewy bodies but did not have substantia nigra Lewy bodies. The second two met McKeith criteria for the neocortical stage of dementia with Lewy bodies and both had substantia nigra Lewy bodies. The fourth had AD but no Lewy bodies. A cousin without the APP717 mutation who was APOE 3, 4, developed dementia at age 60 and died at age 75. She had severe cerebrovascular atherosclerosis, less severe AD, Braak stage V, with sparing of area 17. She also had Lewy bodies in the substantia nigra and in the cortex and met McKeith criteria for neocortical stage of dementia with Lewy bodies. Extrapyramidal features were present in all five. Lewy bodies have been described in 53% of reported autopsies on individuals with the APP717 Val to Ile mutation coincident with dementia and AD neuropathologic changes. These observations suggest an association between the chromosome 21 APP mutation and Lewy body formation, possibly mediated by other environmental or genetic factors.
 ...
PMID:Lewy body and Alzheimer pathology in a family with the amyloid-beta precursor protein APP717 gene mutation. 1096 61

An interest in the ageing process has increased greatly with increasing the population of the aged. The goal of this interest is to improve the quality of life(QOL) in the aged. In this paper, the presidential address "Ageing Society and Laboratory Medicine" at the 46th annual meeting of JSCP in Kumamoto'99 was summarized on the important research for ageing in the past decades. The paper presented was age- and gene-related changes, the latent variation of serum constituents and lipids abnormality in the ageing process. Concerning to the definition of reference value of healthy populations and the subjects who had no combined ailments, the reference interval of individuals(intra-personal), followed 5 years categorized by age, sex, and social conditions, gave a narrow range of variation than did a larger mixed populations(inter-personal). The reference intervals set would be a more sensitive reference than is the customary "normal range" for values occurring in inter-personal. Concerning to the study of the relationship between laboratory test and activity of daily living(ADL), the higher serum levels for TP, Alb, Hb, Glu, TC were observed in the higher ADL. The basic research techniques were also evaluated in the paper. The serum lipoperoxides were correlated with serum lipoprotein free radicals which caused atherosclerosis. The higher frequency of cerebral- and myocardial-infarction in the aged were observed in the higher serum LDL-C and lower serum level of arachidonic acid(AA), eicosapentaenoic acid(EPA), and AA/EPA ratio were observed in AMI patients with lower HDL-C groups than the healthy aged. Although Alzheimer(AD)'s disease had a progressive memory loss and immobile dementia and was reported the decrease of acetyltransferase activity in the brain, decrease of serum level of free choline, lyso-phosphatidylcholine, phosphatidylcholine(PC) and sphingomyelin(SM)/PC ratio were observed in spite of keeping normal serum level of SM. The decreased serum levels of pseudocholin esterase and albumin, especially mercaptoalbumin were observed in the healthy aged with advancing age. The early diagnosis and prediction of prognosis for the latent ailments in the aged was stressed. As to the study of variations of serum protein levels in the healthy aged, variations of serum proteins were classified into three types, 1) mainly acute phase reactant proteins such as alpha 1AT increased with advancing age, 2) transporting proteins such an albumin decreased and 3) proteins with no significant variation these were useful proteins for the early finding of latent ailments. The higher increase of alpha 1AT/beta 2III in the healthy aged over 60 y.o. was suspected to become severe in near future.
 ...
PMID:[Ageing society and laboratory medicine]. 1105 92

Ischemic vascular dementia (IVD) is a relatively uncommon entity, in the course of which multiple ischemic brain lesions result in progressive cognitive and memory impairment. Ischemic brain lesions may also aggravate the neuropsychologic deficit of Alzheimer disease (AD). In this review we summarize our experience based upon autopsy examination of the central nervous system in 20 patients (age range 68-92 years) enrolled in a longitudinal investigation of structural, neurochemical, functional neuroimaging, and neuropsychologic components of IVD, especially dementia associated with cerebral microvascular disease. While cystic infarcts were present in the CNS of 5 patients, the most commonly observed neuropathologic abnormalities were lacunar infarcts and microinfarcts--both types of lesion were encountered in over half of patients' brains. Evidence of (remote) hippocampal injury was found in 11/20 patients. Severe atherosclerosis and arterio/ arteriolosclerosis were both associated with the occurrence of multiple lacunar infarcts. Pronounced cerebral amyloid angiopathy (CAA) was noted in a single patient, who also showed other microscopic changes of severe AD. While fairly unusual as a nosologic entity, IVD appears to correlate with widespread small ischemic lesions distributed throughout the CNS. We furthermore propose an approach to quantifying the burden of ischemic vascular and parenchymal disease that may be associated with a dementia syndrome. A brief review of neuropathologic features of vascular dementia (both familial and sporadic) is presented.
 ...
PMID:Neuropathologic substrates of ischemic vascular dementia. 1139 42

Progressive cerebrovascular atherosclerosis and consecutive stroke are among the most common causes of dementia. However, specific risk factors for vascular dementia are still not known. Human telomeres shorten with each cell division in vitro and with donor age in vivo. In human fibroblasts in vitro, the telomere shortening rate decreased with increasing antioxidative capacity. There was a good intra-individual correlation between the age-corrected telomere lengths in fibroblasts and peripheral blood mononuclear cells. In 186 individuals including 149 geriatric patients (age range, 55-98 yr), leukocyte telomeres in patients with probable or possible vascular dementia were significantly shorter than in three age-matched control groups, namely in cognitively competent patients suffering from cerebrovascular or cardiovascular disease alone, in patients with probable Alzheimer's dementia, and in apparently healthy control subjects. No correlation was found to polymorphisms in the apolipoprotein E and glutathione-S-transferase genes. Telomere length may be an independent predictor for the risk of vascular dementia.
 ...
PMID:Short telomeres in patients with vascular dementia: an indicator of low antioxidative capacity and a possible risk factor? 1109 34

Binswanger's disease(BD) in an effect of a vascular destruction of deep white matter structures following multiple infarcts leading to disturbances of perception functions, recent memory and characterological disorders. BD is a disease occurring in late 6th decade of life. Computerized tomography and magnetic resonance imaging demonstrate foci of microinfarcts which coexist with arterial hypertension, atheromatous lesions and general cerebral atherosclerosis. BD leads to dementia, certain Parkinson-like signs, pyramidal system involvement, depression, organic brain damage syndrome, dysbasia and sphincter control loss. Ten patients observed by the author are reported.
 ...
PMID:[Binswanger's disease--diagnostic criteria and analysis of cases]. 1110 74

Dietary intake of fatty acids may be related to dementia and cognitive function through a number of plausible mechanisms, such as atherosclerosis and thrombosis, inflammation, via an effect on brain development and membrane functioning, or via accumulation of beta-amyloid. This review gives an overview of the few studies that have investigated the relationship between fatty acid intake (including the fatty acids from fish) and cognitive function or dementia and summarises the results from two Dutch population-based prospective studies: the Zutphen Elderly Study (n=476) and the Rotterdam Study (n=5,386). Additionally, limitations on dietary intake studies are discussed and possible mechanisms behind the investigated associations. Data from the Rotterdam Study showed that high intakes of the following nutrients were associated with an increased risk of dementia after adjustment for confounders: total fat (RR=2.4 (95%CI: 1.1-5.2)), saturated fat (RR=1.9 (95%CI: 0.9-4.0)), and cholesterol (RR=1.7 (95%CI: 0.9-3.2)). A high fish consumption, an important source of n-3 PUFAs, reduced the risk of dementia (RR=0.4 (95%CI: 0.2-0.9)). In the Zutphen Elderly Study a high linoleic acid intake was associated with cognitive impairment (OR=1.8 (95%CI: 1.0-3.0)). A high fish consumption tended to be inversely associated with cognitive impairment and decline (RR=0.5, 95%CI: 0.2-1.2). Since diet is a risk factor that is suitable for intervention these results are hopeful and potentially very important.
 ...
PMID:Fatty acid intake and the risk of dementia and cognitive decline: a review of clinical and epidemiological studies. 1113 99

Acetylcholine, one of the most exemplary neurotransmitters, has been detected in bacteria, algae, protozoa, tubellariae and primitive plants, suggesting an extremely early appearance in the evolutionary process and a wide expression in non-neuronal cells. In plants (Urtica dioica), acetylcholine is involved in the regulation of water resorption and photosynthesis. In humans, acetylcholine and/or the synthesizing enzyme, choline acetyltransferase, have been demonstrated in epithelial (airways, alimentary tract, urogenital tract, epidermis), mesothelial (pleura, pericardium), endothelial, muscle and immune cells (granulocytes, lymphocytes, macrophages, mast cells). The widespread expression of non-neuronal acetylcholine is accompanied by the ubiquitous expression of cholinesterase and acetylcholine sensitive receptors (nicotinic, muscarinic). Both receptor populations interact with more or less all cellular signalling pathways. Thus, non-neuronal acetylcholine can be involved in the regulation of basic cell functions like gene expression, proliferation, differentiation, cytoskeletal organization, cell-cell contact (tight and gap junctions, desmosomes), locomotion, migration, ciliary activity, electrical activity, secretion and absorption. Non-neuronal acetylcholine also plays a role in the control of unspecific and specific immune functions. Future experiments should be designed to analyze the cellular effects of acetylcholine in greater detail and to illuminate the involvement of the non-neuronal cholinergic system in the pathogenesis of diseases such as acute and chronic inflammation, local and systemic infection, dementia, atherosclerosis, and finally cancer.
 ...
PMID:The biological role of non-neuronal acetylcholine in plants and humans. 1124 68

Atherosclerosis involves structural change to the intima and media of medium- and large-sized arteries. Although an atherosclerotic plaque may remain clinically silent, it is prone to disruption, leading to local platelet activation and aggregation. Therefore, the major complication of atherosclerosis is thrombosis, with local occlusion or distal embolism - a generalized disease process known as atherothrombosis. The three main clinical manifestations of atherothrombosis are coronary heart disease (myocardial infarction and angina), peripheral arterial disease and cerebral ischaemia. Atherothrombosis is a leading cause of mortality, and stroke is the leading cause of disability in adults, the second most important cause of dementia and the third most common cause of death in Western countries. Ischaemic stroke accounts for 80% of strokes and atherothrombosis accounts for approximately 20% of all strokes. Criteria for atherothrombotic stroke are evidence of a 50% (or greater) stenosis of a cervical artery and exclusion of other potential causes. The incidence of cerebrovascular events is 2,900 per million inhabitants per year, consisting of 500 transient ischaemic attacks and 2,400 strokes, of which 75% are first-ever stroke. The prevalence of stroke in the same population is 12,000, of which 800 patients (7%) per year have recurrences. The risk of ipsilateral stroke is 5% per year and the risk of a cardiac event is higher at 7%. Besides optimal management of risk factors for atherothrombosis and carotid surgery, antiplatelet therapy is the cornerstone of vascular prevention. In secondary prevention, antiplatelet agents are effective in reducing the risk of further ischaemic events in patients with atherothrombosis. Clopidogrel, a newly licensed ADP receptor antagonist, is the only antiplatelet agent to have demonstrated its superiority versus aspirin for the reduction of major ischaemic events (myocardial infarction, ischaemic stroke, vascular death) in patients whose initial manifestation of atherothrombosis was one of the three main clinical manifestations of the disease (recent ischaemic stroke, myocardial infarction, established peripheral arterial disease).
 ...
PMID:Atherothrombosis: a major health burden. 1131 15

Although it has long been felt that dementia may be due to atherosclerosis, the concept has recently evolved to include multiple pathophysiological mechanisms related to deficiencies in cerebral blood supply. Epidemiological data has identified hypertension and stroke as the most potent risk factors for the development of vascular dementia (VaD). New diagnostic criteria have been proposed and new neuroimaging techniques have led to a better detection of cerebral vascular pathology. However, the differential diagnosis between Alzheimer's disease and VaD, the two most common causes of dementia, remains clinically challenging. Therapeutic interventions for VaD are limited, nevertheless several lines of evidence suggest a strong potential for preventive treatment through the control of vascular risk factors.
 ...
PMID:Vascular dementia. Differential diagnosis and therapeutic issues. 1149 May 47

Dementia in the elderly used to be rare, but why has it become a major social threat today? There can be many potential answers, but an ultimate one is clear: the longer life expectancy today. This knowledge indicates that "advanced aging" is a primary suspect in the origin of senile dementia. If so, then why can many elderly remain healthy at the same old age? We know, for example, that elderly people commonly have a certain degree of atherosclerosis and osteoporosis, but only some of them develop severe clinical symptoms at the same age. These different outcomes generally can be explained by "risk factors" in life (exercise, diet, individual background, etc). It thus appears to be a general pattern that advanced aging (after age 80) will set the stage for various senile disorders, but risk factors largely determine the onset age as well as individual specificity of their clinical manifestations. In this context, senile disorders including senile dementia would differ fundamentally from the pathogen-caused conventional diseases (AIDS, polio, cancer, Down's, etc.) by origin, incidence, and intervention strategy. This view would call into question the current definition of senile dementia as a conventional "disease" (Alzheimer's). The term "Alzheimer's disease" originally referred to "midlife" dementia, but it is defined today to be the same medical entity as senile dementia on the basis that they both display the same hallmarks and symptoms despite their onset age difference. Now, after in-depth scrutiny, we finally come to realize that they are not the same disease, but as different as heart failure at midlife versus the "same" failure at advanced age (i.e., a conventional disease versus a senile condition). Thus, by eliminating the age difference, the new definition has converted a senile condition into a conventional "disease", thereby changing the course of its scientific inquiry to miss the main targets. This may be why after extensive studies for 25 years, the origin of senile dementia has remained an enigma.
 ...
PMID:Alzheimer movement re-examined 25 years later: is it a "disease" or a senile condition in medical nature? 1150 85


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