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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dementia is a rapidly increasing health problem in the industrialized countries. With the ageing of the population the number of demented persons increases both in relative and absolute terms. Obviously, there is a need for prevention and intervention strategies. We describe the methods and baseline findings of a large study aimed at identifying potentially modifiable vascular, thrombogenic, and metabolic determinants of dementia. The study population consists of subjects 55 years of age or older. Since the vascular wall of the cerebral vessels is different from that of the coronary or peripheral vessels, we formed three subgroups in which vascular risk factors for dementia are studied. Subjects with stroke were distinguished from subjects with coronary or peripheral artery disease, and from subjects without stroke or coronary or peripheral artery disease. To obtain a large enough number of subjects with stroke, cases and controls from a stroke registry were combined with cases and controls of a population-based study from the same region. For the diagnosis of dementia the DSM-III-R criteria were used. Extensive information on cardiovascular risk factors was collected, including indicators of atherosclerosis. Blood and urine were sampled to study platelet function and thrombogenic and metabolic factors. The study population consists of 7,466 subjects, of whom 300 were recruited from a hospital-based stroke registry. Coronary or peripheral artery disease was present in 956 subjects and stroke in 617. Dementia was present in 434 (5.8%) of all subjects. The prevalence of dementia was 3.0, 24.0, and 4.4% in subjects with a history of coronary or peripheral artery disease, a history of stroke, and subjects without a history of coronary or peripheral artery disease or stroke, respectively. The study will allow us to investigate the role of vascular factors in dementia, irrespective of its cause.
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PMID:The Dutch Vascular Factors in Dementia Study: rationale and design. 945 26

The aetiology of the common dementias of old age remains incompletely understood. Here we describe some of the biological, neurophysiological and psychological changes associated with ageing of the human brain, in terms of those that occur throughout life and those that are characteristic of senescence. Age-dependent diseases, such as Alzheimer's disease (AD), idiopathic Parkinson's disease (IPD) and dementia with Lewy bodies (DLB), are considered from these viewpoints, and risk factors described. Vascular dementia (VaD) is related to hypertension and atherosclerosis and detailed description of its pathogenesis is outside the scope of this review. The importance of age as the main risk factor raises basic questions about the relationship of these diseases to the ageing process itself. Similarities and differences between ageing and disease may be important for a rational approach to prevention and treatment of cognitive decline and dementia in later life.
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PMID:Some developments in brain ageing and dementia. 949 98

CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy) is a newly discovered inherited cerebrovascular disease characterized clinically by recurrent stroke-like incidents, dementia and often pseudobulbar palsy. Neuroimaging reveals intensive subcortical changes and pathologically one finds apparently systemic changes concerning the vessels such as thickening of the vessel wall, loss of smooth muscle cells and patches of granular material of unknown origin. The disease is not associated with atherosclerosis and vascular risk factors are missing or few. The CADASIL-locus maps to chromosome 19, but the gene has not yet been identified. Treatment and pathogenesis are unknown. In a Danish stroke population (The Copenhagen Stroke Study) no CADASIL-suspected cases were found among patients < or = 55 years, indicating a rare disease as far as Denmark is concerned.
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PMID:["CADASIL"--a newly discovered hereditary cerebrovascular disease]. 952 53

Sterol 27-hydroxylase is important for the degradation of the steroid side chain in conversion of cholesterol into bile acids and has been ascribed a regulatory role in cholesterol homeostasis. Its deficiency causes the autosomal recessive disease cerebrotendinous xanthomatosis (CTX), characterized by progressive dementia, xanthomatosis, and accelerated atherosclerosis. Mice with a disrupted cyp27 (cyp27(-/-)) had normal plasma levels of cholesterol, retinol, tocopherol, and 1,25-dihydroxyvitamin D. Excretion of fecal bile acids was decreased (<20% of normal), and formation of bile acids from tritium-labeled 7alpha-hydroxycholesterol was less than 15% of normal. Compensatory up-regulation of hepatic cholesterol 7alpha-hydroxylase and hydroxymethylglutaryl-CoA reductase (9- and 2-3-fold increases in mRNA levels, respectively) was found. No CTX-related pathological abnormalities were observed. In CTX, there is an increased formation of 25-hydroxylated bile alcohols and cholestanol. In bile and feces of the cyp27(-/-) mice only traces of bile alcohols were found, and there was no cholestanol accumulation. It is evident that sterol 27-hydroxylase is more important for bile acid synthesis in mice than in humans. The results do not support the contention that 27-hydroxylated steroids are critical for maintenance of cholesterol homeostasis or levels of vitamin D metabolites in the circulation.
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PMID:Markedly reduced bile acid synthesis but maintained levels of cholesterol and vitamin D metabolites in mice with disrupted sterol 27-hydroxylase gene. 961 81

Some genes are expressed differently in earlier and later generations of most cell lines. Many diseases become clinically expressed only later in life, and show clustering of the age at onset in the affected siblings, which may be related to the changing expression with age of the genes involved. Because insulin and its receptor are extremely ancient and well preserved structures with almost universal mitogenic effects, insulin may serve a paradigm of this process. It is suggested that by stimulating cell proliferation, hyperinsulinemia speeds up the appearance of later generations of cells with different expression of the genes. Insulin resistance, accompanying any hyperinsulinemia and considered to be a pathogenetic factor of some common later-age diseases, involves only some biochemical, but not mitogenic effects of the hormone. In humans, high levels of insulin in blood are encountered both physiologically after meals and in many pathological conditions: insulin therapy inevitably causes peripheral hyperinsulinemia; in type 2 diabetes hyperinsulinemia precedes hyperglycemia by many years; hyperinsulinemia is an independent risk factor of atherosclerosis, of type 2 diabetes itself, of some forms of dementia and other diseases; obesity is an obligatory hyperinsulinemic condition. The opposite of hyperalimentation, i.e. calorie restriction (at least, in rodents) may exert its life-prolonging effects through decreasing insulinemia and therefore the rate of cell proliferation. Insulin is only one example, and different mitogens regulate proliferation of different cells. It is likely that growth factors in general accelerating the replication of cells, play a role in speeding up the appearance of later-age diseases involving these cells.
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PMID:Mitogenic factors accelerate later-age diseases: insulin as a paradigm. 966 95

The purpose of this study was to concurrently assess the relationship of Apolipoprotein E (APOE) with both dementias and vascular illnesses in the very old. Nine hundred and fifty nine subjects (mean age 85 years) in a long-term care facility were genotyped and cognitively tested with the Mini Mental State Exam. All subjects were studied for the relationship of APOE with atherosclerotic heart disease, hypertension, or stroke without concomitant dementia. Four hundred fifty individuals met criteria for inclusion into one of the following groups: Alzheimer's disease (n = 318), vascular dementia (n = 49), or not demented controls (n = 83) and were investigated for the relationship between APOE and these diagnostic categories. APOE epsilon4 was not associated with atherosclerotic heart disease, hypertension, or stroke without concomitant dementia. The APOE epsilon3 allele was more common in men with atherosclerotic heart disease. In contrast, the APOE epsilon4 allele was more common in patients with Alzheimer's disease (22%) and vascular dementia (26%) than in not demented controls (7%). APOE epsilon4 is associated with dementias in the very old, whereas its relationship with either peripheral or central nervous system vascular disease without dementia is not as robust.
Atherosclerosis 1998 Sep
PMID:The relationship between apolipoprotein E, dementia, and vascular illness. 973 29

A 37-year-old man sought medical advice because of an 8-year history of a slowly progressive dementing illness with no clinically apparent discrete strokelike episodes. Cognitive functioning was markedly, globally impaired without lateralizing or localizing features. Widespread livedo reticularis led to a diagnosis of Sneddon's syndrome. Antiphospholipid antibodies and lupus anticoagulant were negative. Magnetic resonance imaging showed widespread cerebral atrophy, cortical and subcortical cerebral infarcts, and extensive periventricular white matter abnormalities. Cerebral angiography revealed diffuse medium- and small-vessel occlusive disease, with numerous collaterals in the mid and distal circulation but no evidence of atherosclerosis or vasculitis. No other cause of a dementing illness was found. We postulate that our patient's dementia was due to the cumulative effects of multiple cerebral infarcts.
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PMID:Gradually progressive dementia without discrete cerebrovascular events in a patient with Sneddon's syndrome. 1059 61

Platelets play an important role in atherosclerosis, and increased platelet activation is associated with stroke. Stroke is an important risk factor for dementia, as approximately 25% of the patients are demented after stroke. In this review, we describe platelet activation studies in patients with stroke and with dementia. In addition, we review the few studies that have investigated the effect of antiplatelet medication such as aspirin and non-steroidal anti-inflammatory drugs on cognitive function and the occurrence of dementia. We conclude that further studies are needed to characterize the mechanisms and determinants of platelet activation in relation to the development of dementia. Furthermore, the efficacy and safety of antiplatelet intervention will have to be assessed in properly designed randomized trials.
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PMID:Role of platelet activation in dementia. 1042 67

The APOE genotype is involved in atherosclerosis, and atherosclerosis increases the risk of dementia, in particular among carriers of the APOE-epsilon4 allele. We studied, in a population-based setting (244 dementia cases; 1,002 nondemented controls), whether APOE is associated with dementia through atherosclerosis. As neither adjusting nor stratification for atherosclerosis altered the association of APOE with dementia, our study suggests that atherosclerosis is not an intermediate factor.
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PMID:The effect of APOE on dementia is not through atherosclerosis: the Rotterdam Study. 1088 Dec 78

This review describes differing profiles of vascular risk factors in different types of dementia. Although vascular risk factors are related to various types of strokes, their independent effect on the occurrence of poststroke dementia appears to be small. Various risk factors have been identified for microangiopathy-related cerebral abnormalities, such as white matter changes and lacunae, which are the core lesions for the development of a vascular dementia syndrome without stroke symptoms. Most consistently, arterial hypertension and diabetes mellitus have been found to be associated with such brain abnormalities. Diastolic blood pressure seems to be of particular importance as recent investigations demonstrate that this factor is related to the course of multiple lacunar strokes and the progression of white matter disease. Epidemiological studies report that various vascular risk factors including arterial hypertension, diabetes mellitus, and atrial fibrillation may also be associated with Alzheimer's disease. There is also evidence of a direct relationship between Alzheimer's disease and general atherosclerosis. Further investigations are needed to determine whether these associations are due to the weakness of diagnostic criteria, or whether vascular risk factors indeed modulate the clinical expression of primary degenerative dementia. Common susceptibility genes leading to shared risk factors may be one of the reasons for a higher coincidence of Alzheimer's disease and vascular dementia than can be expected by chance. A modulatory effect of vascular risk factors in the development of primary degenerative dementia may extend treatment options.
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PMID:Vascular risk factors in dementia. 1075 Nov 8


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