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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence of apolipoprotein-epsilon 4 (APOE-epsilon 4) significantly increases the risk of Alzheimer's disease (AD). The association between APOE-epsilon 4 status and functional abilities was explored further in a multicultural sample of community-dwelling, non-demented elders. The sample was limited to cognitively-intact, community-dwelling elders, who were free of stroke or other neurologic disability. In 218 elders who met research criteria, the presence of APO-epsilon 4 was associated with poorer functional status, apart from the effects of neuropsychological performance, gender, age, and education (OR = 2.5, 95% CI: 1.3, 4.9). In 158 subjects without an APOE-epsilon 4 allele, 50% reported no functional limitation; in the 60 subjects with an epsilon 4 allele, only 28% reported no functional limitation (P < .01). The relationship was not explained by the distribution of co-morbidities. The association between poorer function and the presence of an APOE-epsilon 4 allele was evident in each ethnic group. In path analyses, the presence of an APOE-epsilon 4 allele was associated with decreased functional ability in non-demented elders not simply through an association with poorer cognitive status, but also independently. These results suggest that the APOE-epsilon 4 genotype is associated with functional deficit in people with normal neuropsychological profiles.
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PMID:APOE genotype influences functional status among elderly without dementia. 882 2

Stroke patients are more likely to develop dementia than age- and sex-matched controls but the pathogenesis of dementia remains unresolved in most of them. The aim of this review is to determine, from the available literature, the theoretical reasons for a stroke patient to become demented. We found three distinct factors that may explain the occurrence of dementia after a stroke. Firstly, post-stroke dementia may be the direct consequence of the vascular lesions of the brain: this is the most likely cause in patients with normal cognitive functions before a strategic infarct, especially in young patients, in Icelandic-type hereditary amyloid angiopathy and in cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy. Secondly, post-stroke dementia may be due to an associated asymptomatic Alzheimer pathology; the reasons for such an association are that (1) some cases of dementia occurring after a stroke are progressive and Alzheimer's disease (AD) is the most frequent cause of progressive dementia; (2) age and APOE epsilon 4 genotype are risk factors for both AD and ischaemic stroke; (3) a vasculopathy is often associated with AD. Lastly, white matter changes may also contribute to dementia because they often indicate small-vessel disease and a higher risk of stroke recurrence, and may lead to slight cognitive impairment. Finally, the summation of vascular lesions of the brain, white matter changes, and Alzheimer pathology might lead to dementia, even when each type of lesion, on its own, is not severe enough to induce dementia. Therefore, in patients followed up after a stroke, the term "post-stroke dementia" is probably more appropriate than that of vascular dementia because it includes all possible causal factors.
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PMID:Why are stroke patients prone to develop dementia? 905 Sep 53

Apolipoprotein E (APOE, gene; ApoE, protein) is the major genetic susceptibility locus for the common forms of Alzheimer's disease (AD). There are three common polymorphisms in the population: epsilon 2, epsilon 3, and epsilon 4. The inheritance of each dose of epsilon 4 increases the risk and lowers the age of onset distribution for AD; epsilon 2 lowers the risk and increases the age of onset distribution. APOE-epsilon 4 has a high positive predictive value for AD, and is clinically useful as an adjunct in the early diagnosis of cognitively impaired patients. The APOE alleles have also been associated with risk of AD with head injury, intraneuronal localization of ApoE in animal stroke models, recovery of function after intracerebral hemorrhage, and recovery of psychological parameters after general cardiac anesthesia. A multifunctional role of ApoE in the brain implicates isoform-specific differences in interactions with several brain proteins including A beta, tau, and MAP-2. Intraneuronal ApoE is increased temporally and in relevant neurons in AD as a function of APOE genotype. Decreased glucose metabolism can be demonstrated by PET imaging in subjects two decades before the median age of onset as a function of APOE genotype. ApoE isoforms may also have different effects as antioxidants. The risk of stroke and vascular dementia has not been confirmed in neuropathological series to be related to specific APOE genotypes.
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PMID:ApoE, Alzheimer's disease, and recovery from brain stress. 932 91

Age-dependent neurodegeneration in Alzheimer disease (AD) may be viewed as a complex interaction among: (i) susceptibility polymorphisms, (ii) somatic mutations or alterations that occur over extended periods of time, and (iii) environmental interactions. Putative "sporadic" diseases appear to have a much stronger genetic component than had been considered previously. For example, in Alzheimer disease, apolipoprotein E is a major susceptibility locus that accounts for approximately half the heritability. Specific APOE genotypes are associated with different relative risks and age of onset distributions. Disease may be expressed as a confluence of several genetic risk factors, superimposed upon the age-dependent increments of somatic mitochondrial mutations, and environmental determinants such as head injury, stroke, or hypoxia. A matrix involving each of these complex factors may influence the age of onset of AD in a particular individual. With careful clinically based family and epidemiological studies, it is now possible to tease out the relevant genetic contributions from the confluence of other factors leading to complex disease affecting specific sets of neurons. The highly intricate maze of contributing factors provides many potential unanticipated opportunities to design rational therapeutic and preventative strategies.
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PMID:Apolipoprotein E, a gene with complex biological interactions in the aging brain. 936 Dec 94

There is increasing evidence that risk factors for vascular disease and stroke are associated with cognitive impairment and Alzheimer's disease. This paper reviews current knowledge on the relationship between risk factors for stroke and Alzheimer's disease. The focus will be on 'classical' risk factors, including age and gender, socioeconomic status, diabetes, cholesterol, prior cardiovascular disease, atrial fibrillation, cigarette smoking and alcohol use; as well as on factors that more recently have been recognized as putative risk factors, including APOE genotype, serum homocysteine concentration, relative abnormalities in the hemostatic and thrombotic systems, and inflammation.
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PMID:Risk factors for vascular disease and dementia. 1042 64

Cytidine 5'-diphosphocholine (citicoline) is a an endogenous intermediate in the biosynthesis of structural membrane phospholipids and brain acetylcholine. Citicoline has been extensively used for the treatment of neurodegenerative disorders associated with head trauma, stroke, brain aging, cerebrovascular pathology and Alzheimer's disease. In this study we have investigated the efficacy and safety of the treatment with citicoline versus placebo in patients with Alzheimer disease. Thirty patients (age = 73.0 +/- 8.5 years; range = 57-87 years) with mild to moderate senile dementia (GDS: stages 3-6) of the Alzheimer type were included in a double-blind, randomized and placebo-controlled clinical trial. After a 2-week period of drug washout, patients were treated with i) placebo (n = 17; age = 73 +/- 5 years) or ii) 1,000 mg/day of citicoline (n = 13; age = 76 +/- 9 years) for 12 weeks (84 days). Examinations were done at baseline (T0) and after the 12 weeks of treatment (T12). As compared to placebo, citicoline improved cognitive performance in Alzheimer's disease patients with APOE E4 (ADAS: difference between groups = -3.2 +/- 1.8 scores, p < 0.05; ADAS-cog: difference between groups = -2.3 +/- 1.5, ns); and this improvement on cognition was more pronounced (ADAS, p < 0.01; ADAS-cog: difference between groups = -2.8 +/- 1.3, p < 0.06) in patients with mild dementia (GDS < 5). Citicoline also increased cerebral blood flow velocities in comparison with placebo (p < 0.05) when transcranial Doppler recordings from both hemispheres were considered together, as well as diastolic velocity in the left middle cerebral artery (p < 0.05). Patients treated with citicoline showed an increase in the percentage of brain bioelectrical activity of alpha (occipital electrodes) and theta type (left side electrodes), accompanied by a decrease in relative delta activity particularly marked in the left temporal lobe. Significant differences with respect to placebo (p < 0.05) were observed for theta activity in several fronto-parieto-temporal electrodes of the left hemisphere. Treatment with citicoline tended to reduce serum IL-1 beta levels, mainly after 4 weeks of administration, with no modified blood histamine content. In addition, neither adverse side effects nor alterations in biological and hematological parameters were induced by citicoline. The present data indicate that citicoline (1,000 mg/day) is well tolerated and improves cognitive performance, cerebral blood perfusion and the brain bioelectrical activity pattern in AD patients. According to our results, it seems that citicoline might be a useful treatment in Alzheimer's disease, and that the efficacy of this compound is greater in patients with mild mental deterioration and/or bearing the epsilon 4 allele of the APOE.
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PMID:Double-blind placebo-controlled study with citicoline in APOE genotyped Alzheimer's disease patients. Effects on cognitive performance, brain bioelectrical activity and cerebral perfusion. 1066 11

Apolipoprotein E fulfills fundamental functions in lipid transport and neural tissue repair after injury.(6,8) Its three most common isoforms (E2, E3, and E4) are critical determinants of diverse human diseases, including major cardiovascular and neurodegenerative disorders.(8,14) Apolipoprotein E4 is associated with an increased risk for Alzheimer's disease(3,5) and poor clinical outcome after head injury or stroke.(11,16) The precise role of apolipoprotein E4 in these conditions remains unknown. To characterize the effects of human apolipoprotein E isoforms in vivo, we analysed transgenic Apoe knockout mice that express apolipoprotein E3 or E4 or both in the brain. Hemizygous and homozygous apolipoprotein E3 mice were protected against age-related and excitotoxin-induced neurodegeneration, whereas apolipoprotein E4 mice were not. Apolipoprotein E3/E4 bigenic mice were as susceptible to neurodegeneration as apolipoprotein E4 singly-transgenic mice. At eight months of age neurodegeneration was more severe in homozygous than in hemizygous apolipoprotein E4 mice consistent with a dose effect. Thus, apolipoprotein E4 is not only less neuroprotective than apolipoprotein E3 but also acts as a dominant negative factor that interferes with the beneficial function of apolipoprotein E3. The inhibition of this apolipoprotein E4 activity may be critical for the prevention and treatment of neurodegeneration in APOE varepsilon4 carriers.
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PMID:Dominant negative effects of apolipoprotein E4 revealed in transgenic models of neurodegenerative disease. 1079 51

To investigate whether the APOE*4 allele modified the relationship between cerebrovascular events and Alzheimer's disease (AD), we collected evidence of previous stroke or transient ischemic attack (TIA) and determined APOE genotype among 102 subjects with AD and 375 nondemented subjects in a community-based study of dementia. Subjects with a history of stroke or TIA were twice as likely to have AD as subjects without such a history. However, APOE*4 carriers with a history of stroke/TIA were 5 times more likely than APOE*4 carriers without such a history to have AD (odds ratio = 5.3, 95% confidence interval = 1.4-20.9). History of stroke/TIA had little effect on the likelihood of having AD in subjects without an APOE*4 allele.
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PMID:Relationships between cerebrovascular events, APOE polymorphism and Alzheimer's disease in a community sample. 1106 May 6

The APOE varepsilon4 allele is associated with a variety of conditions such as Alzheimer's disease, coronary artery disease, stroke and postoperative cognitive dysfunction. The common pathophysiological feature that appears to explain these positive clinical associations with APOE varepsilon4 allele may relate to the decreased endogenous anti-oxidant capability of an individual. A significant body of existing clinical data supports the assumption that diseases associated with the varepsilon4 allele can be alleviated by antioxidant therapies, such as vitamin E. Therefore, we hypothesize that determination of an individual's APOE allele status has medical utility as an efficient method to identify patient subgroups susceptible to oxidative damage. We suggest that prospective studies are needed to determine if individuals at high risk for diseases characterized by oxidative damage and/or who have an APOE varepsilon4 allele might benefit significantly from available antioxidant intervention at a relatively early and asymptomatic age.
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PMID:Medical utility of apoe allele determination in assessing the need for antioxidant therapy. 1135 59

The authors hypothesized that divergent influences of the APOE epsilon4 allele on ischemic and hemorrhagic stroke survival might result from differences in coagulation profiles. In 49 hemorrhagic stroke patients, epsilon4 carriers had higher partial thromboplastin time ratios (p < 0.01) than non-epsilon4 carriers. Among 529 ischemic stroke patients, increasing epsilon4 allele dose was associated with improved survival (p = 0.03) after adjusting for baseline NIH stroke scale (p = 0.00001) and partial thromboplastin time ratio (p = 0.01). Relative anticoagulation does not fully explain the survival advantage in epsilon4-carrying ischemic stroke patients.
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PMID:Apolipoprotein E genotype, coagulation, and survival following acute stroke. 1157 42


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