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 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical and neuropathologic evidence points to the development of Alzheimer's disease (AD) in seven Down's syndrome patients above age 40. Dementia was observed in these patients over periods of 2.5 to 9.2 years. The first clinical sign of AD, visual memory loss, was succeeded by impaired learning capacity and decreased occupational and social functioning, and culminated in seizures and urinary incontinence. The morphometric observations of the brains of these seven patients with AD showed that the numbers of plaques and tangles exceeded 20 per 1.5 X 10(6) microns2 area, in both the prefrontal and hippocampal cortices. Plaques and tangles were also evident in the basal ganglia, thalamus, hypothalamus, and midbrain. In addition, we found that four of the seven brains showed small strokes, and five of the seven amyloid angiopathy. This study also indicates that by longitudinal neuropsychological evaluations and lab tests, which exclude other causes of dementia, the diagnosis of AD can be made even in severely and profoundly retarded patients.
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PMID:Alzheimer's disease in Down's syndrome: clinicopathologic studies. 315 74

Many disorders--including vascular disease, alcoholism, Huntington's disease, drug toxicity, metabolic disorders, brain tumors, depression, and other psychiatric disorders--can cause dementia. Moreover, 50% of all dementia patients have Alzheimer's disease. Guidelines have been established to define the types of dementia. A detailed history, which may note previous depression, and a physical examination are essential. Assessment of the patient's mental status and a neurological examination may help to distinguish other forms of dementia from Alzheimer's disease. Brain imaging and psychometric testing may also help to establish a diagnosis. Metabolic screening for reversible causes of dementia, such as thyroid disturbance or electrolyte-imbalance, is essential. Common features of Alzheimer's disease include memory loss; difficulty with problem solving, abstractions, and calculations; and language and visuospatial deficits. Delusions are common in the early phase of the disease. It is not yet possible to diagnose Alzheimer's disease with complete accuracy. Additional neurophysiological and biochemical markers for diagnosis must be developed.
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PMID:Dementia update: diagnosis and neuropsychiatric aspects. 328 27

Nonconvulsive status epilepticus (NCSE) accounts for approximately 20% of all status epilepticus (SE). Although convulsive SE is recognized as a medical emergency, prompt diagnosis and treatment of patients with NCSE is often not emphasized because its consequences are thought to be benign. We report 10 patients with persistent neurologic deficits or death after well-documented NCSE in the form of complex partial status epilepticus (CPSE). All patients had prolonged CPSE lasting 36 hours or longer, as documented by clinical and EEG findings. Causes for CPSE were preexisting epilepsy with partial and secondarily generalized seizures (3 patients), vascular disease (2 patients), encephalitis (2 patients), and metabolic disease (1 patient); causes were unknown for two patients. Poor outcomes identified included persistent (lasting at least 3 months) or permanent cognitive or memory loss (5 patients), cognitive or memory loss plus motor and sensory dysfunction (3 patients), and death (3 patients). NCSE in the form of CPSE is not a benign entity. Serious morbidity and mortality may occur due to the adverse effects of prolonged seizures and as a result of acute brain disorders that precipitate the seizures.
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PMID:Complex partial status epilepticus accompanied by serious morbidity and mortality. 910 27

Alzheimer's disease (AD) has become recognised as a major cause of morbidity and mortality in the ageing population worldwide. Over 20 million people worldwide are affected by AD, which ensures that the disease imposes a major economic burden. Alzheimer's disease is a progressive neurodegenerative disorder with characteristic clinical and neuropathological features. Neurofibrillary tangles, neuritic plaques and amyloid angiopathy occur in varying severity in brains of patient's with Alzheimer's disease. Biological markers of AD allowing an early definitive premorbid diagnoses are currently not available. Memory loss for recent events is invariable and often the earliest prominent symptom. Language disorders, difficulties with complex tasks, depression, psychotic symptoms and behavioral changes are other common manifestations of AD. Diagnosis involves the early detection of cognitive decline and ruling out other causes of dementia like vascular dementia, Lewy body dementia, fronto-temporal degeneration or reversible causes like hypothyroidism. Acetylcholinesterase inhibitors have shown to be effective in mild to moderate AD in improving the cognitive function of patients in clinical trials. Caregiver intervention programs have considerable potential to improve both the caregiver and patient quality of life.
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PMID:Diagnosis and management of Alzheimer's disease--an update. 1107 82

We describe the clinical phenotype and pathology of a new autosomal dominant late-onset familial form of Alzheimer's disease in four extensive kindred originated in a genetically isolated population. Twelve affected and 16 unaffected members of these kindred were examined clinically, and a brain post-mortem study was carried out in one case. The preliminary genetic assessment included complex segregation analysis, evaluation of the power to detect linkage, and exclusion of candidate genes. Dementia has been recorded for six generations in ancestors of examined cases. Review of death certificates allowed linking of all subjects in four extensive pedigrees. Affected individuals examined had progressive memory loss with onset between 57 and 74 years of age, along with seizures, myoclonus and parkinsonism in advanced stages. The brain of the case examined post-mortem showed widespread neocortical neuritic plaques and neurofibrillary tangles (stage VI of Braak), amyloid angiopathy, and Lewy bodies restricted to limbic areas. Sequencing exons 16 and 17 of amyloid precursor protein, and exons 4-12 of presenilin 1 and presenilin 2 genes did not disclose any mutations. Genotyping with markers D21S265, D14S71, D14S77, D1S2850 and D1S479 located 1-3 cM from the previously reported genes further excluded linkage to these genes. Seven out of 12 cases were apolipoprotein E (APOE) epsilon3/3, although the presence of an APOE epsilon4 allele was associated with an increased risk of dementia (odd ratio 6.17; 95% confidence interval: 1.15-33.15), but not to an earlier age of onset. Complex segregation analysis showed that the best model fitting the data was that of a major gene (dominant) with a gene frequency close to 3% in this population. Simulation analysis predicted an average logarithm of odds (LOD) of 2.2 at = 0.05. These four families, which seem to be part of a common extended pedigree originated by a founder arriving in this region in the 18th century, represent an autosomal dominant late-onset familial Alzheimer's disease not linked to previously known genetic loci. The simulation analysis suggests that it will be feasible to locate a novel responsible gene in these kindred.
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PMID:A multigenerational pedigree of late-onset Alzheimer's disease implies new genetic causes. 1584 24

Extract of Ginkgo biloba EGb 761 has been used in the treatment of various common geriatric complaints including vertigo, short-term memory loss, hearing loss, lack of attention, vigilance and cerebral vascular disorder. Recent results suggest that it can serve as a cognitive enhancer and anti-stress buffer. It raises a possibility that EGb 761 may be involved in the fear conditioning. In this study, we used fear-potentiated startle (FPS) to evaluate the possible effects of EGb 761 on the acquisition stage of fear conditioning. Our results showed that administration of EGb 761 30 min prior to the conditioning facilitated acquisition of conditioned fear in a dose dependent manner. No significant differences had been observed in either basal startle response or shock activity. These results indicated that the facilitation effect of EGb 761 was not the result of impaired basal startle response or enhanced pain perception. Subsequent control experiment results indicated that the facilitation effect of EGb 761 on the acquisition was not due to anxiogenic effect or non-specific effect. Our data present the first evidence that EGb 761 can enhance fear memory formation rather than serve as an anti-stress buffer.
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PMID:Extract of Ginkgo biloba EGb 761 facilitates fear conditioning measured by fear-potentiated startle. 1593 28

Adverse neurologic outcomes after cardiac surgery can have devastating consequences, among them increased mortality risk and, among survivors, loss of independence and a diminished quality of life. They also represent a burden on the health-care system, requiring prolonged hospitalizations and additional aftercare and, therefore, greater costs. Adverse outcomes are classified by their severity. Frank stroke is the most serious. This complication is associated with patient age; however, the presence of significant ascending aortic disease represents the greatest hazard. Multivariable analysis also indicates that prior neurologic events, diabetes, chronic obstructive pulmonary disease, preoperative status, and diffuse vascular disease are predictive. The second type of adverse cerebral outcome includes neurocognitive abnormalities such as memory loss and diminished emotional health. The strongest predictors of these abnormalities are hypertension and a history of alcohol use, as well as age. These predictive factors have been incorporated into the Multicenter Study of Perioperative Ischemia stroke-risk index, which clinicians can use to better assess the risk of adverse neurologic events. Clinical research examining the relationship between the predictive variables for neurologic adverse events and cerebral blood flow has suggested some surgical strategies for minimizing risk, such as limiting manipulation of the ascending aorta. The benefits of strategies such as using low or high mean arterial pressures and manipulating pump flow remain unclear. Off-pump coronary bypass surgery has been proposed as a means of reducing neurologic risk, but its effectiveness is unproved in this area. One pharmacologic strategy, the administration of aprotinin, has been shown to reduce the incidence of stroke in high-risk patients.
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PMID:Predicting and preventing adverse neurologic outcomes with cardiac surgery. 1649 92

The aim of this study was to describe a novel mutation in exon 8 of the presenilin gene (L286P) associated with early-onset autosomal dominant Alzheimer's disease (AD) and lobar haematomas. The proband was a woman who developed cognitive decline with predominant memory loss at the age of 35 years. The patient died at the age of 54 years and the neuropathological examination confirmed the diagnosis of AD. Three of her four siblings, one parent and one sibling of her parent had suffered from cognitive decline at ages between 35 and 42 years. Three of them also presented lobar haematomas. The neuropathological examination, available in one of them, disclosed the presence of severe amyloid angiopathy as the cause of the haematoma. The study of PSEN1 gene with single strand conformation polymorphism technique failed to show abnormalities suggestive of mutations. Direct sequencing disclosed the presence of a missense mutation in codon 286 (L286P) in the proband and her already affected descendent, which was absent in the healthy sibling. L286P is a novel mutation in PSEN1 that causes familial early-onset AD and brain haematomas related to amyloid angiopathy.
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PMID:A novel mutation in the PSEN1 gene (L286P) associated with familial early-onset dementia of Alzheimer type and lobar haematomas. 1802 91

Homocysteine, a sulfur-containing amino acid, is a metabolite of the essential amino acid methionine. High blood levels of homocysteine result in far-reaching biochemical and life-threatening consequences. Homocysteine exists at a critical biochemical intersection in the methionine cycle between S-adenosylmethionine, the ubiquitous methyl donor, and vitamins B(12) and folic acid. Indirect and direct vascular damage can be caused by homocysteine, a putative atherothrombotic risk factor. Homocysteine has been associated with vascular disease, particularly in subjects with significant carotid stenosis. Increasing evidence for a connection between homocysteine metabolism and cognitive function is surfacing, and this includes from mild cognitive decline (age-related memory loss) to vascular dementia and Alzheimer's disease. In the elderly population increase in homocysteine is commonly seen due to significant deficiencies in cobalamin (B(12)), folate and vitamin B(6.) All of these disease associations are thought to be interrelated via increased homocysteine and S-adenosylhomocysteine and subsequent hypomethylation of numerous substances, including DNA and proteins, rendering vascular structures more susceptible to damage. Decreasing plasma homocysteine, by providing nutritional cofactors for its metabolism has been shown to reduce the risk of cardiovascular events. The current methods of evaluation of homocysteine metabolism include assessment of cobalamin (B(12)) and folate and vitamin B(6) status and screening for mutations in the genes encoding the enzymes of metabolism. An accurate method for the estimation of plasma and tissue levels of homocysteine would contribute greatly to a proper understanding of the metabolism. In the current review emphasis will be on the estimation of homocysteine, and evaluation of one of the common mutations encountered in the metabolism of this amino acid.
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PMID:Methods in assessing homocysteine metabolism. 1837 Jun 34

Amyloid-beta (Abeta) deposition is a defining feature of Alzheimer's disease (AD). The toxicity of Abeta aggregation is thought to contribute to clinical deficits including progressive memory loss and cognitive dysfunction. Therefore, Abeta peptide has become the focus of many therapeutic approaches for the treatment of AD due to its central role in the development of neuropathology of AD. In the past decade, taking the advantage of multiphoton microscopy and molecular probes for amyloid peptide labeling, the dynamic progression of Abeta aggregation in amyloid plaques and cerebral amyloid angiopathy has been monitored in real time in transgenic mouse models of AD. Moreover, amyloid plaque-associated alterations in the brain including dendritic and synaptic abnormalities, changes of neuronal and astrocytic calcium homeostasis, microglial activation and recruitment in the plaque location have been extensively studied. These studies provide remarkable insight to understand the pathogenesis and pathogenicity of amyloid plaques in the context of AD. The ability to longitudinally image plaques and related structures facilitates the evaluation of therapeutic approaches targeting toward the clearance of plaques.
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PMID:Multiphoton in vivo imaging of amyloid in animal models of Alzheimer's disease. 2039 80


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