Alzheimer Disease: US Federal Service

Mines M, Ding Y, Fan GH. · Department of Veterans Affairs and the Department of Biomedical Sciences, Division of Neurobiology and Neurotoxicology, Meharry Medical College, Nashville, TN 37208, USA. · Curr Med Chem. · Pubmed #17979699 No free full text.

Abstract: Chemokines and chemokine receptors, primarily found to play a role in leukocyte migration to the inflammatory sites or to second lymphoid organs, have recently been found expressed on the resident cells of the central nervous system (CNS). These proteins are important for the development of the CNS and are involved in normal brain functions such as synaptic transmission. Increasing lines of evidence have implicated an involvement for chemokines and their receptors in several neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), human immunodeficiency virus-associated dementia (HAD), multiple sclerosis (MS), and stroke. Specific inhibition of the biological activities of chemokine receptors could gain therapeutic benefit for these neurodegenerative disorders. In recent years, non-peptide antagonists of chemokine receptors have been disclosed and tested in relevant pharmacological models and some of these inhibitors have entered clinical trials. The aim of this review is to outline the recent progress regarding the role of chemokines and their receptors in neurodegenerative diseases and the advancements in the development of chemokine receptor inhibitors as potential therapeutic approaches for these neurodegenerative diseases.

Vega GL, Weiner MF. · The Nutrition and Metabolism Laboratory, Metabolic Unit, Veterans Affairs Medical Center, Dallas, TX 75390, USA. · J Mol Neurosci. · Pubmed #17901546 No free full text.

Abstract: A number of epidemiologic studies suggest an association between plasma total cholesterol and risk for Alzheimer's disease (AD). Additionally, it has been suggested that treatment with statins, drugs that block cholesterol biosynthesis, lower the incidence and prevalence of AD and of vascular dementia. This review provides an overview of cholesterol transport within the central nervous system and the impact of statins on brain cholesterol metabolism in subjects with AD. Brain cholesterol is converted to 24-S-hydroxycholesterol, a reaction catalyzed by CYP46. The oxysterol traverses the blood-brain barrier and is transported to the liver by plasma lipoproteins. The levels of 24-S-hydroxy-cholesterol are a reflection of brain cholesterol turnover. Subjects with AD reportedly have high levels of the oxysterol possibly reflecting neuronal death with release of cell membrane cholesterol. We show gender dimorphism in plasma levels of 24-S-hydroxycholesterol in subjects with AD and significant reductions in plasma levels of the oxysterol during treatment with standard doses of statins (lovastatin, simvastatin, and pravastatin). Polymorphisms of apolipoprotein E and CYP46 do not influence the effect of statins on plasma levels of 24-S-hydroxycholesterol. There were no untoward effects of the standard doses of statin for the duration of treatment. Statins are currently in trial to determine their effect on the course of AD.

Chuang DM, Manji HK. · Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1363, USA. · Biol Psychiatry. · Pubmed #17572175 links to  free full text

This publication has no abstract.

Tuszynski MH. · Department of Neurosciences-0626, University of California-San Diego, La Jolla 92161, and Veterans Affairs Medical Center, San Diego, CA, USA. · Alzheimer Dis Assoc Disord. · Pubmed #17545746 No free full text.

Abstract: Nervous system growth factors potently stimulate cell function and prevent neuronal death. These broad effects on survival and function arise from direct downstream activation of antiapoptotic pathways, inhibition of proapoptotic pathways, and stimulation of functionally important cellular mechanisms including ERK/MAP kinase and CREB. Thus, as a class, growth factors offer the potential to treat neurodegenerative disorders for the first time by preventing neuronal degeneration rather than compensating for cell loss after it has occurred. Different growth factors affect distinct and specific populations of neurons: the first nervous system growth factor identified, nerve growth factor, potentially stimulates the survival and function of basal forebrain cholinergic neurons, suggesting that nerve growth factor could be a means for reducing the cholinergic component of cell degeneration in Alzheimer disease. This review will discuss the transition of growth factors from preclinical studies to human clinical trials in Alzheimer disease. The implementation of clinical testing of growth factor therapy for neurologic disease has been constrained by the dual need to achieve adequate concentrations of these proteins in specific brain regions containing degenerating neurons, and preventing growth factor spread to nontargeted regions to avoid adverse effects. Gene therapy is one of a limited number of potential methods for achieving these requirements.

Daly JW. · Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, DHHS, Bethesda, Maryland 20892-0820, USA. · Cell Mol Life Sci. · Pubmed #17514358 No free full text.

Abstract: Caffeine, widely consumed in beverages, and many xanthine analogs have had a major impact on biomedical research. Caffeine and various analogs, the latter designed to enhance potency and selectivity toward specific biological targets, have played key roles in defining the nature and role of adenosine receptors, phosphodiesterases, and calcium release channels in physiological processes. Such xanthines and other caffeine-inspired heterocycles now provide important research tools and potential therapeutic agents for intervention in Alzheimer's disease, asthma, cancer, diabetes, and Parkinson's disease. Such compounds also have activity as analgesics, antiinflammatories, antitussives, behavioral stimulants, diuretics/natriuretics, and lipolytics. Adverse effects can include anxiety, hypertension, certain drug interactions, and withdrawal symptoms.

Arispe N, Diaz JC, Simakova O. · Department of Anatomy, Physiology and Genetics, and Institute for Molecular Medicine, Uniformed Services University School of Medicine, USUHS, 4301 Jones Bridge Rd. Bethesda, MD 20814, USA. · Biochim Biophys Acta. · Pubmed #17490607 No free full text.

Abstract: The main pathological features in the Alzheimer's brain are progressive depositions of amyloid protein plaques among nerve cells, and neurofibrillary tangles within the nerve cells. The major components of plaques are Abeta peptides. Numerous reports have provided evidence that Abeta peptides are cytotoxic and may play a role in the pathogenesis of AD. An increasing number of research reports support the concept that the Abeta-membrane interaction event may be followed by the insertion of Abeta into the membrane in a structural configuration which forms an ion channel. This review summarizes experimental procedures which have been designed to test the hypothesis that the interaction of Abeta with a variety of membranes, both artificial and natural, results in the subsequent formation of Abeta ion channels We describe experiments, by ourselves and others, that support the view that Abeta is cytotoxic largely due to the action of Abeta channels in the cell membrane. The interaction of Abeta with the surface of the cell membrane may results in the activation of a chain of processes that, when large enough, become cytotoxic and induce cell death by apoptosis. Remarkably, the blockage of Abeta ion channels at the surface of the cell absolutely prevents the activation of these processes at different intracellular levels, thereby preserving the life of the cells. As a prospect for therapy for Alzheimer's disease, our findings at cellular level may be testable on AD animal models to elucidate the potential role and the magnitude of the contribution of the Abeta channels for induction of the disease.

Craft S. · Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA. · Curr Alzheimer Res. · Pubmed #17430239 No free full text.

Abstract: Insulin modulates cognition and other aspects of normal brain function. Insulin resistance is characterized by chronic peripheral insulin elevations, and it is accompanied by reduced brain insulin levels and insulin activity. Obesity, type 2 diabetes mellitus and hypertension are strongly associated with insulin resistance. In addition, insulin resistance increases the risk of age-related memory impairment and Alzheimer's disease. Possible mechanisms through which these risks are increased include the effects of peripheral hyperinsulinemia on memory, CNS inflammation, and regulation of the beta-amyloid peptide. We have shown that raising plasma insulin in humans to levels that characterize patients with insulin resistance increases the levels of Abeta and inflammatory agents in brain. These convergent effects may impair memory and induce AD pathology. Therapeutic strategies focused on preventing or correcting insulin abnormalities may thus benefit a subset of adults with age-related memory impairment and AD.

Abraham KM. · Division of Diabetes, Endocrinology and Metabolic Diseases, National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, MD 20892-5460, USA. · Curr Alzheimer Res. · Pubmed #17430238 No free full text.

Abstract: Emerging evidence suggests that components of the metabolic syndrome either in isolation or in aggregate may impact the onset or severity of neurodegenerative processes, including those physiologic changes that lead to Alzheimer's Disease (AD). Several animal models that were originally designed to interrogate the metabolic syndrome are readily available. These models can now be used to support studies that may provide new mechanistic links between the metabolic syndrome and neurodegeneration. In addition, animal strains currently being generated and phenotyped through the efforts of an array of NIDDK-supported projects are likely to provide novel and better tools to advance Alzheimer's disease research in the near future.

Norenberg MD, Rao KV. · Veterans Affairs Medical Center, University of Miami Miller School of Medicine, Miami, FL 33101, USA. · Neurochem Int. · Pubmed #17397969 No free full text.

Abstract: Mitochondria, being the principal source of cellular energy, are vital for cell life. Yet, ironically, they are also major mediators of cell death, either by necrosis or apoptosis. One means by which these adverse effects occur is through the mitochondrial permeability transition (mPT) whereby the inner mitochondrial membrane suddenly becomes excessively permeable to ions and other solutes, resulting in a collapse of the inner membrane potential, ultimately leading to energy failure and cell necrosis. The mPT may also bring about the release of various factors known to cause apoptotic cell death. The principal factors leading to the mPT are elevated levels of intracellular Ca2+ and oxidative stress. Characteristically, the mPT is inhibited by cyclosporin A. This article will briefly discuss the concept of the mPT, its molecular composition, its inducers and regulators, agents that influence its activity and describe the consequences of its induction. Lastly, we will review its potential contribution to acute neurological disorders, including ischemia, trauma, and toxic-metabolic conditions, as well as its role in chronic neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis.

Driscoll I, Resnick SM. · Laboratory of Personality and Cognition, National Institute on Aging, Baltimore, MD 21224, USA. · Curr Alzheimer Res. · Pubmed #17316164 No free full text.

Abstract: There is evidence to suggest that testosterone loss constitutes a risk for cognitive decline and possibly dementia, and that elderly men might benefit from exogenous supplementation of testosterone. Studies in non-human animals repeatedly report neuroexcitatory and neuroprotective properties of testosterone and enhanced memory performance after acute or chronic treatment. Positive effects of testosterone supplementation in older men have been reported in several, but not all, studies and require replication in larger randomized clinical trials before recommendations for clinical practice can be made. The current review summarizes recent studies on the neurobiological connection between testosterone and cognitive function in humans and non-human animals. When appropriate, we use the hippocampus as a model structure given it's involvement in sexually dymorphic spatial ability and sensitivity to both androgens and aging. In addition, a number of potential explanations of the discrepancy between data obtained in humans and non-human animals are discussed.

Puglielli L. · Department of Medicine, University of Wisconsin-Madison, and Geriatric Research Education Clinical Center, VA Medical Center, VAH-GRECC 11G, 2500 Overlook Terrace, Madison, WI 53705, USA. · Neurobiol Aging. · Pubmed #17313996 links to  free full text

Abstract: The last decade has revealed that the lifespan of an organism can be modulated by the signaling pathway that acts downstream of the insulin/insulin-like growth factor 1 receptors (IR/IGF1-R), indicating that there is a "program" that drives the process of aging. New results have now linked the same pathway to the neurogenic capacities of the aging brain, to neurotrophin signaling, and to the molecular pathogenesis of Alzheimer's disease. Therefore, a common signaling cascade now seems to link aging to age-associated pathologies of the brain, suggesting that pharmacologic approaches aimed at the modulation of this pathway can serve to delay the onset of age-associated disorders and improve the quality of life. Work from a wide range of fields performed with different approaches has already identified some of the signaling molecules that act downstream of IGF1-R, and has revealed that a delicate checkpoint exists to balance excessive growth/"immortality" and reduced growth/"senescence" of a cell. Future research will determine how far the connection goes and how much of it we can influence.

Hardy J. · Laboratory of Neurogenetics, National Institute on Aging, Porter Neuroscience Building, NIH Main Campus, Bethesda, MD 20892, USA. · Neurochem Res. · Pubmed #17186373 No free full text.

Abstract: In this review, I discuss the possibility that Abeta42 has a physiologic function in blood vessel homeostasis and the consequences that this might have for theories concerning the pathogenesis of Alzheimer's disease and for treatment.

Cole GM, Frautschy SA. · Greater Los Angeles Veterans Affairs Healthcare System, Geriatric Research, Education and Clinical Center, California, USA. · Nutr Health. · Pubmed #17180870 No free full text.

Abstract: Genetic data argues that Alzheimer's disease (AD) can be initiated by aggregates of a 42 amino acid beta amyloid peptide (Abeta42). The Abeta aggregates, notably small oligomer species, cause a cascade of events including oxidative damage, inflammation, synaptic toxicity and accumulation of intraneuronal inclusions; notably neurofibrillary tangles. Cognitive deficits are likely to begin with a failure of synaptogenesis and synaptic plasticity with dendritic spine loss and dying back of dendritic arbor. This is followed by neuron loss in key areas involved in learning and memory. Significant prevention or delay of clinical onset may be achievable by modifying environmental risk factors that impact the underlying pathogenic pathways. Because low fish intake and low blood levels of the marine lipid, docosahexaenoic acid (DHA) have been associated with increased AD risk we have tested the impact of depleting or supplementing with dietary DHA on AD pathogenesis in transgenic mice bearing a mutant human gene known to cause AD in people. We reported that even with intervention late in life dietary DHA depletion dramatically enhanced oxidative damage and the loss of dendritic markers, while DHA supplementation markedly reduced Abeta42 accumulation and oxidative damage, corrected many synaptic deficits and improved cognitive function. Loss of brain DHA was exacerbated in mice expressing the mutant human AD transgene, this is consistent with evidence for increased oxidative attack on DHA oxidation in AD. Treatment with the curry spice extract curcumin, a polyphenolic antioxidant that inhibits AP aggregation, has been strongly protective in the same mouse model. Many Western diets are typically deficient in DHA and low in polyphenolic antioxidant intake. These and other data argue that increasing dietary intake of both DHA and polyphenolic antioxidants may be useful for AD prevention.

Craft S. · Department of Psychiatry and Behavioral Sciences, Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, University of Washington School of Medicine, Seattle, WA 98108, USA. · Alzheimer Dis Assoc Disord. · Pubmed #17132977 No free full text.

Abstract: Insulin plays a key role in cognition and other aspects of normal brain function. Insulin resistance induces chronic peripheral insulin elevations, reduces insulin activity, and reduces brain insulin levels. The insulin resistance syndrome and associated conditions such as type 2 diabetes mellitus and hypertension, are associated with age-related memory impairment and Alzheimer disease. Our work has focused on potential mechanisms through which this association is forged, including the effects of peripheral hyperinsulinemia on memory, inflammation, and regulation of the beta-amyloid peptide. We have shown that raising plasma insulin to levels that characterize patients with insulin resistance invokes synchronous increases in levels of beta-amyloid and inflammatory agents. These convergent effects may impair memory and induce AD pathology. Therapeutic strategies focused on preventing or correcting insulin abnormalities may thus benefit adults with age-related memory impairment and AD.

Rouault TA, Cooperman S. · Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. · Semin Pediatr Neurol. · Pubmed #17101452 No free full text.

Abstract: Brain iron uptake is regulated by the expression of transferrin receptor 1 in endothelial cells of the blood-brain barrier. Transferrin-bound iron in the systemic circulation is endocytosed by brain endothelial cells, and elemental iron is released to brain interstitial fluid, likely by the iron exporter, ferroportin. Transferrin synthesized by oligodendrocytes in the brain binds much of the iron that traverses the blood-brain barrier after oxidation of the iron, most likely by a glycophosphosinositide-linked ceruloplasmin found in astrocytic foot processes that ensheathe brain endothelial cells. Neurons acquire iron from diferric transferrin, but it is less clear how glial cells acquire iron. In aging mammals, iron accumulates in the basal ganglia, and iron accumulation is believed to contribute to neurodegenerative diseases, including Parkinson and Alzheimer disease. Here we consider the possibility that iron accumulations, which are often thought to facilitate free radical generation and oxidative damage, may contain insoluble iron that is unavailable for cellular use, and the pathology associated with iron accumulations may result from functional iron deficiency in some diseases.

Cole GM, Frautschy SA. · Greater Los Angeles Veterans Affairs Healthcare System, Geriatric Research, Education and Clinical Center, 16111 Plummer Street, Sepulveda, CA 91343, USA. · Exp Gerontol. · Pubmed #17049785 No free full text.

Abstract: Although increased lifespan is associated with reduced insulin signaling, insulin signaling is essential for neuronal development and survival. Insulin resistance is central to Type II diabetes and is also implicated in the pathogenesis of Alzheimer's Disease (AD). This has prompted ongoing clinical trials in AD patients to test the efficacy of improving insulin - like signaling with dietary omega-3 fatty acids or insulin - sensitizing drugs as well as exercise regimens. Here we review the role of insulin signaling in brain aging and AD, concluding that the signaling pathways downstream to neurotrophic and insulin signaling are defective and coincident with aberrant phosphorylation and translocation of key components, notably AKT and GSK3beta, but also rac> PAK signaling. These responses are likely to contribute to defects in synaptic plasticity, learning and memory. Both oligomers of beta-amyloid (which are elevated in the AD brain) and pro-inflammatory cytokines (which are elevated in the aged or AD brain) can be used to mimic the trophic factor/insulin resistance observed in AD, but details on other factors and mechanisms contributing to this resistance remain elusive. A better understanding of the precise mechanisms underlying alterations in the insulin/neurotrophic factor signal transduction pathways should aid the search for better AD therapeutic and prevention strategies.

Hardy J. · Laboratory of Neurogenetics, National Institute on Aging, Porter Neuroscience Building, Bethesda, Maryland 20892, USA. · Neuron. · Pubmed #17015223 No free full text.

Abstract: On the 100th anniversary of Alzheimer's lecture describing the clinicopathological entity which bears his eponym, this article reviews the major areas of progress in our understanding of the disease and outlines the many gaps still remaining. The progress toward effective mechanistic therapy is reviewed.

Meeks TW, Ropacki SA, Jeste DV. · Division of Geriatric Psychiatry, Department of Psychiatry, University of California, San Diego, and Veterans Affairs San Diego Healthcare System, San Diego, California 92161, USA. · Curr Opin Psychiatry. · Pubmed #17012935 No free full text.

Abstract: PURPOSE OF REVIEW: Neuropsychiatric disturbances in dementia are prevalent, and research is uncovering their neurobiological correlates. RECENT FINDINGS: Late-onset depression appears to be associated with Alzheimer's disease pathology at autopsy, and lifetime depression episodes may worsen Alzheimer's disease pathology in the hippocampus. Vascular disease and elevated homocysteine increase risk for both late-onset depression and Alzheimer's disease and may partly mediate their relationship. Monoamine changes are robust finding in Alzheimer's disease and may account for many observed depression symptoms. Risk of psychosis of Alzheimer's disease appears to be increased by several genes also implicated in schizophrenia (e.g., catechol-O-methyltransferase, neuregulin-1). Psychosis in dementia with Lewy bodies appears to be related to cholinergic deficits. Alzheimer's disease is associated with changes in the circadian sleep-wake cycles, including decreased night-time melatonin. Sleep apnea may be related to apolipoprotein E genotype and impact cognition in Alzheimer's disease. Rapid eye movement sleep behavior disorder is intricately related to synucleinopathies, such as dementia with Lewy bodies, but synuclein changes may not totally explain this relationship. SUMMARY: Neuropsychiatric disturbances are a core feature of dementia and worsen many clinical outcomes. Among the most validated syndromes are depression, psychosis, and sleep disturbance of Alzheimer's disease. Neuropathology, neuroimaging, and genetic studies increasingly provide insight into the origins of these psychiatric symptoms in dementia.

Friedlander AH, Norman DC, Mahler ME, Norman KM, Yagiela JA. · VA Greater Lost Angeles Healthcare System, Hospital Dental Service, University of California Los Angeles Medical Center, USA. · J Am Dent Assoc. · Pubmed #16946428 links to  free full text

Abstract: BACKGROUND: The authors review the clinical features, epidemiology, pathophysiology, medical management, dental findings and dental treatment of patients with Alzheimer's disease (AD). STUDIES REVIEWED: The authors conducted MEDLINE searches for 2000 through 2005 using the terms "Alzheimer's disease," "geriatric," "epidemiology," "pathophysiology," "treatment" and "dentistry." Reports selected for further review included those published in English in peer-reviewed journals. The authors gave preference to articles reporting randomized, controlled trials. RESULTS: AD is a progressive and fatal neurodegenerative disorder characterized by cognitive dysfunctions, particularly in learning and memory, and the emergence of behavioral abnormalities. Deficiencies in the cells responsible for storage and processing of information underlie the cognitive, functional and behavioral changes seen in patients with the disorder. CLINICAL IMPLICATIONS: As the elderly population grows, increasing numbers of Americans with AD will require dental treatment. The prevalence of dental disease likely will be extensive, because of diminished salivary flow and patients' inability to perform appropriate oral hygiene techniques. Preventive dental education for the caregiver and use of saliva substitutes and anticaries agents by the patient are indicated.

Bergmann C, Sano M. · Alzheimer Disease Research Center of Mount Sinai School of Medicine, NYC, James J Peters VAMC, Bronx, NY 10468, USA. · Neurol Res. · Pubmed #16945210 No free full text.

Abstract: Dementia is one of the commonest neurological disorders in the elderly population. In regards to the increasing longevity of populations worldwide, prevention of dementia has become a major public health challenge. There has been an intense research in the identification of modifiable risk factors for dementia. These risk factors could then be used as targets for intervention, pharmacologic or non-pharmacologic. Numerous reports of the relation between cardiovascular risk factors and cognitive decline and dementia have been published over the past years. This review focuses on the cardiovascular risk factors hypertension, hyperlipidemia and diabetes mellitus as targets for prevention of cognitive decline, overall dementia and Alzheimer's disease. Observational studies and clinical trials regarding the association between antihypertensive, lipid lowering and antidiabetic medications and the risk of impaired cognition, dementia or Alzheimer's disease are reviewed. Based on these data, we propose that early interventions at reducing these cardiovascular risk factors may have an impact on future incidence and prevalence of cognitive deficits of many etiologies including Alzheimer's disease.

Gasior M, Rogawski MA, Hartman AL. · Epilepsy Research Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-3702, USA. · Behav Pharmacol. · Pubmed #16940764 links to  free full text

Abstract: The ketogenic diet has been in clinical use for over 80 years, primarily for the symptomatic treatment of epilepsy. A recent clinical study has raised the possibility that exposure to the ketogenic diet may confer long-lasting therapeutic benefits for patients with epilepsy. Moreover, there is evidence from uncontrolled clinical trials and studies in animal models that the ketogenic diet can provide symptomatic and disease-modifying activity in a broad range of neurodegenerative disorders including Alzheimer's disease and Parkinson's disease, and may also be protective in traumatic brain injury and stroke. These observations are supported by studies in animal models and isolated cells that show that ketone bodies, especially beta-hydroxybutyrate, confer neuroprotection against diverse types of cellular injury. This review summarizes the experimental, epidemiological and clinical evidence indicating that the ketogenic diet could have beneficial effects in a broad range of brain disorders characterized by the death of neurons. Although the mechanisms are not yet well defined, it is plausible that neuroprotection results from enhanced neuronal energy reserves, which improve the ability of neurons to resist metabolic challenges, and possibly through other actions including antioxidant and anti-inflammatory effects. As the underlying mechanisms become better understood, it will be possible to develop alternative strategies that produce similar or even improved therapeutic effects without the need for exposure to an unpalatable and unhealthy, high-fat diet.

Launer LJ. · Laboratory for Epidemiology, Demography and Biometry, National Institute on Aging, National Institutes of Health, 7201 Wisconsin Avenue, Bethesda, MD 20892, USA. · Alzheimer Dis Assoc Disord. · Pubmed #16917200 No free full text.

This publication has no abstract.

Howe EG. · Programs in Medical Ethics, Uniformed Services University of the Health Sciences in Bethesda, Maryland, USA. · J Clin Ethics. · Pubmed #16913144 No free full text.

This publication has no abstract.

Hardy J, Myers A, Wavrant-De Vrieze F. · Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892-3707, USA. · Neurodegener Dis. · Pubmed #16908992 No free full text.

Abstract: The identification of the apolipoprotein E gene as a risk factor for late-onset Alzheimer's disease was a spectacularly successful application of genetic analysis to a complex trait, and it led to the hope and expectation that other risk loci for the disease would soon be forthcoming. Twelve years later, despite a huge amount of work, no other loci have been identified. In this article, we discuss the complexity of the problem and the pitfalls in the analytical methods that have been used and how we are approaching this problem.

Ganzini L. · Department of Psychiatry and Medicine, Oregon Health & Science University, Portland, Oregon 97239, USA. · Palliat Support Care. · Pubmed #16903584 No free full text.

Abstract: The case of Terri Schiavo resulted in substantial media attention about the use of artificial nutrition and hydration (ANH) especially by percutaneous endoscopic gastrostomy (PEG). In this article, I review ethical and legal principles governing decisions to choose or forgo ANH at the end of life, including issues of autonomy and decision-making capacity, similarities and differences between ANH and other medical treatments, the role of proxies when patients lack decision-making capacity, and the equivalence of withholding and withdrawing treatment. Evidence for palliative or life-sustaining benefits for ANH are reviewed in three disease processes: amyotrophic lateral sclerosis (ALS), cancer, and dementias, including Alzheimer's disease. Although more recent studies suggest a possible palliative role for ANH in ALS and terminal cancer, feeding tubes do not appear to prolong survival or increase comfort in advanced dementia of the Alzheimer's type.