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Brain Power Genesis

Brain Power Genesis is a recently launched nootropic stack that will help you supercharge your brain power in just a day. The product is in the form of capsules, which is recommended that you take 2 per day with or without food. Brain Power genesis is a product of Christopher Hatton. It made by a mixture of 8 all-natural ingredients including L-Tyrosine, Bacopa Monnieri Extract, L-Theanine, Vitamin B6, Lion's Mane, Cognizin, N-Acetyl-L-Tyrosine, and Maritime Pine Bark Extract. Brain Power Genesis has countless benefits, such as boost focus, saves time, support memory, enhances mental energy, increases motivation, as well as improves mood balance. Anyone can use Brain Power Genesis. It has tremendous effects on students, gamers, athletes, professionals, and active seniors. This product also comes with a special bonus. If you purchase Brain Power Genesis, you will receive a link to download a copy of the bestselling book How To Detox From Brain Fog by Christopher Hatton for free. If you buy more two bottles of Brain Power Genesis, you will get free extra bottles. Read more here...

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Alzheimers Disease DRG 012

Alzheimer's disease (AD) is a degenerative disorder of the brain that is manifested by dementia and progressive physiological impairment. It is the most common cause of dementia in the elderly but is not a normal part of aging. More than 4 million Americans suffer from AD. Dementia involves progressive decline in two or more of the following areas of cognition memory, language, calculation, visual-spatial perception, judgment, abstraction, and behavior. Dementia of the Alzheimer's type (DAT) accounts for approximately half of all dementias. The average time from onset of symptoms to death is 8 to 10 years. The pathophysiological changes that occur in DAT include the following

Alcoholrelated Dementia

The existence of alcohol-related dementia is complicated by the various syndromes described in individuals who abuse alcohol, as well as other possible comorbidities contributing to cognitive dysfunction in these individuals (vitamin B12 deficiency, subdural hematomas and head injuries, cerebrovascular disease, etc.). Knowledge about whether alcohol abuse may be a risk factor for other dementias is also sparse. The Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), classification relies on alcohol use to identify alcohol-related dementia, a process that may be subjective or based on limited information. Oslin et al. propose diagnostic criteria following the model used in the National Institute of Neurological and Communicative Diseases and Stroke Alzheimer's Disease and Related Disorders Association (NINCDS ADRDA) criteria for Alzheimer's disease (AD). It also uses cutoffs for heavy drinking of 28 drinks per week for women and 35 for men. As the authors...

Dementia With Lewy Bodies

Combining both features of a primary degenerative dementia and an akinetic-rigid, parkinsonian syndrome with prominent behavioral features, dementia with Lewy bodies (DLB) illustrates some of the shortcomings of current nosological schemata. Lewy bodies are the pathological hallmark of Parkinson's disease, where they are primarily restricted to substantia nigra and pigmented brainstem nuclei. However, the presence of Lewy bodies in the cerebral cortex coupled with behavioral symptoms, such as visual hallucinations, led to the recognition of DLB as a distinct syndrome. Complicating this assessment is the presence of AD pathology in about 50 of autopsies of clinically diagnosed cases of DLB, leading to the concept of a Lewy body variant of AD. A number of diagnostic criteria have been proposed and are summarized in Table 46. A number of studies, utilizing varying proportions of DLB cases have reported validity, and reliability of the clinical criteria of DLB, often in relation to...

Frontotemporal Dementia

Frontotemporal dementia (FTD) is a term encompassing a number of disorders now grouped together on the basis both of clinical expression and pathology. Some of the disorders now included under FTD are Pick's disease, progressive nonfluent aphasia, and semantic dementia. About 15 of FTD cases are familial, associated with mutations in the microtubule-associated protein, tau, whose

HIVAssociated Dementia

It is worth noting that the classification of these neuropsychiatric manifestations of HIV infection is undergoing revision after a joint conference of the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke on June 13, 2005, identified and defined criteria for three levels of HIV-associated neurocognitive disorders or conditions asymptomatic neurocognitive impairment, mild neurocognitive disorder (previously MCMD), and HIV-associated dementia. Clinicians should update themselves regularly by accessing Web sites such as that of the American Psychiatric Association's Office of HIV Psychiatry ( hiv), which has downloadable curricula on the complete array of HIV-related neuropsychiatric conditions.

Relationship to Alzheimers Disease

Alzheimer's disease is neuropathologically defined by the presence in the brain of two features, amyloid deposits of the Ap peptide and neurofibrillary tangles (NFT) of the tau protein. The risk of AD is increased by inheritance of the e4 allele of apoE, and decreased by inheritance of the e2 allele of apoE.1 Apolipoprotein E e4 is associated with increased amy-loid,23,77,78 but not increased NFTs.78 Thus, it has been postulated that apoE4 is involved either in increased deposition of Ap, or decreased clearance of Ap. In summary, recent investigations have revealed a complex family of exchangeable apolipoproteins which can be synthesized by resident CNS cells and contribute to the classes of lipoproteins found in the brain. These lipoproteins form a unique class of particles, distinct from that seen in the periphery, which appears to be capable of mediating both lipid removal and delivery. The CNS lipoproteins have available a wide array of at least five potential receptors, each with...

Prevention of dementia I

Ittow can I STOP myself getting dementia ' is a question _L _Lcommonly posed to dementia specialists. Until recently, it has not been possible to provide any advice based on reputable research. The situation is rapidly changing, however, and in this and the next chapter I describe the known risk factors for dementia and strategies that may possibly counteract them. One of the features of recent research has been the convergence of identified risk factors for the two most common types of dementia, Alzheimer's disease and vascular dementia. Thus I discuss prevention strategies for dementia as a whole and indicate where particular strategies may be important for specific types of dementia. It is important to appreciate that intentional efforts to prevent any disease imply that there is some reasonable understanding of what causes it. The disease process by which the causal factors turn a normal state into a pathological (diseased) state must also be understood. Recognition of 'risk...

Prevention of dementia II

IN CHAPTER 2, PREVENTION strategies that are applicable to everybody were considered. In this chapter, strategies that are applicable either to individuals at increased risk of dementia or to individuals already experiencing mild symptoms of possible dementia (mild cognitive impairment) are considered. Selective dementia prevention strategies Selective prevention strategies are directed towards individuals at high risk with established risk factors for a disease. Common examples include weight reduction in overweight people to reduce the risk of coronary artery disease and diabetes, smoking cessation to reduce the risk of lung, heart and blood vessel disease, and increased calcium intake in people with osteoporosis to reduce the risk of fractures. Some dementia prevention strategies in this category may be useful for everybody, not just those with risk factors for dementia, and I indicate those which are most promising. Not all established dementia risk factors currently have...

Alcohol Induced Persisting Dementia

This disorder develops in approximately 9 of alcoholics (Evert & Oscar-Berman, 1995) and consists of memory impairment combined with aphasia, apraxia, agnosia, and impairment in executive functions, such as planning, organizing, sequencing, and abstracting. These deficits are not part of a delirium and persist beyond intoxication and withdrawal. The dementia is caused by the direct effects of alcohol, as well as by vitamin deficiencies. individual with a history of alcoholism are early clues suggestive of alcohol-induced persisting dementia.

Specificity to Alzheimers Disease

Upregulation of clusterin and abnormal staining of lesions for apoE is not limited to AD. Brain levels of clusterin seem to be elevated in many conditions involving injury or chronic inflammation of the brain. Elevated levels of the mRNA for clusterin are seen in the hippocampus in Pick's disease as well as in AD.4 Abnormal staining for clusterin has been seen in dystrophic neurites and some NFTs in the Parkinson's dementia complex of Guam (Fig. 7.1). It has also been seen in humans in ischemic Purkinje cells which showed the shrunken and pyknotic appearance characteristic of irreversible damage.45 Intense staining for clusterin has been seen in hypertrophic astrocytes in cases of multiple sclerosis, stroke and AIDS encephalitis. In these cases, however, the distribution of clusterin did not appear to correlate with that of the MAC,46 a correlation which does appear to occur in AD.9 Apolpoprotein E staining has been found associated with the amyloid in various types of human cerebral...

Vascular dementia

Vascular dementia (VD) represents a heterogeneous group of disorders, approximately eight in number, the common feature being a dementia associated with a disturbance in blood supply to the brain. Diagnostic criteria for VD are not considered robust but the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherch et l' Enseignement en Neurosciences (NINDS-AIREN) criteria15 describe VD in terms of an abrupt deterioration in cognitive function, gait disturbance or frequent falls, urinary frequency, focal neurological findings including sensory loss, lower facial weakness, depression, mood lability, and psychiatric symptoms. Treatment of VD is primary prevention with education regarding risk factors that include many of the same factors for stroke, e.g., smoking, coronary artery disease, alcohol abuse, age, etc.

Alzheimers Disease

AD is the most common form of dementia, accounting for an estimated 65-75 of cases of dementia, especially in aged individuals. Dementia itself is a symptom, not a diagnosis. Dementia is defined as acquired loss of cognitive functioning, and occurs in clear consciousness. This distinguishes it from mental retardation developmental delay and cases where consciousness is fluctuating or impaired, such as delirium or coma. Classification of Alcohol-Related Dementia Dementia Dementia is defined as a significant deterioration of cognitive function sufficient to interfere in social or occupational functioning. As defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, this requires a deterioration in memory and at least one other area of intellectual functioning. Moreover, the cognitive changes are not attributable to the presence of delirium or substance-induced intoxication or withdrawal. Definite Alcohol-Related Dementia At the current time, there are no...


Bruce Miller and his coworkers (Miller et al., 1998 Miller, Boone, Cummings, Read, & Mishkin, 2000) wrote a series of papers on the emergence of artistic talents in a form of degenerative dementia called frontotemporal dementia, or frontal temporal lobar atrophy. The two most common forms of degenerative dementia that are seen in the clinic are Alzheimer's disease and frontotemporal dementia. Most patients with Alzheimer's disease start off with a memory loss and then develop other cognitive deficits, such as problems with naming, route finding, drawing, copying, and even performing learned skilled movements (ideomotor apraxia). The signs and symptoms associated with frontotemporal dementia are often different from those seen with Alzheimer's disease. In one form, patients lose their social skills and perform antisocial acts. Some patients may also become abulic and sit around all day doing nothing useful. Other patients with frontotempo-ral dementia might have a language deficit that...

Clusterin Expression Clusterin Protein

Clusterin is conserved in mammals, though more divergent in vertebrates as a whole. We first identified clusterin as a lipid binding and transport protein in human plasma,1,2 but we have been most impressed by its expression at critical boundary interfaces in both normal and pathophysiologic circumstances. Clusterin is expressed constitutively and de-velopmentally in an interesting series of epithelial cells, frequently at the interfaces of fluid-tissue boundaries.3,4 The induction or deposition of clusterin has been associated in humans and other species with a variety of pathological disorders, including neurodegeneration, viral infection, prostatic involution, renal injury, Alzheimer's disease, and atherosclerotic vascular disease.5-7

Clusterin Immunoreactivity and Its Colocalization with Clusterin mRNA

In contrast to aged rats, either light staining of some temporal cortex neurons and the neuropil or no clusterin immunoreactivity at all was observed in the hippocampus, as well as in several cortical regions of the brain, in elderly humans, using a monoclonal antibody against human clusterin.19,44,45 It should be specified that in these studies, the antibody strongly stained brain tissues of Alzheimer's disease patients. Unfortunately, data regarding clusterin's distribution in other regions of the normal human brain are lacking and therefore comparison with the rat brain is not possible.

Apolipoprotein E Expression in the Adult Brain of Mammals

Interest in the importance of apoE in the CNS grew substantially since the first published reports linking one of the three common human alleles, namely the apoE e4 allele, to both familial and sporadic late-onset Alzheimer's disease.72-75 Accordingly, the e4 allele frequency was shown to increase significantly ( 3-fold, i.e., from 14 up to 40 -50 ) in the Alzheimer population.73,75,76 Furthermore, a gene dosage effect was observed which translates into the fact that inheritance of one or two apoE e4 alleles is associated with a dose-related higher risk and younger age of onset distribution of AD.72,75-77

David J Stone and Irina Rozovsky Introduction

The steroidal regulation of apolipoproteins in the brain is of interest in light of recent research in Alzheimer's Disease (AD). Both an estrogen-deficient state1-2 and the apoE e4 allele3-4 increase the risk of late-onset AD, although neither is a necessary condition for the disease. There are indications that the apoE e4 allele is a greater risk factor in women than in men4-5 with risk in heterozygous women being twice that in heterozygous men (OR 2.11 p

Estrogen AD and Possible Mechanisms of Estrogen Induced Neuroprotection

Recent evidence indicates that ERT both reduces the risk of AD in women and slows cognitive decline.1-2 The duration of ERT also seems to be important, because women with long-term use of ERT have the lowest risk.2 Gender differences were suggested as a possible explanation for the higher incidence of the familial AD in women that is also linked to the apoE-associated risk factor.5 In addition, Phillips and Sherwin32 showed that exogenous E2 maintains short-term memory in surgically-induced menopausal young women. Several levels of evidence demonstrated multiple sites of estrogen actions in the brain. The specific mechanism s by which estrogen reduces dementia are unclear, and they might be combined in order to be beneficial in improvement of clinical symptoms. Estrogen and several other estrogenic steroids which are contained in Premarin (the most common ERT drug) were also indicated as potential neurotrophins that increased survival and growth of hippocam-pal and cortical neurons in...

William Rebeck and Bradley T Hyman

Interest in the biology of apoE in the CNS has increased with the recognition that apoE is a genetic risk factor for AD1 and is involved in the nervous system's response to lesion,2 synaptic stability,3 and neurite outgrowth.4 Apolipoprotein E is present in the CNS on lipoproteins, and its metabolism is mediated via lipoprotein receptors.5 In this chapter, we will focus on the structure and functions of CNS lipoproteins containing exchangeable apolipoproteins (apoE, apoJ, apoA-I), the expression of lipoprotein receptors (the LDL receptor family, scavenger receptors) in the CNS, and the potential roles of these molecules in the pathophysiology of Alzheimer's disease.

Berislav V Zlokovic Blas Frangione and Jorge Ghiso

Deposition of amyloid p peptide (Ap) in the central nervous system (CNS) and cerebral vessels occurs during normal aging and is accelerated by Alzheimer's disease (AD).1,2 AD is the most common form of human amyloidosis and the major cause of dementia, affecting 5 of the population over the age of 65 years. Neuropathologically, AD is characterized by

Potential Roles for apoE and apoJ in CNS Disease

Further studies to understand the structure and function of apoE and apoJ-containing lipoproteins produced by cells within the brain is likely to provide important insights into the role of these proteins in neurodegenerative and other diseases of the CNS. This issue will be considered in regard to Alzheimer's disease (AD) and brain repair following CNS injury. Genetic epidemiological studies have shown that the e4 allele of apoE is a major risk factor for AD.43 In addition, recent data suggests that apoE4 is also a risk factor for poor outcome after head trauma,44,45 cerebral hemorrhage,46 cardiac bypass,47 and possibly stroke.48 ApoE4 also appears to influence the age of onset of Parkinson's disease.49 In regard to AD, one hypothesis is that the association between apoE4 and AD is due to the ability of apoE to interact with the Ap protein. Ap deposition in the AD brain appears to be an early and important pathogenetic event in AD.50 A recent in vivo study highlights the potential...

Edith G McGeer Claudia Schwab and Patrick L McGeer Introduction

The apolipoproteins are a class of proteins which bind to insoluble fats so as to solubilize them in body fluids. Two members of this class, apolipoprotein E (apoE) and apolipoprotein J (clusterin, SP-40,40, complement lysis inhibitor, TRPM-2, SGP-2) have been shown to be associated with the lesions in the brain in Alzheimer's disease (AD). Additional reasons for interest in these two materials in regard to AD exist. Inheritance of one particular form of apoE, apoE4, is a risk factor for AD. The many names given to clusterin suggest its multiple functions. One of these is to bind the membrane attack complex (the MAC), the terminal complex of the complement cascade, and thus protect host tissue against bystander lysis. The appearance of clusterin in AD brain may, therefore, be partly a protective response against the chronic inflammation which exists in such a brain.1,2 In this chapter, we will review the literature on the appearance of these two apolipoproteins in AD brain.

Possible Functional Implications of Clusterin Expression Following Acute Insults of the Nervous System

Undoubtedly, clusterin has attracted considerable interest in Alzheimer's disease and in experimental models relevant for this disease this review underscores the potential significance of this molecule for a wide variety of pathological conditions in the CNS. From the present descriptive stage, we now need to explore the experimental models discussed here with biological, genetic, molecular and pharmacological probes which specifically interfere with clusterin function.

Clusterin Expression and Localization in the Brain

Clusterin mRNA and protein levels increase in a variety of human neurologic disorders, including Alzheimer's disease (AD),7-9,16,17 multiple sclerosis,18 acquired immune deficiency syndrome (AIDS),18 Pick's disease,9 epilepsy19 and gliomas19 (see chapter 7 for complete review). Clusterin expression is also increased in a variety of experimentally-induced brain injury rodent models representing ischemia,20,21 synaptic repair,22,23 epilepsy,8,24,25 or hormonal alterations26,27 (see chapter 3 for complete review). Human CSF clusterin is increased in patients with evidence for de-myelination, but at normal levels in patients with neurodegenerative and meningeal disease.28,29

Clues from Localization Studies

Clusterin immunoreactivity is associated with both parenchymal and vascular deposits of Ap as well as neurofibrillary tangles,17,28,31,32,34,44,45 the pathologic hallmarks of Alzheimer's disease. Despite these numerous reports demonstrating clusterin immunore-activity with amyloid deposits, there is no consensus about whether clusterin associates preferentially with one or all of the different plaque types observed in AD. For example, Harr and colleagues observed clusterin immunoreactivity in neuritic Ap deposits but not in diffuse deposits of Ap,44 while Kida et al45 observed clusterin immunoreactivity in numerous neuritic plaques as well as diffuse deposits of Ap (but the latter association with diffuse deposits varied by brain region). This distinction is important ,as the principal neuropatho-logic features of Alzheimer's, e.g., neuronal degeneration and glial activation, are associated predominantly with the neuritic Ap plaques, while diffuse deposits of amyloid appear to be...

Clusterin in the Central Nervous System Historical Overview

Clusterin was originally described as a major glycoprotein synthesized in the male reproductive systems of the ram and rat.1,2 Since then it has been identified in a wide range of biological fluids and tissues in many species.1,3-9 Identification of rat clusterin messenger ribonucleic acid (mRNA) to TRPM-2 (testosterone repressed prostatic message 2),10-12 a transcript found to be prevalent in vivo in involuting tissues whether induced in experimental models or naturally during development of the embryo, raised the question of a possible involvement of clusterin in programmed cell death.13,14 Reports by several independent groups of researchers on the upregulation of the clusterin gene in brains of hamsters infected with the scrapie agent15 and of humans afflicted with Alzheimer's disease (AD),16 epilepsy,17 or gliomas,17 as well as in the degenerating human retina18 gave support to the apoptosis hypothesis and generated strong interest in the role of clusterin in the central nervous...

Current Clinical Neurology

Varelas, 2005 Vascular Dementia Cerebrovascular Mechanisms and Clinical Management, edited by and Peter J. Kelly, 2004 Clinical Handbook of Insomnia, edited by Hrayr P. Attarian, 2004 Critical Care Neurology and Neurosurgery, edited by Jose I. Suarez, 2004 Alzheimer's Disease A Physician's Guide to Practical Management, edited by

Neurodegenerative Diseases

Neurodegenerative diseases (see 6.08 Neurodegeneration) include AD Parkinson's disease amyotrophic lateral sclerosis (ALS) demyelinating diseases, e.g., multiple sclerosis neuropathies, e.g., diabetic, HIV, and chemotoxin-induced Down's syndrome (DS) prion diseases, e.g., Creutzfeldt-Jakob disease tauopathies, e.g., Pick's disease, frontal temporal dementia with Parkinsonism (FTDP) trinucleotide repeat or polyglutamine (polyQ) diseases, e.g., Huntington's disease (HD) spinocerebellar ataxias (SCA) dentatorubral-pallidolysian atrophy (DRPLA) Friedreich's ataxia multiple systems atrophy (MSA) stroke and traumatic brain injury.

Autoimmuneneuromuscular disorders

A number of autoimmune neuroinflammatory disorders (see 6.09 Neuromuscular Autoimmune Disorders) affect either the central or peripheral nervous system. Many of these disorders are exceptionally rare such as Moersch-Woltman syndrome (stiff-man), Lambert-Eaton myasthenic syndrome, and myasthenia gravis (MG). While uncommon, these disorders tend to be highly debilitating as they directly alter neuromuscular transmission. The most common of these disorders is MG which affects an estimated 60 000 people in the USA. The primary pathology underlying MG appears to be the production of autoantibodies directed against the alpha subunit of the neuromuscular nicotinic acetylcholine receptor. Through direct interference and complement-mediated lysis of the postsynaptic muscle membrane, the autoantibodies cause disruption in the motor endplate that leads to a weakness in skeletal muscle throughout the body. The autoimmune disorder systemic lupus erythematosus (SLE) and the neuroinflammatory...

Psychiatric Disorders 601411 Schizophrenia

Delirium, dementia and amnestic and other cognitive disorders Dementia, e.g., dementia of the Alzheimer's type, vascular dementia Dementia due to human immnodeficiency virus (HIV) disease, head trauma, Parkinson's disease, Huntington's disease, etc. Amnestic disorders Catatonic disorder

With Subcortical Infarcts And Leukoencephalopathy

CADASIL often presents in early adulthood, and most affected individuals show symptoms by age 60. In addition to migraine with or without aura, there may be depression and mood disturbances, focal neurological deficits, pseudobulbar palsy, and dementia. Approximately 10 of patients have seizures.

Anticipated Challenges And Achievements

Several factor-analytic studies since DSM-IV was published have raised questions about the nature and processes underlying PTSD (Foa, Riggs, & Gershuny, 1995 King, Leskin, King, & Weathers, 1998). These studies reveal that, contrary to the DSM-IV, there appear to be four, not three, clusters of PTSD symptoms. Symptoms of effortful avoidance and emotional numbing, included together in the DSM-IV, appear to have different properties, functions, and possible etiologies, according to these studies. Moreover, memory loss, a symptom included in the DSM-IV's avoidance numbing cluster, does not appear to be associated with the overall construct of PTSD or the symptom clusters. Interestingly, the most conclusive of these studies (King et al., 1998) does not support the notion that PTSD is an overarching, unitary disorder comprised of four symptom clusters. Rather, PTSD appears to be best conceptualized as a heterogeneous disorder with correlated, but separate, symptom manifestations. Recent...

Autistic Spectrum Disorders

Probable Alzheimer's Disease According to NINCDS-ADRDA Criteria I. Criteria for the clinical diagnosis of probable Alzheimer's disease a. Dementia established by clinical examination and documented by the mini-mental test, Blessed Dementia Scale, or some similar examination, and confirmed by neuropsychological tests. II. The diagnosis of probable Alzheimer's disease is supported by the following III. Other clinical features consistent with the diagnosis of probable Alzheimer's disease, after exclusion of causes of dementia other than Alzheimer's disease, include the following IV. Features that make the diagnosis of probable Alzheimer's disease uncertain or unlikely include the following Adapted from McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984 34 939-944. The roots of this...

Delirium And Intoxications

Criteria for probable sporadic CJD The clinical diagnosis of CJD is currently based on the combination of progressive dementia, myoclonus, and multifocal neurological dysfunction, associated with a characteristic periodic electroencephalogram (EEG). However, new variant CJD, most growth hormone-related iatrogenic cases, and up to 40 of sporadic cases are not noted to have the characteristic EEG appearance. This hampers clinical diagnosis, and hence surveillance, and illustrates the need for additional diagnostic tests. Proposed criteria for probable sporadic CJD a. Progressive dementia. and of the effects of intoxication (e.g., alcohol or phencyclidine, etc.). The cardinal finding in delirium is altered mental status, which helps distinguish it from dementia, generally conceived of as occurring in clear consciousness. Not all individuals with delirium are agitated or hyperexcitable. In that regard, there is broad overlap with conditions capable of causing stupor or coma. The...

How Does MS Affect the Nervous System

The central nervous system (CNS) is the part of the nervous system involved in MS. The CNS includes the brain and spinal cord. The nerves in the CNS communicate with each other through long, wire-like processes that have a central fiber (axon) surrounded by an insulating material (myelin). In MS, the immune system cells produce inflammation that injures the myelin. In addition, damage occurs to the axon. This damage is known as degeneration, which is the process that occurs in aging-related neurologic diseases such as Alzheimer's and Parkinson's disease. The injury to the myelin and axons results in a slowing or blocking of nerve impulses that prevents the affected parts of the nervous system from functioning normally.

Mild Cognitive Impairment

Mild cognitive impairment (MCI) describes a condition that lies intermediately between normal cognition and dementia, defined broadly as acquired loss of cognitive abilities. The major operational Validity and Reliability of Consensus Criteria for Dementia With Lewy Bodies Validity and Reliability of Consensus Criteria for Dementia With Lewy Bodies

Studies in MS and Other Conditions

Aromatherapy has been studied in a few other unrelated conditions. Small studies on older people with dementia have produced mixed results. Inhalation of black pepper extract may decrease the craving for cigarettes. People with a form of baldness called alopecia areata may benefit from scalp massage using a mixture of thyme, rosemary, lavender, and cedar-wood oils.

Normal Pressure Hydrocephalus

Since its first descriptions in the early 1960s, normal pressure hydrocephalus (NPH) has been difficult to recognize, and conclusive diagnosis relied on response to cerebrospinal fluid shunting. The clinical manifestations classically consist of the triad of gait apraxia, urinary incontinence, and dementia.

Primary Progressive Aphasia

As originally formulated by Mesulam, primary progressive aphasia is recognized by the presence of aphasia dissociated from the general cognitive decline in other cognitive spheres characterizing the dementing illnesses. The original description emphasized the long clinical course, without progression to a more generalized dementia. Subsequent to that, cases progressing to dementia with wide variety of pathological entities have been described in case reports.

Transient Global Amnesia

Transient global amnesia was first described by Fisher and Adams in 1964 as a transient event in which there is altered behavior with prominent memory loss. Patients with this condition are typically 4. The memory loss should be transient. APPENDIX DEFINITION OF TERMS FOR FRONTOTEMPORAL LOBE DEMENTIA IN TABLE 55 All features (see Table 55) must be absent. Early severe amnesia, early spatial disorientation, logoclonic speech with loss of train of thought, and myoclonus are features designed to exclude Alzheimer's disease. These are features (see Table 55) that caution against, but do not firmly exclude, a diagnosis of frontotemporal lobar degeneration (FTLD). A history of alcohol abuse raises the possibility of an alcohol-related basis for a frontal lobe syndrome. However, excessive alcohol intake may also occur in patients with frontotemporal dementia (FTD) as a secondary manifestation of social disinhibition or hyperoral tendencies. The presence of vascular risk factors, such as...

Neuropsychiatric Manifestations Of Hiv Infection

HIV is a neurotropic virus that enters the central nervous system at the time of initial infection and persists there. Subtle neuropsychological impairment may be found in 22 to 30 of otherwise asymptomatic patients with HIV infection (Wilkie et al., 1990 White et al., 1995) these findings may or may not have functional significance. Neuropsychiatric complications of the direct effects of HIV in the brain become more frequent as illness advances (Bartlett and Ferrando, 2004). Common problems include decreased attention and concentration, psychomotor slowing, reduced speed of information processing, executive dysfunction, and, in more advanced cases, verbal memory impairment (Bartlett and Ferrando, 2004). Neuropsy-chiatric manifestations occur with a range of severity varying from subclinical to specific disorders that include, most commonly, minor cognitive-motor disorder (MCMD) and HIV-associated dementia (HAD). Psychiatric illnesses associated with HAD, where symptoms range from...

Abortifacients Compound Q

Compound Q is an herbal preparation of the Chinese Trichosanthin plant, which can inactivate viral ribosomes and inhibit HIV replication. Pharmacology Poor oral availability and intense diarrhea on oral administration severe biphasic neurotoxicity on parenteral administration. Toxicity CNS dermatologic (hypersensitivity and anaphylaxis) metabolic (hypoglycemia) CNS (1) Encephalomyelitis in 24-72 hours with fever, delirium, dementia, myalgias, paresis (2) coma within 1 week. Treatment Immediate ipecac on observed ingestion, lavage and activated charcoal (AC), supportive.

Minor Cognitive Motor Disorder

This disorder has a clinical course and onset that can vary its diagnosis can be missed, and it does not necessarily progress to dementia. It is characterized by mild impairment in functioning, impaired attention or concentration, memory problems, low energy and or slowed movements, impaired coordination, and personality change, irritability, or emotional lability. The prevalence of MCMD has been estimated at 20 to 30 for asymptomatic clients and at 60 to 90 for late-stage clients (Goodkin et al., 1997) these

New Research Areas

Sankar Chatterjee obtained his PhD degree in organic chemistry from the Pennsylvania State University (University Park) under the supervision of Prof Maurice Shamma in 1984 working on total synthesis of natural products and study of reaction mechanisms. He then did his postdoctoral research with Prof Steven M Weinreb at the same university in the area of total synthesis of natural product and with Prof Franklin A Davis at Drexel University (Philadelphia, PA) in the area of development of novel synthetic reagents, respectively. In 1987, he joined Franklin Research Center (Philadelphia, PA) to work in the area of parasitic diseases. In 1990, he joined Cephalon, Inc. (West Chester, PA), where he has been involved in the discovery of novel medicinal agents in the areas of neuroscience (wake and cognition promoting agents, stroke, and Alzheimer's disease) and oncology. Currently he holds the title of Associate Director, CNS Medicinal Chemistry.

Injury and Autoimmunity

Autoantibodies, including antibodies reactive with neural antigens, can be found in normal healthy subjects and although of low titre these can be of high affinity.63 Such antibodies appear to be more frequently seen in patients with a variety of neurological diseases, particularly those of a chronic neurodegenerative type,64 65 and chronic viral encephalopathy.66 Antineurofilament antibodies occur with higher frequency in patients with CJD, familial Alzheimer's, and Parkinson's dementia, but also in viral encephalopathies such as subacute sclerotic panencephalomyelitis (SSPE) and acute herpes simplex encephalitis.67 In experiments in the rat, lesioning of the hippocampus or anterior olfactory nucleus does not generate antineurofilament antibodies, whereas they are produced after lesioning of the olfactory bulb and the grafting of PC12 cells in all sites,68 indicating again that the site within the brain strongly determines the immunological outcome. Antineurofilament antibodies are...

Interleukin1 and neurodegeneration

Alzheimer's disease is a chronic neurodegenerative disease in which the role of IL-1 in neuronal damage has been extensively investigated. The intimate association of IL-1-expressing microglia with P-amyloid in senile plaques suggested that IL-1 might trigger an inflammatory cascade that ultimately contributes to neuronal demise 56,63,64 . Exposure of cultured cells to insoluble aggregates of P-amyloid leads to production of a number of inflammatory molecules, including proinflammatory cytok-ines and nitric oxide. IL-1 mediates the pathological effects of microglia on neurons such as abnormal phosphorylation of tau and reduced synthesis of synaptophysin 65 . Polymorphisms in the IL-1 a and IL-1P genes have also been linked to the increased risk for AD 64 .

Background and Introduction

The female sex hormone estrogen plays an essential role in reproduction and is important for the overall maintenance of physiologic homeostasis in a woman's body.1'2 During menopause, which occurs in women at an average age of 51, the amount of estrogen produced by the ovaries decreases and this estrogen deficiency causes menstrual periods to become less frequent and then stop.3-5 The loss of estrogen is responsible for many of the uncomfortable symptoms associated with menopause, including hot flashes, mood swings or depression, sleep disorders, vaginal dryness, and urinary dysfunction.6 Osteoporosis or bone loss is another consequence of reduced estrogen levels after menopause.7-11 In women, bone density increases until ages 30-35,12 but slowly declines after menopause.13 Postmenopausal women are also at increased risk for coronary heart disease (CHD)14,15 and Alzheimer's disease,16-18 as a result of estrogen deficiency. The realization that the symptoms reported by postmenopausal...

Uses for Engineered Animals in Drug Discovery and Development

A second purpose for using GEM and GER models in basic research is to probe the impact of pharmacologic intervention. Engineered models are used in this setting to address two basic needs will chronic therapy elicit undesirable side effects' and what will be the nature of such effects An instance in which GEM have been used in DDD to evaluate the impact of long-term treatment is provided by mice engineered to lack the beta-secretase' the brain enzyme proposed as the primary molecule responsible for the generation of neurotoxic amyloid beta (A beta) fibrils in patients with Alzheimer's disease.199 Ablation of beta-secretase has been shown to effectively halt A beta production in knockout mice 72 but the extensive distribution of this enzyme in extraneural tissues200 raises the possibility that chronic beta-secretase inhibition will lead to undesirable systemic side effects. This concern was eased by determining that older knockout animals did not develop clinical or anatomic...

Mary Ann Cohen and David Chao

In 1967 Lipowski provided a classification of commonly encountered problems at the medical-psychiatric interface that is still relevant to AIDS psychiatry today. These problems (with a modification of the fifth item, discussed in Chapter 1 of this book) include psychiatric presentation ofmedical illness, psychiatric complications of medical illnesses or treatments, psychological response to medical illness or treatments, medical presentation of psychiatric illness or treatments, and comorbid medical and psychiatric illness. These five problems have been illustrated with casevignettes in Chapter 1. Somepersons withHIVand AIDS have no psychiatric disorder, while others have a multiplicity of complex psychiatric disorders that are responses to illness or treatments or are associated with HIV AIDS (such as HIV-associated dementia) or co-morbid medical illnesses and treatments (such as hepatitis C, cirrhosis, or HIV nephropathy and end-stage renal disease). Persons with HIV and AIDS may...

Disease State Diagnosis

AD or dementia of the Alzheimer's type (DAT) is named for Alois Alzheimer, who first described the cognitive impairment and later the neuropathological hallmarks of the disease in 1907 amyloid plaques, neurofibrillary tangles (NFTs), and inflammation marked by astrocytic gliosis and reactive microglia. AD is a mentally debilitating disease with profound socio- and pharmaco-economic impact. Over 4 million individuals in the US and 15-20 million individuals worldwide have AD. AD onset typically occurs at 60-65 years, with the risk of disease doubling every 5 years above the age of 65. AD prevalence is 3 at ages 65-74 and 50 at 85 and older. Early memory impairment, specifically episodic memory, and progressive decline in executive function are overt clinical signs of AD accompanied by drastic alterations in personality, including aggressive behavior, which make management of AD patients challenging. The mean survival time postdiagnosis ranges from 5 to 10 years and can be as long as 20...

The cholinergic hypothesis

The cholinergic hypothesis of AD, now some 40 years old, resulted from the discovery of reduced choline acetyltransferase activity, the enzyme that synthesizes acetylcholine (ACh), and basal forebrain cholinergic neurons in postmortem AD brain.12 These findings led to the hypothesis that dementia resulted from cholinergic neuron dysfunction and or loss. This hypothesis was supported by animal studies in which cholinergic neuron loss or dysfunction impaired tasks requiring memory or cognitive abilities. The exact relationship between cholinergic dysfunction and dementia is unclear however, it is generally accepted that cholinergic systems are involved in both cognitive (e.g., attention and memory) and noncognitive (e.g., apathy, depression, pychosis, aggression, and sleep disturbances) behaviors that manifest during AD progression. Patients with MCI have increased choline acetyltransferase activity in the frontal cortex and hippocampus at autopsy, suggesting that upregulation of this...

Clinical Trial Issues

Various clinical instruments have been used in the diagnosis of AD and can be used to monitor drug efficacy. These include the AD Assessment Scale (ADAS), noncognitive versus cognitive (cog), the Blessed Dementia Scale (BDS), the Blessed Information Memory Concentration (BIMC), the Behavior Rating Scale for Dementia (BRSD), the Clinical Dementia Rating (six categories CDR), the Clinician's Interview-based Impression of Change (CIBIC), the Sum of Boxes (Global CDR, CDR-SB), the Dementia Rating Scale (DRS), the Extended Scale for Dementia (ESD), Global Deterioration Scale (GDS), the Mini-Mental State Examination (MMSE), the Progressive Deterioration Scale (PDS), and the Severe Impairment Battery (SIB).27 Each scale measures both cognitive ability and activity of daily living but they are difficult to compare as their absolute ranges are very different, making comparison of results across clinical trials using different scales difficult. Thus, the only basis to compare data is on the...

The Physiological Role Of Somatodendritic Dopamine Release In Motor Control

The clinical characteristics of Parkinson's disease can be diverse, but always include at least two of the following symptoms hypokinesia bradykinesia, tremor, rigidity and postural imbalance with a semiflected stance. W ith progression o f the disease, there is also a risk of autonomic failure and an increased risk of depression and dementia, symptoms that develop as complications to a more generalised neurodegeneration.

NMethyl Daspartate NMDA receptor antagonists

Memantine binds weakly to the ion channel-binding site on the NMDA receptor when it is in an open state and thus blocks the tonic pathological activation, induced by micromolar glutamate concentrations. It also normalizes NMDA receptor activation in AD patients, allowing physiological responses to occur, preventing excitotoxic events.32 In nine randomized, double-blind, placebo-controlled clinical trials in dementia and AD patients over a 12-year period, memantine showed improvement in at least one, if not multiple, primary endpoints (1992-2004).

Hormone replacement therapy HRT gonadatropinreleasing hormone GnRH agonists estrogen

Epidemiological studies showing an increased prevalence of AD in postmenopausal females focused interest on the regulation of the hypothalamic-pituitary-gonadal (HPG) axis in AD. Additionally, females with high levels of endogenous estrogen were less prone to develop AD.42 The possibility that estrogen might serve as an AD preventive led to several preclinical studies examining its protective effects against amyloid toxicity and on cognitive performance. HRTwas found not only to be ineffective in preventing AD in postmenopausal women over the age of 65 years in the National Institute of Health-sponsored Women's Health Initiative Memory Study, but increased the risk of dementia. Despite this finding, regulation of the HPG axis is still thought to be key in the development of AD, since AD patients show a twofold increase in gonadotropins, specifically luteinizing hormone in AD patients. Luteinizing hormone is thought to cause reactivation of the cell cycle in neurons leading to cell...

Prolyl endopeptidase inhibitors

Prolyl endopeptidases hydrolyze proline-containing peptide hormones, several of which are implicated in learning and memory. 0N0-1603 (31) is a potent prolyl endopeptidase inhibitor (Ki 12 nM) that reverses scopolamine-induced deficits in learning and memory in rats, restores decreased levels of choline and 5HT in aged rats and improves cognitive performance, and is also neuroprotective to CNS neurons undergoing apoptosis.44 While 0N0-1603 was advanced to phase II trials for senile dementia in Japan, it was discontinued in 1995.

Clinical Diagnosis Some Possible Meanings

Psychiatry, the branch of medicine concerned with psychopathology, has modeled itself after the practices of the parent field. Various neurologists and psychiatrists during the latter part of the nineteenth century and thereafter identified specific mental illnesses which they discovered or described, for example, general paresis, Korsakoff's syndrome, and Alzheimer's disease. This process has been relatively more successful in organic or neurological disorders where both the symptomatology and the course of the disorder can be more successfully described and the etiology more clearly ascertained. This, however, has not kept psychiatrists from describing and designating forms of mental illness which do not always fit the disease entity model successfully. Since the time that catatonia and hebephrenia were identified as separate types of mental illness more than 100 years ago, numerous designations and classifications have been devised by psychiatrists, individually or in organized...

Heart Pacemaker Cellm2 Receptor Activation

The Effect Nicotine Receptor Sites

The quaternary carbamate neostigmine is employed as an indirect parasympathomimetic in postoperative atonia of the bowel or bladder. Furthermore, it is needed to overcome the relative ACh-deficiency at the motor endplate in myasthenia gravis or to reverse the neuromuscular blockade (p. 184) caused by nondepolarizing muscle relaxants (decurarization before discontinuation of anesthesia). The tertiary carbamate physostigmine can be used as an antidote in poisoning with para-sympatholytic drugs, because it has access to AChE in the brain. Carbamates (neostigmine, pyridostigmine, physos-tigmine) and organophosphates (para-oxon, ecothiopate) can also be applied locally to the eye in the treatment of glaucoma however, their long-term use leads to cataract formation. Agents from both classes also serve as insecticides. Although they possess high acute toxic-ity in humans, they are more rapidly degraded than is DDT following their emission into the environment. Tacrine is not an ester...

Table 13 Some of the common terms used to describe clinical studies

Ultimately, the path to drug approval is not always a straight line - far from it in many cases. Tacrine, an aminoacridine, was the first drug approved by the FDA to treat Alzheimer's disease, in 1993, just a few years after gaining notoriety in a controversial 1986 publication on studies in Alzheimer's patients.130 Yet, it was originally identified as an antibacterial agent in 1945.131

Macrophages And Tissue Injury In The

Stimulation of microglia by IFN-y also induces cytotoxicity towards tumour cells89 and activated microglia produce reactive oxygen species91 and nitric oxide,92 both of which are highly cytotoxic. Indeed, the generation of oxygen radicals by microglia could contribute to the formation of amyloid deposits93 in Alzheimer's disease and Down's syndrome.9495 Identification of myelin debris within microglia at the edge of MS lesions96 and their secretion of cytotoxic agents that induce death of neurons and demyelination of oligodendrocytes9798 has advanced speculation that the cells are actively participating in a number of CNS disorders. Microglia expressing MHC class II molecules are readily identifiable in the CNS of animals with experimental allergic encephalomyelitis (EAE)99 and of patients with MS,100 and the demonstration that depletion of macrophages in EAE severely impedes disease progression101

Current Treatment

There are currently no drugs approved for use in the treatment of HD. The major clinical focus has been on management of the motor problems. However, in HD, there are a host of associated psychiatric conditions that include aggression, and irritability ( 40 of cases), depression and suicide ( 30 of cases), mania 10 of cases), apathy (b60 of cases), anxiety ( 30 of cases, with a greater prevalence in men), obsessive-compulsive disorder (50 ), and dementia. Anti-dopaminergic agents such as tetrabenazine 80 and DA receptor antagonists, including tiapride 81, pimozide 82, haloperidol 83, olanzapine 84, risperidone 85, and quetiapine 86,79'83 are used to treat chorea. Psychiatric conditions associated with HD are treated with amantadine 55, fluphenazine, SSRIs, and mirtazapine.79

Pharmacological Properties And Therapeutic Potential Of Coenzyme Q Analogs

Idebenone is currently administered to ameliorate cognitive status in patients with clinical history of stroke, Alzheimer's disease, and multiinfarct dementia.39-41 Idebenone has been reported to improve cerebral energy metabolism,39,42 to decrease excitotoxic neuronal degeneration,43 and to stimulate nerve growth factor synthesis.39,44 Idebenone also appears to minimize platelet formation of thromboxane45 as well as the toxicity of oxidized low density lipoprotein to endothelial cells.46 In so doing, idebenone inhibits platelet aggregation and contributes to the maintenance of vascular wall integrity and functions. The mechanism by which IDB exerts its pharmacological effects remains to be precisely defined, although it seems to be mainly related to its antioxidant activity, which is already appreciable at 2 pM, that is well in the range of idebenone plasma levels attainable in patients after oral supplementation.39

Background Information

In the absence of an exogenously added platelet agonist (see Basic Protocol 1), the activation state of circulating platelets in vivo, as judged by the binding of an activation-dependent monoclonal antibody or similar reagent, can be determined. Circulating activated platelets have been detected in patients with stable and unstable angina, acute myocardial infarction, acute cerebrovascular ischemia, peripheral arterial occlusive disease, diabetes mellitus, pre-eclampsia, hemodialysis, systemic inflammatory response syndrome, septic multiple organ dysfunction syndrome, myeloproliferative disorders, and Alzheimer disease. Platelet-derived microparticles are increased in acute coronary syndromes, cardiopulmonary bypass, transient ischemic attacks, and patients with prosthetic heart valves. Platelet hyporeactivity has been reported in very-low-birth-weight preterm neo-nates and may contribute to the propensity of intraventricular hemorrhage in that patient group.

What Comes First Microglial Activation Or Neurodegeneration

Axotomy models have shown that neuronal death is not necessary to activate microglial cells.39 59 65 66 Conversely, they have also shown that microglial activation does not result in neuronal death, but instead coincides with neuron regeneration. A particularly fascinating aspect of the microglial response to axotomy of motoneurons is the rapid ensheathment of axotomized neurons by microglial cell processes. Not only does this result in synaptic stripping, 59 but it also brings the microglial cell membrane into direct contact with the neuronal membrane. This is a situation which could clearly enhance any neuronal-microglial interactions, such as the transfer of neuronal injury signals, as well as any transfer of growth factors from microglia to neurons. At the same time, the ensheathment of axotomized neurons by microglial cell processes is very reminiscent of a phagocytic engulfment, and one could argue that if, in fact, a neuron was not going to recover from axotomy and was going to...

Psychomotor Functioning

HIV has a predilection for the basal ganglia (Berger and Arendt, 2000 von Giessen et al., 2001), which plays a pivotal role in control of movement. Psycho-motor slowing (i.e., minor motor deficits) predicts HIV-associated dementia, AIDS, and death (Arendt et al., 1994 Sacktor et al., 1996) but can be ameliorated by HAART (Ferrando et al., 1998 Sacktor et al., 2001). Psychomotor slowing is so central to HIV that it appears to be the underlying cause of the various cognitive deficits in HIV (Becker and Salthouse, 1999).

Unmet Medical Needs

Concerns have been raised in regard to current screening paradigms used in AED discovery, e.g., the NINDS in vivo panel, that are viewed as generating AEDs of similar efficacy (and limitations) to those already in use.29,43 In the 10 years encompassing the 1990 Decade of the Brain, eight new AEDs were introduced, none of which appears to have had any impact on the treatment of intractable epileptic patients.43 This same period also saw a doubling of the finding for epilepsy research from 40 million to 80 million and, in 1999, a major White House initiative, 'Curing Epilepsy - Focus on the Future,' focused on translational research initiatives to use the evolving knowledge of basic brain function at the genomic and proteomic levels to develop new models that would lead to new treatments for epilepsy, new AEDs as well as possible cures and prevention of the disorder(s). Like many of the debatably successful outcomes from the Decade of the Brain,44 the transition of research findings to...

Laterality and Modularity

Women appear to be more likely to develop degenerative dementia than are men. Women also live longer than men and the older a person is the more likely he or she is to get dementia. When corrected for age, however, the incidence of dementia is higher in woman. In degenerative dementia, such as Alzheimer's disease, there is a loss of cortical neurons, and the higher incidence of Alzheimer's disease in women might be related to a decreased reservoir of cortical neurons (de Courten-Myers, 1999). That men have more neurons than do women might suggest that men's brains might be more modular. As described earlier, the modularity or localizationist hypothesis was first put forth by Franz Gall in the latter part of the 18th century and the early part of the 19th century when he suggested that specific portions of the brain mediate specific functions. He also proposed what might now be termed anatomically distributed modular cognitive systems. According to this hypothesis, although the...

American Academy of Neurology AIDS Task Force Algorithm and Dana Modification

Of Neurology's (AAN) AIDS task force (AAN, 1991). The AAN criteria functioned to standardize and objectify a rating system for HIV-associated dementia (HAD) and HIV-associated minor cognitive motor disorder (MCMD). Please refer to Chapter 10 of this book for a more extensive discussion ofthese issues. In general, AAN criteria require impaired cognition in at least two domains (each of which may be represented by a single test), neurological abnormalities or decline in motivation, behavior, or emotional control, and related impairment in functional status. These criteria were further refined and operationalized by the Dana consortium (1996). Importantly, both the Dana modification and the AAN criteria require the use of age-and education-corrected normative data when interpreting neuropsychological data. This recommendation is very important and should not be overlooked. Without the proper matching of demographic characteristics between patients and the normative data used to interpret...

Hepatitis C Comorbidity

Patients, especially among intravenous drug users, so we will focus primarily on this comorbidity and its cognitive effects. HCV has been shown to cause neuropsychological deficits among HIV- and HCV-positive individuals. Among advanced seropositive participants of the Manhattan HIV Brain Bank, HIV-and HCV-positive coinfected patients were more likely to receive a diagnosis of HIV-associated dementia and have greater impairment in executive functioning (Ryan et al., 2004). These cognitive differences were associated with HCV serology but did not correlate with indices of liver disease severity. Deficits in learning, motor skills (Cherner et al., 2005), attention and concentration, and psychomotor speed (von Geisen et al., 2004 Perry et al., 2005) among coinfected patients have also been reported. Thus, the neuro-psychological impairments reported among HCV patients are similar to those of HIV-infected patients, with both diseases affecting cognitive domains subserved by...

Alcohol and Sedatives

Alcohol is rapidly absorbed from the duodenum with blood alcohol concentrations of 100-200 mg , causing impaired motor function and judgment concentrations of200-400 mg lead to stupor and coma. Alcohol activates GABA receptors, inhibits NMDA receptors, and has additional effects on 5-HT3, nico-tinic, and opioid receptors. It is metabolized by alcohol dehyrogenase at a constant rate of 100 mg kg hour. Medical complications of alcohol dependence are listed in Table 8.3. Problems such as anemia, peripheral neuropathy, and dementia are of particular concern in HIV patients, who are already predisposed to these complications. More importantly, alcohol-induced liver disease may be worse in those coinfected Dementia

Detection and Analysis of Proteins Modified by OLinked NAcetylglucosamine

The functional consequences of modifying proteins with O-GlcNAc is unclear, but it is required for survival at the single-cell level (Shafi et al., 2000). Three features suggest that O-GlcNAc performs a regulatory role (1) O-GlcNAc occurs at sites on the protein backbone that are similar to those modified by protein kinases (2) O-GlcNAc is reciprocal with phosphorylation on some well-studied proteins, such as RNA Pol II, estrogen receptor-P, SV40 large T-antigen, and the c-Myc proto-oncogene product and (3) like phosphorylation, O-GlcNAc is highly dynamic, with rapid cycling in response to cellular signals or cellular stages. Perturbations in the metabolism of GlcNAc, which alter the regulation of many O-GlcNAc proteins, have been implicated in Alzheimer's disease, diabetes, and cancer (Wells et al., 2001).

The P75 Neurotrophin Receptor

A second neurotrophin receptor was originally described as a low-affinity binding site for NGF. Now known as p75NTR (75 kD neurotrophin receptor), this gly-coprotein is a member of the tumor necrosis factor (TNFR) family of receptors (Johnson et al., 1986 Lock-sley et al., 2001). It binds to each of the neurotrophins, as well as to other proteins, at nanomolar levels. For example, the beta amyloid peptide also binds to the p75NTR, and this may contribute to degeneration of cholinergic brainstem neurons in Alzheimer's disease (Yaar et al., 1997). It now appears that the uncleaved proform of NGF is biologically active. The proforms of NGF and BDNF are released and cleaved in the extracellular space, and proNGF is a high-affinity ligand for the p75NTR receptor (Lee et al., 2001).

Subacute Sclerosing Panencephalitis

The clinical course begins (stage I) with a slowly progressive dementia, often affecting behavior and associated with school performance decline. Stage II features include spasticity, weakness, and myoclonic jerks, and seizures occur. Optic manifestations are common and include a macular chorioretinitis and optic atrophy. There may be cerebellar ataxia and dystonia. Stage III is marked by stupor and coma, often with autonomic instability leading to marked fluctuations in body temperature and abnormal sweating. Diagnosis may be made with the presence of one major and one minor criterion.

Corticobasal Degeneration

Cortical manifestations of corticobasal degeneration include not only dementia and alien limb sign, but also apraxia and cortical sensory loss. The basal ganglionic component includes parkinsonism and limb dystonia. There may be postural tremor and a focal reflex myoclonus. Dementia may be the presenting sign. Not all patients exhibit the alien limb sign throughout the clinical course.

Major Depressive Disorder

As noted in the chapter segment on depression, HIVseropositive individuals are at an increased risk of developing mood disorders across the spectrum of their disease as compared to the general population. Mania can occur at any point along the course of HIV illness, but the occurrence generally clusters into two categories (a) a preexisting bipolar disorder that predated HIV seroconversion or is not directly related to the disease, which can occur at any point during the course of the disease and (b) the late-stage manic syndrome that occurs most commonly but not exclusively in the context of HIV dementia (Lyketsos et al., 1997 Treisman et al., 1998). Primary bipolar disorder is more likely to appear consistent with the usual course of the illness, including euphoric mood, expansiveness, and signs or symptoms of poor judgment. In addition, the presence of a family history of bipolar disorder is more common in this category, and it is less likely to be associated with a preexisting...

Diagonal Band Of Broca

Diagonal Band Broca

Cholinergic neuron systems occur in the peripheral and central nervous systems. In the CNS, they are widespread, and release ACh opposite muscarinic (M) and ni-cotinic (N) receptors. M receptors outnumber N receptors 10-100-fold in the CNS. In the CNS, major cholinergic pathways originate from cell bodies in the septum, diagonal band of Broca, and basal nucleus in the ventral forebrain, and project to the hippocampus, interpeduncu-lar nuclei, and neocortex, respectively. Cortical cholinergic innervation appears to play a role in memory, and may be involved in the etiology of Alzheimer's disease (see p. 376). Within the striatum there are smaller cholinergic neurons involved in control of fine movement blockade of these muscarinic receptors with atropine, a muscarinic antagonist, can be used to treat parkinsonian tremor. There are cholinergic cell bodies in the brain stem tegmentum, and these project to hypothalamus and thalamus. Choliner-gic cell bodies of the cranial parasympa-thetic...

Secondary Sleep Disorders

Secondary Sleep Disorders

Sleep can be impaired by dementia, Parkinson disease, dys-tonia, respiratory disturbances secondary to neuromuscular disease (muscular dystrophy, amyotrophic lateral sclerosis), epilepsy (nocturnal attacks), and headache syndromes (cluster headaches, migraine). Fatal familial insomnia is a genetic disorder of autosomal dominant inheritance (p. 252). Sleep disorders due to systemic disease. Sleep can be impaired by pulmonary diseases (asthma, COPD), angina pectoris, nocturia, fibromyalgia, and chronic fatigue syndrome. Disorders of arousal. Wakefulness normally follows a circadian rhythm (p. 112). Sleep apnea syndrome, narcolepsy, and parasomnia are disorders of arousal (dyssomnias, p. 114). Hyper-somnia is caused by bilateral paramedian thalamic infarcts, tumors in the third ventricular region, and lesions of the midbrain tegmen-tum (p. 70 ff). The level and content of consciousness may also be affected. In patients with bilateral paramedian thalamic...

Stephen J Ferrando and Constantine G Lyketsos

The clinical and neuropathological manifestations of the AIDS dementia complex (ADC) were described in two classical papers by Navia and colleagues in 1986 (Navia et al., 1986a, 1986b). These authors described what came to be known as the ADC triad of cognitive, motor, and behavioral symptoms that occurred in nearly one-fourth of AIDS patients and was often progressive to severe dementia. In autopsy specimens of patients with the disorder, the authors described characteristic changes in the white matter and In response to work in this area during the first 10 years of the epidemic, the American Academy of Neurology (AAN) published in 1991 diagnostic criteria for two HIV-associated CNS disorders HIV-associated minor cognitive motor disorder (MCMD) and HIV-associated dementia (HAD, known previously as ADC) (American Academy of Neurology AIDS Task Force, 1991). These criteria contained the classical triad of clinical symptoms and stipulated that the symptoms must cause everyday...

And Diagnostic Criteria

Neuropsychological deficits in HIV-associated neuro-cognitive disorders reflect underlying subcortical-frontal pathology (see Chapter 19 for a full discussion of neuropsychological deficits in HIV infection). Briefly, impairments are seen in the areas of attention, concentration, psychomotor processing speed, speed of information processing, executive function (abstraction, divided attention, shifting cognitive sets, response inhibition), and verbal memory (particularly retrieval of stored information) (Heaton etal., 1995). Disorders of language, visuospatial abilities, and praxis generally occur in later-stage dementia. Associated neuropsy-chiatric symptoms include apathy, depression, mania, and psychosis. Table 10.1 contains the 1991 AAN diagnostic criteria for HIV-associated minor cognitive motor disorder (MCMD) and HIV-associated dementia (HAD). Note that diagnostic criteria for both disorders are based primarily on severity of neuropsychological test impairment and on degree of...

Differential Diagnosis

(up to 25 of patients meet criteria for a current depressive disorder and up to 70 have elevated scores on depression rating scales), and cognitive dysfunction (up to 82 impairment on some measures) (Crone and Gabriel, 2003). Compared to patients with HIV alone, patients with comorbid HIV and hepatitis C are more likely to have disturbances in executive function and dementia (Ryan et al., 2004). The pattern of cognitive impairment associated with hepatitis C is similar to that of HIV. Patients with mild liver disease tend to have impairment in attention and concentration, and patients with more severe liver fibrosis have problems with learning, psychomotor speed, and cognitive flexibility. Patients with end-stage liver disease and cirrhosis experience superimposed delirium ( hepatic encephalopathy ). Combination pegylated interferon alpha 2a and ribavirin treatment for hepatitis C is well known to be a cause ofdysphoria, suicidal ideation, anxiety, sleep disturbance, fatigue, mania,...

Progressive Supranuclear Palsy

First described by Steele, Richardson, and Olzweski in 1964, progressive supranuclear palsy (PSP) is also known by its acronym. The original descriptions focused on the parkinsonian movement disorder with progressive eye movement abnormality and frequent falls. Dementia also occurs as part of the clinical expression of PSP. PSP is almost never familial in nature. More recent investigations have tended to widen the scope of the clinical spectrum, and clinical overlaps occur, particularly with corti-cobasal degeneration. PSP may be misdiagnosed as PD or vascular dementia. False-negative diagnoses confirmed pathologically may include not only corticobasal degeneration but also multiple-system atrophy, central nervous system Whipple's disease, diffuse Lewy body disease, subcortical gliosis, and prion diseases.

Cognitive And Functional Assessment

Formal neuropsychological assessment, administered by a licensed clinical neuropsychologist, is the gold standard for assessing for HIV-associated neu-rocognitive disorders (see Chapter 7 for a full review of this topic). Several batteries sensitive to HIV-associated deficits have been proposed (Butters et al., 1990). Unfortunately, such testing is time intensive, expensive, and not readily available in HIV clinics. Regardless of the availability of neuropsychological testing, a thorough psychiatric and cognitive assessment, such as that suggested in Chapter 6, is an important aide in making a diagnosis of neurocogni-tive disorder. In this context, commonly used bedside cognitive assessments, such as the Mini Mental Status Exam (Folstein et al., 1975), are typically insensitive to HIV-associated deficits, since they were designed to assess the global deficits found in cortical dementias. The HIV Dementia Scale (HDS) was developed as a rapid screening test to assess for HIV-associated...

National Institute of Neurological Disorders and Stroke and Society for Progressive Supranuclear Palsy Clinical

Recent history of encephalitis alien limb syndrome cortical sensory deficits focal frontal or temporoparietal atrophy hallucinations or delusions unrelated to dopaminergic therapy cortical dementia of Alzheimer's type prominent, early cerebellar symptoms or unexplained dysautonomia or evidence of other diseases that could explain the clinical features

Alcohol related disorders

Chronic alcohol use may be associated with cerebral atrophy, although this is a disputed effect of alcoholism.3 The cerebral atrophy involves the upper dorsolateral frontal lobes and may extend inferiorly to the inferior frontal gyri and posteriorly to the superior parietal lobule.1 There is mild ventricular enlargement. Microscopic changes are not specific. The cerebral atrophy may be associated with a dementia that is potentially reversible at its early stages.9

Mental Health Findings Population Studies

More recently, other Eastern European studies have investigated the mental health impact of the disaster. Rahu et al. 16 reported that suicide was the leading cause of death among Estonian clean-up workers. However, methods of registration of causes of death among the heavily monitored clean-up workers group differed substantially from those used in the general population, thereby making comparison with the general population risky. Another report suggested that there was an increase in the rates of schizophrenia and dementia in clean-up workers 17 , but this finding has not been verified. More likely, selection bias, non-blind evaluations, confounding variables (especially alcoholism), and other methodological factors explain these implausible findings.

Current Treatment 608251 Cholinesterase inhibitors

Dopamine Receptor Picture

Unlike rivastigmine, galantamine is metabolized by cytochrome P450 enzymes, CYP2D6 and CYP3A4, with doses of this drug being lowered if it is co-administered with other drugs that inhibit these enzymes.30 Phase III trials of 3-6 months' duration, with one study extending to 12 months, showed improvements in the ADAS-cog, the disability assessment for dementia (DAD), and the AD cooperative study activities of daily living (ADCS ADL) inventory following galantamine treatment.30,31

Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is also known as motor neuron disease, and popularly, as Lou Gehrig's disease. Motor neuron diseases occur throughout life, with different syndromes having different eponyms. One of the distinguishing features of motor neuron diseases is their varying combinations of both upper motor and lower neuron features. Other neurological features may occur, such as dementia or retinal degeneration ('ALS-Plus ). Motor neuron disease may also occur as part of other disorders, such as Creutzfeldt-Jakob disease, frontotemporal dementia, and spinocerebellar degeneration. ALS may be mimicked by delayed postpoliomyelitis, multifocal motor neuropathy with or without conduction block, endocrinopathies, lead intoxication, or infections. Motor neuron diseases may occur

Disorders of Brain Function

The underlying causes of certain neurological disorders such as Alzheimer's disease are not yet known. However, much is known about other neurological disorders such as Parkinson's disease, multiple sclerosis, and migraines although they are not yet fully understood. Research is ongoing to understand these disorders better and to develop effective treatments. Alzheimer's Disease Alzheimer's disease is a progressive disease in which brain cells degenerate and die, causing memory loss, confusion, loss of intellectual abilities (including thinking, reasoning, judgment, and memory), physical deterioration, and eventually death. It can also cause significant changes in mood, personality, and behavior. Alzheimer's disease is the most common form of irreversible dementia (progressive deterioration of mental functioning). The disease usually occurs The cause of Alzheimer's disease is unknown. Most people who develop Alzheimer's disease have no family history of it. Women are affected more...

Comprehensive Hiv Services Lead To Improved Outcomes For Patients And Providers

Alterman AI, Erdlen FR, and LaPorte DJ (1982). Effects of illicit drug use in an inpatient psychiatric population. Addict Behav 7 231-242. Bleuler, E (1911). Dementia praecox oder Gruppe der Schizophrenien', In G. Aschaffenburg (ed.), Handbuch der Psychiatrie. Spezieller Teil. 4. Abteilung, 1. H lfte. Leipzig und Wien Franz Deuticke. Carey MP, Carey KB, Weinhardt LS, and Gordon CM (1997). Behavioral risk for HIV infection among adults with a severe and persistent mental illness patterns and psychological antecedents. Community Ment Health J 33(2) 133-142. Caton CLM, Gralnick A, Bender S, and Robert S (1989). Young chronic patients and substance abuse. Hosp Community Psychiatry 40 1037-1040. Chander G, Himelhoch S, and Moore RD (2006). Substance abuse and psychiatric disorders in AIDS patients epidemiology and impact on antiretroviral

Disorders Of Fatty Acid Oxidation

X-ALD has a very variable expression even within the same kindred. At least six phenotypic variants can be distinguished. Classification of patients is somewhat arbitrary and is based upon the age of onset and the principal organs involved (Moser et al.5 ). The most devastating form is childhood cerebral ALD (CC ALD) which is characterized by rapidly progressive cerebral demyelination.54 Age of onset is between 3 and 10 years of age. Early neurologic symptoms frequently include behavioural disturbances, diminished school performance, deterioration of vision and impaired auditory discrimination. There is a rapid downhill progression and seizures, spastic tetraplegia and dementia develop within months (see53 for more information). The diagnostic hallmark in X-ALD patients is the accumulation of very-long-chain fatty acids in plasma. VLCFA-measurement is generally regarded to be conclusive in all clinical forms of X-ALD although one or two occasional misdiagnoses have been described. In...

Diffuse Lewy Body Disease

Diffuse Lewy body disease (DLBD) is considered to be a variant or overlapping condition lying between Alzheimer's disease and Parkinson's disease. Clinical differentiation may therefore be difficult. In most patients with DLBD, however, psychosis and dementia are often found to precede parkinsonism (gait disturbance, rigidity, and resting tremor). The differentiation between DLBD and other parkinsonian syndromes, especially progressive supranuclear palsy, is particularly difficult when a patient with parkinsonism and dementia is also found to have oculomotor deficit. Dementia Lewy bodies Neuroimaging studies, including magnetic resonance imaging (MRI) and positron-emission tomography (PET) scanning, cannot reliably differentiate between Parkinson's disease, Alzheimer's disease, and DLBD. Immunocytochemical staining techniques using antibodies against ubiquitin have improved the identification of Lewy bodies. More than 30 of patients with Alzheimer's disease have Lewy bodies in the...

NOC Risk Detection

Headache, nausea, vomiting, diplopia, blurred vision, seizures, irritability, restlessness, decrease in school performance, decreased motor performance, sleep loss, weight loss, memory loss progressing to lethargy and drowsiness. Late signs decreased level of consciousness, decreased motor response to commands, decreased response to pain, change in pupils, posturing, papilledema.

Medical Use And Abuse

Several important health concerns about benzodiazepine use that are unrelated to addiction have been expressed, especially about the long-term use of benzodiazepines, including the effects on the brain, the possibility of cerebral atrophy associated with prolonged benzodiazepine use, and other problems, such as memory loss and personality change (American Psychiatric Associa

Gender Ethnicracial And Life Span Considerations

Ask the patient to describe any endocrine or neurological symptoms. Usually, patients give a history of slowly developing, progressive symptoms. They frequently complain of headaches, visual disturbances (blurred vision or double vision progressing to blindness), decreased sexual interest, menstrual irregularities, and impotence. Family members may report central nervous system (CNS) changes, such as anxiety, personality changes, seizure activity, and even dementia. Depending on tumor type, patients may describe weakness, fatigue, sensitivity to cold, and constipation.

Sexual behavior and biological orientation gaits

Elderly patients with severe bilateral cerebral disease secondary to Alzheimer's disease, multi-infarct dementia, or senility have difficulty in initiating the sequence of movements for rising, standing, and walking. When starting to walk, patients makes several efforts to move the feet, appearing somewhat puzzled as if searching for lost motor engrams, or the right buttons to press in order to set off

Classification Vitamin B complex

Action Kinetics Niacin (nicotinic acid) and niacinamide are water-soluble, heat-resistant vitamins prepared synthetically. Niacin (after conversion to the active niacina-mide) is a component of the coen-zymes nicotinamide-adenine dinu-cleotide and nicotinamide-adenine dinucleotide phosphate, which are essential for oxidation-reduction reactions involved in lipid metabolism, glycogenolysis, and tissue respiration. Deficiency of niacin results in pellagra, the most common symptoms of which are dermatitis, diarrhea, and dementia. In high doses niacin also produces vasodilation. Reduces serum cholesterol and triglycerides in types II, III, IV, and V hy-perlipoproteinemia (mechanism unknown). Peak serum levels 45 min tV2 45 min.

As Sources Of Distress

Mapou and colleagues (1993) studied neuropsy-chological performance of 79 military medical beneficiaries infected with HIV and that of 27 HIVseronegative control subjects. Seropositive subjects who complained of subjective difficulties had more deficits in attention, response speed, motor function, and memory than those not reporting difficulties. Seropositive individuals also had increased rates of anxiety and depression, illustrating the need for screening for both disturbances in seropositive individuals, as each may become a significant source of distress. The pathophysiology and potential treatment of dementia are discussed further in Chapters 3, 10, and 19.

Basal Ganglia Lesions in Striatum and Subthalamic Nucleus

The disease often presents during the fourth decade of life, with behavioral symptoms, including nervous irritability, depression, absent-mindedness, manipulative difficulties, and sudden falling down. With time, choreiform movements become more frequent, and the patient cannot control the jerky, rapid movements of limbs and face. At the same time, the mood changes become more frequent and intense, and cognitive powers begin to diminish. The patient becomes bedridden, and in advanced stages dementia sets in. Patients usually die within 15 years of onset of overt symptoms. There is no effective treatment for the disease. Greenstein, Color Atlas of Neuroscience

Clinical and Medical Uses of Chronometry

Because the medical literature involving RT is so surprisingly vast, yet so specialized and heterogeneous, no attempt is made to review it in detail or to provide specific references. Those wishing to delve into these specialized uses of RT will find most of the literature referenced and abstracted, with an option to obtain the full articles in the Internet website http www. MEDLINE. com (also, by entering the key words with the name of the medical condition of interest + reaction time (e.g., Alzheimer disease + reaction time). Prominent among the highly diverse medical topics involving research with RT tests are cognitive effects of normal aging, mild cognitive impairment, senile dementia, traumatic brain and closed head injuries, mortality, under-nutrition and malnutrition in children, eating disorders, parasitic infections, neurological effects of HIV and AIDS, drug effects and addictions, multiple sclerosis, sleep disorders, diabetes, attention deficit and...

Neuronal PCD Subsequent to Ischemia or Hypoxia

Premature neuronal death is observed with a number of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis (ALS). Although frankly necrotic cells are observed in some instances, PCD has long been suspected to play an important role in many neurodegenerative diseases. In recent years, descriptive and experimental studies have begun to provide support for this hypothesis (reviewed in References 198-200).

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