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As a population ages, neurodegenerative diseases become increasingly prevalent. These are different clinical entities, though they display many common features in their clinical, biochemical, and morphological appearance. The majority of them have both genetic and environmental components in their pathomechanism. The genetic background involves a single gene mutation (for example, spinocerebellar ataxias 1, 2, and 3 and Huntington's disease [PD]), heterozygote gene modifications following the patterns of the Mendelian laws (familial Parkinson's disease [PD] and familial Alzheimer's disease [AD]), multiple predisposing genes (sporadic PD and sporadic AD), or mitochondrial DNA defects. Protein misfolding, mitochondrial impairment, oxidative stress, endoplasmic reticulum stress, excitotoxicity, caspase cascade activation, and apoptosis are common mechanisms acknowledged to lead to cell death in the different neurodegenerative disorders.

Alzheimer's disease and other neurodegenerative diseases that lead to progressive cognitive impairment are conventionally classified as ‘the dementias’. Dementia is traditionally defined as a generalized impairment of intellect, the implication being that all aspects of mental function are uniformly impaired. A logical corollary is that the dementia associated with different disorders should be indistinguishable. This is far from the case. Degenerative diseases do not affect the brain in an undifferentiated manner. Rather, they have predilections for certain brain regions and show relative of sparing of others. In consequence, they are associated with distinct profiles of cognitive and behavioural change that can be identified with a high degree of accuracy. This chapter describes the neuropsychological presentations of the most common neurodegenerative disorders associated with cognitive change: Alzheimer's disease, frontotemporal lobar degeneration, dementia with Lewy bodies, Huntington's disease, motor neurone disease, progressive supranuclear palsy, and corticobasal degeneration.

This chapter examines the needs, conditions, and experiences of family carers of people with neurodegenerative disorders and advanced organ failure. It focuses on six disorders which currently receive limited attention from hospices and specialist palliative care services. These are multiple sclerosis, motor neurone disease (MND), Parkinson's disease, Huntington's disease, chronic heart failure, and chronic obstructive pulmonary disease (COPD). The findings reveal that these conditions pose distinct caregiving challenges and they negatively affect the physical and emotional well-being of the family carer, their quality of life, their social life, and their finances.

This chapter explores some ethical and legal issues arising from the impact of the neuroscience of decision-making and emotion on end-of-life decisions of patients with certain neurodegenerative disorders. It suggests that the current means of assessing capacity to make decisions over medical treatment should be read as measuring emotional as well as cognitive factors; that the ethics of clinician/carer relations should be monitored carefully to minimize conflicts of interest and exploitation; and that behavioural variant frontotemporal dementia (bvFTD) exemplifies certain difficulties arising with advance decisions to refuse treatment (ADRTs) that must be resolved.

Huntington's disease (HD) is an inherited neurodegenerative disorder for which there is currently no known cure. Disease onset usually occurs around thirty-five to forty-five years of age and may be signalled by early cognitive changes that progress to dementia; voluntary and involuntary movement disorders such as bradykinesia, akinesia, postural instability, chorea, dystonia, and dysphagia; and emotional changes such as depression, aggression, apathy, and anxiety. HD can be challenging for people with the disease and their families owing to the combination of dementia, movement disorders, and emotional changes. This chapter discusses supportive care in HD, models of supportive care, supportive care for people who are at risk or pre-symptomatic, and supportive care for people in the early, middle, or late stages of the disease.

The contribution that distinguishing among motor speech disorders (MSDs) can make to the localization and diagnosis of neurological disease is frequently ignored by medicine and, at the least, underappreciated by speech-language pathology. This is of no small consequence because speech abnormalities can be the presenting or most prominent sign of neurologic disease. This chapter addresses the relationship between the differential diagnosis of acquired MSDs and the localization and diagnosis of neurologic disease. It highlights the clinical reality of the relationship through five case studies and a summary of the specific lessons they provide that illustrate the sometimes crucial importance of recognizing the meaning of speech signs in clinical diagnostic settings. The chapter reviews foundations on which such clinical contributions have been built, and a few examples of recent studies of dysarthria or apraxia of speech associated with neurodegenerative disorders (paraneoplastic cerebellar degeneration, tauopathies) that are helping to refine those abilities. Finally, it offers some thoughts about how future clinical practice and training, and clinical and more basic research, can improve the contributions that MSD diagnosis can make to medical diagnostic efforts in clinical practice.

The research we have discussed suggests that schizophrenia occurs when ab­normal genes and environmental risk factors combine to cause brain dys­function. In the past two decades, several researchers— notably Drs Daniel Weinberger, Larry Seidman, and Patricia Goldman- Rakic— have concluded that schizophrenia is a neurodevelopmental brain disorder. This suggests that schizophrenia emerges because of the way the brain is built early in life. To understand this concept, consider brain disorders that do not have a neurodevelopmental origin but instead, come about because of the way the brain breaks down after it is developed. We call these disorders neurodegenerative be­cause the causes of the disease attack and degrade a normal brain. The senility of old age, which doctors call dementia, is a common example. When some people age, their brain is degraded by events such as many strokes or the rav­ages of Alzheimer’s disease. After a few years, a person who once functioned normally can no longer do simple tasks. Other examples are acquired brain syndromes, which occur after an injury to the head, and disorders due to the in­gestion of toxic substances (e.g., drugs, lead paint). In each of these cases, some external agent has acted on a normal brain to make it abnormal. In neurodevelopmental disorders, the brain does not develop (i.e., grow) prop­erly. In other words, it was never really normal to begin with. We know that genes contain the ‘blueprint’ for building the brain. For schizophrenia, this blueprint contains errors so that the brain is not ‘built’ correctly. Dr Patricia Goldman- Rakic suggested that certain brain cells in individuals with schizophrenia do not ‘migrate’ correctly during development. That is, normal brain development re­quires that cells locate themselves in the right spot and connect to one another in specific patterns. In schizophrenia, it may be that some cells are in the wrong place, some do not make necessary connections, and others make connections that should not be made. It is as if the blueprint for a home told the electrician to put the light switch for the kitchen in the living room.

The potential clinical applications of N-methyl-d-aspartate (NMDA) antagonists were initially defined on the basis of animal models. Epilepsy was the first target syndrome identified and remains an important potential therapeutic area. Today stroke and traumatic injury of the spinal cord and brain are the most important clinical targets. The possibility of using NMDA antagonists as long-term therapies in chronic neurodegenerative disorders seems relatively remote, largely because of the problem of side effects. This chapter lists potential therapeutic targets for NMDA antagonists. Before reviewing preclinical and clinical data relating to the therapeutic prospects of NMDA antagonists this chapter briefly reviews currently available compounds.

Modern medical ethics and law place a very high value on individual autonomy. But the prevalence of decision-making incapacity-i.e., when a person lacks the capacity to exercise that autonomy-will continue to increase as the populations of western nations age. Abnormal brain aging due to neurodegenerative disease is very common and often impairs the cognitive processes needed to give informed consent for medical treatment and participation in research. This chapter reviews the ethico-legal framework for the assessment of decisional capacity, discusses in detail the empirical research on various risk factors for incapacity, and provides a practical guide for assessment. Special issues in assessment of decisional capacity in the research consent context is also discussed.

This chapter defines Parkinson’s disease for readers who are unfamiliar with this degenerative disease, which affects the brain, adversely impacting activities that are controlled by the central nervous system. The disease is a neurodegenerative disorder affecting senior citizens who are over 60 years of age and continues for a period of around 13 years with death occurring approximately at the age of 73. Its symptoms include tremors in limbs in the resting position, stiffness, slow movement, and irregularities in body postures. Parkinson’s appears mainly in the form of non-motor disorders, such as autonomic disorder, pain, mood swings, problems sleeping, and cognitive disorders. The degenerative disease occurs due to excessive secretion of pigmented dopamine in neurons in the nigra pars compacta region of the brain, along with adverse impacts of protein inclusions known as Lewy bodies.

Among neurodegenerative disorders, Alzheimer’s disease has held a special position during the last 40 years. It represents a huge burden of disease with more than 40 million people affected worldwide. The economic effect it has on society is enormous, and the specific challenges of dementia are tremendous. Now that science has demonstrated that the disease starts two or three decades before any symptoms occur, possibilities exist for diagnosis or testing increasingly early through the capabilities of predictive medicine. The related ethical debate is on the multiple meanings and the impact of preclinical diagnosis of Alzheimer’s disease before the onset of symptoms. To guide this discussion, this chapter draws upon lessons from other fields of medicine and the identification of high-risk individuals bearing pathogenic genetic mutations that predispose them to the disease. It concludes with thoughts on value and choice in the complex, fine balance between anticipating, knowing, and doing.

An alternative approach to the management of patients with brain damage is the rehabilitation of behavioural and psychological skills. Rehabilitative approaches have been developed in particular in the context of treatment and recovery of non-progressive brain damage, as for example occurs in stroke and trauma, rather than for progressive neurodegenerative disorders. This chapter reviews such approaches. Rehabilitation addresses both the development of behavioural and cognitive strategies that can allow patients to develop alternative strategies to achieve their goals, and the fact that behavioural experience and training can alter the course of the structural reorganisation itself.

Neurons are unique among cells with their highly polarized and elaborate dendritic and axonal arbors. Synapses, the sites of communication, are located from microns up to a meter from the cell body and rely on proteins for communication and plasticity. In order to acquire proteins to replace those that turn over and to modify synapses, neurons use mRNAs and local protein synthesis. Local translation from dendritically localized mRNAs provides the possibility for rapid and localized response of the neuron to outside stimuli. This chapter reviews and discusses the evidence for local translation in dendrites, its regulation, roles in synaptic plasticity, learning, and memory as well as how it is dysregulated in neurodegenerative and neurodevelopmental disorders. A number of technologies that are used, or could be used, to deepen our understanding of the contribution of local translation to neuronal function are presented.

This chapter finds Parkinson’s disease (PD) to be the main cause of excessive secretion of pigmented dopamine in brain cells, which results in degenerating agentic functions and neuropsychiatric disorders. A patient suffering from PD fails to perform basic agentic functions properly due to the side effects of dopamine secretion, and to degenerating memory and neuropsychiatric disorders. Dopamine is mainly produced in three leading nuclei of the midbrain: The retrorubral area, the substantia nigra pars, and the ventral tegmental area. Many significant motor, motivational, and cognitive components are affected by excessive dopamine secretions from these three major midbrain nuclei, giving rise to neurodegenerative disorders.