Rachel Mistur, Lisa Mosconi, Remigiusz Switalski, Susan De Santi, Yi Li, Lidia Glodzik, Miroslaw Brys, Wai Tsui, Henry Rusinek, and Mony J. de Leon
- Published in print:
- 2009
- Published Online:
- February 2010
- ISBN:
- 9780195328875
- eISBN:
- 9780199864836
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780195328875.003.0011
- Subject:
- Neuroscience, Techniques, Development
Reductions in the cerebral metabolic rate of glucose (CMRglc), a measure of neuronal function, have proven to be a promising tool in the early diagnosis of Alzheimer's disease (AD). FDG-PET imaging ...
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Reductions in the cerebral metabolic rate of glucose (CMRglc), a measure of neuronal function, have proven to be a promising tool in the early diagnosis of Alzheimer's disease (AD). FDG-PET imaging demonstrates progressive CMRglc reductions in AD patients, the extent and topography of which correlate with symptom severity. There is increasing evidence that hypometabolism appears during the preclinical stages of AD and can predict decline years before the onset of symptoms. This chapter provides an overview of FDG-PET results in individuals at risk for developing dementia, including presymptomatic individuals carrying mutations responsible for early-onset familial AD, patients with mild cognitive impairment (MCI), nondemented carriers of the Apolipoprotein E (ApoE) e4 allele, cognitively normal subjects with a family history of AD, subjects with subjective memory complaints, and the normal elderly followed longitudinally until they expressed the clinical symptoms of AD. Finally, this chapter discusses the potential to combine different PET tracers and cerebrospinal fluid (CSF) markers of pathology to improve the early detection of AD.Less
Reductions in the cerebral metabolic rate of glucose (CMRglc), a measure of neuronal function, have proven to be a promising tool in the early diagnosis of Alzheimer's disease (AD). FDG-PET imaging demonstrates progressive CMRglc reductions in AD patients, the extent and topography of which correlate with symptom severity. There is increasing evidence that hypometabolism appears during the preclinical stages of AD and can predict decline years before the onset of symptoms. This chapter provides an overview of FDG-PET results in individuals at risk for developing dementia, including presymptomatic individuals carrying mutations responsible for early-onset familial AD, patients with mild cognitive impairment (MCI), nondemented carriers of the Apolipoprotein E (ApoE) e4 allele, cognitively normal subjects with a family history of AD, subjects with subjective memory complaints, and the normal elderly followed longitudinally until they expressed the clinical symptoms of AD. Finally, this chapter discusses the potential to combine different PET tracers and cerebrospinal fluid (CSF) markers of pathology to improve the early detection of AD.
Walker Matthew, Chan Dennis, and Thom Maria
- Published in print:
- 2006
- Published Online:
- May 2009
- ISBN:
- 9780195100273
- eISBN:
- 9780199864133
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780195100273.003.0016
- Subject:
- Neuroscience, Molecular and Cellular Systems, Behavioral Neuroscience
This chapter focuses on two disorders in which the role of the hippocampus has been extensively investigated: Alzheimer's disease and temporal lobe epilepsy. Although in Alzheimer's disease the ...
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This chapter focuses on two disorders in which the role of the hippocampus has been extensively investigated: Alzheimer's disease and temporal lobe epilepsy. Although in Alzheimer's disease the disease eventually results in widespread destruction of the cerebral cortex, the damage in the earliest stages of disease is restricted to the entorhinal cortex and the hippocampus, and the memory impairment that results from this disruption of the hippocampal formation represents one of the common characteristics of early onset Alzheimer's disease. In temporal lobe epilepsy, the pathological damage is often restricted to the hippocampus in the form of hippocampal sclerosis. However, unlike Alzheimer's disease, in which the hippocampal damage is secondary to the underlying pathological process, the hippocampus in temporal lobe epilepsy is not only sensitive to damage by seizure activity but can also act as the substrate for epileptic seizure generation.Less
This chapter focuses on two disorders in which the role of the hippocampus has been extensively investigated: Alzheimer's disease and temporal lobe epilepsy. Although in Alzheimer's disease the disease eventually results in widespread destruction of the cerebral cortex, the damage in the earliest stages of disease is restricted to the entorhinal cortex and the hippocampus, and the memory impairment that results from this disruption of the hippocampal formation represents one of the common characteristics of early onset Alzheimer's disease. In temporal lobe epilepsy, the pathological damage is often restricted to the hippocampus in the form of hippocampal sclerosis. However, unlike Alzheimer's disease, in which the hippocampal damage is secondary to the underlying pathological process, the hippocampus in temporal lobe epilepsy is not only sensitive to damage by seizure activity but can also act as the substrate for epileptic seizure generation.
Frank Jessen and Harald Hampel
- Published in print:
- 2009
- Published Online:
- February 2010
- ISBN:
- 9780195328875
- eISBN:
- 9780199864836
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780195328875.003.0019
- Subject:
- Neuroscience, Techniques, Development
The rapid development of novel treatment targets for Alzheimer's disease (AD) requires tools to assess the effects of these treatments on disease progression. Structural neuroimaging with CCT and ...
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The rapid development of novel treatment targets for Alzheimer's disease (AD) requires tools to assess the effects of these treatments on disease progression. Structural neuroimaging with CCT and magnetic resonance imaging (MRI) has been extensively applied in patients with AD over the last two decades. Today longitudinal MRI is integrated in the majority of clinical trials with novel compounds that aim at modifying the disease process. This makes MRI one of the major surrogate marker candidates in AD. A surrogate marker according to the definition of the regulatory agencies must correlate with the disease process and with drug-induced modifications of the disease. Beyond this, effects on the surrogate marker need to predict future clinical outcomes. Brain volume measures obtained from structural imaging studies in AD reflect the underlying pathology and correlate with clinical symptoms cross-sectionally and longitudinally. The effects of drugs on brain volume measures and the prediction of clinical outcomes by brain volume changes, however, are not yet sufficiently defined.Less
The rapid development of novel treatment targets for Alzheimer's disease (AD) requires tools to assess the effects of these treatments on disease progression. Structural neuroimaging with CCT and magnetic resonance imaging (MRI) has been extensively applied in patients with AD over the last two decades. Today longitudinal MRI is integrated in the majority of clinical trials with novel compounds that aim at modifying the disease process. This makes MRI one of the major surrogate marker candidates in AD. A surrogate marker according to the definition of the regulatory agencies must correlate with the disease process and with drug-induced modifications of the disease. Beyond this, effects on the surrogate marker need to predict future clinical outcomes. Brain volume measures obtained from structural imaging studies in AD reflect the underlying pathology and correlate with clinical symptoms cross-sectionally and longitudinally. The effects of drugs on brain volume measures and the prediction of clinical outcomes by brain volume changes, however, are not yet sufficiently defined.
Lorene M. Nelson, Caroline M. Tanner, Stephen K. Van Den Eeden, and Valerie M. McGuire
- Published in print:
- 2004
- Published Online:
- September 2009
- ISBN:
- 9780195133790
- eISBN:
- 9780199863730
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780195133790.003.05
- Subject:
- Public Health and Epidemiology, Public Health, Epidemiology
This chapter explores the frequency with which dementing illnesses occur in populations, their distributions by personal characteristics, and what is known about their causes and potential protective ...
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This chapter explores the frequency with which dementing illnesses occur in populations, their distributions by personal characteristics, and what is known about their causes and potential protective factors. The primary focus is on the most common forms of dementia: Alzheimer's disease and vascular dementia. The chapter summarizes clinical and pathologic features of Alzheimer's disease and vascular dementia, and highlights recent theories of how risk factors affect brain reserve. With the evolution of the epidemiology of dementia from case-control studies to prospective cohort studies has come a new set of methodological challenges. These include identification of representative populations, enhancing subject participation and retention in studies, the need to include institutionalized as well as community-dwelling populations, the non-standardized use of cognitive tests to screen for dementia, and the complexities of the diagnostic process itself. Finally, the chapter summarizes risk and protective factors for disease expression, including cardiovascular risk factors, lifestyle factors, and factors that affect brain reserve.Less
This chapter explores the frequency with which dementing illnesses occur in populations, their distributions by personal characteristics, and what is known about their causes and potential protective factors. The primary focus is on the most common forms of dementia: Alzheimer's disease and vascular dementia. The chapter summarizes clinical and pathologic features of Alzheimer's disease and vascular dementia, and highlights recent theories of how risk factors affect brain reserve. With the evolution of the epidemiology of dementia from case-control studies to prospective cohort studies has come a new set of methodological challenges. These include identification of representative populations, enhancing subject participation and retention in studies, the need to include institutionalized as well as community-dwelling populations, the non-standardized use of cognitive tests to screen for dementia, and the complexities of the diagnostic process itself. Finally, the chapter summarizes risk and protective factors for disease expression, including cardiovascular risk factors, lifestyle factors, and factors that affect brain reserve.
Maija Pihlajamäki and Hilkka Soininen
- Published in print:
- 2012
- Published Online:
- September 2012
- ISBN:
- 9780199592388
- eISBN:
- 9780199949922
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780199592388.003.0012
- Subject:
- Neuroscience, Disorders of the Nervous System, Behavioral Neuroscience
The clinical spectrum of hippocampal dysfunction encompasses a wide range of neuropsychiatric symptoms. The present chapter aims at addressing the hippocampal involvement in the most common form of ...
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The clinical spectrum of hippocampal dysfunction encompasses a wide range of neuropsychiatric symptoms. The present chapter aims at addressing the hippocampal involvement in the most common form of memory disorders, that is Alzheimer’s disease (AD), focusing on neurobiological changes revealed by structural and functional imaging. AD results in progressive brain atrophy and inevitable neurological deterioration. Routine clinical evaluation of cognitively impaired elderly subjects includes structural computed tomography or magnetic resonance imaging (MRI), and, for example, the presence of atrophy in the hippocampus and other medial temporal lobe memory structures strongly supports the diagnosis of AD. Clinical functional MRI has proved to be an interesting tool in investigating the neural correlates of cognitive impairment characteristic of AD in vivo and has provided novel insights into the pathognomonic alterations in the hippocampal formation and related whole-brain memory networks. In addition to clinical AD, this chapter reviews recent advances in our understanding of the neuroimaging correlates of subjects at increased risk to develop AD, such as subjects with amnestic mild cognitive impairment and cognitively intact elderly subjects carrying the apolipoprotein E ε4 allele, focusing again on the most intensively studied structure, the hippocampus. Large-scale, worldwide, multimodal imaging studies on predictors of AD are ongoing and there is great hope that imaging of the hippocampus and related memory structures would facilitate early diagnosis of AD and other dementias as well as improve treatment options of these devastating diseases in the near future.Less
The clinical spectrum of hippocampal dysfunction encompasses a wide range of neuropsychiatric symptoms. The present chapter aims at addressing the hippocampal involvement in the most common form of memory disorders, that is Alzheimer’s disease (AD), focusing on neurobiological changes revealed by structural and functional imaging. AD results in progressive brain atrophy and inevitable neurological deterioration. Routine clinical evaluation of cognitively impaired elderly subjects includes structural computed tomography or magnetic resonance imaging (MRI), and, for example, the presence of atrophy in the hippocampus and other medial temporal lobe memory structures strongly supports the diagnosis of AD. Clinical functional MRI has proved to be an interesting tool in investigating the neural correlates of cognitive impairment characteristic of AD in vivo and has provided novel insights into the pathognomonic alterations in the hippocampal formation and related whole-brain memory networks. In addition to clinical AD, this chapter reviews recent advances in our understanding of the neuroimaging correlates of subjects at increased risk to develop AD, such as subjects with amnestic mild cognitive impairment and cognitively intact elderly subjects carrying the apolipoprotein E ε4 allele, focusing again on the most intensively studied structure, the hippocampus. Large-scale, worldwide, multimodal imaging studies on predictors of AD are ongoing and there is great hope that imaging of the hippocampus and related memory structures would facilitate early diagnosis of AD and other dementias as well as improve treatment options of these devastating diseases in the near future.
Andrew J. Larner
- Published in print:
- 2008
- Published Online:
- March 2012
- ISBN:
- 9780198569275
- eISBN:
- 9780191724213
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780198569275.003.0012
- Subject:
- Neuroscience, Techniques
The diagnosis of Alzheimer's disease (AD) may be possible, probable, or definite. In clinical practice, most diagnoses are of probable AD: dementia is established on the basis of clinical examination ...
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The diagnosis of Alzheimer's disease (AD) may be possible, probable, or definite. In clinical practice, most diagnoses are of probable AD: dementia is established on the basis of clinical examination and neuropsychological testing, and there is evidence of progressive worsening of memory and other cognitive functions without disturbance of consciousness. Supportive features include impaired activities of daily living (ADL), behavioural changes, and a positive family history of similar disease, particularly if confirmed by neuropathology. Supportive investigations include a normal cerebrospinal fluid (CSF), normal or non-specific electroencephalographic (EEG) changes, and cerebral atrophy on computerized tomography (CT) with progression documented by serial observation. Other features deemed consistent with probable AD include plateaus in the course of the illness, various associated behavioural features, and certain neurological signs including myoclonus and seizures. Features that make the diagnosis uncertain or unlikely include sudden onset, focal neurological findings, or seizures early in the course, though none of these excludes the diagnosis.Less
The diagnosis of Alzheimer's disease (AD) may be possible, probable, or definite. In clinical practice, most diagnoses are of probable AD: dementia is established on the basis of clinical examination and neuropsychological testing, and there is evidence of progressive worsening of memory and other cognitive functions without disturbance of consciousness. Supportive features include impaired activities of daily living (ADL), behavioural changes, and a positive family history of similar disease, particularly if confirmed by neuropathology. Supportive investigations include a normal cerebrospinal fluid (CSF), normal or non-specific electroencephalographic (EEG) changes, and cerebral atrophy on computerized tomography (CT) with progression documented by serial observation. Other features deemed consistent with probable AD include plateaus in the course of the illness, various associated behavioural features, and certain neurological signs including myoclonus and seizures. Features that make the diagnosis uncertain or unlikely include sudden onset, focal neurological findings, or seizures early in the course, though none of these excludes the diagnosis.
Eric Salmon, Fabienne Collette, and Gaëtan Garraux
- Published in print:
- 2009
- Published Online:
- February 2010
- ISBN:
- 9780195328875
- eISBN:
- 9780199864836
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780195328875.003.0015
- Subject:
- Neuroscience, Techniques, Development
Functional neuroimaging in neurodegenerative dementias provides 3D representations of brain activity that are relatively characteristic of the underlying phenotypic distribution of cerebral lesions. ...
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Functional neuroimaging in neurodegenerative dementias provides 3D representations of brain activity that are relatively characteristic of the underlying phenotypic distribution of cerebral lesions. They are not specific for a given brain pathology and the heterogeneity of brain diseases must always be considered. However, when methodologies are optimized, the values for sensitivity, specificity, and early diagnostic accuracy approach 80%. A lot of studies have shown that Alzheimer's disease can be distinguished from depression, vascular dementia or frontotemporal dementia, and Lewy body dementia when two techniques are used. General recommendations are to rely on multiple key regions and to combine different neuroimaging techniques to make a differential diagnosis among dementias.Less
Functional neuroimaging in neurodegenerative dementias provides 3D representations of brain activity that are relatively characteristic of the underlying phenotypic distribution of cerebral lesions. They are not specific for a given brain pathology and the heterogeneity of brain diseases must always be considered. However, when methodologies are optimized, the values for sensitivity, specificity, and early diagnostic accuracy approach 80%. A lot of studies have shown that Alzheimer's disease can be distinguished from depression, vascular dementia or frontotemporal dementia, and Lewy body dementia when two techniques are used. General recommendations are to rely on multiple key regions and to combine different neuroimaging techniques to make a differential diagnosis among dementias.
António J. Bastos-Leite and Philip Scheltens
- Published in print:
- 2009
- Published Online:
- February 2010
- ISBN:
- 9780195328875
- eISBN:
- 9780199864836
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780195328875.003.0016
- Subject:
- Neuroscience, Techniques, Development
Magnetic resonance imaging (MRI) has opened up the way to diagnose dementia in vivo. It provides clear evidence for hippocampal atrophy in Alzheimer's disease (AD), lobar atrophy in frontotemporal ...
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Magnetic resonance imaging (MRI) has opened up the way to diagnose dementia in vivo. It provides clear evidence for hippocampal atrophy in Alzheimer's disease (AD), lobar atrophy in frontotemporal lobar degeneration (FTLD), vascular changes in VaD, and specific findings in some rare forms of dementia. In addition, the traditional role of excluding space-occupying lesions has been kept and the combination of both aspects has rendered MRI indispensable in the diagnostic work-up.Less
Magnetic resonance imaging (MRI) has opened up the way to diagnose dementia in vivo. It provides clear evidence for hippocampal atrophy in Alzheimer's disease (AD), lobar atrophy in frontotemporal lobar degeneration (FTLD), vascular changes in VaD, and specific findings in some rare forms of dementia. In addition, the traditional role of excluding space-occupying lesions has been kept and the combination of both aspects has rendered MRI indispensable in the diagnostic work-up.
Ian McDowell
- Published in print:
- 2006
- Published Online:
- September 2009
- ISBN:
- 9780195165678
- eISBN:
- 9780199864034
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780195165678.003.0008
- Subject:
- Public Health and Epidemiology, Public Health, Epidemiology
Population aging has highlighted the importance of disorders of cognition such as Alzheimer's disease. This chapter outlines a range of approaches to assessing cognitive ability and reviews thirteen ...
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Population aging has highlighted the importance of disorders of cognition such as Alzheimer's disease. This chapter outlines a range of approaches to assessing cognitive ability and reviews thirteen brief assessment scales, mainly intended for use with elderly people. These include screening instruments and longer bedside assessments, but do not include neuropsychological assessment instruments for which formal qualifications are required for their administration and interpretation.Less
Population aging has highlighted the importance of disorders of cognition such as Alzheimer's disease. This chapter outlines a range of approaches to assessing cognitive ability and reviews thirteen brief assessment scales, mainly intended for use with elderly people. These include screening instruments and longer bedside assessments, but do not include neuropsychological assessment instruments for which formal qualifications are required for their administration and interpretation.
Robert Veerhuis, Jeroen J.M. Hoozemans, Annachiara Cagnin, Piet Eikelenboom, and Richard B. Banati
- Published in print:
- 2004
- Published Online:
- May 2009
- ISBN:
- 9780195152227
- eISBN:
- 9780199865024
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780195152227.003.0045
- Subject:
- Neuroscience, Development, Disorders of the Nervous System
This chapter focuses on the contribution of activated microglia to the progression of Alzheimer's disease (AD) at various stages of the pathological cascade. Clusters of activated microglia occur ...
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This chapter focuses on the contribution of activated microglia to the progression of Alzheimer's disease (AD) at various stages of the pathological cascade. Clusters of activated microglia occur only in complement-positive amyloidβ (Aβ) plaques, and effector functions of complement include the modulation of microglial activity in vitro. It addresses the question of whether microglia are detrimental or beneficial in AD pathogenesis, especially in relation to the presence and modulating activities of activation products of the complement system.Less
This chapter focuses on the contribution of activated microglia to the progression of Alzheimer's disease (AD) at various stages of the pathological cascade. Clusters of activated microglia occur only in complement-positive amyloidβ (Aβ) plaques, and effector functions of complement include the modulation of microglial activity in vitro. It addresses the question of whether microglia are detrimental or beneficial in AD pathogenesis, especially in relation to the presence and modulating activities of activation products of the complement system.
Julie Snowden
- Published in print:
- 2010
- Published Online:
- September 2010
- ISBN:
- 9780199234110
- eISBN:
- 9780191594250
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780199234110.003.028
- Subject:
- Psychology, Neuropsychology, Clinical Psychology
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 ...
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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.Less
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.
Adriane Mayda, Mitsuhiro Yoshita, and Charles DeCarli
- Published in print:
- 2009
- Published Online:
- February 2010
- ISBN:
- 9780195328875
- eISBN:
- 9780199864836
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780195328875.003.0017
- Subject:
- Neuroscience, Techniques, Development
Both advancing age and cognitive impairment are associated with increased prevalence of various brain diseases, with Alzheimer's disease (AD) and cerebrovascular disease (CVD) being the most common. ...
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Both advancing age and cognitive impairment are associated with increased prevalence of various brain diseases, with Alzheimer's disease (AD) and cerebrovascular disease (CVD) being the most common. Abnormalities of cerebral white matter commonly seen on a magnetic resonance image (MRI) as white matter hyperintensities (WMH) are non-specific, but are increased with aging, CVD, and as a possible consequence of AD. In this chapter, we review current scientific evidence regarding the impact of white matter changes, particularly WMH, on cognition with aging and in the setting of cognitive impairment syndromes such as mild cognitive impairment (MCI) and AD.Less
Both advancing age and cognitive impairment are associated with increased prevalence of various brain diseases, with Alzheimer's disease (AD) and cerebrovascular disease (CVD) being the most common. Abnormalities of cerebral white matter commonly seen on a magnetic resonance image (MRI) as white matter hyperintensities (WMH) are non-specific, but are increased with aging, CVD, and as a possible consequence of AD. In this chapter, we review current scientific evidence regarding the impact of white matter changes, particularly WMH, on cognition with aging and in the setting of cognitive impairment syndromes such as mild cognitive impairment (MCI) and AD.
Agnieszka Jaworska
- Published in print:
- 2004
- Published Online:
- September 2009
- ISBN:
- 9780198567219
- eISBN:
- 9780191724084
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780198567219.003.0007
- Subject:
- Neuroscience, Behavioral Neuroscience
This chapter presents a case study that illustrates the interplay between ethical conceptual analysis and neuroscientific findings in the resolution of moral dilemmas that arise in Alzheimer's ...
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This chapter presents a case study that illustrates the interplay between ethical conceptual analysis and neuroscientific findings in the resolution of moral dilemmas that arise in Alzheimer's disease. It defends the philosophical view that the immediate interests of an individual cannot be overridden as long as the individual possesses the capacity to value. In the context of each particular neurodegenerative disease, this recommendation must be guided by a scientifically informed assessment of when in the course of the disease the capacity to value could possibly be lost, and when it is likely to be retained. In the case of Alzheimer's disease, neuroscientific evidence indicates that the capacity to value is slowly and gradually weakened, and in some cases may not be completely lost until relatively far along in the disease's progression. Similar neuroethical analyses must be carried out for other diseases and disorders, and will probably yield different results.Less
This chapter presents a case study that illustrates the interplay between ethical conceptual analysis and neuroscientific findings in the resolution of moral dilemmas that arise in Alzheimer's disease. It defends the philosophical view that the immediate interests of an individual cannot be overridden as long as the individual possesses the capacity to value. In the context of each particular neurodegenerative disease, this recommendation must be guided by a scientifically informed assessment of when in the course of the disease the capacity to value could possibly be lost, and when it is likely to be retained. In the case of Alzheimer's disease, neuroscientific evidence indicates that the capacity to value is slowly and gradually weakened, and in some cases may not be completely lost until relatively far along in the disease's progression. Similar neuroethical analyses must be carried out for other diseases and disorders, and will probably yield different results.
Christian Humpel
- Published in print:
- 2009
- Published Online:
- January 2010
- ISBN:
- 9780195326697
- eISBN:
- 9780199864874
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780195326697.003.0015
- Subject:
- Neuroscience, Molecular and Cellular Systems
Alzheimer's disease (AD) is a progressive chronic disorder characterized by β-amyloid plaques, tau pathology, cell death of cholinergic neurons, and inflammatory responses. The reasons for this ...
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Alzheimer's disease (AD) is a progressive chronic disorder characterized by β-amyloid plaques, tau pathology, cell death of cholinergic neurons, and inflammatory responses. The reasons for this disease are unknown, but damage of the cerebrovascular system are thought to play an important role. This chapter summarizes the most important hypotheses: the role of the β-amyloid cascade, tau pathology, cerebrovascular damage, glutamate-induced cell death, silent stroke and acidosis, the cell death of cholinergic neurons, the neurovascular unit, growth factor effects, and inflammation. Vascular risk factors are discussed by focusing on the idea that the cerebrovascular dysfunction triggers the development of the disease. A common hypothesis tries to link the different pathologies of the disease. Different forms of dementia, such as mild cognitive impairment, vascular dementia, and finally AD may overlap at certain stages.Less
Alzheimer's disease (AD) is a progressive chronic disorder characterized by β-amyloid plaques, tau pathology, cell death of cholinergic neurons, and inflammatory responses. The reasons for this disease are unknown, but damage of the cerebrovascular system are thought to play an important role. This chapter summarizes the most important hypotheses: the role of the β-amyloid cascade, tau pathology, cerebrovascular damage, glutamate-induced cell death, silent stroke and acidosis, the cell death of cholinergic neurons, the neurovascular unit, growth factor effects, and inflammation. Vascular risk factors are discussed by focusing on the idea that the cerebrovascular dysfunction triggers the development of the disease. A common hypothesis tries to link the different pathologies of the disease. Different forms of dementia, such as mild cognitive impairment, vascular dementia, and finally AD may overlap at certain stages.
Noureddine Brakch and Mohamed Rholam
- Published in print:
- 2009
- Published Online:
- January 2010
- ISBN:
- 9780195326697
- eISBN:
- 9780199864874
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780195326697.003.0016
- Subject:
- Neuroscience, Molecular and Cellular Systems
Proteases are extremely important signaling molecules that are involved in numerous vital processes. Protease signaling pathways are strictly regulated, and therefore the dysregulation of their ...
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Proteases are extremely important signaling molecules that are involved in numerous vital processes. Protease signaling pathways are strictly regulated, and therefore the dysregulation of their activity can lead to pathologies such as cardiovascular and inflammatory diseases, cancer, and neurological disorders. An illustration of the functional role of proteases in physiological processes is demonstrated in the metabolism of β-amyloid. Under normal physiological conditions, the steady-state level of β-amyloid peptide in the brain is determined by the rate of production from amyloid precursor protein via β- and γ-secretases and rate of degradation by the activity of several known metallopeptidases. In conditions that affect the activity of these proteases (for example, genetic mutations, environmental factors, or age), overactive secretases or underactive β-amyloid-degrading enzymes could shift the balance of amyloid metabolism toward abnormal β-amyloid deposition in the brain, an early and invariant feature of all forms of Alzheimer's disease (AD). These proteases thus represent potential therapeutic targets against AD, and consequently, regulation of their activity by drugs is now considered as an important strategy in the neuroprotection.Less
Proteases are extremely important signaling molecules that are involved in numerous vital processes. Protease signaling pathways are strictly regulated, and therefore the dysregulation of their activity can lead to pathologies such as cardiovascular and inflammatory diseases, cancer, and neurological disorders. An illustration of the functional role of proteases in physiological processes is demonstrated in the metabolism of β-amyloid. Under normal physiological conditions, the steady-state level of β-amyloid peptide in the brain is determined by the rate of production from amyloid precursor protein via β- and γ-secretases and rate of degradation by the activity of several known metallopeptidases. In conditions that affect the activity of these proteases (for example, genetic mutations, environmental factors, or age), overactive secretases or underactive β-amyloid-degrading enzymes could shift the balance of amyloid metabolism toward abnormal β-amyloid deposition in the brain, an early and invariant feature of all forms of Alzheimer's disease (AD). These proteases thus represent potential therapeutic targets against AD, and consequently, regulation of their activity by drugs is now considered as an important strategy in the neuroprotection.
William S. Brooks, Clement T. Loy, John B. J. Kwok, and Peter R. Schofield
- Published in print:
- 2008
- Published Online:
- March 2012
- ISBN:
- 9780198569275
- eISBN:
- 9780191724213
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780198569275.003.0016
- Subject:
- Neuroscience, Techniques
The clinical syndrome of dementia can occur in a range of conditions. Some dementia causing diseases are clearly genetic in origin, such as Huntington's disease (HD) or familial Alzheimer's disease ...
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The clinical syndrome of dementia can occur in a range of conditions. Some dementia causing diseases are clearly genetic in origin, such as Huntington's disease (HD) or familial Alzheimer's disease (AD). However, most people with dementia have no obvious cause for their condition. The clearest risk factor for dementia is increasing age, with prevalence approximately doubling with each increase of 5.1 years. This chapter provides an overview of familial AD and its causative genes, familial frontotemporal dementias, and related conditions with non-Alzheimer pathology: these are the most common conditions likely to be seen in memory clinics. It then mentions rarer dementia causing diseases, including HD and familial prion diseases, and concludes by considering some practical questions that occur in clinical settings.Less
The clinical syndrome of dementia can occur in a range of conditions. Some dementia causing diseases are clearly genetic in origin, such as Huntington's disease (HD) or familial Alzheimer's disease (AD). However, most people with dementia have no obvious cause for their condition. The clearest risk factor for dementia is increasing age, with prevalence approximately doubling with each increase of 5.1 years. This chapter provides an overview of familial AD and its causative genes, familial frontotemporal dementias, and related conditions with non-Alzheimer pathology: these are the most common conditions likely to be seen in memory clinics. It then mentions rarer dementia causing diseases, including HD and familial prion diseases, and concludes by considering some practical questions that occur in clinical settings.
Joseph Rogers, Carl J. Kovelowski, and Ron Strohmeyer
- Published in print:
- 2002
- Published Online:
- March 2012
- ISBN:
- 9780198509806
- eISBN:
- 9780191724596
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780198509806.003.0010
- Subject:
- Neuroscience, Disorders of the Nervous System
This chapter examines the immune reactions of the central nervous system in Alzheimer's disease (AD), analysing the role of microglia in the mechanisms of inflammation in the AD brain and their ...
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This chapter examines the immune reactions of the central nervous system in Alzheimer's disease (AD), analysing the role of microglia in the mechanisms of inflammation in the AD brain and their relevance to new therapeutic strategies. It explains that the AD brain features a loss of neurones and neurites and that it also shows chronic accumulation of aggregated, highly insoluble amyloid beta deposits, and paired helical filaments.Less
This chapter examines the immune reactions of the central nervous system in Alzheimer's disease (AD), analysing the role of microglia in the mechanisms of inflammation in the AD brain and their relevance to new therapeutic strategies. It explains that the AD brain features a loss of neurones and neurites and that it also shows chronic accumulation of aggregated, highly insoluble amyloid beta deposits, and paired helical filaments.
Carl W. Cotman and Aileen J. Anderson
- Published in print:
- 1995
- Published Online:
- March 2012
- ISBN:
- 9780195082944
- eISBN:
- 9780199847877
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780195082944.003.0008
- Subject:
- Psychology, Cognitive Neuroscience
This chapter describes the basic deficits in learning and memory observed in Alzheimer's disease (AD), along with the functional disconnection of cortical-hippocampal circuitry associated with its ...
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This chapter describes the basic deficits in learning and memory observed in Alzheimer's disease (AD), along with the functional disconnection of cortical-hippocampal circuitry associated with its pathology. It also discusses the mechanisms driving pathology and the pivotal role that amyloid-β (Aβ) may play in the disconnection of neuronal circuitry. β-amyloid exists in multiple assembly states: a soluble form and several aggregated forms with β sheet structures. In its soluble form Aβ appears to have trophic properties, participating in plasticity events. As it assembles into aggregates, Aβ gathers other molecules and can lower the threshold for neuronal degeneration via secondary mechanisms, for example, excitotoxicity. Furthermore, the accumulation of Aβ over time may initiate apoptosis (programmed cell death) in neurons exposed to such an increased Aβ load. In this context, Aβ may play a pivotal role in the events leading to neuron dysfunction and loss in AD.Less
This chapter describes the basic deficits in learning and memory observed in Alzheimer's disease (AD), along with the functional disconnection of cortical-hippocampal circuitry associated with its pathology. It also discusses the mechanisms driving pathology and the pivotal role that amyloid-β (Aβ) may play in the disconnection of neuronal circuitry. β-amyloid exists in multiple assembly states: a soluble form and several aggregated forms with β sheet structures. In its soluble form Aβ appears to have trophic properties, participating in plasticity events. As it assembles into aggregates, Aβ gathers other molecules and can lower the threshold for neuronal degeneration via secondary mechanisms, for example, excitotoxicity. Furthermore, the accumulation of Aβ over time may initiate apoptosis (programmed cell death) in neurons exposed to such an increased Aβ load. In this context, Aβ may play a pivotal role in the events leading to neuron dysfunction and loss in AD.
Paul A. Dudchenko
- Published in print:
- 2010
- Published Online:
- September 2010
- ISBN:
- 9780199210862
- eISBN:
- 9780191594199
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780199210862.003.0009
- Subject:
- Psychology, Cognitive Neuroscience, Cognitive Psychology
This chapter considers spatial cognition in relation to three neurological conditions: Alzheimer's disease, parietal cortex dysfunction, and topographical disorientation. For Alzheimer's disease, one ...
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This chapter considers spatial cognition in relation to three neurological conditions: Alzheimer's disease, parietal cortex dysfunction, and topographical disorientation. For Alzheimer's disease, one of the most common impairments is an inability to find one's way and to remember locations. As there is overlap between the brain regions affected in this disease and the brain regions that contain head direction, grid, and place cells, it may be that disruption of these neural circuits underlies spatial difficulties. For parietal cortex damage, difficulties with spatial representation, including contralateral neglect, are described. These merge with different types of topographical disorientation, based on neuropsychological studies.Less
This chapter considers spatial cognition in relation to three neurological conditions: Alzheimer's disease, parietal cortex dysfunction, and topographical disorientation. For Alzheimer's disease, one of the most common impairments is an inability to find one's way and to remember locations. As there is overlap between the brain regions affected in this disease and the brain regions that contain head direction, grid, and place cells, it may be that disruption of these neural circuits underlies spatial difficulties. For parietal cortex damage, difficulties with spatial representation, including contralateral neglect, are described. These merge with different types of topographical disorientation, based on neuropsychological studies.
John Darrell, Van Horn, and Arthur W. Toga
- Published in print:
- 2009
- Published Online:
- February 2010
- ISBN:
- 9780195328875
- eISBN:
- 9780199864836
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780195328875.003.0021
- Subject:
- Neuroscience, Techniques, Development
Large-scale archives of primary neuroimaging data of older populations are an essential element for contemporary research into normal and disease processes associated with aging. In this chapter, we ...
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Large-scale archives of primary neuroimaging data of older populations are an essential element for contemporary research into normal and disease processes associated with aging. In this chapter, we describe the role of digital atlases of the human brain in aging research and how these resources are created, point to several such formal atlases that may be used for neuroimage data processing, as well as discuss why atlases require periodic revision. We also discuss neuroimaging data repositories related specifically to aging and to age-related disease, the role of databases in making inferences concerning functional activation, and their potential for data mining, meta-analysis, and model construction.Less
Large-scale archives of primary neuroimaging data of older populations are an essential element for contemporary research into normal and disease processes associated with aging. In this chapter, we describe the role of digital atlases of the human brain in aging research and how these resources are created, point to several such formal atlases that may be used for neuroimage data processing, as well as discuss why atlases require periodic revision. We also discuss neuroimaging data repositories related specifically to aging and to age-related disease, the role of databases in making inferences concerning functional activation, and their potential for data mining, meta-analysis, and model construction.
