Margaret Lock
- Published in print:
- 2013
- Published Online:
- October 2017
- ISBN:
- 9780691149783
- eISBN:
- 9781400848461
- Item type:
- chapter
- Publisher:
- Princeton University Press
- DOI:
- 10.23943/princeton/9780691149783.003.0002
- Subject:
- Anthropology, Social and Cultural Anthropology
This chapter focuses on the “discovery” of Alzheimer disease (AD) and a somewhat condensed genealogy of its history to the present time. Emphasis is given to the virtual disappearance of AD for over ...
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This chapter focuses on the “discovery” of Alzheimer disease (AD) and a somewhat condensed genealogy of its history to the present time. Emphasis is given to the virtual disappearance of AD for over four decades after its initial identification, followed by its rediscovery in the late 1960s in association with government and medical recognition of aging populations and their impending burden on society. The chapter also discusses the consolidation of what has been the dominant research paradigm in AD research for the past four decades-the amyloid cascade hypothesis, grounded in localization theory. Throughout the study, difficulties in attempting to unravel the entanglement of “normal” aging from dementia, evident from Alois Alzheimer's time, are pointed out.Less
This chapter focuses on the “discovery” of Alzheimer disease (AD) and a somewhat condensed genealogy of its history to the present time. Emphasis is given to the virtual disappearance of AD for over four decades after its initial identification, followed by its rediscovery in the late 1960s in association with government and medical recognition of aging populations and their impending burden on society. The chapter also discusses the consolidation of what has been the dominant research paradigm in AD research for the past four decades-the amyloid cascade hypothesis, grounded in localization theory. Throughout the study, difficulties in attempting to unravel the entanglement of “normal” aging from dementia, evident from Alois Alzheimer's time, are pointed out.
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.
Margaret Lock
- Published in print:
- 2013
- Published Online:
- October 2017
- ISBN:
- 9780691149783
- eISBN:
- 9781400848461
- Item type:
- chapter
- Publisher:
- Princeton University Press
- DOI:
- 10.23943/princeton/9780691149783.003.0003
- Subject:
- Anthropology, Social and Cultural Anthropology
This chapter considers repeated attempts at diagnostic refinement and standardization of Alzheimer disease (AD). It explores the difficulties of reconciling repeated mismatches between a clinical and ...
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This chapter considers repeated attempts at diagnostic refinement and standardization of Alzheimer disease (AD). It explores the difficulties of reconciling repeated mismatches between a clinical and a neuropathological diagnosis of AD, as are the discrepancies in diagnoses between specialized memory clinics and general and family practice settings. A diagnosis of AD involves the demonstration at autopsy of neuritic amyloid plaques, neurofibrillary tangles, and also cell loss or shrinkage of brain tissue. For two decades the preeminent model to account for plaque buildup has been the “amyloid cascade hypothesis” that, it is argued, initiates the eventual formation of tangles and other neuropathological changes. The model is currently being questioned by an increasing number of key researchers and continues to be a driving force, even as the entire Alzheimer enterprise moves to include prevention as a major goal.Less
This chapter considers repeated attempts at diagnostic refinement and standardization of Alzheimer disease (AD). It explores the difficulties of reconciling repeated mismatches between a clinical and a neuropathological diagnosis of AD, as are the discrepancies in diagnoses between specialized memory clinics and general and family practice settings. A diagnosis of AD involves the demonstration at autopsy of neuritic amyloid plaques, neurofibrillary tangles, and also cell loss or shrinkage of brain tissue. For two decades the preeminent model to account for plaque buildup has been the “amyloid cascade hypothesis” that, it is argued, initiates the eventual formation of tangles and other neuropathological changes. The model is currently being questioned by an increasing number of key researchers and continues to be a driving force, even as the entire Alzheimer enterprise moves to include prevention as a major goal.
Margaret Lock
- Published in print:
- 2013
- Published Online:
- October 2017
- ISBN:
- 9780691149783
- eISBN:
- 9781400848461
- Item type:
- chapter
- Publisher:
- Princeton University Press
- DOI:
- 10.23943/princeton/9780691149783.003.0005
- Subject:
- Anthropology, Social and Cultural Anthropology
This chapter illustrates an account of the shift, commencing in the late 1980s, to the molecularization of Alzheimer disease (AD), and the attempt to identify significant bodily changes as much as 20 ...
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This chapter illustrates an account of the shift, commencing in the late 1980s, to the molecularization of Alzheimer disease (AD), and the attempt to identify significant bodily changes as much as 20 years before behavioral changes can be diagnosed in individuals. It considers the rationale for efforts to formulate a “prodromal” diagnosis before behavioral symptoms or memory loss are detected, followed by a presentation of the involved molecular diagnostic tools (biomarkers) with emphasis on spinal taps, neuroimaging, and genetic testing. The significance of the first two of these biomarkers is attributed to their apparent ability to detect the onset of the amyloid cascade process. The chapter also discusses the anomalies and uncertainties associated with biomarker testing.Less
This chapter illustrates an account of the shift, commencing in the late 1980s, to the molecularization of Alzheimer disease (AD), and the attempt to identify significant bodily changes as much as 20 years before behavioral changes can be diagnosed in individuals. It considers the rationale for efforts to formulate a “prodromal” diagnosis before behavioral symptoms or memory loss are detected, followed by a presentation of the involved molecular diagnostic tools (biomarkers) with emphasis on spinal taps, neuroimaging, and genetic testing. The significance of the first two of these biomarkers is attributed to their apparent ability to detect the onset of the amyloid cascade process. The chapter also discusses the anomalies and uncertainties associated with biomarker testing.
Margaret Lock
- Published in print:
- 2013
- Published Online:
- October 2017
- ISBN:
- 9780691149783
- eISBN:
- 9781400848461
- Item type:
- chapter
- Publisher:
- Princeton University Press
- DOI:
- 10.23943/princeton/9780691149783.003.0006
- Subject:
- Anthropology, Social and Cultural Anthropology
This chapter introduces Alzheimer genetics, including an account of the genes associated with rare, familial, early-onset Alzheimer disease (AD). Discussion is included about why such patients are ...
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This chapter introduces Alzheimer genetics, including an account of the genes associated with rare, familial, early-onset Alzheimer disease (AD). Discussion is included about why such patients are thought of as excellent research subjects in the search for a “cure” not only for early-onset AD but also for the much more common form of late-onset Alzheimer's. The chapter examines the recruitment of a group of Colombian research subjects who come from families with early-onset AD. It then turns to the susceptibility gene, APOE, the ε4 variation of which is associated with increased risk for late-onset AD. Epidemiological research makes it clear that the way in which the APOE genotype functions is elusive because its effects are modified by the presence of other genes and by environmental variables.Less
This chapter introduces Alzheimer genetics, including an account of the genes associated with rare, familial, early-onset Alzheimer disease (AD). Discussion is included about why such patients are thought of as excellent research subjects in the search for a “cure” not only for early-onset AD but also for the much more common form of late-onset Alzheimer's. The chapter examines the recruitment of a group of Colombian research subjects who come from families with early-onset AD. It then turns to the susceptibility gene, APOE, the ε4 variation of which is associated with increased risk for late-onset AD. Epidemiological research makes it clear that the way in which the APOE genotype functions is elusive because its effects are modified by the presence of other genes and by environmental variables.
Julian C. Knight
- Published in print:
- 2009
- Published Online:
- September 2009
- ISBN:
- 9780199227693
- eISBN:
- 9780191711015
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780199227693.003.0002
- Subject:
- Biology, Evolutionary Biology / Genetics, Disease Ecology / Epidemiology
In this chapter different approaches to defining the genetic basis of disease are introduced including linkage analysis, positional cloning, linkage disequilibrium mapping and genetic association ...
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In this chapter different approaches to defining the genetic basis of disease are introduced including linkage analysis, positional cloning, linkage disequilibrium mapping and genetic association studies. The basis and applications of such approaches to diseases showing Mendelian patterns of inheritance and common multifactorial traits are reviewed. Considerable success has been achieved for Mendelian traits using a linkage and positional cloning based approach and this is illustrated for cystic fibrosis and Treacher Collins syndrome. The application of linkage disequilibrium mapping is described for diastrophic dysplasia. Genetic association studies to dissect the genetic factors contributing to susceptibility to common multifactorial disease are described including the limitations and successes of candidate gene analysis. A detailed review of the genetics of Alzheimer disease and venous thrombosis is presented which illustrates different approaches to defining the genetic basis of disease, and the underlying functional genetic variants which can be resolved.Less
In this chapter different approaches to defining the genetic basis of disease are introduced including linkage analysis, positional cloning, linkage disequilibrium mapping and genetic association studies. The basis and applications of such approaches to diseases showing Mendelian patterns of inheritance and common multifactorial traits are reviewed. Considerable success has been achieved for Mendelian traits using a linkage and positional cloning based approach and this is illustrated for cystic fibrosis and Treacher Collins syndrome. The application of linkage disequilibrium mapping is described for diastrophic dysplasia. Genetic association studies to dissect the genetic factors contributing to susceptibility to common multifactorial disease are described including the limitations and successes of candidate gene analysis. A detailed review of the genetics of Alzheimer disease and venous thrombosis is presented which illustrates different approaches to defining the genetic basis of disease, and the underlying functional genetic variants which can be resolved.
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.
Margaret Lock
- Published in print:
- 2013
- Published Online:
- October 2017
- ISBN:
- 9780691149783
- eISBN:
- 9781400848461
- Item type:
- chapter
- Publisher:
- Princeton University Press
- DOI:
- 10.23943/princeton/9780691149783.003.0001
- Subject:
- Anthropology, Social and Cultural Anthropology
This introductory chapter discusses the generation and transformation of expert knowledge and practices in connection with the phenomenon of Alzheimer disease (AD) in an era of increasing ...
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This introductory chapter discusses the generation and transformation of expert knowledge and practices in connection with the phenomenon of Alzheimer disease (AD) in an era of increasing uncertainties and recognition of apparently boundless complexity. Emphasis is given to the way in which debates in the Alzheimer world are played out in research and clinical settings, in medical and media publications, at major conferences, and in talks for public consumption, and with what potential effects on the millions of healthy people who will be systematically monitored if and when an era of prevention becomes routinized. Also included are excerpts from extensive interviews with individuals who have undergone testing in research settings, including genetic testing.Less
This introductory chapter discusses the generation and transformation of expert knowledge and practices in connection with the phenomenon of Alzheimer disease (AD) in an era of increasing uncertainties and recognition of apparently boundless complexity. Emphasis is given to the way in which debates in the Alzheimer world are played out in research and clinical settings, in medical and media publications, at major conferences, and in talks for public consumption, and with what potential effects on the millions of healthy people who will be systematically monitored if and when an era of prevention becomes routinized. Also included are excerpts from extensive interviews with individuals who have undergone testing in research settings, including genetic testing.
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.
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.
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.
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.
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.
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.
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.
Margaret Lock
- Published in print:
- 2013
- Published Online:
- October 2017
- ISBN:
- 9780691149783
- eISBN:
- 9781400848461
- Item type:
- chapter
- Publisher:
- Princeton University Press
- DOI:
- 10.23943/princeton/9780691149783.003.0007
- Subject:
- Anthropology, Social and Cultural Anthropology
This chapter examines findings from the newly developed technology of genome-wide association studies (GWAS) being applied to the investigation of Alzheimer disease (AD), primarily in the United ...
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This chapter examines findings from the newly developed technology of genome-wide association studies (GWAS) being applied to the investigation of Alzheimer disease (AD), primarily in the United States, United Kingdom, and France. These linked research projects make use of many thousands of DNA samples procured from individuals diagnosed with AD, which are then assessed using high-speed throughput technology and compared with control samples, in an attempt to find out what combinations of genes put individuals at increased risk. To date, these enormously expensive projects have provided few if any startling new insights, and many researchers are highly skeptical as to their value. However, others believe that GWAS is a first step toward a more sophisticated way of understanding the interrelated pathways of the numerous genes that appear to be implicated in AD.Less
This chapter examines findings from the newly developed technology of genome-wide association studies (GWAS) being applied to the investigation of Alzheimer disease (AD), primarily in the United States, United Kingdom, and France. These linked research projects make use of many thousands of DNA samples procured from individuals diagnosed with AD, which are then assessed using high-speed throughput technology and compared with control samples, in an attempt to find out what combinations of genes put individuals at increased risk. To date, these enormously expensive projects have provided few if any startling new insights, and many researchers are highly skeptical as to their value. However, others believe that GWAS is a first step toward a more sophisticated way of understanding the interrelated pathways of the numerous genes that appear to be implicated in AD.
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.
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.
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.
