Alzheimer's disease is the most common form of dementia in elderly individuals. A... more Alzheimer's disease is the most common form of dementia in elderly individuals. Approximately 11% of the population older than 65, and up to 50% of individuals over 85 qualify as having "probable Alzheimer's disease" on the basis of clinical evaluation. Since the early description of the clinical symptoms and neuropathologic features of Alzheimer's disease, there has been an extraordinary growth in the knowledge of the morphologic and molecular characteristics of Alzheimer's disease. Although the pathogenetic events that lead to dementia are not yet fully understood, several hypotheses regarding the formation of the hallmark pathologic structures of Alzheimer's disease have been proposed. In this context, the use of specific histochemical techniques in the primate brain has greatly expanded our understanding of neuron typology, connectivity and circuit distribution in relation to neurochemical identity. In this respect, very specific subsets of cortical neurons and cortical afferents can be identified by their particular content of certain neurotransmitters and structural proteins. In this article, we discuss the possible relationships between the distribution of pathologic changes in aging, Alzheimer's disease, and possibly related dementing conditions, in the context of the specific elements of the cortical circuitry that are affected by these alterations. Also, evidence for links between the neurochemical phenotype of a given neuron and its relative vulnerability or resistance to the degenerative process are presented in order to correlate the distribution of cellular pathologic changes, neurochemical characteristics related to vulnerability, and affected cortical circuits.
This article reviews the possible relationships between the localization of cellular pathologic c... more This article reviews the possible relationships between the localization of cellular pathologic changes in Alzheimer's disease (AD), and the distribution of neuronal components of the neocortical circuitry that are affected by these alterations. In particular, evidence from the study of large autopsy series supporting the role of the inferior temporal cortex as a key area in the progression of the dementing process is presented. The notion of selective vulnerability in AD at the level of affected neocortical association areas, layers, and specific cell populations is discussed to provide insight into the molecular background of the development of neurofibrillary tangles within the cerebral cortex. Moreover, recent data on pathological correlates of apraxia in AD are examined in the light of the hypothesis of global corticocortical disconnection in this disorder.
The term frontotemporal dementia has been used to classify several clinical syndromes previously ... more The term frontotemporal dementia has been used to classify several clinical syndromes previously described based on a relatively homogeneous symptomatology. Patients in this diagnostic group present with an insidious and gradual change in personality and social conduct, early deficits of mental manipulation, sequencing and hierarchical organization processes, frontal-type amnesia, contrasting with preserved orientation, visuoconstructive and visuospatial abilities. Frontotemporal dementia may represent more than 20% of degenerative dementias and is currently considered as the third most common cause of dementia after Alzheimer's disease and Lewy body dementia. Biochemical and molecular genetic studies have made it possible to identify at least three biologically homogeneous subgroups of frontotemporal dementias: typical frontotemporal dementia cases with no tau or ubiquitin-positive neuronal and glial inclusions, two tauopathies, namely Pick's disease and frontotemporal dementia with parkinsonism linked to chromosome 17, and one ubiquitin-related disorder, the frontotemporal dementia with motor neuron disease. We provide here a detailed overview of current concepts regarding the clinical characteristics and etiopathogenesis of these conditions.
During a recent clinical and neuropathologic evaluation of a large population of brains collected... more During a recent clinical and neuropathologic evaluation of a large population of brains collected at autopsy, attention was drawn to a subset of Alzheimer's disease (AD) patients presenting with prominent visual symptomatology as the first sign of the disease. In this population, a shift in the distribution of pathologic profiles had occurred such that the primary visual areas and the visual association areas had an increased number of lesions, whereas the prefrontal cortex had fewer lesions than usually observed in AD. Previous quantitative analyses have shown that generally in AD, primary sensory cortical areas are less damaged than association areas of the frontal and temporal lobes, as demonstrated by the laminar and regional distribution of two neuropathologic hallmarks of the disease, neurofibrillary tangles and neuritic plaques. Furthermore, the distribution of pathologic lesions in the AD cases with visual symptomatology revealed the disruption of specific visual association pathways, which are normally affected to a lesser degree in AD. These data suggest that in some cases of AD, the particular psychologic and neurologic symptomatology may be caused by the selective loss of specific corticocortical systems, as reflected by a differential distribution of the neuropathologic markers of the disease.
The purpose of this study is to report a case of a very large arachnoid cyst in a patient having ... more The purpose of this study is to report a case of a very large arachnoid cyst in a patient having spent a very active life and who had never presented any neurological or psychiatric symptomatology beside a dementia in the last years of her life. The gross examination of the brain revealed the presence of a voluminous frontal bilateral cyst, located in the midline and displacing laterally the frontal lobes, so they displayed a foliated aspect. Microscopically, the examination of the cyst walls confirmed its arachnoid origin and the cerebral cortex contained lesions typical for senile dementia. This case exemplifies the histological nature and the pathogeny of arachnoid cysts, in particular of congenital origin. This also shows that the very early occurrence of such a malformation does not prevent the development of functional neuronal pathways, owing to the important plasticity of the central nervous system.
Recent accumulated evidence indicates that episodic memory impairments could be part of the initi... more Recent accumulated evidence indicates that episodic memory impairments could be part of the initial clinical expression of frontotemporal dementia (FTD). An early study on this issue was carried out by Constantinidis and colleagues in 1974, but it was subsequently overlooked for a long period of time. The scope of the present research was: (a) to explore the presence of early episodic memory impairments in the entire population of neuropathologically confirmed FTD patients from the Geneva brain collection; and (b) to expand the present insight on the association between the initial symptomatology and various characteristics, namely gender, age at onset, disease duration, and presence of Pick body neuropathology. A careful review of the records of 50 FTD patients hospitalized at the Department of Psychiatry of the Bel-Air Hospital, Geneva, Switzerland, from 1929 to 1999, was conducted. Further in-depth neuropathological analysis with novel immunohistological methods was carried out i...
Alzheimer's disease is the most common form of dementia in elderly individuals. A... more Alzheimer's disease is the most common form of dementia in elderly individuals. Approximately 11% of the population older than 65, and up to 50% of individuals over 85 qualify as having "probable Alzheimer's disease" on the basis of clinical evaluation. Since the early description of the clinical symptoms and neuropathologic features of Alzheimer's disease, there has been an extraordinary growth in the knowledge of the morphologic and molecular characteristics of Alzheimer's disease. Although the pathogenetic events that lead to dementia are not yet fully understood, several hypotheses regarding the formation of the hallmark pathologic structures of Alzheimer's disease have been proposed. In this context, the use of specific histochemical techniques in the primate brain has greatly expanded our understanding of neuron typology, connectivity and circuit distribution in relation to neurochemical identity. In this respect, very specific subsets of cortical neurons and cortical afferents can be identified by their particular content of certain neurotransmitters and structural proteins. In this article, we discuss the possible relationships between the distribution of pathologic changes in aging, Alzheimer's disease, and possibly related dementing conditions, in the context of the specific elements of the cortical circuitry that are affected by these alterations. Also, evidence for links between the neurochemical phenotype of a given neuron and its relative vulnerability or resistance to the degenerative process are presented in order to correlate the distribution of cellular pathologic changes, neurochemical characteristics related to vulnerability, and affected cortical circuits.
This article reviews the possible relationships between the localization of cellular pathologic c... more This article reviews the possible relationships between the localization of cellular pathologic changes in Alzheimer's disease (AD), and the distribution of neuronal components of the neocortical circuitry that are affected by these alterations. In particular, evidence from the study of large autopsy series supporting the role of the inferior temporal cortex as a key area in the progression of the dementing process is presented. The notion of selective vulnerability in AD at the level of affected neocortical association areas, layers, and specific cell populations is discussed to provide insight into the molecular background of the development of neurofibrillary tangles within the cerebral cortex. Moreover, recent data on pathological correlates of apraxia in AD are examined in the light of the hypothesis of global corticocortical disconnection in this disorder.
The term frontotemporal dementia has been used to classify several clinical syndromes previously ... more The term frontotemporal dementia has been used to classify several clinical syndromes previously described based on a relatively homogeneous symptomatology. Patients in this diagnostic group present with an insidious and gradual change in personality and social conduct, early deficits of mental manipulation, sequencing and hierarchical organization processes, frontal-type amnesia, contrasting with preserved orientation, visuoconstructive and visuospatial abilities. Frontotemporal dementia may represent more than 20% of degenerative dementias and is currently considered as the third most common cause of dementia after Alzheimer's disease and Lewy body dementia. Biochemical and molecular genetic studies have made it possible to identify at least three biologically homogeneous subgroups of frontotemporal dementias: typical frontotemporal dementia cases with no tau or ubiquitin-positive neuronal and glial inclusions, two tauopathies, namely Pick's disease and frontotemporal dementia with parkinsonism linked to chromosome 17, and one ubiquitin-related disorder, the frontotemporal dementia with motor neuron disease. We provide here a detailed overview of current concepts regarding the clinical characteristics and etiopathogenesis of these conditions.
During a recent clinical and neuropathologic evaluation of a large population of brains collected... more During a recent clinical and neuropathologic evaluation of a large population of brains collected at autopsy, attention was drawn to a subset of Alzheimer's disease (AD) patients presenting with prominent visual symptomatology as the first sign of the disease. In this population, a shift in the distribution of pathologic profiles had occurred such that the primary visual areas and the visual association areas had an increased number of lesions, whereas the prefrontal cortex had fewer lesions than usually observed in AD. Previous quantitative analyses have shown that generally in AD, primary sensory cortical areas are less damaged than association areas of the frontal and temporal lobes, as demonstrated by the laminar and regional distribution of two neuropathologic hallmarks of the disease, neurofibrillary tangles and neuritic plaques. Furthermore, the distribution of pathologic lesions in the AD cases with visual symptomatology revealed the disruption of specific visual association pathways, which are normally affected to a lesser degree in AD. These data suggest that in some cases of AD, the particular psychologic and neurologic symptomatology may be caused by the selective loss of specific corticocortical systems, as reflected by a differential distribution of the neuropathologic markers of the disease.
The purpose of this study is to report a case of a very large arachnoid cyst in a patient having ... more The purpose of this study is to report a case of a very large arachnoid cyst in a patient having spent a very active life and who had never presented any neurological or psychiatric symptomatology beside a dementia in the last years of her life. The gross examination of the brain revealed the presence of a voluminous frontal bilateral cyst, located in the midline and displacing laterally the frontal lobes, so they displayed a foliated aspect. Microscopically, the examination of the cyst walls confirmed its arachnoid origin and the cerebral cortex contained lesions typical for senile dementia. This case exemplifies the histological nature and the pathogeny of arachnoid cysts, in particular of congenital origin. This also shows that the very early occurrence of such a malformation does not prevent the development of functional neuronal pathways, owing to the important plasticity of the central nervous system.
Recent accumulated evidence indicates that episodic memory impairments could be part of the initi... more Recent accumulated evidence indicates that episodic memory impairments could be part of the initial clinical expression of frontotemporal dementia (FTD). An early study on this issue was carried out by Constantinidis and colleagues in 1974, but it was subsequently overlooked for a long period of time. The scope of the present research was: (a) to explore the presence of early episodic memory impairments in the entire population of neuropathologically confirmed FTD patients from the Geneva brain collection; and (b) to expand the present insight on the association between the initial symptomatology and various characteristics, namely gender, age at onset, disease duration, and presence of Pick body neuropathology. A careful review of the records of 50 FTD patients hospitalized at the Department of Psychiatry of the Bel-Air Hospital, Geneva, Switzerland, from 1929 to 1999, was conducted. Further in-depth neuropathological analysis with novel immunohistological methods was carried out i...
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