Lewy body dysphagia

The presence of Lewy bodies (LB) in autonomic structures of the central and peripheral nervous system in Parkinson's disease (PD) is well known and could explain clinical signs of pure autonomic failure (PAF) or dysphagia, frequently associated with the disorder. There are many neuropathological reports in the literature with detailed descriptions of PAF, however, LB dysphagia has thus far only been reported once. In the present study, we describe two cases of isolated dysphagia without extrapyramidal syndrome, diagnosed clinically as progressive supranuclear palsy and amyotrophic lateral sclerosis, where detailed neuropathological examination identified LBs in the dorsal vagal motor nuclei in the medulla. These findings confirm the existence of isolated LB dysphagia and emphasize the importance of detailed neuropathological and immunohistochemical examination in cases of dysphagi

Cortical ubiquitin-positive inclusions in frontotemporal dementia without motor neuron disease: a quantitative immunocytochemical study

Ubiquitin-positive tau-negative inclusions were initially described in the rare form of frontotemporal dementia (FTD) associated with motor neuron disease. However, recent studies have indicated that these inclusions are also present in typical FTD, which is usually characterized by nonspecific histological changes. To examine the contribution of these inclusions to neuronal loss and to explore their relationship with disease duration, we performed a quantitative immunocytochemical analysis of 38 typical FTD cases. Relationships between neuron and ubiquitin inclusion densities as well as between duration of illness and neuropathological parameters was studied using linear regression in both univariate and multivariate models. Ubiquitin-positive tau-negative intracytoplasmic inclusions were present in 65.8% of cases in the dentate gyrus, 57.9% in temporal cortex and 31.6% in frontal cortex. The highest densities of ubiquitin-positive inclusions were consistently observed in the dentate gyrus, followed by the temporal and frontal cortex. There was no statistically significant relationship between neuron and ubiquitin-positive inclusion densities in any of the areas studied. In contrast, ubiquitin-positive inclusion densities in the dentate gyrus were negatively related to the duration of illness. Our data suggest that the development of ubiquitin-related pathology is the rule and not the exception in typical FTD, yet is not causally related to neuronal loss. They also reveal that the development of ubiquitin-positive inclusion densities in the dentate gyrus may be associated with a more aggressive form of the diseas

Identification of Alzheimer and vascular lesion thresholds for mixed dementia

To explore the pathological substrates of mixed dementia, we performed a detailed analysis of lacunar and microvascular pathology in 156 autopsied, elderly individuals with various degrees of Alzheimer's disease (AD) pathology. Cognitive status was assessed prospectively using the Clinical Dementia Rating (CDR) scale; neuropathological evaluation included Braak neurofibrillary tangle (NFT) and Aß-protein deposition staging and bilateral semi-quantitative assessment of microvascular ischaemic pathology and lacunes; statistics included univariate and multiple regression models controlling for age, and receiver-operating characteristic analysis. Sensitivity analysis was performed in a randomized derivation sub-sample and tested in a validation sub-sample. White matter lacunes, periventricular and diffuse white matter demyelination and focal and diffuse cortical gliosis were not associated with cognition. Braak NFT, Aß deposition, cortical microinfarcts (CMI) and thalamic and basal ganglia lacunes (TBGL) predicted 27% of CDR variability and 49% of the presence of dementia. Braak NFT, CMI and TBGL thresholds determined in a derivation sample yielded 0.88 sensitivity, 0.79 specificity and 0.85 correct classification rate for dementia in a validation sample. The same thresholds distinguished three groups of demented cases consistent with mixed dementia, pure vascular dementia and AD. These findings indicate that the clinical expression of the vascular component in mixed cases is highly dependent on lesion type and location as well as severity of concomitant AD-related pathology. Proposed thresholds for vascular and degenerative lesions predict the presence of dementia with great accuracy and provide a basis for distinguishing pure vascular dementia or AD from mixed case

Neuropathological substrates and structural changes in late-life depression: the impact of vascular burden

A first episode of depression after 65years of age has long been associated with both severe macrovascular and small microvascular pathology. Among the three more frequent forms of depression in old age, post-stroke depression has been associated with an abrupt damage of cortical circuits involved in monoamine production and mood regulation. Late-onset depression (LOD) in the absence of stroke has been related to lacunes and white matter lesions that invade both the neocortex and subcortical nuclei. Recurrent late-life depression is thought to induce neuronal loss in the hippocampal formation and white matter lesions that affect limbic pathways. Despite an impressive number of magnetic resonance imaging (MRI) studies in this field, the presence of a causal relationship between structural changes in the human brain and LOD is still controversial. The present article provides a critical overview of the contribution of neuropathology in post-stroke, late-onset, and late-life recurrent depression. Recent autopsy findings challenge the role of stroke location in the occurrence of post-stroke depression by pointing to the deleterious effect of subcortical lacunes. Despite the lines of evidences supporting the association between MRI-assessed white matter changes and mood dysregulation, lacunes, periventricular and deep white matter demyelination are all unrelated to the occurrence of LOD. In the same line, neuropathological data show that early-onset depression is not associated with an acceleration of aging-related neurodegenerative changes in the human brain. However, they also provide data in favor of the neurotoxic theory of depression by showing that neuronal loss occurs in the hippocampus of chronically depressed patients. These three paradigms are discussed in the light of the complex relationships between psychosocial determinants and biological vulnerability in affective disorder

Regional Distribution of Neurofibrillary Tangles and Senile Plaques in the Cerebral Cortex of Elderly Patients: A Quantitative Evaluation of a One-Year Autopsy Population from a Geriatric Hospital

Detailed analyses of the neuropathologic changes in the cerebral cortex of elderly individuals and Alzheimer's disease patients have demonstrated that certain components of the neocortical and hippocampal circuits are likely to be selectively vulnerable. Based on the distribution of neurofibrillary tangles (NFTs) and senile plaques, it has been proposed that a global cortico-cortical disconnection leads to the loss of integrated functions observed in Alzheimer's disease. In order to investigate the distribution of lesions associated with aging as well as with the earliest symptoms of senile dementia, we performed a quantitative neuropathologic avaluation of a large series of elderly patients representing the entire autopsy population for the year 1989 from a geriatric hospital. Among the 145 cases quantitatively assessed, there were 102 nondemented patients, 33 patients presenting clinically with globally intact intellectual function but early signs of impairment of specific cognitive functions, and 10 cases with senile dementia of the Alzheimer type. All of the cases had NFTs in layer II of the entorhinal cortex, regardless of their clinical diagnosis, and most cases had some NFTs in the CA1 field of the hippocampus. Severe pathologic changes within the inferior temporal neocortex were observed only in the demented cases. The extent of amyloid deposition was not correlated with the clinical diagnosis and seemed to be present in the neocortical areas earlier than in the hippocampal formation. Also, several cases contained NFTs without amyloid deposition, but amyloid never occurred without NFTs. These results suggests that involvement of certain structures within the hippocampal formation is a consistent feature of aging. Thus, involvement of the hippocampal formation may be a necessary, but not sufficient, condition for the clinical expression of dementia, which is likely to be more closely related to the progressive degeneration of select neuronal populations in the neocorte

Metabolic correlates of behavioraland affective disturbances in frontal lobepathologies

Abstract.: Objective: Although previous studies have shown that the human frontal cortex is involved in the experience of emotions as well as in social behavior, data regarding the exact anatomical substrates of behavioral and affective deficits in frontal lobe pathologies are still scarce. The aim of this study was to investigate the metabolic correlates of these deficits in a group of non-selected consecutive patients with frontal lobe lesions. Patients and Methods: Clinicometabolic correlations between several emotional and social parameters and metabolic patterns in the frontal cortex and amygdala were investigated in 32 patients with frontal lobe pathologies. The behavioral disturbances were evaluated using the Lhermitte's informant questionnaire. Regional cerebral glucose metabolism was measured with [18F] fluorodeoxyglucose and high-resolution positron emission tomography. Statistical analysis was performed using both single variable correlation and multiple regression analyses. Results: Both single variable and multivariate analyses demonstrate that decreased regional glucose metabolism in the right medial area 10 was associated with apathy. There were also significant negative relationships between metabolism in the right orbitofrontal cortex and stereotypy and indifference to rules. Impulsiveness, personality disturbances and loss of emotional control were associated with decreased metabolism in the left amygdala. Conclusions: In terms of clinicometabolic correlations, the present data support the implication of different functional anatomic systems in frontal lobe-related behavioral and affective disturbances. In particular, they imply that the classically described symptoms of impaired behavioral control may be related to right orbitofrontal cortex hypometabolism whereas impaired regulation of emotions may result from a functional damage of the left amygdal

Identification of Alzheimer and vascular lesion thresholds for mixed dementia

To explore the pathological substrates of mixed dementia, we performed a detailed analysis of lacunar and microvascular pathology in 156 autopsied, elderly individuals with various degrees of Alzheimer's disease (AD) pathology. Cognitive status was assessed prospectively using the Clinical Dementia Rating (CDR) scale; neuropathological evaluation included Braak neurofibrillary tangle (NFT) and Ass-protein deposition staging and bilateral semi-quantitative assessment of microvascular ischaemic pathology and lacunes; statistics included univariate and multiple regression models controlling for age, and receiver-operating characteristic analysis. Sensitivity analysis was performed in a randomized derivation sub-sample and tested in a validation sub-sample. White matter lacunes, periventricular and diffuse white matter demyelination and focal and diffuse cortical gliosis were not associated with cognition. Braak NFT, Ass deposition, cortical microinfarcts (CMI) and thalamic and basal ganglia lacunes (TBGL) predicted 27% of CDR variability and 49% of the presence of dementia. Braak NFT, CMI and TBGL thresholds determined in a derivation sample yielded 0.88 sensitivity, 0.79 specificity and 0.85 correct classification rate for dementia in a validation sample. The same thresholds distinguished three groups of demented cases consistent with mixed dementia, pure vascular dementia and AD. These findings indicate that the clinical expression of the vascular component in mixed cases is highly dependent on lesion type and location as well as severity of concomitant AD-related pathology. Proposed thresholds for vascular and degenerative lesions predict the presence of dementia with great accuracy and provide a basis for distinguishing pure vascular dementia or AD from mixed cases

Metabolic correlates of behavioral and affective disturbances in frontal lobe pathologies

OBJECTIVE: Although previous studies have shown that the human frontal cortex is involved in the experience of emotions as well as in social behavior, data regarding the exact anatomical substrates of behavioral and affective deficits in frontal lobe pathologies are still scarce. The aim of this study was to investigate the metabolic correlates of these deficits in a group of non-selected consecutive patients with frontal lobe lesions. PATIENTS AND METHODS: Clinicometabolic correlations between several emotional and social parameters and metabolic patterns in the frontal cortex and amygdala were investigated in 32 patients with frontal lobe pathologies. The behavioral disturbances were evaluated using the Lhermitte's informant questionnaire. Regional cerebral glucose metabolism was measured with [(18)F] fluorodeoxyglucose and high-resolution positron emission tomography. Statistical analysis was performed using both single variable correlation and multiple regression analyses. RESULTS: Both single variable and multivariate analyses demonstrate that decreased regional glucose metabolism in the right medial area 10 was associated with apathy. There were also significant negative relationships between metabolism in the right orbitofrontal cortex and stereotypy and indifference to rules. Impulsiveness, personality disturbances and loss of emotional control were associated with decreased metabolism in the left amygdala. CONCLUSIONS: In terms of clinicometabolic correlations, the present data support the implication of different functional anatomic systems in frontal lobe-related behavioral and affective disturbances. In particular, they imply that the classically described symptoms of impaired behavioral control may be related to right orbitofrontal cortex hypometabolism whereas impaired regulation of emotions may result from a functional damage of the left amygdala

Neuroimaging of dementia in 2013: what radiologists need to know

The structural and functional neuroimaging of dementia have substantially evolved over the last few years. The most common forms of dementia, Alzheimer disease (AD), Lewy body dementia (LBD) and fronto-temporal lobar degeneration (FTLD), have distinct patterns of cortical atrophy and hypometabolism that evolve over time, as reviewed in the first part of this article. The second part discusses unspecific white matter alterations on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images as well as cerebral microbleeds, which often occur during normal aging and may affect cognition. The third part summarises molecular neuroimaging biomarkers recently developed to visualise amyloid deposits, tau protein deposits and neurotransmitter systems. The fourth section reviews the utility of advanced image analysis techniques as predictive biomarkers of cognitive decline in individuals with early symptoms compatible with mild cognitive impairment (MCI). As only about half of MCI cases will progress to clinically overt dementia, whereas the other half remain stable or might even improve, the discrimination of stable versus progressive MCI is of paramount importance for both individual patient treatment and patient selection for clinical trials. The fifth and final part discusses the inter-individual variation in the neurocognitive reserve, which is a potential constraint for all proposed methods. Key Points • Many forms of dementia have spatial atrophy patterns detectable on neuroimaging. • Early treatment of dementia is beneficial, indicating the need for early diagnosis. • Advanced image analysis techniques detect subtle anomalies invisible on radiological evaluation. • Inter-individual variation explains variable cognitive impairment despite the same degree of atroph