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Query: UMLS:C0752347 (Dementia with Lewy bodies)
 1,653 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the brains of 10 patients with clinically and pathologically defined Huntington's disease and graded the degree of striatal pathology according to the Vonsattel grading system. Sections from nine cerebral cortical areas (Brodmann areas 8, 10, 24, 33, 28, 38, 7, 39, 18), the cerebellum, hypothalamus, medulla and caudate nucleus were stained with antibodies to ubiquitin and ubiquitin C-terminal hydrolase (PGP 9.5). Dystrophic neurites, immunoreactive with ubiquitin and PGP 9.5 were detected in all cortical areas, in layers 3, 5 and 6, of all brains studied. No dystrophic neurites were found in subcortical areas or cerebellum. Sections from cortical areas 8 and 24 from the two brains with the most and least ubiquitin-immunoreactive neurites were stained with antibodies to beta-amyloid precursor protein, tau, glial fibrillary acidic protein, neurofilament protein, alpha B crystallin, GABA, cholecystokinin and somatostatin. The dystrophic neurites were found to also react with beta-amyloid precursor protein. Electron microscopy showed the abnormal neurites to contain granulofilamentous material. Granular deposits with a diameter of 40-100 nm were interspersed between randomly orientated 'fuzzy' or coated, straight or slightly curved filaments measuring 10-15 nm in diameter. These structures have not been seen in control brain and differ from age-related neuritic degeneration and neurites associated with amyloid. Immunohistochemically these structures most resemble CA 2/3 neurites seen in Lewy body disease, and, ultrastructurally, the intraneuronal filamentous inclusions in motor neuron disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The cortical neuritic pathology of Huntington's disease. 777 Jan 16

Newly proposed criteria for Lewy body dementia include alterations in consciousness. Lewy body dementia is also associated with a disturbance in cholinergic transmission; neocortical cholinergic deficits in this disorder are more extensive than in Alzheimer's disease and are correlated with symptoms commonly associated with delirium, such as visual hallucinations. The traditional view that derangements of the basal forebrain cholinergic system in Alzheimer's disease relate specifically to memory impairment is assessed in terms of a more general role for cortical acetylcholine in consciousness. This extends the concept that cortical acetylcholine enhances neuronal signal to noise ratio. It is suggested that muscarinic receptor activation in the cortex is involved in confining the contents of the discrete self-reported conscious "stream." In the absence of cortical acetylcholine, currently irrelevant intrinsic and sensory information, which is constantly processed in parallel at the subconscious level, enters conscious awareness. This is consistent with the ability of anti-muscarinic drugs administered medically, recreationally, or ritualistically to induce visual hallucinations and other perceptual disturbances. The hypothesis is explored through comparisons between muscarinic and nicotinic receptor psychopharmacology and between the pathology of the basal forebrain as opposed to pedunculopontine cholinergic systems in different diseases of the human brain affecting consciousness and cognition. The paradoxical effects of muscarinic receptor blockade to induce hallucinations and of REM sleep-associated cholinergic activation of the thalamus to induce dreaming may be related to the differential distribution and activity of muscarinic receptor subtypes or to the differing responses of intrinsic GABA neurons in cortex and thalamus.
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PMID:Acetylcholine and hallucinations: disease-related compared to drug-induced alterations in human consciousness. 854 52

Dementia with Lewy bodies (DLB) patients frequently experience well formed recurrent complex visual hallucinations (RCVH). This is associated with reduced blood flow or hypometabolism on imaging of the primary visual cortex. To understand these associations in DLB we used pathological and biochemical analysis of the primary visual cortex to identify changes that could underpin RCVH. Alpha-synuclein or neurofibrillary tangle pathology in primary visual cortex was essentially absent. Neurone density or volume within the primary visual cortex in DLB was also unchanged using unbiased stereology. Microarray analysis, however, demonstrated changes in neuropeptide gene expression and other markers, indicating altered GABAergic neuronal function. Calcium binding protein and GAD65/67 immunohistochemistry showed preserved interneurone populations indicating possible interneurone dysfunction. This was demonstrated by loss of post synaptic GABA receptor markers including gephyrin, GABARAP, and Kif5A, indicating reduced GABAergic synaptic activity. Glutamatergic neuronal signalling was also altered with vesicular glutamate transporter protein and PSD-95 expression being reduced. Changes to the primary visual cortex in DLB indicate that reduced GABAergic transmission may contribute to RCVH in DLB and treatment using targeted GABAergic modulation or similar approaches using glutamatergic modification may be beneficial.
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PMID:Analysis of primary visual cortex in dementia with Lewy bodies indicates GABAergic involvement associated with recurrent complex visual hallucinations. 2735 12