Cortical Lewy body

About: Cortical Lewy body is a research topic. Over the lifetime, 104 publications have been published within this topic receiving 26012 citations.

Diagnosis and management of dementia with Lewy bodies: Third report of the DLB Consortium

Abstract: The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them. REM sleep behavior disorder, severe neuroleptic sensitivity, and reduced striatal dopamine transporter activity on functional neuroimaging are given greater diagnostic weighting as features suggestive of a DLB diagnosis. The 1-year rule distinguishing between DLB and Parkinson disease with dementia may be difficult to apply in clinical settings and in such cases the term most appropriate to each individual patient should be used. Generic terms such as Lewy body (LB) disease are often helpful. The authors propose a new scheme for the pathologic assessment of LBs and Lewy neurites (LN) using alpha-synuclein immunohistochemistry and semiquantitative grading of lesion density, with the pattern of regional involvement being more important than total LB count. The new criteria take into account both Lewy-related and Alzheimer disease (AD)-type pathology to allocate a probability that these are associated with the clinical DLB syndrome. Finally, the authors suggest patient management guidelines including the need for accurate diagnosis, a target symptom approach, and use of appropriate outcome measures. There is limited evidence about specific interventions but available data suggest only a partial response of motor symptoms to levodopa: severe sensitivity to typical and atypical antipsychotics in ∼50%, and improvements in attention, visual hallucinations, and sleep disorders with cholinesterase inhibitors.

Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB) Report of the consortium on DLB international workshop

Abstract: Recent neuropathologic autopsy studies found that 15 to 25% of elderly demented patients have Lewy bodies (LB) in their brainstem and cortex, and in hospital series this may constitute the most common pathologic subgroup after pure Alzheimer's disease (AD). The Consortium on Dementia with Lewy bodies met to establish consensus guidelines for the clinical diagnosis of dementia with Lewy bodies (DLB) and to establish a common framework for the assessment and characterization of pathologic lesions at autopsy. The importance of accurate antemortem diagnosis of DLB includes a characteristic and often rapidly progressive clinical syndrome, a need for particular caution with neuroleptic medication, and the possibility that DLB patients may be particularly responsive to cholinesterase inhibitors. We identified progressive disabling mental impairment progressing to dementia as the central feature of DLB. Attentional impairments and disproportionate problem solving and visuospatial difficulties are often early and prominent. Fluctuation in cognitive function, persistent well-formed visual hallucinations, and spontaneous motor features of parkinsonism are core features with diagnostic significance in discriminating DLB from AD and other dementias. Appropriate clinical methods for eliciting these key symptoms are described. Brainstem or cortical LB are the only features considered essential for a pathologic diagnosis of DLB, although Lewy-related neurites, Alzheimer pathology, and spongiform change may also be seen. We identified optimal staining methods for each of these and devised a protocol for the evaluation of cortical LB frequency based on a brain sampling procedure consistent with CERAD. This allows cases to be classified into brainstem predominant, limbic (transitional), and neocortical subtypes, using a simple scoring system based on the relative distribution of semiquantitative LB counts. Alzheimer pathology is also frequently present in DLB, usually as diffuse or neuritic plaques, neocortical neurofibrillary tangles being much less common. The precise nosological relationship between DLB and AD remains uncertain, as does that between DLB and patients with Parkinson's disease who subsequently develop neuropsychiatric features. Finally, we recommend procedures for the selective sampling and storage of frozen tissue for a variety of neurochemical assays, which together with developments in molecular genetics, should assist future refinements of diagnosis and classification.

The Lewy body variant of Alzheimer's disease A clinical and pathologic entity

Abstract: Thirty-six clinically diagnosed and pathologically confirmed Alzheimer9s disease (AD) patients included 13 with cortical and subcortical Lewy bodies (LBs). The patients with LBs appeared to constitute a distinct neuropathologic and clinical subset of AD, the Lewy body variant (LBV). The LBV group showed gross pallor of the substantia nigra, greater neuron loss in the locus ceruleus, substantia nigra, and substantia innominata, lower neocortical ChAT levels, and fewer midfrontal tangles than did the pure AD group, along with a high incidence of medial temporal lobe spongiform vacuolization. Analysis of neuropsychological tests from 9 LBV subjects and 9 AD patients matched for age and degree of dementia revealed greater deficits in attention, fluency, and visuospatial processing in the LBV group. Similar comparisons of neurologic examinations showed a significant increase in masked facies; in addition there was an increase in essential tremor, bradykinesia, mild neck rigidity, and slowing of rapid alternating movements in the LBV group. Extremity rigidity, flexed posture, resting tremor, or other classic parkinsonian features were not characteristic of the LBV patient. In some cases, it may be possible to diagnose LBV premortem on the basis of the clinical and neuropsychological features.

Evolution of cognitive dysfunction in an incident Parkinson's disease cohort

Abstract: We have previously performed detailed clinical and neuropsychological assessments in a community-based cohort of patients with newly diagnosed parkinsonism, and through analysis of a subcohort with idiopathic Parkinson's disease (PD), we have demonstrated that cognitive dysfunction occurs even at the time of PD diagnosis and is heterogeneous. Longitudinal follow-up of the cohort has now been performed to examine the evolution of cognitive dysfunction within the early years of the disease. One hundred and eighty (79%) eligible patients from the original cohort with parkinsonism were available for re-assessment at between 3 and 5 years from their initial baseline assessments. PD diagnoses were re-validated with repeated application of the UKPDS Brain Bank criteria in order to maximize sensitivity and specificity, following which a diagnosis of idiopathic PD was confirmed in 126 patients. Thirteen out of 126 (10%) had developed dementia at a mean (SD) of 3.5 (0.7) years from diagnosis, corresponding to an annual dementia incidence of 30.0 (16.4-52.9) per 1000 person-years. A further 57% of PD patients showed evidence of cognitive impairment, with frontostriatal deficits being most common amongst the non-demented group. However, the most important clinical predictors of global cognitive decline following correction for age were neuropsychological tasks with a more posterior cortical basis, including semantic fluency and ability to copy an intersecting pentagons figure, as well as a non-tremor dominant motor phenotype at the baseline assessment. This work clarifies the profile of cognitive dysfunction in early PD and demonstrates that the dementing process in this illness is heralded by both postural and gait dysfunction and cognitive deficits with a posterior cortical basis, reflecting probable non-dopaminergic cortical Lewy body pathology. Furthermore, given that these predictors of dementia are readily measurable within just a few minutes in a clinical setting, our work may ultimately have practical implications in terms of guiding prognosis in individual patients.