Semantic memory is impaired in both dementia with Lewy Bodies (DLB) and dementia of Alzheimer's type (DAT): a comparative neuropsychological study and literature review

OBJECTIVE---To test the hypothesis that semantic impairment is present in both patients with dementia with Lewy bodies (DLB) and those with dementia of Alzheimer's type (DAT). METHODS---A comprehensive battery of neuropsychological tasks designed to assess semantic memory, visuoperceptual function, verbal fluency, and recognition memory was given to groups of patients with DLB (n=10), DAT (n=10) matched pairwise for age and mini mental state examination (MMSE), and age matched normal controls (n=15). RESULTS---Both DLB and DAT groups exhibited impaired performance across the range of tasks designed to assess semantic memory. Whereas patients with DAT showed equivalent comprehension of written words and picture stimuli, patients with DLB demonstrated more severe semantic deficits for pictures than words. As in previous studies, patients with DLB but not those with DAT were found to have impaired visuoperceptual functioning. Letter and category fluency were equally reduced for the patients with DLB whereas performance on letter fluency was significantly better in the DAT group. Recognition memory for faces and words was impaired in both groups. CONCLUSIONS---Semantic impairment is not limited to patients with DAT. Patients with DLB exhibit particular problems when required to access meaning from pictures that is most likely to arise from a combination of semantic and visuoperceptual impairments

Tau protein, A beta 42 and S-100B protein in cerebrospinal fluid of patients with dementia with Lewy bodies

The intra vitam diagnosis of dementia with Lewy bodies (DLB) is still based on clinical grounds. So far no technical investigations have been available to support this diagnosis. As for tau protein and beta-amyloid((1-42)) (Abeta42), promising results for the diagnosis of Alzheimer's disease ( AD) have been reported; we evaluated these markers and S-100B protein in cerebrospinal fluid (CSF), using a set of commercially available assays, of 71 patients with DLB, 67 patients with AD and 41 nondemented controls (NDC) for their differential diagnostic relevance. Patients with DLB showed significantly lower tau protein values compared to AD but with a high overlap of values. More prominent differences were observed in the comparison of DLB patients with all three clinical core features and AD patients. Abeta42 levels were decreased in the DLB and AD groups versus NDC, without significant subgroup differences. S-100B levels were not significantly different between the groups. Tau protein levels in CSF may contribute to the clinical distinction between DLB and AD, but the value of the markers is still limited especially due to mixed pathology. We conclude that more specific markers have to be established for the differentiation of these diseases. Copyright (C) 2005 S. Karger AG, Basel

Differentiation of dementia with Lewy bodies from Alzheimer's disease using a dopaminergic presynaptic ligand

Background: Dementia with Lewy bodies (DLB) is one of the main differential diagnoses of Alzheimer's disease (AD). Key pathological features of patients with DLB are not only the presence of cerebral cortical neuronal loss, with Lewy bodies in surviving neurones, but also loss of nigrostriatal dopaminergic neurones, similar to that of Parkinson's disease (PD). In DLB there is 40-70% loss of striatal dopamine.Objective: To determine if detection of this dopaminergic degeneration can help to distinguish DLB from AD during life.Methods: The integrity of the nigrostriatal metabolism in 27 patients with DLB, 17 with AD, 19 drug naive patients with PD, and 16 controls was assessed using a dopaminergic presynaptic ligand, I-123-labelled 2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl)nortropane (FP-CIT), and single photon emission tomography (SPET). A SPET scan was carried out with a single slice, brain dedicated tomograph (SME 810) 3.5 hours after intravenous injection of 185 MBq FP-CIT. With occipital cortex used as a radioactivity uptake reference, ratios for the caudate nucleus and the anterior and posterior putamen of both hemispheres were calculated. All scans were also rated by a simple visual method.Results: Both DLB and PD patients had significantly lower uptake of radioactivity than patients with (p<0.01) and controls (p<0.001) in the caudate nucleus and the anterior and posterior Putamen.Conclusion: FP-CIT SPET provides a means of distinguishing DLB from AD during life

Translocator protein in late stage Alzheimer\u27s disease and Dementia with Lewy bodies brains

OBJECTIVE: Increased translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), in glial cells of the brain has been used as a neuroinflammation marker in the early and middle stages of neurodegenerative diseases, such as Alzheimer\u27s disease (AD) and Dementia with Lewy Bodies (DLB). In this study, we investigated the changes in TSPO density with respect to late stage AD and DLB. METHODS: TSPO density was measured in multiple regions of postmortem human brains in 20 different cases: seven late stage AD cases (Braak amyloid average: C; Braak tangle average: VI; Aged 74-88, mean: 83 ± 5 years), five DLB cases (Braak amyloid average: C; Braak tangle average: V; Aged 79-91, mean: 84 ± 4 years), and eight age-matched normal control cases (3 males, 5 females: aged 77-92 years; mean: 87 ± 6 years). Measurements were taken by quantitative autoradiography using [ RESULTS: No significant changes were found in TSPO density of the frontal cortex, striatum, thalamus, or red nucleus of the AD and DLB brains. A significant reduction in TSPO density was found in the substantia nigra (SN) of the AD and DLB brains compared to that of age-matched healthy controls. INTERPRETATION: This distinct pattern of TSPO density change in late stage AD and DLB cases may imply the occurrence of microglia dystrophy in late stage neurodegeneration. Furthermore, TSPO may not only be a microglia activation marker in early stage AD and DLB, but TSPO may also be used to monitor microglia dysfunction in the late stage of these diseases

Analytical performance and clinical utility of the INNOTEST (R) PHOSPHO-TAU(181P) assay for discrimination between Alzheimer's disease and dementia with Lewy bodies

Background: Total tau (T-tau) and beta-amyloid((1-42)) (A beta(1-42)) levels in cerebrospinal fluid (CSF) can differentiate Alzheimer's disease (AD) from normal aging or depressive pseudo-dementia. Differential diagnosis from dementia with Lewy bodies (DLB) in clinical settings is difficult. Methods: The analytical performance of the INNOTEST (R) PHOSPHO-TAU((181P)) assay was validated in terms of selectivity, sensitivity, specificity, precision, robustness, and stability. Clinical utility of the assay alone, or combined with T-tau and AP1-421 for discrimination of AD (n=94) from patients suffering from DLB (n=60) or from age-matched control subjects (CS) (n=60) was assessed in a multicenter study. Results: CSF concentrations of tau phosphorylated at threonine 181 (P-tau(181P)) in AD was significantly higher than in DLB and CS. Discriminant analysis, a classification tree, and logistic regression showed that P-tau(181P) was the most statistically significant single variable of the three biomarkers for discrimination between AD and DLB. Conclusions: P-tau(181P) quantification is a robust and reliable assay that may be useful in discriminating AD from DLB

Isolated learners from diverse language backgrounds in the mainstream primary classroom: A sociocultural perspective

This paper focuses on the linguistic and cultural (‘languaculture’, Agar, 1994) challenges faced by learners from diverse language backgrounds (DLB) in New Zealand schools. It describes the typical learning context in primary classrooms terms of interactional, instructional, and cognitive dimensions. It then presents vignettes of four DLB learners and explains their relative competence in terms of Cummin’s (1981) distinction between BICS and CALP (Basic Interactional Communication Skills and Cognitive-Academic Language Proficiency). It goes on to discuss the extent to which such proficiency is the result of linguistic and cultural distance, and how that distance might be bridged by applying key constructs from sociocultural theory, and the implementation of Individual Languaculture Plans for DLB learners. The paper concludes with discussing the issue of where responsibility lies for coping with the challenges face by DLB learners

Cognitive fluctuations in connection to disgraphia a comparison of Alzheimer's disease with dementia Lewy bodies

Background: The purpose of the present study was to examine the relationship between cognitive impairment and the performance of handwritten scripts presented as “letter-writing” to a close relative by patients with dementia Lewy bodies (DLB), as fluctuations of the symptoms phase, and in a matched group of patients with Alzheimer’s disease (AD). The degree of writing disability and personal, spatial, and temporal orientation was compared in these two groups. Design and methods: Fourteen simple questions, designed in a form that could be utilized by any general practitioner in order to document the level of cognitive functioning of each patient, were presented to 30 AD patients and 26 DLB patients. The initial cognition test was designated PQ1. The patients were examined on tests of letter-writing ability. Directly after the letter-writing, the list of 14 questions presented in PQ1 was presented again in a repeated procedure that was designated PQ2. The difference between these two measures (PQ1 – PQ2) was designated D∆. This test of letter-writing ability and cognitive performance was administered over 19 days. Results: Several markedly strong relationships between dysgraphia and several measures of cognitive performance in AD patients and DLB patients were observed, but the deterioration of performance from PQ1 to PQ2 over all test days were markedly significant in AD patients and not significant in DLB patients. It is possible that in graphic expression even by patients diagnosed with moderate to relatively severe AD and DLB there remains some residual capacity for understanding and intention that may be expressed. Furthermore, the deterioration in performance and the differences noted in AD and DLB patients may be due to the different speed at which the process of the protein degradation occurs for functional modification of synapses. Conclusion: Our method can be used as part of neuropsychological tests to differentiate the diagnosis between AD and DL

The Alzheimer variant of Lewy body disease: A pathologically confirmed case-control study

The objective of the study was to identify clinical features that distinguish patients with dementia with Lewy bodies (DLB), who were classified as Alzheimer's disease ( AD) patients, from patients with AD. We examined a group of 27 patients from our memory clinic, originally diagnosed with AD, of whom 6 were postmortem found to have DLB. For the present study, we compared cognitive, noncognitive and neurological symptoms between the two groups. We found that there were no differences on ratings of dementia and scales for activities of daily living. Patients with DLB performed better on the MMSE and the memory subtest of the CAMCOG, but there was no difference in any other cognitive domain. Furthermore, genetic risk factors, including family history of dementia or allele frequency of the apolipoprotein epsilon 4, did not discriminate between the two groups, and there were no differences on CCT scans. Taken together, our findings suggest that Lewy body pathology may be present in patients who do not show the typical clinical features which distinguish DLB from AD. Copyright (C) 2005 S. Karger AG, Basel

Serum heart-type fatty acid-binding protein and cerebrospinal fluid tau: Marker candidates for dementia with Lewy bodies

Background: The measurement of biomarkers in cerebrospinal fluid (CSF) has gained increasing acceptance in establishing the diagnosis of some neurodegenerative diseases. Heart-type fatty acid-binding protein (H-FABP) was recently discovered in CSF and serum of patients with neurodegenerative diseases. Objective: We investigated H-FABP in CSF and serum alone and in combination with CSF tau protein to evaluate these as potential biomarkers for the differentiation between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Methods: We established H-FABP and tau protein values in a set of 144 persons with DLB (n = 33), Parkinson disease with dementia (PDD; n = 25), AD (n = 35) and nonclemented neurological controls (NNC; n = 51). Additionally, serum H-FABP levels were analyzed in idiopathic Parkinson disease patients without evidence of cognitive decline (n = 45) using commercially available enzyme-linked immunosorbent assays. We calculated absolute values of HFABP and tau protein in CSF and serum and established relative ratios between the two to obtain the best possible match for the clinical working diagnosis. Results: Serum HFABP levels were elevated in DLB and PDD patients compared with NNC and AD subjects. To better discriminate between DLB and AD, we calculated the ratio of serum H-FABP to CSF tau protein levels. At the arbitrary chosen cutoff ratio >= 8 this quotient reached a sensitivity of 91% and a specificity of 66%. Conclusion: Our results suggest that the measurement of CSF tau protein, together with H-FABP quantification in serum and CSF, and the ratio of serum H-FABP to CSF tau protein represent marker candidates for the differentiation between AD and DLB. Copyright (c) 2007 S. Karger AG, Basel

Occipital atrophy signature in prodromal Lewy bodies disease

Introduction: Dementia with Lewy bodies (DLB) is typically characterized by parietal, temporal, and occipital atrophy, but less is known about the newly defined prodromal phases. The objective of this study was to evaluate structural brain alterations in prodromal DLB (p-DLB) as compared to healthy controls (HC) and full-blown dementia (DLB-DEM). Methods: The study included 42 DLB patients (n = 20 p-DLB; n = 22 DLB-DEM) and 27 HC with a standardized neurological assessment and 3-tesla magnetic resonance imaging. Voxel-wise analyses on gray-matter and cortical thickness were implemented to evaluate differences between p-DLB, DLB-DEM, and HC. Results: p-DLB and DLB-DEM exhibited reduced occipital and posterior parieto-temporal volume and thickness, extending from prodromal to dementia stages. Occipital atrophy was more sensitive than insular atrophy in differentiating p-DLB and HC. Occipital atrophy correlated to frontotemporal structural damage increasing from p-DLB to DLB-DEM. Discussion: Occipital and posterior-temporal structural alterations are an early signature of the DLB continuum and correlate with a long-distance pattern of atrophy