The organization of narrative discourse in Lewy body spectrum disorder

Narrative discourse is an essential component of day-to-day communication, but little is known about narrative in Lewy body spectrum disorder (LBSD), including Parkinson’s disease (PD), Parkinson’s disease with dementia (PDD), and dementia with Lewy bodies (DLB). We performed a detailed analysis of a semi-structured speech sample in 32 non-aphasic patients with LBSD, and we related their narrative impairments to gray matter (GM) atrophy using voxel-based morphometry. We found that patients with PDD and DLB have significant difficulty organizing their narrative speech. This was correlated with deficits on measures of executive functioning and speech fluency. Regression analyses associated this deficit with reduced cortical volume in inferior frontal and anterior cingulate regions. These findings are consistent with a model of narrative discourse that includes executive as well as language components and with an impairment of the organizational component of narrative discourse in patients with PDD and DLB.     

Impairments of speech fluency in Lewy body spectrum disorder

Few studies have examined connected speech in demented and non-demented patients with Parkinson’s disease (PD). We assessed the speech production of 35 patients with Lewy body spectrum disorder (LBSD), including non-demented PD patients, patients with PD dementia (PDD), and patients with dementia with Lewy bodies (DLB), in a semi-structured narrative speech sample in order to characterize impairments of speech fluency and to determine the factors contributing to reduced speech fluency in these patients. Both demented and non-demented PD patients exhibited reduced speech fluency, characterized by reduced overall speech rate and long pauses between sentences. Reduced speech rate in LBSD correlated with measures of between-utterance pauses, executive functioning, and grammatical comprehension. Regression analyses related non-fluent speech, grammatical difficulty, and executive difficulty to atrophy in frontal brain regions. These findings indicate that multiple factors contribute to slowed speech in LBSD, and this is mediated in part by disease in frontal brain regions.     

Difficulty processing temporary syntactic ambiguities in Lewy body spectrum disorder

While grammatical aspects of language are preserved, executive deficits are prominent in Lewy body spectrum disorder (LBSD), including Parkinson’s disease (PD), Parkinson’s dementia (PDD) and dementia with Lewy bodies (DLB). We examined executive control during sentence processing in LBSD by assessing temporary structural ambiguities. Using an on-line word detection procedure, patients heard sentences with a syntactic structure that has high-compatibility or low-compatibility with the main verb’s statistically preferred syntactic structure, and half of the sentences were lengthened strategically between the onset of the ambiguity and its resolution. We found selectively slowed processing of lengthened ambiguous sentences in the PDD/DLB subgroup. This correlated with impairments on measures of executive control. Regression analyses related the working memory deficit during ambiguous sentence processing to significant cortical thinning in frontal and parietal regions. These findings emphasize the role of prefrontal disease in the executive limitations that interfere with processing ambiguous sentences in LBSD.     

Genetic-Evidence That the Lewy Body Variant Is Indeed a Phenotypic Variant of Alzheimers-Disease

Lewy Body Variant (LBV) patients present as Alzheimers disease (AD) clinically; about two-thirds also have mild extrapyramidal features. At autopsy, neocortical and brain stem Lewy bodies are present in addition to changes diagnostic of AD. We have found that the Apolipoprotein E4 allele is a major genetic risk factor for LBV as it is for ′pure AD," in contrast to subjects with diffuse Lewy body disease or Parkinsons disease. This genetic evidence supports the concept that LBV-the second most common neurodegenerative form of dementia-is a phenotypic variant of AD.     

Sentence processing in Lewy body spectrum disorder: the role of working memory

Prior work has related sentence processing to executive deficits in non-demented patients with Parkinson's disease (PD). We extended this investigation to patients with dementia with Lewy bodies (DLB) and PD dementia (PDD) by examining grammatical and working memory components of sentence processing in the full range of patients with Lewy body spectrum disorder (LBSD). Thirty-three patients with LBSD were given a two-alternative, forced-choice sentence-picture matching task. Sentence type, working memory, and grammatical structure were systematically manipulated in the sentences. We found that patients with PDD and DLB were significantly impaired relative to non-demented PD patients and healthy controls. The deficit in PDD/DLB was most pronounced for sentences lengthened by the strategic placement of an additional prepositional phrase and for sentences with an additional proposition due to a center-embedded clause. However, there was no effect for subject-relative versus object-relative grammatical structure. An MRI voxel-based morphometry analysis in a subset of patients showed significant gray matter thinning in the frontal lobe bilaterally, and this extended to temporal, parietal and occipital regions. A regression analysis related sentence processing difficulty in LBSD to frontal neocortex, including inferior prefrontal, premotor, and dorsolateral prefrontal regions, as well as right superior temporal cortex. These findings are consistent with the hypothesis that patients with PDD and DLB have difficulty processing sentences with increased working memory demands and that this deficit is related in part to their frontal disease.     

Intellectual, mnemonic, and frontal functions in dementia with Lewy bodies: A comparison with early and advanced Parkinson's disease

Both Parkinson's disease (PD) and dementia with Lewy bodies (DLB) share a common neuropathological marker, the presence of Lewy bodies in brain stem and basal forebrain nuclei. DLB, in addition, is associated with Lewy bodies in the neocortex, and, in it's more common form, with Alzheimer-type pathological markers, particularly amyloid plaques. Published neuropsychological studies have focused on the differential profiles of DLB and Alzheimer's disease (AD). However, it is presently unclear whether DLB should be classified as a variant of AD or PD. In the present study we compare a healthy age-matched control group with three groups of patients, one with DLB, and two with PD. One of the PD groups was early in the course (PD-E) and the second, more advanced group (PD-A), was matched on severity of cognitive impairment with the DLB group. The results show that DLB was associated with a different pattern of neuropsychological impairment than the PD-A group, particularly in tests believed to be mediated by prefrontal cortical regions.     

Intellectual, mnemonic, and frontal functions in dementia with Lewy bodies: A comparison with early and advanced Parkinson's disease

Both Parkinson's disease (PD) and dementia with Lewy bodies (DLB) share a common neuropathological marker, the presence of Lewy bodies in brain stem and basal forebrain nuclei. DLB, in addition, is associated with Lewy bodies in the neocortex, and, in it's more common form, with Alzheimer-type pathological markers, particularly amyloid plaques. Published neuropsychological studies have focused on the differential profiles of DLB and Alzheimer's disease (AD). However, it is presently unclear whether DLB should be classified as a variant of AD or PD. In the present study we compare a healthy age-matched control group with three groups of patients, one with DLB, and two with PD. One of the PD groups was early in the course (PD-E) and the second, more advanced group (PD-A), was matched on severity of cognitive impairment with the DLB group. The results show that DLB was associated with a different pattern of neuropsychological impairment than the PD-A group, particularly in tests believed to be mediated by prefrontal cortical regions.     

Diffuse Lewy Body Disease: Clinical,Pathological, and Neuropsychological Review

The pathophysiological etiologies and clinical presentations of neurodegenerative dementias have been found to be complex and heterogeneous. Recently, Lewy body inclusions have been identified as an etiological factor in 20–34% of autopsied dementia cases. The term diffuse Lewy body disease (DLBD) is generally accepted as the diagnostic term representative of this currently under-reported and under-recognized disease. This article reviews the literature on the clinical, pathological, and neuropsychological features of this disorder. Differential diagnostic issues are discussed as well as current pharmacological treatment. Nine confirmed cases of DLBD are presented to demonstrate the various features of this disorder. The diagnostic implications of neuropsychological examination results are discussed in relation to other common dementing neurologic diseases.     

Dreaming and hallucinations - continuity or discontinuity? Perspectives from dementia with Lewy bodies

Comparing the phenomenology, neurochemical pathology, and psychopharmacology of hallucinations and dreaming is limited by the available data. Evidence to date reveals no simple correspondence between the two states. Differences in the phenomenology of visual hallucinations and the visual component of dreams may reflect variations in visual context acting on the same underlying mechanism – the minimal visual input during dreaming contrasts with the more substantial perceived context in hallucinations. Variations in cholinergic, dopaminergic and serotonergic neurotransmitter function during sleep and during hallucinations in Lewy body dementias, together with relevant drug effects suggest that, on the whole, different, potentially opposite, changes characterise the two states. A similar analysis of other psychotic features in Lewy body dementia and other disorders suggests that, in contrast to hallucinations, there may be more convincing parallels between dreaming and delusional states.     

Comments on the paradox of analysis

A version of the so‐called paradox of analysis is enunciated which involves two principles of synonymy, referred to respectively as that of substitution and that of triviality. It is argued that for most “familiar” concepts of synonymy the former principle can be maintained whereas the latter one has to be rejected. I deal with some solutions to the paradox that have been proposed or discussed by Carnap, Lewy, Feyerabend and Hare, and adhere to Carnap's view that the puzzle arises from the use of unclarified and imprecise notions of synonymy.     

Dementia with Lewy bodies: a pure case

A pure case of autopsy-confirmed dementia with Lewy bodies (DLB) is described. The patient presented with distinctive verbal fluency deficits in the context of mild language impairment, intact recognition memory, and impaired paragraph recall. Neuroimaging (CT and SPECT) showed progressive medial temporal lobe atrophy. Neuropathology revealed Lewy bodies, degeneration in the substantia nigra, nucleus basalis of Meynert (Nakano & Hirano, 1984), and locus ceruleus, but no pathology characteristic of Alzheimer's disease. It is in this sense that the case is "pure" DLB. Early neuropsychological diagnosis of DLB is essential (Salmon et al., 1996) given the potentially fatal hazard of neuroleptics (McKeith et al., 1992) and the difficulties associated with clinical neurological diagnoses (Litvan et al., 1998).     

Different defense mechanisms among men with different sex role orientations

Thirty male college students completed the Bem Sex Role Inventory and the Defense Mechanism Inventory. Results demonstrated that sex role orientation moderates the use of defense mechanisms in men, so that men with different orientations differed in the defenses they used. Masculine men used externalizing defenses such as turning against object and rationalizing defenses such as principalization more often than feminine men. Feminine men used an internalizing mode of defense, such as turning against self, more often than masculine and androgynous men. Results were compared with similar studies and the implications were discussed.The order of the authors was alphabetically determined. The authors wish to thank Michal T. Lewy and Jacqueline Franko for their help in conducting the study.     

Spectrum inversion without a difference in representation is impossible

Even if spectrum inversion of various sorts is possible, spectrum inversion without a difference in representation is not. So spectrum inversion does not pose a challenge for the intentionalist thesis that, necessarily, within a given sense modality, if two experiences are alike with respect to content, they are also alike with respect to their phenomenal character. On the contrary, reflection on variants of standard cases of spectrum inversion provides a strong argument for intentionalism. Depending on one’s views about the possibility of spectrum inversion, the impossibility of spectrum inversion without a difference in representation can also be used as an argument against a variety of reductive theories of mental representation.     

Stimulus energy does not account for 2-month-olds' face preferences

We examined the determinants of 2-month-olds' preferences among facelike and abstract patterns. Observed preferences were compared with the predictions of two preference models--one based on stimulus energy (as measured by the amplitude spectrum) and the other based on stimulus structure (as measured by the phase spectrum). It is known that the phase spectrum is the primary determinant of perceived identity to adults. Twenty-five 2-month-olds saw six pairings of four patterns: a schematic face, a lattice, a pattern composed of the amplitude spectrum of the lattice and the phase spectrum of the face, and a pattern composed of the amplitude spectrum of the face and the phase spectrum of the lattice. Only patterns with the face's phase spectrum look facelike to adults. Unlike the preferences of newborns (Kleiner, 1987), 2-month-olds' preferences could be predicted from the phase spectrum but not from the amplitude spectrum. In other words, the 2-month-olds preferred the patterns that looked facelike to adults. These results offer clear evidence that 2-month-olds' preferences for facelike patterns are not governed by stimulus energy.     

Current and emerging pharmacological treatment options for dementia

Treatments for the symptomatic relief of Alzheimer's disease are available but despite advances in our ability to treat persons with various forms of dementia, more effective treatments are needed. The cholinesterase inhibitors donepezil, rivastigmine, and galantamine have demonstrated efficacy in improving cognition and global status and to a lesser extent, behavioral abnormalities relative to placebo in patients with mild-to-moderate Alzheimer's disease. Rivastigmine has been shown to benefit patients with dementia with Lewy Bodies and with dementia associated with Parkinson's disease. Donepezil and galantamine have also been shown to be mildly effective in dementia due to cerebral ischemia. Memantine has a distinct mechanism of action and is effective in moderate-to-severe AD. The benefits from these drugs, however, are limited and their long-term effectiveness has not been well-demonstrated. Their clinical utility is controversial. Many novel approaches that promise to provide more effective treatments are currently being pursued.     

帕金森病早期诊断之生物学标记物

帕金森病是老年人神经系统变性疾病之一,也是老年人最常见的锥体外系疾病,以黑质多巴胺能神经元变性、缺失以及路易小体形成为其主要病理特征。其临床症状主要包括运动症状及非运动症状。目前对于帕金森病仍缺乏最直接有效的诊断方法,常导致帕金森病患者错过最佳的早期诊断时机,故近年来研究发现血液生物化学标记物、脑脊液生物化学标记物、功能神经影像学、基因学等有望成为帕金森病早期诊断的新方法,故本文将对此逐一进行介绍。     

Incommensurability and vagueness in spectrum arguments: options for saving transitivity of betterness

The spectrum argument purports to show that the better-than relation is not transitive, and consequently that orthodox value theory is built on dubious foundations. The argument works by constructing a sequence of increasingly less painful but more drawn-out experiences, such that each experience in the spectrum is worse than the previous one, yet the final experience is better than the experience with which the spectrum began. Hence the betterness relation admits cycles, threatening either transitivity or asymmetry of the relation. This paper examines recent attempts to block the spectrum argument, using the idea that it is a mistake to affirm that every experience in the spectrum is worse than its predecessor: an alternative hypothesis is that adjacent experiences may be incommensurable in value, or that due to vagueness in the underlying concepts, it is indeterminate which is better. While these attempts formally succeed as responses to the spectrum argument, they have additional, as yet unacknowledged costs that are significant. In order to effectively block the argument in its most typical form, in which the first element is radically inferior to the last, it is necessary to suppose that the incommensurability (or indeterminacy) is particularly acute: what might be called radical incommensurability (radical indeterminacy). We explain these costs, and draw some general lessons about the plausibility of the available options for those who wish to save orthodox axiology from the spectrum argument.     

Amplitude and phase spectra as indices of infants' pattern preferences

This study examined whether the linear systems model of infants' visual preferences (Banks & Salapatek, 1981) could predict neonates' preferences, among facelike and abstract patterns. To do so, the study assessed the relative importance of stimulus energy (as measured by the amplitude spectrum) and stimulus structure (as measured by the phase spectrum) in determining early preferences. Forty-eight neonates viewed six pairings of four stimuli: (a) a schematic face, (b) a lattice, (c) a pattern composed of the amplitude spectrum of the lattice and the phase spectrum of the face, and (d) a pattern composed of the amplitude spectrum of the face and the phase spectrum of the lattice. The linear systems model predicted the observed preferences quite accurately. That is, the infants' preferences could be predicted from knowledge of the amplitude spectrum but not the phase spectrum. These results are interpreted as showing that neonates' preferences for facelike patterns are governed primarily by simulus energy and not by the familiarity or social significance of such patterns.     

Differential Diagnosis of the Major Progressive Dementias and Depression in Middle and Late Adulthood: A Summary of the Literature of the Early 1990s

There is a preponderance of research on the neuropsychology of the various dementias. There are also direct comparisons between two or more dementias available in the literature. This paper sought to summarize the most recent literature, primarily from 1990 through mid-1996, including recent reviews of the literature from previous decades. The purpose was to provide, in one location, a summary of neuropsychological (i.e., cognitive, motor, and psychiatric) characteristics of major noninfectious, progressive dementias and depression of middle and late adulthood. It is hoped that this review, particularly a summary table provided, will serve as a guide in the differential diagnosis of the dementias by clinicians. In addition to Alzheimer's disease, vascular dementias, Parkinson's disease, Lewy body dementia, Huntington's disease, and frontal lobe dementia, the impact of depression on cognitive functioning is covered given the frequency with which neuropsychologists are asked to differentiate depression from primary dementia.     

心身障碍共病与慢性疼痛关联的结构模型

常见的心身障碍共病可以理解为一种新的精神疾病结构模型：情绪障碍、抑郁、焦虑及躯体化障碍等归为内化性疾病谱系的组成元素,物质滥用和反社会行为障碍归为外化性疾病谱系的组成元素。本文分析探讨评估慢性疼痛与这一模型的联系。社会心理和生物学的研究证据表明慢性疼痛与内化性障碍密切相关,提示内化-外化性疾病模型可以作为一个有效的研究架构,为探讨慢性疼痛与情感、抑郁焦虑及其他相关精神障碍的关联共病机制提供新的研究方向和新思路。