Prodromal dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementing disorder after Alzheimer's disease (AD), but there is limited information regarding the prodromal DLB state compared with that of AD. Parkinson's disease (PD) and DLB share common prodromal symptoms with Lewy body disease (LBD), allowing us to use a common strategy for identifying the individuals with an underlying pathophysiology of LBD. Dysautonomia, olfactory dysfunction, rapid eye movement sleep behavior disorder (RBD) and psychiatric symptoms antedate the onset of dementia by years or even decades in patients with DLB. Although RBD is the most potentially accurate prodromal predictor of DLB, disease progression before the onset of dementia could differ between the prodromal DLB state with and without RBD. Experts who specialize in idiopathic RBD and DLB might need communication in order to clarify the clinical relevance of RBD with the disease progression of DLB. The presence of prodromal LBD symptoms or findings of occipital hypoperfusion/hypometabolism helps us to predict the possible pathophysiological process of LBD in non‐demented patients. This approach might provide the opportunity for additional neuroimaging, including cardiac ¹²³I‐metaiodobenzylguanidine scintigraphy and dopamine transporter imaging. Although limited radiological findings in patients with prodromal DLB states have been reported, there is now a need for larger clinical multisite studies with pathological verification. The long prodromal phase of DLB provides a critical opportunity for potential intervention with disease‐modifying therapy, but only if we are able to clearly identify the diversity in the clinical courses of DLB. In the present article, we reviewed the limited literature regarding the clinical profiles of prodromal DLB. Geriatr Gerontol Int 2015; 15: 817–826.     

Respiratory chemosensitivity in dementia with Lewy bodies]

The incidence of dementia with Lewy bodies (DLB) is increasing rapidly due to the increasing longevity of the population. In DLB, autonomic dysfunction, such as sleep disorders, and cardiopulmonary arrest, together with unconsciousness, can occur. Such cases have poor prognosis and may have dysfunction of chemosensitivity in the respiratory center. We have assessed the function of the respiratory center, especially chemosensitivity to hypercapnia. Twelve probable DLB patients (Group 1) and twelve age-matched healthy subjects (Group 2) were examined. Chemosensitivities to hypercapnia expressed by delta expiratory volume/delta partial pressure of carbon dioxide/body surface area: mean 0.16 (1/min/Torr/m(2)) in Group 1 and 0.49 in Group 2. Thus, patients with DLB had a subnormal hypercapnic response in chemosensitivity of the respiratory center, suggesting dysfunction of the respiratory center. Respiratory center dysfunction may be related to cardiopulmonary arrest together with unconsciousness, so, patients with DLB should not use drugs affecting the respiratory center.     

Carers' narratives: Finding dementia with Lewy bodies experiences

Carers' narratives provide a unique insight into the caring experience. From a human interest perspective they have appeal to the general population; however, they also target and are read by niche audiences – families striving to understand the challenges of the caring role. This article examines four carer narratives and their relevance to particular niche audiences; three classified from the information provided on their book covers as pertaining to Alzheimer's disease and one to Parkinson's disease. It explores the impact of care on the caregivers and reviews the promoted diagnoses in light of the current understanding of dementia with Lewy bodies. The author argues that the information provided in the titles, in good faith, may not reflect the content of the narratives and that three of these narratives may provide carers of people who have dementia with Lewy bodies with insights into the challenges that this disease presents.     

Distinguishing dementia with Lewy bodies from dementia occurring in Parkinson's disease: A literature review

There has been considerable debate as to whether dementia with Lewy bodies (DLB) represents a distinct diagnosis or lies on a spectrum with Parkinson's disease dementia (PDD). The objective of this review was to identify whether conceptualising these dementias as distinct diagnostic entities is meaningful, or indeed possible. A literature review was conducted using the databases MEDLINE and PSYCHINFO. DLB and PDD share many clinical features including the pattern of cognitive deficits and Lewy‐body pathology. However, they may be usefully distinguished by their clinical course and differential response to treatment. Some patients with DLB have a rapidly progressive dementia and may be particularly sensitive to neuroleptic medication, resulting in considerable morbidity and mortality.     

A systematic review of prevalence and incidence studies of dementia with Lewy bodies

BACKGROUND: Substantial variation in the prevalence of Dementia with Lewy Bodies (DLB) has been reported with estimates ranging from 0 to 26.3% of all dementia cases, potentially making it the second most common dementia subtype. OBJECTIVES: The aim of this study was to review systematically and critically for the first time previous studies of the clinical prevalence and incidence of DLB in the population. METHODS: A systematic literature search was performed using PubMed. Selected articles had to describe an original study that provided a prevalence and/or incidence number for the whole population for DLB as defined by pre-set clinical criteria and findings. RESULTS: Six studies reporting the prevalence of DLB and one study reporting the incidence of DLB met the inclusion criteria. Prevalence estimates, depending on case criteria, range from 0 to 5% with regard to the general population, and from 0 to 30.5% of all dementia cases. The only estimate for DLB incidence is 0.1% a year for the general population and 3.2% a year for all new dementia cases. The number of available studies was too small to hypothesise on the potential effect of age, sex and genetic background on the results. CONCLUSIONS: Although the literature on the prevalence and incidence of DLB is limited, there is a general consensus that DLB must be considered in the range of neurodegenerative conditions in the elderly. The move towards use of consensus criteria facilitates comparison and is welcome. Their application in a more routine way towards rigorously defined and selected study populations will lead to more comparable and generalisable studies in the future.     

Dementia with Lewy bodies

The presence of a high number of Lewy bodies--the morphological marker of Parkinson's disease--in the cerebral cortex of some cases of dementia has been frequently observed in association to Alzheimer type lesions (mainly senile plaques) and changes in the substantia nigra, that may be held responsible for the frequently associated symptoms of parkinsonism. The term "dementia with Lewy body" (DLB) has recently been suggested by a consensus conference and indicates that the pathogenetic mechanism of the dementia remains poorly understood. Marked fluctuations of alertness and of the cognitive performances, moderate parkinsonism and episodes of visual hallucinations may lead to suspect this diagnosis in cases of dementia. Unexplained falls, syncopes, delirium or alterations of consciousness may also be observed, and the patients may then be admitted in departments of internal medicine or geriatrics. The Lewy body is an intraneuronal spherical inclusion, present in Parkinson's disease. It is observed in the brainstem (substantia nigra, locus coeruleus, dorsal nucleus of the Xth nerve) and in the nucleus basalis of Meynert. The cortical Lewy bodies have a different aspect, but retain their antigenic characteristics: they are, in particular, stained by the antiubiquitin antibodies. Recently, they were found to be also labeled by antisynuclein antibodies. A mutation of the synuclein gene was recently identified in cases of familial Parkinson's disease. Clinically as well as pathologically, DLB may thus be difficult to distinguish from Alzheimer's disease on the one hand, and from Parkinson's disease, on the other. That diagnosis, however, is associated with a poor prognosis and should lead to specific therapeutic measures.     

Dementia with Lewy bodies

Dementia with Lewy bodies (DLB), the second most frequent cause of primary degenerative dementias following Alzheimer's disease, has been increasingly recognized since the proposal of the consensus name and clinical diagnostic criteria. Although DLB overlaps in clinical, pathological, and genetic features with Alzheimer's disease and Parkinson's disease, DLB should be understood as an entity with the essential feature of the presence of Lewy bodies in the brain stem and cerebral cortex. From the clinical point of view, DLB is characterized by the presence of progressive dementia without severe memory disorders at the early stage, with significant cognitive fluctuations, well-formed recurrent visual hallucinations, and spontaneous Parkinsonism. This article reviews recent clinical and research findings, including our own, to facilitate clinical recognition of DLB. In addition to the supportive features described in the consortium clinical diagnostic criteria for DLB such as falls and great sensitivity to neuroleptic drugs, our studies found other frequent disorders including disproportionately severe visuoconstructive and visuoperceptual disturbances, transitory alterations in consciousness with reduplication phenomena, misidentification delusions, and non-aphasic misnamings. Neuroimaging features include relatively preserved hippocampal volume on MRI and occipital involvement on metabolic and blood flow imagings. The correct diagnosis of DLB is important to administer adequate treatment, to avoid adverse effects with neuroleptic drugs, and to establish precise prognosis. The present summary of the clinical features is hopefully helpful for clinical diagnosis of DLB. From a therapeutic point of view, cholinesterase inhibitors seemingly show some efficacy in the treatment of cognitive alterations. Further research would result in advances in diagnostic methods and therapeutic approaches in the near future.     

路易体痴呆与帕金森病伴认知功能损害患者分子影像特点研究

目的探讨路易体痴呆与帕金森病伴认知功能损害(Parkinson's disease with cognitive impairment,PD-CI)患者分子影像特点。方法选择2014年2月~2016年12月解放军总医院南楼神经内科诊治的可能路易体痴呆患者6例及PD-CI患者15例,回顾分析临床病史、神经心理学特点以及~(11)C-甲基-N-2β-甲基酯-3β-(4-氟苯基)托烷(~(11)C-β-CFT)、~(11)C-匹兹堡复合物B(~(11)C-PIB)、~(11)C-雷氯必利(~(11)C-RAC)和18F-氟脱氧葡萄糖(18F-FDG)正电子发射断层显像特点。结果路易体痴呆患者双侧壳核~(11)C-β-CFT摄取对称性减低比例、皮质~(11)C-PIB摄取增高比例以及顶枕连接区18F-FDG下降比例明显高于PD-CI患者(50.0%vs 13.3%,80.0%vs 16.7%,100.0%vs 40.0%,P0.05);而双侧壳核~(11)C-β-CFT摄取不对称性减低比例明显低于PD-CI患者(33.3%vs 86.7%,P0.05)。3例行~(11)C-RAC显像的路易体痴呆患者中,双侧摄取减低1例(33.3%),双侧摄取增高2例(66.7%);15例(100.0%)PD-CI患者均呈现双侧摄取增高。结论路易体痴呆与PD-CI的分子影像特征性改变,有助于两者的鉴别诊断。     

六例痴呆患者脑内含Lewy小体的临床病理观察

目的 探讨痴呆患者脑内含Ｌｅｗｙ小体的临床和病理意义。 方法 用光镜及组织化学方法对我院６例痴呆患者的尸检材料进行临床和病理对照分析。 结果 Ｌｅｗｙ小体仅见于皮质下核，尤其是蓝斑核，而大脑皮质少见。 结论 有３个特点：（１）病程越长、病情越严重的病例，Ｌｅｗｙ小体体积越大，数量越多；（２）Ｌｅｗｙ小体不仅发现在细胞质内，也发现有孤立存在者，此种孤立的比一般的体积大，可能细胞已坏死；（３）Ｌｅｗｙ     

Lewy bodies

Lewy bodies (LB) in the substantia nigra are a cardinal pathological feature of Parkinson's disease, but they occur in a number of neurodegenerative diseases and can be widespread in the nervous system. The characteristics, locations, and composition of LB are reviewed, with particular attention to alpha-synuclein (alpha-SYN), which appears to be the major component of LB. The propensity for alpha-SYN, a presynaptic protein widely expressed in the brain, to aggregate is because of an amyloidogenic central region. The factors that favor the aggregation of alpha-SYN and mechanisms of toxicity are examined, and a mechanism through which aggregates of alpha-SYN could induce mitochondrial dysfunction and/or release of proapoptotic molecules is proposed.     

Tissue transglutaminase-induced aggregation of alpha-synuclein: Implications for Lewy body formation in Parkinson's disease and dementia with Lewy bodies

Proteinaceous aggregates containing alpha-synuclein represent a feature of neurodegenerative disorders such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Despite extensive research, the mechanisms underlying alpha-synuclein aggregation remain elusive. Previously, tissue transglutaminase (tTGase) was found to contribute to the generation of aggregates by cross-linking pathogenic substrate proteins in Huntington's and Alzheimer's diseases. In this article, the role of tTGase in the formation of alpha-synuclein aggregates was investigated. Purified tTGase catalyzed alpha-synuclein cross-linking, leading to the formation of high molecular weight aggregates in vitro, and overexpression of tTGase resulted in the formation of detergent-insoluble alpha-synuclein aggregates in cellular models. Immunocytochemical studies demonstrated the presence of alpha-synuclein-positive cytoplasmic inclusions in 8% of tTGase-expressing cells. The formation of these aggregates was significantly augmented by the calcium ionophore and prevented by the inhibitor cystamine. Immunohistochemical studies on postmortem brain tissue confirmed the presence of transglutaminase-catalyzed epsilon (gamma-glutamyl)lysine cross-links in the halo of Lewy bodies in Parkinson's disease and dementia with Lewy bodies, colocalizing with alpha-synuclein. These findings, taken together, suggest that tTGase activity leads to alpha-synuclein aggregation to form Lewy bodies and perhaps contributes to neurodegeneration.     

路易体痴呆中西医治疗现状及展望

路易体痴呆(DLB)是由大脑神经元内α-突触核蛋白积聚引起继阿尔兹海默症(AD)之后常见的神经退行性痴呆,表现出波动性认知功能障碍、帕金森症及视觉幻觉等症状,与AD相比具有更早的死亡率和更高的发病率。但大众对其认识局限,学术研究相对不足加之发病机制不清,治疗手段匮乏,成为当今世界亟待解决的医学难题。祖国医学与现代医学在DLB的认识上具有差异,但临床均能取得良好的治疗效果。本文就近年来路易体痴呆中西医诊疗现状进行汇总并提出展望,为临床治疗及相关研究提供参考。