Cambios en la marcha asociados con demencia por cuerpos de Lewy: una revisión narrativa de la literatura / Gait changes associated with Lewy body dementia: a narrative review of the literature

RESUMEN INTRODUCCIÓN: La demencia por cuerpos de Lewy (DCL) es una enfermedad neurodegenerativa con alta prevalencia y a menudo subdiagnosticada. En las demencias pueden presentarse alteraciones en la marcha que potencialmente permitan identificar su subtipo y dar una orientación clínica, diagnóstica y terapéutica temprana. Esta revisión narrativa de la literatura busca revisar los cambios de la marcha que se han descrito asociados con DCL. MATERIALES Y MÉTODOS: Se realizó una revisión de la literatura sobre la relación de las alteraciones de la marcha con la DCL. Se seleccionaron los siguientes parámetros de búsqueda mediante el buscador Scopus: ((falls and dementia and gait and (evaluation or analysis))). Los datos se ordenaron según relevancia y se obtuvieron 267 resultados. Igualmente, se hizo una búsqueda en PubMed, para a la que se introdujeron los términos (gait and lewy-body-disease), y no se utilizaron otros filtros; se obtuvieron 139 resultados. Se hizo una selección no sistemática de los artículos para llevar a cabo una revisión narrativa acerca de los cambios en la marcha asociados con DCL. RESULTADOS: Las alteraciones en la marcha pueden tener un valor predictor importante en la DCL. Los pacientes con demencias no debido a EA o causas vasculares muestran un deterioro de la funcionalidad física más rápido comparado con pacientes con EA y sin problemas cognitivos. La priorización incorrecta de las tareas, evidenciada en la EP, también es observable en los pacientes con DCL, y se asocia con el paradigma de doble tarea en el paciente con trastorno neurocognitivo mayor. El congelamiento de la marcha, también conocido como bloqueo de la marcha, se ha asociado con mayor progresión de la alteración cognitiva. Los pacientes con DCL también presentan un mayor compromiso en el tiempo de balanceo y la variabilidad de duración de la zancada, como también peor desempeño en ritmo y variabilidad de la marcha, e inestabilidad de la marcha, con posturas inadecuadas. CONCLUSIONES: Existe una relación entre la DCL y las caídas en el adulto mayor. En este grupo de edad, los cambios en la marcha y en las pruebas de desempeño podrían tener una utilidad clínica como factores asociados a con DCL, así como con las caídas. Al parecer, existe una variación característica entre los parámetros de la marcha y los subtipos de demencias que puede tener un valor como marcador diagnóstico. Se requieren más estudios con respecto a este tema puesto que hay escasa evidencia disponible hasta el momento, lo cual impide definir con mayor precisión las alteraciones más sensibles de cada dominio de la marcha que permitan diferenciar el envejecimiento normal del patológico.

ABSTRACT INTRODUCTION: Lewy body dementia is a highly prevalent neurodegenerative disease and often goes unnoticed due to little knowledge about it. In dementias there may be gait alterations that potentially allow the identification of its subtype and provide early clinical, diagnostic, and therapeutic guidance. This narrative review of the literature aims to review gait changes that have been described as associated with Lewy body dementia. MATERIALS AND METHODS: A literature review was carried out on the relationship of gait disturbances and LBD. The following search parameters were selected using the Scopus search engine: ((falls and dementia and gait and (evaluation or analysis))). The data were ordered according to relevance, obtaining 267 results. Likewise, a search was made in PubMed, using the terms (gait and lewy-body-disease), and no other filters were used, obtaining 139 results. A non-systematic selection of literature was made to carry out a narrative review about the changes in gait associated with LBD. RESULTS: We found that gait disturbances may have an important predictive value in LBD. Patients with dementias not due to AD or vascular causes have a faster deterioration of physical function compared to patients with AD and without cognitive problems. The incorrect prioritization of tasks evidenced in PD is also observable in patients with LBD and is associated with the "dual-task" paradigm in patients with major neurocognitive disorder. Freezing of gait, also known as motor block or "freezing of gait" has been associated with a greater progression of cognitive impairment. Patients with LBD also show greater compromise in swing time, stride duration variability, poorer performance in gait pace and variability, and gait instability with inappropriate postures. CONCLUSIONS: We observe that there is a relationship between LBD and falls in the elderly. Changes in gait and performance tests could have clinical utility as factors associated with LBD as well as falls in the elderly. There appears to be a characteristic variation between gait parameters and dementia subtypes that may have value as a diagnostic marker. More studies are required on this subject since there is little evidence available to date, which makes it impossible to define with greater precision the most sensitive alterations in each domain of gait that make it possible to differentiate normal from pathological aging.

Role of positron emission tomography in etiological evaluation of patients with dementia / 国际脑血管病杂志

Dementia is a syndrome mainly characterized by acquired cognitive impairment, which is mainly manifested by the decrease of cognitive functions such as understanding, orientation, and visuospatial ability. Due to different intervention methods for different types of dementia, differential diagnosis is extremely important. Positron emission tomography (PET) can reflect the changes of brain function from multiple angles through different tracers, providing imaging basis for the differential diagnosis of dementia. This article reviews the characteristics of PET in patients with different types of dementia in order to provide ideas for the differential diagnosis of patients with different types of dementia.

Analysis of visual scores of brain magnetic resonance imaging features of dementia with Lewy bodies / 中华老年医学杂志

Objective:To assess the practical value of visual scores of magnetic resonance imaging(MRI)features in the diagnosis and classification of dementia with Lewy bodies(DLB).Methods:In this study, 102 DLB patients were prospectively recruited, with 102 cognitively normal elderly people as the normal control group(NC).All included subjects underwent MRI examinations and neuropsychological assessments.Based on the clinical dementia rating(CDR)scale, DLB patients were divided into a mild(CDR=1.0), a moderate(CDR=2.0)and a severe(CDR=3.0)group.The results of MRI were scored visually and the rating scales included medial temporal lobe atrophy(MTA), global cortical atrophy-frontal subscale(GCA-F), posterior cortical atrophy(PCA), white matter lesions(the Fazekas scale), cerebral microbleeds(CMBs), and the Evans Index(EI).Statistical differences were compared between the DLB and NC groups and between DLB patients with different degrees of cognitive impairment.Results:In terms of neuropsychology, the Mini-Mental State Examination(MMSE) score of the DLB group[16.0(11.0, 21.0)]was statistically significantly lower than that of the NC group[29.0(28.0, 30.0)]( Z=-12.31, P<0.001), the Montreal Cognitive Assessment(MoCA)score of the DLB group[9.5(6.0, 15.0)]was statistically significantly lower than that of the NC group[28.0(27.0, 29.0)]( Z=-12.40, P<0.001), and the Activities of Daily Living(ADL)score of the DLB group[32.0(23.8, 40.0)]was statistically significantly higher than that of the NC group[20.0(20.0, 20.0)]( Z=-11.98, P<0.001).The scores of all MRI visual assessment scales in DLB patients were statistically significantly higher than those in the NC group( P<0.001).There were significant differences in MTA scores between DLB patients with different degrees of cognitive impairment( P0<0.001).The MTA score of the mild group[1.0(1.0, 1.0)]was statistically significantly lower than that of the moderate group[2.0(1.0, 2.0)]( P1<0.001, P2<0.001); The MTA score of the moderate group[2.0(1.0, 2.0)]was statistically significantly lower than that of the severe group[2.0(2.0, 3.0)]( P1=0.003, P2=0.010). Conclusions:This study has for the first time after comprehensively evaluated the value of various visual scores in DLB diagnosis, MTA can be used to help diagnose DLB and distinguish the severity of DLB, providing a new supplemental tool for clinical diagnosis.

Anosognosia in dementia with Lewy bodies: a systematic review / Anosognosia na demência com corpos de Lewy: uma revisão sistemática

ABSTRACT Background: Anosognosia, i.e. lack of awareness of one's own symptoms, is a very common finding in patients with dementia and is related to neuropsychiatric symptoms and worse prognosis. Although dementia with Lewy bodies (DLB) is the second most common form of degenerative dementia, literature on anosognosia in this disease is scarce. Objectives: This paper aimed to review the current evidence on anosognosia in patients with DLB, including its prevalence in comparison with other neurological conditions, its severity and anatomical correlations. Methods: Database searches were performed in PubMed, Web of Knowledge and PsycINFO for articles assessing anosognosia in DLB. A total of 243 studies were retrieved, but only six were included in the review. Results: Potential risk of selection, comparison or outcome biases were detected in relation to all the studies selected. Most of the studies used self-report memory questionnaires to assess cognitive complaints and compared their results to scores from informant-based instruments or to participants' cognitive performance in neuropsychological tasks. Subjects with DLB had worse awareness regarding memory than healthy older controls, but the results concerning differences in anosognosia between DLB and Alzheimer's disease (AD) patients were inconsistent across studies. Presence of AD pathology and neuroimaging biomarkers appeared to increase the prevalence of anosognosia in individuals with DLB. Conclusion: Anosognosia is a common manifestation of DLB, but it is not clear how its prevalence and severity compare with AD. Co-existence of AD pathology seems to play a role in memory deficit awareness in DLB.

RESUMO Introdução: Anosognosia, i.e. a perda da consciência dos próprios sintomas, é um achado muito comum em pacientes com demência e está relacionada a sintomas neuropsiquiátricos e a pior prognóstico. Embora a doença por Corpos de Lewy (DCL) seja a segunda demência degenerativa mais comum, há pouca evidência sobre anosognosia nessa doença. Objetivos: Este artigo teve como objetivo revisar a evidência disponível sobre anosognosia em pacientes com DCL, incluindo sua prevalência em comparação a outras condições neurológicas, gravidade e correlações anatômicas. Métodos: Foram feitas buscas nos bancos de dados PubMed, Web of Knowledge e PsycINFO por artigos que avaliassem anosognosia na DCL. Um total de 243 estudos foi encontrado, mas apenas 6 foram incluídos nesta revisão. Resultados: Potenciais riscos de viés de seleção, comparação ou resultado foram encontrados em todos os estudos selecionados. A maior parte dos estudos utilizou questionários de memória preenchidos pelo próprio paciente e os comparou a resultados de instrumentos preenchidos por informantes ou à performance cognitiva em tarefas neuropsicológicas. Indivíduos com DCL têm pior consciencia de memória do que idosos saudáveis, mas os resultados tocantes à diferença de anosognosia entre DCL e doença de Alzheimer (DA) são inconsistentes entre estudos. A presença de achados patológicos e de neuroimagem de DA parece aumentar a prevalência de anosognosia entre pacientes com DCL. Conclusão: Anosognosia é uma manifestação comum da DCL, mas não é possível afirmar como sua prevalência e gravidade se comparam à DA. A coexistência de achados patológicos de DA parece influenciar a consciência de déficits de memória na DCL.

Investigation of the frequency and location of cerebral microbleeds in dementia with Lewy bodies versus in Alzheimer's disease / 中华老年医学杂志

Objective To investigate the frequency and location of cerebral microbleeds(CMB) in dementia with Lewy bodies(DLB)versus in Alzheimer's disease(AD).Methods This retrospective study included three groups of probable AD patients (n =156),dementia with Lewy bodies (n =67) and normal controls(n=172).Frequencies and location of CMBs in the three groups were calculated and recorded.The foci of MRI signal for CMB were confirmed by two radiologists at moments of unknowingness about diagnosis.The correlations of cerebral small vessel disease and cerebral amyloid angiopathy with the development of cognitive decline in AD were analyzed.Results The incidence rate of CMBs was higher in patients with groups of DLB(22.4 ％,15/67) and AD(19.8 ％,31/156) than in normal controls (8.2 ％,14/172) (P =0.002 and 0.002),while there was no significant difference in incidence rate of CMBs between DLB and AD groups(P＞0.05).The MRI signal intensity of CMBs was the highest in the occipital lobe of the DLB group,and was higher in the deep temporal lobe or temporal lobe in the AD group.Conclusions The frequency of CMB is higher in patients with DLB or AD than in normal controls and there is no significant difference in frequency of CMB between DLB and AD groups,which suggests that the pathophysiological mechanisms of CMB may be similar between AD and DLB.

Characteristics of facial expression recognition ability in patients with Lewy body disease

BACKGROUND@#The facial expression of medical staff has been known to greatly affect the psychological state of patients, making them feel uneasy or conversely, cheering them up. By clarifying the characteristics of facial expression recognition ability in patients with Lewy body disease, the aim of this study is to examine points to facilitate smooth communication between caregivers and patients with the disease whose cognitive function has deteriorated.@*METHODS@#During the period from March 2016 to July 2017, we examined the characteristics of recognition of the six facial expressions of "happiness," "sadness," "fear," "anger," "surprise," and "disgust" for 107 people aged 60 years or more, both outpatient and inpatient, who hospital specialists had diagnosed with Lewy body diseases of Parkinson's disease, Parkinson's disease with dementia, and dementia with Lewy bodies. Based on facial expression recognition test results, we classified them by cluster analysis and clarified features of each type.@*RESULTS@#In patients with Lewy body disease, happiness was kept unaffected by aging, age of onset, duration of the disease, cognitive function, and apathy; however, recognizing the facial expression of fear was difficult. In addition, due to aging, cognitive decline, and apathy, the facial expression recognition ability for sadness and anger decreased. In particular, cognitive decline reduced recognition of all of the facial expressions except for happiness. The test accuracy rates were classified into three types using the cluster analysis: "stable type," "mixed type," and "reduced type". In the "reduced type", the overall facial recognition ability declined except happiness, and in the mixed type, recognition ability of anger particularly declined.@*CONCLUSION@#There were several facial expressions that the Lewy body disease patients were unable to accurately identify. Caregivers are recommended to make an effort to compensate for such situations with language or body contact, etc., as a way to convey correct feeling to the patients of each type.

¹²³I-Meta-iodobenzylguanidine Sympathetic Imaging: Standardization and Application to Neurological Diseases / 전남의대학술지

¹²³I-meta-iodobenzylguanidine (MIBG) has become widely applied in Japan since its introduction to clinical cardiology and neurology practice in the 1990s. Neurological studies found decreased cardiac uptake of ¹²³I-MIBG in Lewy-body diseases including Parkinson's disease and dementia with Lewy bodies. Thus, cardiac MIBG uptake is now considered a biomarker of Lewy body diseases. Although scintigraphic images of ¹²³I-MIBG can be visually interpreted, an average count ratio of heart-to-mediastinum (H/M) has commonly served as a semi-quantitative marker of sympathetic activity. Since H/M ratios significantly vary according to acquisition and processing conditions, quality control should be appropriate, and quantitation should be standardized. The threshold H/M ratio for differentiating Lewy-body disease is 2.0-2.1, and was based on standardized H/M ratios to comparable values of medium-energy collimators. Parkinson's disease can be separated from various types of parkinsonian syndromes using cardiac ¹²³I-MIBG, whereas activity is decreased on images of Lewy-body diseases using both ¹²³I-ioflupane for the striatum and ¹²³I-MIBG. Despite being a simple index, the H/M ratio of ¹²³I-MIBG uptake is reproducible and can serve as an effective tool to support a diagnosis of Lewy-body diseases in neurological practice.

¹²³I-Meta-iodobenzylguanidine Sympathetic Imaging: Standardization and Application to Neurological Diseases / 전남의대학술지

¹²³I-meta-iodobenzylguanidine (MIBG) has become widely applied in Japan since its introduction to clinical cardiology and neurology practice in the 1990s. Neurological studies found decreased cardiac uptake of ¹²³I-MIBG in Lewy-body diseases including Parkinson's disease and dementia with Lewy bodies. Thus, cardiac MIBG uptake is now considered a biomarker of Lewy body diseases. Although scintigraphic images of ¹²³I-MIBG can be visually interpreted, an average count ratio of heart-to-mediastinum (H/M) has commonly served as a semi-quantitative marker of sympathetic activity. Since H/M ratios significantly vary according to acquisition and processing conditions, quality control should be appropriate, and quantitation should be standardized. The threshold H/M ratio for differentiating Lewy-body disease is 2.0-2.1, and was based on standardized H/M ratios to comparable values of medium-energy collimators. Parkinson's disease can be separated from various types of parkinsonian syndromes using cardiac ¹²³I-MIBG, whereas activity is decreased on images of Lewy-body diseases using both ¹²³I-ioflupane for the striatum and ¹²³I-MIBG. Despite being a simple index, the H/M ratio of ¹²³I-MIBG uptake is reproducible and can serve as an effective tool to support a diagnosis of Lewy-body diseases in neurological practice.

A study of sleep architecture and cognitive functions in dementia with Lewy bodies / 中国医师杂志

Objective To investigate the sleep architecture in dementia with Lewy bodies (DLB),and study the sleep architecture and cognitive functions in DLB.Methods We described polysomnography (PSG) findings in 34 consecutive subjects diagnosed with DLB.All the patients underwent Mini-Mental State Examination (MMSE),Montreal Cognitive Assessment (MoCA),Clinical Dementia Rating (CDR) to quantify cognitive functions.Results (1)Sleep architecture analysis:DLB group compared to normal control group,the sleep period time (SPT) was reduced (P ＜ 0.05),total sleep time (TST) and sleep efficiency (SE) were decreased,total wake time (TWT) and wake after sleep onset (WASO) were increased,1 non-rapid eye movement (NREM) sleep (TS1),2NREM sleep (TS2),total NREM sleep (TNREMS),and REM sleep (TREMS) time were significantly decreased (P ＜0.01).(2)The DLB patients were divided into groups based on MMSE,MoCA,qnd CDR scores,the sleep architecture of each group was no significant difference (P ＞ 0.05).Conclusions Patients with DLB exists sleep architecture disorder.The cognitive functions and sleep architecture changes in patients with DLB have no obvious correlation.It is different from other degenerative dementia.

Qualidade de vida de quem cuida de portadores de demência com corpos de Lewy / Quality of life of caregivers of patients with Lewy body dementia

INTRODUÇÃO: Cuidar de portadores de demência pode provocar impacto na qualidade de vida dos familiares. OBJETIVO: Verificar a qualidade de vida de familiares que cuidam de portadores de demência com corpos de Lewy (DCL). MÉTODO: Estudo transversal, realizado com 90 familiares de portadores de DCL atendidos em hospital universitário de Goiânia/GO (Brasil), que responderam ao instrumento de avaliação de qualidade de vida WHOQOL-BREF. RESULTADOS: Os entrevistados eram 53,3% homens, na maioria casados e com ensino médio de escolaridade, com idade média de 47,4 ± 13,8 anos e média de tempo como cuidador de 13,9 ± 9,3 meses. O domínio Meio Ambiente obteve maior média (26,92 ± 5,88) e o Psicológico (19,66 ± 4,32) e Relação social (9,84 ± 2,18), as menores. A média dos domínios foi influenciada pelo sexo e pelo tempo que o familiar era cuidador. CONCLUSÃO: Atenção especial deve ser dada às alterações na saúde do cuidador, para que ele não se torne um "paciente oculto" e incapaz de lidar com as demandas do portador de DCL. O conhecimento das especificidades e compreensão dos sintomas da patologia auxiliam na adequação dos recursos pessoais para enfrentar as alterações comportamentais, apontadas como o fator mais impactante na vida do cuidador.

INTRODUCTION: Taking Taking care of people with dementia may have an impact on the quality of life for family members. OBJECTIVE: To verify the quality of life for family members who take care of people with dementia with Lewy bodies (DLB). METHOD: A cross-sectional study with 90 relatives of patients with DLB treated in a University hospital in Goiânia/GO (Brazil), who responded to the instrument of evaluation for the quality of life WHOQOL-BREF. RESULTS: From the people who were interviewed, 53.3% were male, most married and high school graduated, average age of 47.4 ± 13.8 years and average time as a care taker 13.9 ± 9.3 months. The Environment Domain got the highest average (26.92 ± 5.88), the Psychological (19,66 ± 4,32) and the Social Relationship (9.84 ± 2.18) the lowest. The average for the domains was influenced by genus and by the time that the family member was a care taker. CONCLUSION: Special attention should be given to changes in the health of caretakers, so they do not become a "hidden patient", and unable to deal with the demands of patients with DLB. The knowledge and understanding of the specific symptoms of the pathology helps to accommodate the human resources to face the behavioral changes, identified as the most impacting factor in the lives of caretakers.

As diversas faces da síndrome demencial: como diagnosticar clinicamente?: [revisão] / The several faces of dementia syndrome: how to diagnose clinically?: [review]

Objetivos: a presente revisão descreve aspectos clínicos relacionados às diferentes síndromes demenciais, objetivando tornar comum, no meio médico, o conhecimento das nuanças que permeiam o diagnóstico diferencial dessas afecções. Fonte de Dados: foi realizada uma revisão da literatura através das bases de dados Medline, Ovid e Scopus até outubro de 2009, assim como de livros-texto. Artigos com enfoque na fisiopatogenia e na patologia não foram priorizados, tendo em vista os objetivos deste estudo. Síntese dos Dados: este artigo revisa aspectos dealgumas síndromes demenciais reversíveis e irreversíveis, como Doença de Alzheimer e Demência Vascular, enfocando principalmente as características clínicas e diagnósticas que as tornam entidades distintas. Conclusões: a literatura sugere que o processo diagnóstico das síndromes demenciais assenta-se fundamentalmente na clínica, priorizando uma avaliação rigorosa do estado mental. Entretanto, a avaliação por neuroimagem e exames laboratoriais tem participação considerável em determinar a causa subjacente ao quadro demencial, revelando peculiaridades que podem nortear o diagnóstico diferencial. Diagnosticar diferentes etiologias é importante para o prognóstico e conduta terapêutica específica.

Aims: This review describes the clinical aspects related to different dementia syndromes, aiming to become common in the medical , the knowledge of the nuances that permeate the differential diagnosis of these disorders. Data Source: A review of literature published up to October 2009 was conducted on Medline, Ovid, and Scopus databases, as well as on textbooks. Articles that focused on the pathogenesis and pathology were not prioritized, given the objectives of this study. Summary of the Findings: This article reviews some aspects of reversible and irreversible dementia syndromes, such as Alzheimer?s disease and Vascular Disease, focusing on the clinic and diagnostic features that make them distinct entities. Conclusions: The literature suggests that the diagnostic process of dementia syndromes is based mainly on clinical practice, prioritizing a rigorous assessment of mental status. However, neuroimaging evaluation and laboratory tests have considerable input in determining the underlying cause of dementia, revealing peculiarities that can guide the differential diagnosis. The diagnosis of different etiologies is important to the prognosis and the specific therapeutic approach.

DIAGNOSIS OF DEMENTIA WITH LEWY BODIES(REPORT OF 3 PATIENTS) / 解放军医学杂志

To define the definite diagnosis of dementia with Lewy bodies(DLB). Three cases of DLB diagnosed by bedside examination,cerebral image or pathology were analysed. These patients had been diagnosed as Alzheimer disease(AD) or AD with Parkinson disease (PD). DLB consisted of the following features as compared with AD:①Slow progressive congnitive decline, especially fluctuating congnitive defect was prominent;② Recurrent visual hallucinations that were typically well formed and detailed;③The extrapyramidal symptoms usually included mild rigidity and bradykinesia, and they almost appeared simultaneously in the extremities; ④Cerebral atrophy was relatively mild. The clinical diagnosis of DLB might be possible on the detailed basis of their peculiar features, but other neurodegeration disorders should be ruled out.

Clinicopathological study on Lewy body disease / 中华神经科杂志

Objective To investigate the pathological features of Lewy body disease. Methods An autopsy case of an 80 year old Chinese woman suffering from Lewy body disease was studied The patient had progressive dementia and myotonia for three years and was suspected with Alzheimer dementia clinically Brain tissue was analyzed neuropathologically by using HE staining and specific staining for nervous system, immunohistochemical staining for ubiquitin and by using ? synuclein and electronic microscopy. Results Neuropathological examination revealed the most characteristic features as follows: (1) The number of melanin pigmented neurons were markedly decreased in the substantia nigra and locus ceruleus, and some typical brain stem type Lewy bodies in the residual neurons with moderate gliosis were found (2) There appeared numerous cortical type Lewy bodies in deep layers of the cerebral cortex particularly in the cingulate gyrus, hippocampus, parahippocampal gyrus, transentorhinal contex, amygdala and insula (3) There were selective spongiform changes and many Lewy related neurites in positive ubiquitin immunohistochemical staining on the CA2/3 sectors, parahippocampal gyrus and transentorhinal cortex (4) A strong positive ? synuclein immunoreactivity was found in all Lewy bodies and Lewy related neurites (5) Alzheimer disease related changes such as senile plaques and neurofibrillary tangles were scarcely found only in hippocampus and parahippocampal gyrus. Conclusion Lewy body disease is a new group of degenerative disease of the central nervous system ? synuclein may play an important role in the degeneration of neurons and their neurites may be a major component of Lewy bodies in Lewy body disease It is considered that the present case should be a pure type of diffuse Lewy body disease

Association of Ubiquitin-Positive Neuritic Threads in the CA 2-3 Region of the Hippocampus with Cortical Lewy Bodies

Ubiquitin-positive neuritic threads (UNTS) in the hippocampal CA 2-3 region are reported to occur exclusively in association with so-called diffuse Lewy body disease (DLBD). hi order to assess the association between the occurrence of Lewy bodies (LBs) and that of the UNTs, an immunohistochemical study on the hippocampus including the parahippocampal gyrus with antiubiquitin antibody (Chemicon Co., California, U.S.A.) was perfon-ned in four groups of patient's brains. All brains were selected from the large pool of brains referred to the Neuropadiology Laboratory of the University of Minnesota for studies of Alzheimer's disease. Group 1 consisted of 34 cases (20 male and 14 female) with LBs widespread in the frontal and temporal cortex and the brain stem nuclei (basal nucleus, substantia nigra, locus ceruleus and dorsal vagal nucleus) associated with varying degrees of degeneration of the substantia nigra; 21 (11 male and 10 female) combined with and 13 (9 male and 4 female) without Alzheimer's disease (AD) pathology. Group 2 included 12 cases (9 male and 3 female) in which LBs were observed only in the brain stem nuclei; 7 with and 4 without AD pathology. Group 3 consisted of 30 cases (9 male and 21 female) without LBs but with AD pathology and degeneration of the substantia nigra. Group 4 included 23 cases (11 male and 12 female) with neither LBs nor AD pathology but with degeneration of the substantia nigra. Ages of the patients varied among the groups. In the 46 cases in the first two groups with LBs. The mean age in the 28 cases with AD pathology was 77.3+/-8.9 and in the 18 cases without AD pathology it was 71.6+/-8.8 (P<0.05). In the 53 cases in groups 3 and 4 without LBs, which served as the controls, the mean ages were 80.8+/-7.7 and 74.0+/-9.7 respectively. UNTs were encountered in all (100%) of 34 cases of group I with widespread LBs which met the histological criteria of DLBD regardless of combined AD pathology. In 12 cases of group 2 with LBs confined to the brain stem, UNTs occurred in 3 (25%), 1 with and 2 without AD pathology. hi the group 3 cases with only AD pathology, UNTs occurred in 4 (13%) of 30 cases, while no UNTs were encountered in the 23 cases of group 4 without AD pathology or LBs. In conclusion, UNTs in the hippocampal CA 2-3 region occur invariably but not exclusively in association with widespread LBs, frequently when LBs are confined to the brain stem, and infrequently with AD pathology. It seems, therefore, that the UNTs are closely related to LBs and increase in ftequency as LBs spread beyond the brain stem with time, but the pathogenesis of the UNTs is little understood.