Lewy小体型痴呆（dementia with Lewy body；DLB），首先由小阪于1980年报道，初老期或老年期发病呈进行性认知功能低下及Parkinson症状，并伴特有精神症状的痴呆性变性疾病。1996年国际会议制定出临床及病理诊断标准。临床上以进行性...Lewy小体型痴呆（dementia with Lewy body；DLB），首先由小阪于1980年报道，初老期或老年期发病呈进行性认知功能低下及Parkinson症状，并伴特有精神症状的痴呆性变性疾病。1996年国际会议制定出临床及病理诊断标准。临床上以进行性认知功能低下为必有的症状，此外还有核心症状以伴随有注意或觉醒度变动的认知功能的动摇；反复出现幻视以及Parkinson症状。最近又注意到病人于REM睡眠期出现行动异常。自1996年发表了DLB的诊断标准后，临床医生们才对其有所重视。目前欧美认为DLB已成为仅次于Alzheimer痴呆（AD）的第二位痴呆，日本现在将AD、血管性痴呆（VD）以及DLB列为三大痴呆疾病。展开更多
Introduction Recurrent complex visual hallucinations are a core clinical feature of dementia with Lewy bodies(DLB)and are typically well-formed,often consisting of figures,such as people or animals(1)Despite the profo...Introduction Recurrent complex visual hallucinations are a core clinical feature of dementia with Lewy bodies(DLB)and are typically well-formed,often consisting of figures,such as people or animals(1)Despite the profound impact upon patients and caregivers in DLB,the aetiopathology of visual hallucinations remains largely unknown.In this article we discuss the anatomy of the human visual system,hypotheses of the genesis of visual hallucinations in DLB,and imaging and neuropathological studies that have attempted to understand visual hallucinations on a functional and anatomical basis.展开更多
Neurodegenerative diseases are a class of chronic and complex disorders featuring progressive loss of neurons in distinct brain areas.The mechanisms responsible for the disease progression in neurodegeneration are not...Neurodegenerative diseases are a class of chronic and complex disorders featuring progressive loss of neurons in distinct brain areas.The mechanisms responsible for the disease progression in neurodegeneration are not fully illustrated.In this observational study,we have examined diverse biochemical parameters in the caudate and putamen of patients with Lewy body diseases(LBDs)and Alzheimer disease(AD),shedding some light on the involvement of oxidative damage and neuroinflammation in advanced neurodegeneration.We performed Spearman and Mantel-Cox analyses to investigate how oxidative stress and neuroinflammation exert comprehensive effects on disease progression and survival.Disease progression in LBDs correlated positively with poly(ADP-Ribose)and triggering receptors expressed on myeloid cell 2 levels in the striatum of LBD cohorts,indicating that potential parthanatos was a dominant feature of worsening disease progression and might contribute to switching microglial inflammatory phenotypes.Disease progression in AD corresponds negatively with 8-oxo-7,8-dihydro-2′-deoxyguanosine(8-oxo-d G)and myeloperoxidase concentrations in the striatum,suggesting that possible mitochondria dysfunction may be involved in the progression of AD via a mechanism ofβ-amyloid entering the mitochondria and subsequent free radicals generation.Patients with lower striatal 8-oxo-d G and myeloperoxidase levels had a survival advantage in AD.The age of onset also affected disease progression.Tissue requests for the postmortem biochemistry,genetics,and autoradiography studies were approved by the Washington University Alzheimer's Disease Research Center(ADRC)Biospecimens Committee(ethics approval reference number:T1705,approval date:August 6,2019).Recombinant DNA and Hazardous Research Materials were approved by the Washington University Environmental Health&Safety Biological Safety Committee(approval code:3739,approval date:February 25,2020).Radioactive Material Authorization was approved by the Washington University Environmental Health&Safety Radiation Safety Committee(approval code:1056,approval date:September 18,2019).展开更多
Immune-mediated mechanisms are involved in the pathogenesis of both cerebral vasculitis and Parkinson’s disease（PD, brainstem-predominant Lewy pathology）, but the presentation of cerebral vasculitis with comorbid L...Immune-mediated mechanisms are involved in the pathogenesis of both cerebral vasculitis and Parkinson’s disease（PD, brainstem-predominant Lewy pathology）, but the presentation of cerebral vasculitis with comorbid Lewy pathology has not yet been reported. Here we present a case of pathologically confirmed vasculitis in a 73-year-old male patient whose postmortem examination revealed Lewy pathology diagnostic of PD. This case study suggests a comorbidity of cerebral vasculitis and Lewy pathology, as well as potential pathogenic interactions between these two disorders with immune-mediated mechanisms.展开更多
Neurodegeneration in Parkinson’s disease dementia (PDD) and dementia with Lew y bodies (DLB) affect cortical and subcortical networks involved in saccade gene ration. We therefore expected impairments in saccade perf...Neurodegeneration in Parkinson’s disease dementia (PDD) and dementia with Lew y bodies (DLB) affect cortical and subcortical networks involved in saccade gene ration. We therefore expected impairments in saccade performance in both disorde rs. In order to improve the pathophysiological understanding and to investigate the usefulness of saccades for differential diagnosis, saccades were tested in a ge-and education-matched patients with PDD (n=20) and DLB (n=20), Alzheimer’s disease (n=22) and Parkinson’s disease (n=24), and controls (n=24). Reflexive (gap, overlap) and complex saccades (prediction, decision and antisaccade) were tested with electrooculography. PDD and DLB patients had similar impairment in a ll tasks (P > 0.05, not signifi cant). Compared with controls, they were impaire d in both reflexive saccade execution (gap and overlap latencies, P < 0.0001; ga ins, P < 0.004) and complex saccade performance (target prediction, P < 0.0001; error decisions, P < 0.003; error antisaccades: P < 0.0001). Patients with Alzhe imer’s disease were only impaired in complex saccade performance (Alzheimer’s disease versus controls, target prediction P < 0.001, error decisions P < 0.0001 , error antisaccades P < 0.0001), but not reflexive saccade execution (for all, P >0.05). Patients with Parkinson’s disease had, compared with controls, similar complex saccade performance (for all, P > 0.05) and only minimal impairment in reflexive tasks, i.e. hypometric gain in the gap task (P=0.04). Impaired saccade execution in re flexive tasks allowed discrimination between DLB versus Alzheimer’s disease (se nsitivity ≥60%, specificity ≥77%)-and between PDD versus Parkinson’s disea se (sensitivity ≥60%, specificity ≥88%) when ±1.5 standard deviations was u sed for group discrimination. We conclude that impairments in reflexive saccades may be helpful for differential diagnosis and are minimal when either cortical (Alzheimer’s disease) or nigrostriatal neurodegeneration (Parkinson’s disease) exists solely; however, they become prominent with combined cortical and subcor tical neurodegeneration in PDD and DLB. The similarities in saccade performance in PDD and DLB underline the overlap between these conditions and underscore dif ferences from Alzheimer’s disease and Parkinson’s disease.展开更多
Objective: To examine the neuropsychological profile of dementia patients fro m a community- based autopsy sample of dementia, comparing Alzheimer disease (A D), Lewy body pathology (LBP) alone, and LBP with coexisten...Objective: To examine the neuropsychological profile of dementia patients fro m a community- based autopsy sample of dementia, comparing Alzheimer disease (A D), Lewy body pathology (LBP) alone, and LBP with coexistent AD (AD/LBP). Methods: The authors reviewed 135 subjects from a community- based study of dementia for wh om autopsy and brain tissue was available. Diagnostic groups were determined acc ording to standard neuropathologic methods and criteria, and the presence of LBs was determined using α - synuclein immunostaining. Neuropathologically define d diagnostic groups of AD, AD/LBP, and LBP were examined for differences on neur opsychological test performance at the time of initial study enrollment. Results : There were 48 patients with AD alone, 65 with LB and AD pathology (AD/LBP), an d 22 with LBP alone (LBP alone). There were no significant differences between g roups demographically or on performance of enrollment Mini- Mental State Examin ation (MMSE) or Dementia Rating Scale (DRS). AD patients performed worse than th e LBP patients on memory measures (Fuld Object Memory Evaluation Delayed Recall, Wechsler Memory Scale Logical Memory Immediate and Delayed Recall; p < 0.05) an d a naming task (Consortium to Establish a Registry for Alzheimer’ s Disease Na ming; p < 0.05). LBP patients were more impaired than AD patients on executive f unction (Trail Making Test Part B; p < 0.05) and attention tasks (Wechsler Adult Intelligence Scale- Revised Digit Span; p < 0.05). Decline in MMSE and DRS sco res over time were greatest in the patients with AD/LBP. Conclusions: In a commu nity- based sample of older, medically complicated patients with dementia, ther e are neuropsychological differences between dementia subtypes at the time of di agnosis. In particular, patients with Alzheimer disease (AD) alone and AD/Lewy b ody pathology (LBP) had more severe memory impairment than patients with LBP. LB P alone was associated with more severe executive dysfunction. Patients with AD/ LBP had the most rapid rate of cognitive decline.展开更多
Background Prevalence of neurocognitive disorder with Lewy bodies （NCDLB） is low in Asian populations, which may partially refect its diagnostic diffculty. The Mayo Fluctuations Scale, a short questionnaire that ev...Background Prevalence of neurocognitive disorder with Lewy bodies （NCDLB） is low in Asian populations, which may partially refect its diagnostic diffculty. The Mayo Fluctuations Scale, a short questionnaire that evaluates cognitive fuctuation, has been shown to signifcantly differentiate NCDLB from Alzheimer＇s disease.Aim This study aimed to develop the Mayo Fluctuations Scale-Thai version and assess its validity to screen NCDLB in an elderly population.Methods The Mayo Fluctuations Scale was translated into Thai. The process involved back-translation, cross-cultural adaptation, feld testing of the prefnal version, as well as fnal adjustments. From all patients attending the Psychiatric and Memory Clinic at Ramathibodi Hospital, 135 patients accompanied by their primary caregivers were included. Caregivers were interviewed by research assistants using a four-item scale, and psychiatrists determined patients＇ diagnosis based on the diagnostic and statistical manual of mental disorders （DSM）-5 criteria. Evaluations performed by psychiatrists and research assistants were blinded.Results Seventeen participants had been diagnosed with major NCDLB. At a cut-off score of 2 or over, the Mayo Fluctuations Scale exhibited excellent performance to differentiate major NCDLB from other major neurocognitive disorders （NCDs）, with a sensitivity of 94.1% and a specifcity of 71.4%, and acceptable performance to differentiate mild NCDLB from other mild NCDs, with a sensitivity of 60% and a specifcity of 93.1%.Conclusion The Mayo Fluctuations Scale-Thai version is an excellent screening tool for major NCDLB and an acceptable tool that may be used with other additional tests for mild NCDLB. The tool is practical for use in memory and psychiatric clinics. Further validation studies in participants with other specifc clinical conditions are required.展开更多
Dementia is mainly a neurodegenerative disorder involved in several systems, including central nervous system, endocrinology/metabolism system and circulatory system. Alzheimer’s disease (AD) and dementia with Lewy b...Dementia is mainly a neurodegenerative disorder involved in several systems, including central nervous system, endocrinology/metabolism system and circulatory system. Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) are the most common forms of the dementia, accounting for 60% - 80% and 10% - 20% of all cases, respectively. DLB is defined by widespread neocortical, limbic and brainstem Lewy bodies but frequently accompanied by variable levels of AD pathology. This pathological and clinical overlap makes their differential diagnosis complicated. Recent advances in the identification of disease bio-markers now make it possible to detect and distinguish their pathology in the early or preclinical stage of the diseases, even in cognitively normal individuals. In addition to the key biomarkers (amyloid β or Aβ, tau and α-synuclein), neurotrophins such as cocaine- and amphetamine-regulated transcript (CART) have also drawn attention due to their expressions and functions. This article summarizes the progress in the definition, pathology and diagnosis of dementia, with a focus on potential biochemical markers in the cere-brospinal fluid (CSF) in the differential diagnosis of the main forms of dementia. To prediction or early diagnosis of dementia, the role of specific and sensitive CSF biomarkers seems to be crucial in a routine clinical setting. The concerns and challenges in the biomarker field are also discussed.展开更多
文摘Lewy小体型痴呆（dementia with Lewy body；DLB），首先由小阪于1980年报道，初老期或老年期发病呈进行性认知功能低下及Parkinson症状，并伴特有精神症状的痴呆性变性疾病。1996年国际会议制定出临床及病理诊断标准。临床上以进行性认知功能低下为必有的症状，此外还有核心症状以伴随有注意或觉醒度变动的认知功能的动摇；反复出现幻视以及Parkinson症状。最近又注意到病人于REM睡眠期出现行动异常。自1996年发表了DLB的诊断标准后，临床医生们才对其有所重视。目前欧美认为DLB已成为仅次于Alzheimer痴呆（AD）的第二位痴呆，日本现在将AD、血管性痴呆（VD）以及DLB列为三大痴呆疾病。
文摘Introduction Recurrent complex visual hallucinations are a core clinical feature of dementia with Lewy bodies(DLB)and are typically well-formed,often consisting of figures,such as people or animals(1)Despite the profound impact upon patients and caregivers in DLB,the aetiopathology of visual hallucinations remains largely unknown.In this article we discuss the anatomy of the human visual system,hypotheses of the genesis of visual hallucinations in DLB,and imaging and neuropathological studies that have attempted to understand visual hallucinations on a functional and anatomical basis.
文摘Neurodegenerative diseases are a class of chronic and complex disorders featuring progressive loss of neurons in distinct brain areas.The mechanisms responsible for the disease progression in neurodegeneration are not fully illustrated.In this observational study,we have examined diverse biochemical parameters in the caudate and putamen of patients with Lewy body diseases(LBDs)and Alzheimer disease(AD),shedding some light on the involvement of oxidative damage and neuroinflammation in advanced neurodegeneration.We performed Spearman and Mantel-Cox analyses to investigate how oxidative stress and neuroinflammation exert comprehensive effects on disease progression and survival.Disease progression in LBDs correlated positively with poly(ADP-Ribose)and triggering receptors expressed on myeloid cell 2 levels in the striatum of LBD cohorts,indicating that potential parthanatos was a dominant feature of worsening disease progression and might contribute to switching microglial inflammatory phenotypes.Disease progression in AD corresponds negatively with 8-oxo-7,8-dihydro-2′-deoxyguanosine(8-oxo-d G)and myeloperoxidase concentrations in the striatum,suggesting that possible mitochondria dysfunction may be involved in the progression of AD via a mechanism ofβ-amyloid entering the mitochondria and subsequent free radicals generation.Patients with lower striatal 8-oxo-d G and myeloperoxidase levels had a survival advantage in AD.The age of onset also affected disease progression.Tissue requests for the postmortem biochemistry,genetics,and autoradiography studies were approved by the Washington University Alzheimer's Disease Research Center(ADRC)Biospecimens Committee(ethics approval reference number:T1705,approval date:August 6,2019).Recombinant DNA and Hazardous Research Materials were approved by the Washington University Environmental Health&Safety Biological Safety Committee(approval code:3739,approval date:February 25,2020).Radioactive Material Authorization was approved by the Washington University Environmental Health&Safety Radiation Safety Committee(approval code:1056,approval date:September 18,2019).
文摘Immune-mediated mechanisms are involved in the pathogenesis of both cerebral vasculitis and Parkinson’s disease（PD, brainstem-predominant Lewy pathology）, but the presentation of cerebral vasculitis with comorbid Lewy pathology has not yet been reported. Here we present a case of pathologically confirmed vasculitis in a 73-year-old male patient whose postmortem examination revealed Lewy pathology diagnostic of PD. This case study suggests a comorbidity of cerebral vasculitis and Lewy pathology, as well as potential pathogenic interactions between these two disorders with immune-mediated mechanisms.
文摘Neurodegeneration in Parkinson’s disease dementia (PDD) and dementia with Lew y bodies (DLB) affect cortical and subcortical networks involved in saccade gene ration. We therefore expected impairments in saccade performance in both disorde rs. In order to improve the pathophysiological understanding and to investigate the usefulness of saccades for differential diagnosis, saccades were tested in a ge-and education-matched patients with PDD (n=20) and DLB (n=20), Alzheimer’s disease (n=22) and Parkinson’s disease (n=24), and controls (n=24). Reflexive (gap, overlap) and complex saccades (prediction, decision and antisaccade) were tested with electrooculography. PDD and DLB patients had similar impairment in a ll tasks (P > 0.05, not signifi cant). Compared with controls, they were impaire d in both reflexive saccade execution (gap and overlap latencies, P < 0.0001; ga ins, P < 0.004) and complex saccade performance (target prediction, P < 0.0001; error decisions, P < 0.003; error antisaccades: P < 0.0001). Patients with Alzhe imer’s disease were only impaired in complex saccade performance (Alzheimer’s disease versus controls, target prediction P < 0.001, error decisions P < 0.0001 , error antisaccades P < 0.0001), but not reflexive saccade execution (for all, P >0.05). Patients with Parkinson’s disease had, compared with controls, similar complex saccade performance (for all, P > 0.05) and only minimal impairment in reflexive tasks, i.e. hypometric gain in the gap task (P=0.04). Impaired saccade execution in re flexive tasks allowed discrimination between DLB versus Alzheimer’s disease (se nsitivity ≥60%, specificity ≥77%)-and between PDD versus Parkinson’s disea se (sensitivity ≥60%, specificity ≥88%) when ±1.5 standard deviations was u sed for group discrimination. We conclude that impairments in reflexive saccades may be helpful for differential diagnosis and are minimal when either cortical (Alzheimer’s disease) or nigrostriatal neurodegeneration (Parkinson’s disease) exists solely; however, they become prominent with combined cortical and subcor tical neurodegeneration in PDD and DLB. The similarities in saccade performance in PDD and DLB underline the overlap between these conditions and underscore dif ferences from Alzheimer’s disease and Parkinson’s disease.
文摘Objective: To examine the neuropsychological profile of dementia patients fro m a community- based autopsy sample of dementia, comparing Alzheimer disease (A D), Lewy body pathology (LBP) alone, and LBP with coexistent AD (AD/LBP). Methods: The authors reviewed 135 subjects from a community- based study of dementia for wh om autopsy and brain tissue was available. Diagnostic groups were determined acc ording to standard neuropathologic methods and criteria, and the presence of LBs was determined using α - synuclein immunostaining. Neuropathologically define d diagnostic groups of AD, AD/LBP, and LBP were examined for differences on neur opsychological test performance at the time of initial study enrollment. Results : There were 48 patients with AD alone, 65 with LB and AD pathology (AD/LBP), an d 22 with LBP alone (LBP alone). There were no significant differences between g roups demographically or on performance of enrollment Mini- Mental State Examin ation (MMSE) or Dementia Rating Scale (DRS). AD patients performed worse than th e LBP patients on memory measures (Fuld Object Memory Evaluation Delayed Recall, Wechsler Memory Scale Logical Memory Immediate and Delayed Recall; p < 0.05) an d a naming task (Consortium to Establish a Registry for Alzheimer’ s Disease Na ming; p < 0.05). LBP patients were more impaired than AD patients on executive f unction (Trail Making Test Part B; p < 0.05) and attention tasks (Wechsler Adult Intelligence Scale- Revised Digit Span; p < 0.05). Decline in MMSE and DRS sco res over time were greatest in the patients with AD/LBP. Conclusions: In a commu nity- based sample of older, medically complicated patients with dementia, ther e are neuropsychological differences between dementia subtypes at the time of di agnosis. In particular, patients with Alzheimer disease (AD) alone and AD/Lewy b ody pathology (LBP) had more severe memory impairment than patients with LBP. LB P alone was associated with more severe executive dysfunction. Patients with AD/ LBP had the most rapid rate of cognitive decline.
基金funded by a grant from the Faculty of MedicineRamathibodi Hospital,Mahidol University,Bangkok,Thailand
文摘Background Prevalence of neurocognitive disorder with Lewy bodies （NCDLB） is low in Asian populations, which may partially refect its diagnostic diffculty. The Mayo Fluctuations Scale, a short questionnaire that evaluates cognitive fuctuation, has been shown to signifcantly differentiate NCDLB from Alzheimer＇s disease.Aim This study aimed to develop the Mayo Fluctuations Scale-Thai version and assess its validity to screen NCDLB in an elderly population.Methods The Mayo Fluctuations Scale was translated into Thai. The process involved back-translation, cross-cultural adaptation, feld testing of the prefnal version, as well as fnal adjustments. From all patients attending the Psychiatric and Memory Clinic at Ramathibodi Hospital, 135 patients accompanied by their primary caregivers were included. Caregivers were interviewed by research assistants using a four-item scale, and psychiatrists determined patients＇ diagnosis based on the diagnostic and statistical manual of mental disorders （DSM）-5 criteria. Evaluations performed by psychiatrists and research assistants were blinded.Results Seventeen participants had been diagnosed with major NCDLB. At a cut-off score of 2 or over, the Mayo Fluctuations Scale exhibited excellent performance to differentiate major NCDLB from other major neurocognitive disorders （NCDs）, with a sensitivity of 94.1% and a specifcity of 71.4%, and acceptable performance to differentiate mild NCDLB from other mild NCDs, with a sensitivity of 60% and a specifcity of 93.1%.Conclusion The Mayo Fluctuations Scale-Thai version is an excellent screening tool for major NCDLB and an acceptable tool that may be used with other additional tests for mild NCDLB. The tool is practical for use in memory and psychiatric clinics. Further validation studies in participants with other specifc clinical conditions are required.
文摘Dementia is mainly a neurodegenerative disorder involved in several systems, including central nervous system, endocrinology/metabolism system and circulatory system. Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) are the most common forms of the dementia, accounting for 60% - 80% and 10% - 20% of all cases, respectively. DLB is defined by widespread neocortical, limbic and brainstem Lewy bodies but frequently accompanied by variable levels of AD pathology. This pathological and clinical overlap makes their differential diagnosis complicated. Recent advances in the identification of disease bio-markers now make it possible to detect and distinguish their pathology in the early or preclinical stage of the diseases, even in cognitively normal individuals. In addition to the key biomarkers (amyloid β or Aβ, tau and α-synuclein), neurotrophins such as cocaine- and amphetamine-regulated transcript (CART) have also drawn attention due to their expressions and functions. This article summarizes the progress in the definition, pathology and diagnosis of dementia, with a focus on potential biochemical markers in the cere-brospinal fluid (CSF) in the differential diagnosis of the main forms of dementia. To prediction or early diagnosis of dementia, the role of specific and sensitive CSF biomarkers seems to be crucial in a routine clinical setting. The concerns and challenges in the biomarker field are also discussed.
