An Autopsy-Proven Case of Lewy Body Disease Presenting with Severe Dysphagia.
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ABSTRACT:
SUBMITTER: Jo S
PROVIDER: S-EPMC8490184 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundRecent studies raised questions about the severity of cognitive impairment associated with dementia with Lewy bodies (DLB). However, there have been few analyses of large, multicenter data registries for clinical-pathologic correlation.MethodsWe evaluated data from the National Alzheimer's Coordinating Center registry (n = 5,813 cases meeting initial inclusion criteria) and the University of Kentucky Alzheimer's Disease Center autopsy series (n = 527) to compare quantitatively the severity of cognitive impairment associated with DLB pathology vs Alzheimer disease (AD) and AD+DLB pathologies.ResultsMini-Mental State Examination (MMSE) scores showed that persons with pure DLB had cognitive impairment of relatively moderate severity (final MMSE score 15.6 +/- 8.7) compared to patients with pure AD and AD+DLB (final MMSE score 10.7 +/- 8.6 and 10.6 +/- 8.6). Persons with pure DLB pathology from both data sets had more years of formal education and were more likely to be male. Differences in final MMSE scores were significant (p < 0.01) between pure DLB and both AD+DLB and pure AD even after correction for education level, gender, and MMSE-death interval. Even in cases with extensive neocortical LBs, the degree of cognitive impairment was most strongly related to the amount of concomitant AD-type neurofibrillary pathology.ConclusionsDementia with Lewy bodies can constitute a debilitating disease with associated psychiatric, motoric, and autonomic dysfunction. However, neocortical Lewy bodies are not a substrate for severe global cognitive impairment as assessed by the Mini-Mental State Examination. Instead, neocortical Lewy bodies appear to constitute or reflect an additive disease process, requiring Alzheimer disease or other concomitant brain diseases to induce severe global cognitive deterioration.
| S-EPMC2764396 | biostudies-literature
Project description:Lewy body disease (LBD) is a spectrum of progressive neurodegenerative disorders characterized by the wide distribution of Lewy bodies and neurites in the central and peripheral nervous system (CNS, PNS). Clinical diagnoses include Parkinson's disease (PD), dementia with Lewy bodies, or pure autonomic failure. All types of LBD are accompanied by non-motor symptoms (NMSs) including gastrointestinal dysfunctions such as constipation. Its relationship to Lewy body-related α-synucleinopathy (Lewy pathology) of the enteric nervous system (ENS) is attracting attention because it can precede the motor symptoms. To clarify the role of ENS Lewy pathology in disease progression, we performed a clinicopathological study using the Brain Bank for Aging Research in Japan. Five-hundred and eighteen cases were enrolled in the study. Lewy pathology of the CNS and PNS, including the lower esophagus as a representative of the ENS, was examined via autopsy findings. Results showed that one-third of older people (178 cases, 34%) exhibited Lewy pathology, of which 78 cases (43.8%) exhibited the pathology in the esophagus. In the esophageal wall, Auerbach's plexus (41.6%) was most susceptible to the pathology, followed by the adventitia (33.1%) and Meissner's plexus (14.6%). Lewy pathology of the esophagus was significantly associated with autonomic failures such as constipation (p < 0.0001) and among PNS regions, correlated the most with LBD progression (r = 0.95, p < 0.05). These findings suggest that the propagation of esophageal Lewy pathology is a predictive factor of LBD.
| S-EPMC7785549 | biostudies-literature
Project description:Although an insidious history of episodic memory difficulty is a typical presenting symptom of Alzheimer's disease, detailed neuropsychological profiling frequently demonstrates deficits in other cognitive domains, including language. Previous studies from our group have shown that language changes may be reflected in connected speech production in the earliest stages of typical Alzheimer's disease. The aim of the present study was to identify features of connected speech that could be used to examine longitudinal profiles of impairment in Alzheimer's disease. Samples of connected speech were obtained from 15 former participants in a longitudinal cohort study of ageing and dementia, in whom Alzheimer's disease was diagnosed during life and confirmed at post-mortem. All patients met clinical and neuropsychological criteria for mild cognitive impairment between 6 and 18 months before converting to a status of probable Alzheimer's disease. In a subset of these patients neuropsychological data were available, both at the point of conversion to Alzheimer's disease, and after disease severity had progressed from the mild to moderate stage. Connected speech samples from these patients were examined at later disease stages. Spoken language samples were obtained using the Cookie Theft picture description task. Samples were analysed using measures of syntactic complexity, lexical content, speech production, fluency and semantic content. Individual case analysis revealed that subtle changes in language were evident during the prodromal stages of Alzheimer's disease, with two-thirds of patients with mild cognitive impairment showing significant but heterogeneous changes in connected speech. However, impairments at the mild cognitive impairment stage did not necessarily entail deficits at mild or moderate stages of disease, suggesting non-language influences on some aspects of performance. Subsequent examination of these measures revealed significant linear trends over the three stages of disease in syntactic complexity, semantic and lexical content. The findings suggest, first, that there is a progressive disruption in language integrity, detectable from the prodromal stage in a subset of patients with Alzheimer's disease, and secondly that measures of semantic and lexical content and syntactic complexity best capture the global progression of linguistic impairment through the successive clinical stages of disease. The identification of disease-specific language impairment in prodromal Alzheimer's disease could enhance clinicians' ability to distinguish probable Alzheimer's disease from changes attributable to ageing, while longitudinal assessment could provide a simple approach to disease monitoring in therapeutic trials.
| S-EPMC3859216 | biostudies-literature
Project description:Sex-linked factors may alter risk for neurodegenerative diseases. Definitive diagnoses are not established until autopsy, so neuropathological studies are critical. There have not been reported gender-related differences in neocortical Lewy bodies (LBs) using large multi-center autopsy series. We evaluated the associations between gender and pathologically characterized neurodegenerative diseases. Cases with Alzheimer's disease (AD), neocortical LBs, AD + neocortical LBs, or neither pathology were evaluated as separate groups. Results were corrected for possible confounders including age at death, smoking history, and education. The settings were the University of Kentucky Alzheimer's Disease Center and the National Alzheimer's Coordinating Center (NACC) Registry autopsy series; 3,830 subjects met inclusion criteria. Patients with neocortical ("diffuse") or intermediate ("limbic") LB pathologies tended to be male (male:female odds ratios ~2.9 with 95% CI 2.02-4.18). The preponderance of males dying with neocortical LB pathology was seen consistently across age groups and was not due to the potential confounders evaluated. By contrast, individuals dying with AD pathology were more likely to be female if dying over 80 (male:female odds ratio 0.66, 95% CI 0.50-0.88), but that tendency was not seen in individuals dying with AD pathology prior to age 80. Increased understanding of the male predominance in neocortical LB pathology may help guide clinicians, because males are more likely to be "undercalled" for neocortical LBs clinically, and females are more likely to be "overcalled" (P < 0.05 for both). Males are far more likely than females to die with neocortical LB pathology. This phenomenon may help guide medical practice including clinical trial study design.
| S-EPMC3040648 | biostudies-literature
Project description:Although Gaucher disease can be accompanied by Lewy pathology (LP) and extrapyramidal symptoms, it is unknown if LP exists in Fabry disease (FD), another progressive multisystem lysosomal storage disorder. We aimed to elucidate the distribution patterns of FD-related inclusions and LP in the brain of a 58-year-old cognitively unimpaired male FD patient suffering from predominant hypokinesia. Immunohistochemistry (CD77, ?-synuclein, collagen IV) and neuropathological staging were performed on 100-µm sections. Tissue from the enteric or peripheral nervous system was unavailable. As controls, a second cognitively unimpaired 50-year-old male FD patient without LP or motor symptoms and 3 age-matched individuals were examined. Inclusion body pathology was semiquantitatively evaluated. Although Lewy neurites/bodies were not present in the 50-year-old individual or in controls, severe neuronal loss in the substantia nigra pars compacta and LP corresponding to neuropathological stage 4 of Parkinson disease was seen in the 58-year-old FD patient. Major cerebrovascular lesions and/or additional pathologies were absent in this individual. We conclude that Lewy body disease with parkinsonism can occur within the context of FD. Further studies determining the frequencies of both inclusion pathologies in large autopsy-controlled FD cohorts could help clarify the implications of both lesions for disease pathogenesis, potential spreading mechanisms, and therapeutic interventions.
| S-EPMC7092358 | biostudies-literature
Project description:We examined the effect of vascular or Lewy body co-pathologies in subjects with autopsy-confirmed Alzheimer's disease (AD) on the rate of cognitive and functional decline and transition to dementia.In an autopsy sample of prospectively characterized subjects from the National Alzheimer's Coordinating Center database, neuropathology diagnosis was used to define the groups of pure AD (pAD, n = 84), mixed vascular and AD (ADV, n = 54), and mixed Lewy body disease and AD (ADLBD, n = 31). Subjects had an initial Clinical Dementia Rating-Global (CDR-G) score <1, Mini-Mental State Examination ?15, a final visit CDR-G >1, ?3 evaluations, and Braak tangle stage ?III. We compared the rate of cognitive and functional decline between the groups.The rate of functional and cognitive decline was lower for ADV, and ADV patients had less severe deficits on CDR-G and the CDR-Sum of Boxes scores at the last visit than pAD and ADLBD patients. No significant differences were noted between ADLBD and pAD patients. After controlling for age at death, the odds of reaching CDR ?1 at the last visit were lower in the ADV subjects compared to the pAD subjects.The mean rate of functional and cognitive decline among ADV subjects was slower than among either pAD or ADLBD patients. Vascular pathology did not increase the odds of attaining CDR ?1 when occurring with AD in this national cohort.
| S-EPMC5451902 | biostudies-literature
Project description:Lewy body dementia is the second most common neurodegenerative dementia after Alzheimer's disease. Disease-modifying therapies for this disabling neuropsychiatric condition are critically needed. To identify drugs associated with the risk of developing Lewy body dementia, we performed a population-based case-control study of 148 170 US Medicare participants diagnosed with Lewy body dementia between 1 January 2008 and 31 December 2014 and of 1 253 043 frequency-matched controls. We estimated odds ratios and 95% confidence intervals for the association of Lewy body dementia risk with 1017 prescription drugs overall and separately for the three major racial groups (Black, Hispanic and White Americans). We identified significantly reduced Lewy body dementia risk associated with drugs used to treat cardiovascular diseases (anti-hypertensives: odds ratio = 0.72, 95% confidence interval = 0.70-0.74, P-value = 0; cholesterol-lowering agents: odds ratio = 0.85, 95% confidence interval = 0.83-0.87, P-value = 0; anti-diabetics: odds ratio = 0.83, 95% confidence interval = 0.62-0.72, P-value = 0). Notably, anti-diabetic medications were associated with a larger risk reduction among Black Lewy body dementia patients compared with other racial groups (Black: odds ratio = 0.67, 95% confidence interval = 0.62-0.72, P-value = 0; Hispanic: odds ratio = 0.86, 95% = 0.80-0.92, P-value = 5.16 × 10-5; White: odds ratio = 0.85, 95% confidence interval = 0.82-0.88, P-value = 0). To independently confirm the epidemiological findings, we looked for evidence of genetic overlap between Lewy body dementia and cardiovascular traits using whole-genome sequence data generated for 2591 Lewy body dementia patients and 4027 controls. Bivariate mixed modelling identified shared genetic risk between Lewy body dementia and low-density lipoprotein cholesterol levels, Type 2 diabetes and hypertension. By combining epidemiological and genomic data, we demonstrated that drugs treating cardiovascular diseases are associated with reduced Lewy body dementia risk, and these associations varied across racial groups. Future randomized clinical trials need to confirm our findings, but our data suggest that assiduous management of cardiovascular diseases may be beneficial in this understudied form of dementia.
| S-EPMC10754316 | biostudies-literature
Project description:Clinicogenetic and pathological studies have shown that mutations of the glucocerebrosidase gene (GBA) are a risk factor for Parkinson's disease and Lewy body disorders. In the present study, we have identified GBA mutations in 6.8% (4/59) of cases with a pathological diagnosis of diffuse Lewy body disease. Taken with previous studies, it appears that GBA mutations are associated with a more diffuse pattern of Lewy body distribution involving the cerebral cortex than the brainstem/limbic distribution observed in typical Parkinson's disease.
| S-EPMC4721925 | biostudies-literature
Project description:Early identification of neurodegenerative diseases before extensive neuronal loss or disabling symptoms have occurred is imperative for effective use of disease-modifying therapies. Emerging data indicate that central Lewy body diseases - Parkinson disease and dementia with Lewy bodies - can begin in the peripheral nervous system, opening up a therapeutic window before central involvement. In this issue of the JCI, Goldstein et al. report that cardiac 18F-dopamine positron emission tomography reveals lower activity selectively in individuals with several self-reported Parkinson disease risk factors who later develop Parkinson disease or dementia with Lewy bodies. Accurately identifying which at-risk individuals will develop central Lewy body disease will optimize early patient selection for disease-modifying therapies.
| S-EPMC10760943 | biostudies-literature
Project description:Progressive supranuclear palsy (PSP) is a relatively common neurodegenerative tauopathy clinically characterized by parkinsonism, axial rigidity, and supranuclear gaze palsy. Pathologic findings of PSP are neuronal loss, gliosis, and neurofibrillary tangles in basal ganglia, diencephalon, and brainstem; there is increasing recognition of clinicopathologic variants of PSP.(1.)
| S-EPMC3716405 | biostudies-literature