Dementia with Lewy bodies: findings from an international multicentre study (original) (raw)
Related papers
Clinical Subtypes of Dementia with Lewy Bodies Based on the Initial Clinical Presentation
Journal of Alzheimer's Disease, 2018
Background: Dementia with Lewy bodies (DLB) is a heterogeneous disease in which clinical presentation, symptoms, and evolution widely varies between patients. Objective: To investigate the existence of clinical subtypes in DLB based on the initial clinical presentation. Methods: 81 patients with a clinical diagnosis of probable DLB were consecutively included. All patients underwent a neurological evaluation including a structured questionnaire about neuropsychiatric symptoms and sleep, an assessment of motor impairment (Unified Parkinson Disease Rating Scale subscale III), and a formal neuropsychological evaluation. Onset of core symptoms (hallucinations, parkinsonism, and fluctuations) and dementia were systematically reviewed from medical records. We applied a K-means clustering method based on the initial clinical presentation. Results: Cluster analysis yielded three different groups. Patients in cluster I (cognitive-predominant, n = 46) presented more frequently with cognitive symptoms (95.7%, n = 44, p < 0.001), and showed a longer duration from onset to DLB diagnosis (p < 0.001) than the other clusters. Patients in cluster II (neuropsychiatric-predominant, n = 22) were older at disease onset (78.1 ± 5 versus 73.6 ± 6.1 and 73.6 ± 4.2 in clusters I and III, respectively, both p < 0.01), presented more frequently with psychotic symptoms (77.3%, n = 17), and had a shorter duration until the onset of hallucinations (p < 0.001). Patients in cluster III (parkinsonism-predominant, n = 13) showed a shorter time from onset to presence of parkinsonism (p < 0.001) and dementia (0.008). Conclusions: Three subtypes of clinical DLB can be defined when considering the differential initial presentations. The proposed subtypes have distinct clinical profiles and progression patterns.
Dementia with Lewy bodies: Reliability and validity of clinical and pathologic criteria
Neurology, 1996
Clinical criteria for dementia with Lewy bodies (DLB) have been proposed, but their formulation, reliability, and validity require further study. Pathologic criteria for DLB are also undergoing evolution. Two studies were conducted with the goal of identifying the components of these evolving criteria that may benefit from further refinement; one study evaluated the components of the clinical criteria and another study operationalized the pathologic criteria for DLB. Twenty-four patients with a premorbid diagnosis of probable or possible Alzheimer's disease (AD) (n = 18), Parkinson's disease (PD) (n = 51, or progressive supranuclear palsy (PSP) (n = 1) were studied. Inter-rater reliability and validity of the clinical criteria were determined by a retrospective chart review, done by five neurologists, and a blinded pathologic evaluation. The Consortium on dementia with Lewy bodies (CDLB) pathologic criteria were operationalized to compare past criteria and test the validity of the evolving clinical criteria on the dementia patients. Three or more cortical fields (at 250X magnification) with many (four or more) Lewy bodies (LBs) on ubiquitin immunoreactive sections were required to meet the CDLB neocortical score of >6. Fifteen of the AD patients had at least one LB in a cortical section, four had many LBs, while three had no LBs; all patients with movement disorder had at least one LB in a cortical section. The sensitivityhpecificity ratio of the CDLB probable DLB clinical criteria based upon many LBs being present was 75%/79%. Reformulated clinical criteria that require the presence of extrapyramidal signs significantly predicted those patients with many LBs versus those with few or no LBs (x2 = 5.48, p = 0.02) and increased clinical specificity to 100%. This preliminary study identifies components of the evolving clinical and pathologic criteria for DLB that require further refinement.
Dementia with Lewy Bodies : A Case Report
2010
Dementia with Lewy bodies (DLB) is a type of degenerative dementia marked by progressive cognitive decline with prominent deficits in attention, executive functions and visuospatial abilities, along with other features that are essential for diagnosis of probable or possible DLB, namely cognitive fluctuations, recurrent visual hallucinations, and spontaneous motor features of parkinsonism. Considered a complex condition, patients with DLB are often misdiagnosed, especially when consider a differential diagnosis between DLB and Parkinson’s disease dementia (PDD) and psychiatric primary conditions such as late onset psychosis, leading to less than ideal management. We report the case of a 75-year-old male patient with probable DLB that presented at onset disease high delusional symptoms and that was admitted to clinical and neuropsychological evaluation. We discuss how this case can be interpreted as an important example for DLB differential diagnosis and how clinical and cognitive ev...
Diagnosis and management of dementia with Lewy bodies: Third report of the DLB Consortium
Neurology, 2006
The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them. REM sleep behavior disorder, severe neuroleptic sensitivity, and reduced striatal dopamine transporter activity on functional neuroimaging are given greater diagnostic weighting as features suggestive of a DLB diagnosis. The 1-year rule distinguishing between DLB and Parkinson disease with dementia may be difficult to apply in clinical settings and in such cases the term most appropriate to each individual patient should be used. Generic terms such as Lewy body (LB) disease are often helpful. The authors propose a new scheme for the pathologic assessment of LBs and Lewy neurites (LN) using alpha-synuclein immunohistochemistry and semiquantitative grading of lesion density, with the pattern of regional involvement being more important than total LB count. The new criteria take into account both Lewy-related and Alzheimer disease (AD)-type pathology to allocate a probability that these are associated with the clinical DLB syndrome. Finally, the authors suggest patient management guidelines including the need for accurate diagnosis, a target symptom approach, and use of appropriate outcome measures. There is limited evidence about specific interventions but available data suggest only a partial response of motor symptoms to levodopa: severe sensitivity to typical and atypical antipsychotics in ϳ50%, and improvements in attention, visual hallucinations, and sleep disorders with cholinesterase inhibitors. NEUROLOGY 2005;65:1863-1872 Clinical diagnostic criteria for DLB. Since the publication of Consensus criteria for clinical and pathologic diagnosis of dementia with Lewy bodies (DLB), 1,2 new information indicates that clinical criteria for probable DLB have acceptable specificity, but suboptimal sensitivity. Reasons identified in-clude difficulties in recognition of the core feature fluctuation 5,6 and a low rate of all core features (fluctuation, visual hallucinations, parkinsonism) in the presence of neocortical, neurofibrillary tangle (NFT) pathology. 7-9 The criteria have therefore been modified (table 1) to incorporate additional items indicative of LB pathology. Distinction is made between clinical features or investigations that are suggestive of DLB, i.e., have been demonstrated to be significantly more frequent than in
Probable Dementia with Lewy Body
Romanian Journal of Neurology, 2017
V.A. female, 67 years, old admitted in our clinic for neurological assessment because of a parkinsonian syndrome, in association with neurocognitive disorder established in a psychiatric service. Motor disturbances and cognitive disorders are frecquently associated in Dementia with Lewy body (DLB) and in Parkinson Disease (PD). Psychiatric symptoms are difficult to manage as antipsychotics have frequently motor side effects. Criteria for possible and probable diagnosis of DLB according McKeith criteria and Diagnostic and Statistical Manual of Mental Disorders (DSM 5) are discussed.
Advances in Psychiatric Treatment, 1998
Lewy body formation is central to the pathological phenotype of a spectrum of disorders. The most familiar of these is the extrapyramidal syndrome of idiopathic Lewy-body Parkinson's disease (PD). Studies of dementia in the elderly suggest that another manifestation of Lewy body pathology is equally or more common than Parkinson's disease. This syndrome of Dementia with Lewy bodies (DLB) has been given a number of diagnostic labels and is characterised by dementia, relatively mild parkinsonism, visual hallucinations, and fluctuations in conscious level. Although many of these features can arise in Parkinson's disease, the patients with DLB tend to have early neuropsychiatric features which predominate the clinical picture, and the diagnosis of the syndrome in practice is more concerned with the differential diagnosis of Alzheimer's disease (AD). Distinction from AD has clinical importance because of potentially differing therapeutic implications. Diagnostic guidelines for the clinical diagnosis and pathological evaluation of DLB are reviewed. Research into the disorder has centered around characterising the clinical, neuropsychological, pathological, neurochemical and genetic relationships with Alzheimer's disease on the one hand, and Parkinson's disease on the other. Many cases of DLB have prominent pathological features of AD and there are some shared genetic risk factors. Differences from the pathology of PD are predominantly quantitative rather than qualitative and evidence is discussed which suggests that DLB represents a clinicopathological syndrome within the spectrum of Lewy body disorders. The possibility that the syndrome represents a chance association of PD and AD is not supported by published studies.
Parkinson's Disease Dementia and Lewy Body Disease
2019
Dementia with Lewy Bodies (DLB) and Parkinson's disease dementia (PD-D) are Lewy body (LB)-related neurodegen-erative dementias sharing many clinical and neuropatholo-gical features. Both conditions affect cognition, behavior, movement, and autonomic functions. When the clinical picture is fully developed, DLB and PD-D are practically indistinguishable. Regarding molecular pathology, both are synucleinopathies, characterized by the accumulation of misfolded α-synuclein protein in the form of LBs and Lewy neurites. DLB and PD-D are believed to represent two entities on the same disease spectrum. The main difference between these two conditions is the temporal sequence of symptoms. Motor symptoms precede dementia in PD-D, whereas it coincides with or follows dementia in DLB within 1 year. Dementia with Lewy Bodies DLB is the second most common neurodegenerative dementia following Alzheimer's disease (AD). In contrast to AD, motor and behavioral symptoms appear early in the course of the disease in DLB and may be the major burden of the disease. Epidemiology and Risk Factors DLB accounts for 5% of all dementia cases over the age of 75. 1 In a systematic review, the prevalence of DLB was found to be between 0.02 and 33.3 per 1,000. 1 The incidence rate of DLB is 3.5 per 100,000 person-years overall, 2 and the incidence increases with age. 3 Risk factors associated with DLB are old age, mutations in the glucocerebrosidase (GBA) and α-synuclein genes, and carrying the H1 haplotype of the microtubule-associated protein tau (MAPT). 4-6 There are also new candidate risk genes associated with DLB such as BCL7C and GABRB3. 7 Compared with AD, the findings on apolipoprotein E4 (APOE) polymorphisms in DLB are inconclusive. Vascular risk factors are less associated with DLB compared with AD. Clinical Features The cardinal clinical features of DLB consist of motor, cog-nitive, behavioral, and autonomic symptoms. The cognitive profile is characterized by particularly severe deficits in attention as well as executive and visuospatial functions. In early phases of the disease, memory may be relatively Keywords ► dementia with Lewy bodies ► Parkinson's disease dementia ► synucleinopathy ► imaging Abstract Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PD-D) are Lewy body-related neurodegenerative disorders sharing common clinical and neuropathological findings. The clinical features of both conditions include cognitive impairment, behavioral symptoms, autonomic dysfunction, sleep disorders, and parkinsonism. The cognitive profile of both disorders is characterized by particularly severe deficits in executive and visuospatial functions as well as attention. Clinical differentiation between DLB and PD-D is based on an arbitrary distinction between the time of onset of parkinsonism and cognitive symptoms; extrapyramidal symptoms precede dementia in PD-D, whereas it coincides with or follows dementia within 1 year in DLB. When the clinical picture is fully developed, DLB and PD-D are practically indistinguishable. Although the diagnosis is basically clinical, structural and functional neuroimaging as well as cerebrospinal fluid biomarkers may help the clinician in the diagnosis. Placebo-controlled randomized trials of the cholinesterase inhibitors have shown modest but significant benefits in cognition, global function, and neuropsychiatric symptoms in both disorders. Behavioral symptoms such as hallucinations and delusions should be treated with caution with antipsychotics, as they have the potential to worsen motor and cognitive symptoms.
Pathologic Correlates of Dementia in Individuals with Lewy Body Disease
Brain Pathology, 2010
Cognitive impairment and dementia are more common in patients with Parkinson disease (PD) than age-matched controls, and appear to become more frequent as PD progresses. However, estimates of dementia in patients with PD have varied widely, likely due in part to differences in case definition, case ascertainment, and methodology. First, we review investigations of usual pathologic correlates of dementia in patients with brainstem (b) Lewy Body Disease (LBD) and report our findings from the initial 266 brain autopsies from a population-based study of brain aging and incident dementia. Our results showed that 2.6% of subjects were diagnosed with PD during life but that 20% had bLBD at autopsy. Seventy percent of individuals with bLBD had high-level of one or more cerebral pathologic changes significantly associated with dementia: Alzheimer's disease (AD), cerebral (c) LBD, or microvascular brain injury (μVBI); these were commonly co-morbid. Next we consider proposed contributors to cognitive impairment and dementia in the approximately 30% of patients with only bLBD, including regionally selective dendritic degeneration of neostriatal medium spiny neurons. Diseases contributing to cognitive impairment and dementia in patients with bLBD are heterogeneous, providing diagnostic challenges as well as multiple opportunities for successful intervention in patients with PD.