scholarly journals Subtypes of dementia with Lewy bodies are associated with α-synuclein and tau distribution

Neurology ◽  
2020 ◽  
Vol 95 (2) ◽  
pp. e155-e165 ◽  
Author(s):  
Tanis J. Ferman ◽  
Naoya Aoki ◽  
Bradley F. Boeve ◽  
Jeremiah A. Aakre ◽  
Kejal Kantarci ◽  
...  
Keyword(s):  
Visual Processing ◽  
Lewy Body ◽  
Dementia With Lewy Bodies ◽  
Phenotypic Expression ◽  
Lewy Bodies ◽  
Rem Sleep Behavior Disorder ◽  
Lewy Body Disease ◽  
Diagnostic Sensitivity ◽  
Diffuse Lewy Body Disease ◽  
Braak Staging

ObjectiveTo determine whether Lewy body disease subgroups have different clinical profiles.MethodsParticipants had dementia, autopsy-confirmed transitional or diffuse Lewy body disease (TLBD or DLBD) (n = 244), or Alzheimer disease (AD) (n = 210), and were seen at least twice (mean follow-up 6.2 ± 3.8 years). TLBD and DLBD groups were partitioned based on the presence or absence of neocortical neurofibrillary tangles using Braak staging. Four Lewy body disease subgroups and AD were compared on clinical features, dementia trajectory, and onset latency of probable dementia with Lewy bodies (DLB) or a DLB syndrome defined as probable DLB or dementia with one core feature of parkinsonism or probable REM sleep behavior disorder.ResultsIn TLBD and DLBD without neocortical tangles, diagnostic sensitivity was strong for probable DLB (87% TLBD, 96% DLBD) and the DLB syndrome (97% TLBD, 98% DLBD) with median latencies <1 year from cognitive onset, and worse baseline attention-visual processing but better memory-naming scores than AD. In DLBD with neocortical tangles, diagnostic sensitivity was 70% for probable DLB and 77% for the DLB syndrome with respective median latencies of 3.7 years and 2.7 years from cognitive onset, each associated with tangle distribution. This group had worse baseline attention-visual processing than AD, but comparable memory-naming impairment. TLBD with neocortical tangles had 48% diagnostic sensitivity for probable DLB and 52% for the DLB syndrome, with median latencies >6 years from cognitive onset, and were cognitively similar to AD. Dementia trajectory was slowest for TLBD without neocortical tangles, and fastest for DLBD with neocortical tangles.ConclusionsThe phenotypic expression of DLB was associated with the distribution of α-synuclein and tau pathology.

scholarly journals 18F-fluorodeoxyglucose positron emission tomography in dementia with Lewy bodies

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Jonathan Graff-Radford ◽  
Timothy G Lesnick ◽  
Rodolfo Savica ◽  
Qin Chen ◽  
Tanis J Ferman ◽  
...  
Keyword(s):  
Lewy Body ◽  
Dementia With Lewy Bodies ◽  
Rating Scale ◽  
Clinical Course ◽  
Lewy Bodies ◽  
Lewy Body Disease ◽  
Diffuse Lewy Body Disease ◽  
18F Fluorodeoxyglucose ◽  
Alzheimer’S Pathology ◽  
Fluorodeoxyglucose Pet

Abstract Among individuals with dementia with Lewy bodies, pathologic correlates of clinical course include the presence and extent of coexisting Alzheimer’s pathology and the presence of transitional or diffuse Lewy body disease. The objectives of this study are to determine (i) whether 18F-fluorodeoxyglucose PET signature patterns of dementia with Lewy bodies are associated with the extent of coexisting Alzheimer’s pathology and the presence of transitional or diffuse Lewy body disease and (ii) whether these 18F-fluorodeoxyglucose pattern(s) are associated with clinical course in dementia with Lewy bodies. Two groups of participants were included: a pathology-confirmed subset with Lewy body disease (n = 34) and a clinically diagnosed group of dementia with Lewy bodies (n = 87). A subset of the clinically diagnosed group was followed longitudinally (n = 51). We evaluated whether 18F-fluorodeoxyglucose PET features of dementia with Lewy bodies (higher cingulate island sign ratio and greater occipital hypometabolism) varied by Lewy body disease subtype (transitional versus diffuse) and Braak neurofibrillary tangle stage. We investigated whether the PET features were associated with the clinical trajectories by performing regression models predicting Clinical Dementia Rating Scale Sum of Boxes. Among autopsied participants, there was no difference in cingulate island sign or occipital hypometabolism by Lewy body disease type, but those with a lower Braak tangle stage had a higher cingulate island sign ratio compared to those with a higher Braak tangle stage. Among the clinically diagnosed dementia with Lewy bodies participants, a higher cingulate island ratio was associated with better cognitive scores at baseline and longitudinally. A higher 18F-fluorodeoxyglucose PET cingulate island sign ratio was associated with lower Braak tangle stage at autopsy, predicted a better clinical trajectory in dementia with Lewy body patients and may allow for improved prognostication of the clinical course in this disease.

Behavioral and Psychological Symptoms of Dementia and Dementia With Lewy Bodies

2000 ◽  
Vol 12 (S1) ◽  
pp. 189-193 ◽  
Author(s):  
Ian G. McKeith
Keyword(s):  
Lewy Body ◽  
Dementia With Lewy Bodies ◽  
Psychological Symptoms ◽  
Senile Dementia ◽  
Lewy Bodies ◽  
Lewy Body Disease ◽  
Lewy Body Dementia ◽  
Body Type ◽  
Diffuse Lewy Body Disease ◽  
Clinical Diagnoses

Dementia with Lewy bodies (DLB) is the currently preferred term for a variety of clinical diagnoses that have risen to prominence during the last decade (McKeith et al., 1996). These include diffuse Lewy body disease, dementia associated with cortical Lewy bodies, the Lewy body variant of Alzheimer's disease (AD) (Hansen et al., 1990), senile dementia of the Lewy body type, and Lewy body dementia. Initially thought to be uncommon, DLB is now recognized as the second most common pathologic cause of dementia, accounting for up to 20% of all elderly cases reaching autopsy.

Clinical Aspects of Non-Alzheimer Disease Dementias

2017 ◽  
Author(s):  
David Knopman
Keyword(s):  
Cognitive Impairment ◽  
Alzheimer Disease ◽  
Cerebrovascular Disease ◽  
Lewy Body ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Lewy Body Disease ◽  
Clinical Aspects ◽  
Key Words Dementia ◽  
Sleep Behavior

There are a relatively small number of disorders that account for the majority of dementia in the elderly that is not Alzheimer disease (AD): cerebrovascular disease, Lewy body disease (α-synucleinopathies), and the frontotemporal lobar degenerations. Cerebrovascular disease and Lewy body disease account for most non-AD dementia among persons in the eighth decade of life and beyond. These two frequently co-occur with AD but can occur in their pure forms rarely (in the case of dementia associated with cerebrovascular disease) or more commonly (in the case of Lewy body disease). There is no one cognitive or behavioral syndrome associated with cerebrovascular disease; however, attempts to isolate a common theme suggest that cognitive slowing is typical of cerebrovascular contributions to cognitive impairment. Cerebrovascular pathology relevant to cognitive impairment accumulates subclinically more commonly than it causes acute, strokelike declines in cognition. Dementia with Lewy bodies is a multidimensional disorder that includes a nonamnestic dementia, Parkinson disease or at least some parkinsonian features, a disorder of sleep and wakefulness, autonomic disturbances, and depression. The disorders of sleep prominently include rapid eye movement sleep behavior disorder, excessive daytime sleepiness, visual hallucinations, and marked fluctuations in level of alertness. The frontotemporal lobar degenerations are nearly as common as causes of dementia in persons under age 65 as is AD. The group of disorders includes two cognitive syndromes (primary progressive aphasia and behavior variant frontotemporal dementia) and two neuropathologic subtypes (tauopathy and TDP43 proteinopathy) and is associated with three major autosomal dominant genetic mutations (in MAPT, GRN, and C9ORF72). Key words: dementia with Lewy bodies, frontotemporal lobar degenerations, vascular cognitive impairment

scholarly journals Diagnostic accuracy of dopaminergic imaging in prodromal dementia with Lewy bodies

2018 ◽  
Vol 49 (3) ◽  
pp. 396-402 ◽  
Author(s):  
Alan J. Thomas ◽  
Paul Donaghy ◽  
Gemma Roberts ◽  
Sean J. Colloby ◽  
Nicky A. Barnett ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Lewy Body ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Lewy Body Disease ◽  
High Specificity ◽  
Diagnostic Confidence ◽  
Neuropsychological Assessments ◽  
Diagnostic Symptoms ◽  
Prodromal Dementia

AbstractBackgroundDopaminergic imaging has high diagnostic accuracy for dementia with Lewy bodies (DLB) at the dementia stage. We report the first investigation of dopaminergic imaging at the prodromal stage.MethodsWe recruited 75 patients over 60 with mild cognitive impairment (MCI), 33 with probable MCI with Lewy body disease (MCI-LB), 15 with possible MCI-LB and 27 with MCI with Alzheimer's disease. All underwent detailed clinical, neurological and neuropsychological assessments and FP-CIT [123I-N-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)] dopaminergic imaging. FP-CIT scans were blindly rated by a consensus panel and classified as normal or abnormal.ResultsThe sensitivity of visually rated FP-CIT imaging to detect combined possible or probable MCI-LB was 54.2% [95% confidence interval (CI) 39.2–68.6], with a specificity of 89.0% (95% CI 70.8–97.6) and a likelihood ratio for MCI-LB of 4.9, indicating that FP-CIT may be a clinically important test in MCI where any characteristic symptoms of Lewy body (LB) disease are present. The sensitivity in probable MCI-LB was 61.0% (95% CI 42.5–77.4) and in possible MCI-LB was 40.0% (95% CI 16.4–67.7).ConclusionsDopaminergic imaging had high specificity at the pre-dementia stage and gave a clinically important increase in diagnostic confidence and so should be considered in all patients with MCI who have any of the diagnostic symptoms of DLB. As expected, the sensitivity was lower in MCI-LB than in established DLB, although over 50% still had an abnormal scan. Accurate diagnosis of LB disease is important to enable early optimal treatment for LB symptoms.

A pathological study of Lewy bodies and senile changes in the amygdala in diffuse Lewy body disease

1995 ◽  
Vol 15 (3-4) ◽  
pp. 112-116 ◽  
Author(s):  
Eizo Iseki ◽  
Toshinari Odawara ◽  
Kyoko Suzuki ◽  
Kenji Kosaka ◽  
Haruhiko Akiyama ◽  
...  
Keyword(s):  
Lewy Body ◽  
Lewy Bodies ◽  
Lewy Body Disease ◽  
Pathological Study ◽  
Diffuse Lewy Body Disease ◽  
Senile Changes

scholarly journals Diffuse Lewy body disease manifesting as corticobasal syndrome

Neurology ◽  
2018 ◽  
Vol 91 (3) ◽  
pp. e268-e279 ◽  
Author(s):  
Koji Kasanuki ◽  
Keith A. Josephs ◽  
Tanis J. Ferman ◽  
Melissa E. Murray ◽  
Shunsuke Koga ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Alzheimer Disease ◽  
Progressive Supranuclear Palsy ◽  
Lewy Body ◽  
Disease Onset ◽  
Lewy Bodies ◽  
Lewy Body Disease ◽  
Corticobasal Syndrome ◽  
Imaging Biomarkers ◽  
Diffuse Lewy Body Disease

ObjectiveTo describe clinical and pathologic characteristics of diffuse Lewy body disease (DLBD) manifesting as corticobasal syndrome (CBS).MethodsIn 523 autopsy-confirmed cases of DLBD, we identified 11 patients diagnosed with CBS. For comparison, we studied 22 DLBD brains with antemortem presentation of dementia with Lewy bodies (DLB). Given previous studies suggesting the importance of pathology in peri-Rolandic cortices in CBS, we used digital pathology to count Lewy bodies and to quantify intracytoplasmic and neuritic α-synuclein and phospho-tau burden in the motor cortex.ResultsDLBD patients with antemortem features of CBS were significantly younger at disease onset and less likely to have REM sleep behavior disorder than DLBD cases who met clinical criteria for DLB during life. Patients with DLBD manifesting as CBS had more Lewy bodies in the motor cortex than DLBD manifesting as clinically probable DLB. Three cases had concomitant progressive supranuclear palsy and 4 cases had concomitant Alzheimer disease as probable correlates of CBS.ConclusionThe neuropathology underlying CBS is heterogeneous, including corticobasal degeneration, Alzheimer disease, and progressive supranuclear palsy. This study suggests that atypical variants of Lewy body disease with severe peri-Rolandic Lewy-related pathology can present clinically as CBS. Patients with DLBD who present as CBS tend to have an earlier age at onset and are less likely to have clinical features of DLB, such as dream enactment behavior during sleep, visual hallucinations, and levodopa-responsive parkinsonism. Future studies with biofluid or molecular imaging biomarkers for α-synuclein will permit better recognition of this uncommon pathologic substrate of CBS.

Diffuse Lewy Body Disease without Amyloid Plaques in a Patient Homozygous for Apolipoprotein E Allele Epsilon 4: A Case Report

1996 ◽  
Vol 9 (4) ◽  
pp. 181-184
Author(s):  
Benjamin Seltzer ◽  
Jonathan Fratkin ◽  
Sanda Clejan
Keyword(s):  
Apolipoprotein E ◽  
Lewy Body ◽  
Lewy Bodies ◽  
Lewy Body Disease ◽  
Body Type ◽  
Progressive Dementia ◽  
Diffuse Lewy Body Disease ◽  
Aged Woman ◽  
Extrapyramidal Motor Symptoms ◽  
Middle Aged Woman

A middle-aged woman developed extrapyramidal motor symptoms, personality and behavioral changes, and rapidly progressive dementia. Apolipoprotein E genotyping revealed that she was homozygous for the epsilon 4 allele. At autopsy, there were numerous cortical and subcortical Lewy bodies but no neuritic plaques (NPs) or neurofibrillary tangles (NFTs). This case, the first explicitly reported patient homozygous for the epsilon 4 allele having dementia of the Lewy body type (DLBT) without NPs and NFTs, reinforces the distinction between DLBT and dementia of the Alzheimer type. It calls into question the pivotal role of the epsilon 4 allele in the pathogenesis of NPs and NFTT but raises the possibility of its being an independent risk factor for the development of DLBT.

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