scholarly journals 315 - Prevalence and clinical associations of tau in Lewy body dementias: a systematic review and meta-analysis

2020 ◽  
Vol 32 (S1) ◽  
pp. 73-73
Author(s):  
Kai Sin Chin ◽  
Nawaf Yassi ◽  
Leonid Churilov ◽  
Colin L Masters ◽  
Rosie Watson
Keyword(s):  
Diagnostic Accuracy ◽  
Clinical Outcomes ◽  
Lewy Body ◽  
Dementia With Lewy Bodies ◽  
Random Effect ◽  
Neurofibrillary Tangle ◽  
Lewy Bodies ◽  
Tau Proteins ◽  
Search Term ◽  
Prospective Longitudinal

Background:Neurofibrillary tangles (NFT) formed by tau proteins, a pathological hallmark of Alzheimer’s disease, are a common co-pathology in people with Lewy body dementias, which include dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD).Aims:To investigate the prevalence of tau in Lewy body dementia, and its association with clinical outcomes.Methods:A systematic search was conducted on Medline, Embase and PubMed using the search term: (“dementia with Lewy bodies” OR “diffuse Lewy body disease”) AND (“tau protein” OR “tauopathy” OR “neurofibrillary tangle”). A total of 42 articles met the inclusion criteria for data extraction. Random-effect meta-analyses were performed to obtain pooled estimates for prevalence, and risk ratios (RR) or standardised mean difference (SMD) for clinical outcomes measures.Results:Braak NFT stage ≥III was observed in 67% (n=1399, 95%CI 59%-76%) of DLB and 52% (n=429, 95%CI 26%-78%) of PDD at autopsy. Abnormal CSF phosphorylated-tau levels were present in 27% (n=705, 95%CI 23%-30%) of DLB and 15% (n=172, 95%CI 5%-24%) of PDD cases. Higher tau burden in DLB was associated with reduced likelihood of manifesting visual hallucinations (RR 0.56; 95%CI 0.40-0.77) and motor parkinsonism (RR 0.62; 95%CI 0.40-0.98), lower diagnostic accuracy of DLB during life (RR 0.49; 95%CI 0.38-0.64) and worse cognition prior to death (SMD 0.60; 95%CI 0.44-0.76).Conclusions:Tau is more common in DLB than PDD and may negatively impact clinical diagnostic accuracy in people with DLB. Prospective longitudinal studies are needed to understand the roles of co-morbid neuropathologies in Lewy body dementias.

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.

scholarly journals Increased expression of pathological markers in Parkinson’s disease dementia post-mortem brains compared to dementia with Lewy bodies

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Haitao Tu ◽  
Zhi Wei Zhang ◽  
Lifeng Qiu ◽  
Yuning Lin ◽  
Mei Jiang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lewy Body ◽  
Dementia With Lewy Bodies ◽  
Neurofibrillary Tangle ◽  
Temporal Cortex ◽  
Lewy Bodies ◽  
Post Mortem ◽  
Protein Markers ◽  
Age Related

Abstract Background Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are common age-related neurodegenerative diseases comprising Lewy body spectrum disorders associated with cortical and subcortical Lewy body pathology. Over 30% of PD patients develop PD dementia (PDD), which describes dementia arising in the context of established idiopathic PD. Furthermore, Lewy bodies frequently accompany the amyloid plaque and neurofibrillary tangle pathology of Alzheimer’s disease (AD), where they are observed in the amygdala of approximately 60% of sporadic and familial AD. While PDD and DLB share similar pathological substrates, they differ in the temporal onset of motor and cognitive symptoms; however, protein markers to distinguish them are still lacking. Methods Here, we systematically studied a series of AD and PD pathogenesis markers, as well as mitochondria, mitophagy, and neuroinflammation-related indicators, in the substantia nigra (SN), temporal cortex (TC), and caudate and putamen (CP) regions of human post-mortem brain samples from individuals with PDD and DLB and condition-matched controls. Results We found that p-APPT668 (TC), α-synuclein (CP), and LC3II (CP) are all increased while the tyrosine hydroxylase (TH) (CP) is decreased in both PDD and DLB compared to control. Also, the levels of Aβ42 and DD2R, IBA1, and p-LRRK2S935 are all elevated in PDD compared to control. Interestingly, protein levels of p-TauS199/202 in CP and DD2R, DRP1, and VPS35 in TC are all increased in PDD compared to DLB. Conclusions Together, our comprehensive and systematic study identified a set of signature proteins that will help to understand the pathology and etiology of PDD and DLB at the molecular level.

scholarly journals Diagnostic accuracy of 123I-FP-CIT SPECT in possible dementia with Lewy bodies

2009 ◽  
Vol 194 (1) ◽  
pp. 34-39 ◽  
Author(s):  
John T. O'Brien ◽  
Ian G. McKeith ◽  
Zuzana Walker ◽  
Klaus Tatsch ◽  
Jan Booij ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Diagnostic Accuracy ◽  
Lewy Body ◽  
Dementia With Lewy Bodies ◽  
Photon Emission ◽  
Lewy Bodies ◽  
Lewy Body Dementia ◽  
Emission Computed Tomography

Background123I-FP-CIT SPECT (single photon emission computed tomography) can help in the differential diagnosis of probable dementia with Lewy bodies (Lewy body dementia) and Alzheimer's disease.AimsOur aim was to determine the accuracy of 123I-FP-CIT SPECT in diagnosing people with possible dementia with Lewy bodies.MethodWe undertook a 12-month follow-up of 325 individuals with probable or possible Lewy body or non-Lewy body dementia who had previously undergone 123I-FP-CIT SPECT. A consensus panel masked to SPECT findings, established diagnosis at 12 months in 264 people.ResultsOf 44 people with possible dementia with Lewy bodies at baseline, at follow-up the diagnosis for 19 people was probable dementia with Lewy bodies (43%), in 7 people non-Lewy body dementia (16%) and for 18 individuals it remained possible dementia with Lewy bodies (41%). Of the 19 who at follow-up were diagnosed with probable dementia with Lewy bodies, 12 had abnormal scans at baseline (sensitivity 63%); all 7 individuals with a possible diagnosis who were diagnosed as having Alzheimer's disease at follow-up had normal scans (specificity 100%).ConclusionsOur findings confirm the diagnostic accuracy of 123I-FP-CIT SPECT in distinguishing Lewy body from non-Lewy body dementia and also suggest a clinically useful role in diagnostically uncertain cases, as an abnormal scan in a person with possible dementia with Lewy bodies is strongly suggestive of dementia with Lewy bodies.

scholarly journals Progression to Dementia in Mild Cognitive Impairment With Lewy Bodies or Alzheimer Disease

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012024
Author(s):  
Calum A. Hamilton ◽  
Fiona E. Matthews ◽  
Paul C. Donaghy ◽  
John-Paul Taylor ◽  
John T. O'Brien ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Lewy Body ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Lewy Body Disease ◽  
Hazard Ratio ◽  
Clinical Progression ◽  
Diagnostic Characteristics ◽  
Prospective Longitudinal

ObjectiveTo determine whether mild cognitive impairment with Lewy bodies or Alzheimer's disease differ in their rates of clinical progression to dementia, we undertook longitudinal observation of mild cognitive impairment cases with detailed clinical assessment of Lewy body diagnostic characteristics.MethodsTwo prospective longitudinal cohorts combining to 111 individuals aged 60 years or older with mild cognitive impairment were assessed annually to track cognitive and clinical progression, including the presence or absence of core clinical features and proposed biomarkers of dementia with Lewy bodies. Multi-state modelling was used to assess the associations of diagnostic characteristics of dementia with Lewy bodies with clinical progression from mild cognitive impairment to dementia, with death as a competing outcome.ResultsAfter a mean follow-up of 2.2 years (range = 1–6.7 years), 38/111 (34%) of the participants progressed to dementia: 10 with AD, 3 with possible dementia with Lewy bodies and 25 with probable dementia with Lewy bodies. The presence of any Lewy body disease characteristic was associated with an increased hazard of transition to dementia; this risk further increased as more diagnostic characteristics were observed (Hazard ratio = 1.33 per characteristic, 95% CI: 1.11–1.60), and was especially high for those experiencing complex visual hallucinations (Hazard ratio = 1.98, 95% CI: 0.92–4.29) or cognitive fluctuations (Hazard ratio = 3.99, 95% CI: 2.03–7.84).ConclusionsDiagnostic characteristics of Lewy body disease are associated with an increased risk of transition from mild cognitive impairment to dementia.

Characterization of dementia with Lewy bodies (DLB) and mild cognitive impairment using the Lewy body dementia module (LBD‐MOD)

2021 ◽  
Author(s):  
James E. Galvin ◽  
Stephanie Chrisphonte ◽  
Iris Cohen ◽  
Keri K. Greenfield ◽  
Michael J. Kleiman ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Lewy Body ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Lewy Body Dementia

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

Neuropathology

2020 ◽  
pp. 77-98
Author(s):  
Johannes Attems ◽  
Kurt A. Jellinger
Keyword(s):  
Frontotemporal Lobar Degeneration ◽  
Dementia With Lewy Bodies ◽  
Prion Diseases ◽  
Hippocampal Sclerosis ◽  
Neurofibrillary Tangle ◽  
Lewy Bodies ◽  
Corticobasal Degeneration ◽  
Amyloid Angiopathy ◽  
Argyrophilic Grain ◽  
Cerebral Amyloid

This chapter describes the main neuropathological features of the most common age-associated neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and dementia with Lewy bodies, as well as other less frequent ones such as multiple system atrophy, Pick’s disease, corticobasal degeneration, progressive supranuclear palsy, argyrophilic grain disease, neurofibrillary tangle-dominant dementia, frontotemporal lobar degeneration with TDP-43 pathology, and Huntington’s disease. Likewise, cerebral amyloid angiopathy, hippocampal sclerosis, vascular dementia, and prion diseases are described. A main aim of this chapter is to assist the reader in interpreting neuropathological reports; hence criteria for the neuropathological classifications of the major diseases are provided. One section covers general considerations on neurodegeneration, and basic pathophysiological mechanisms of tau, amyloid-β‎, α‎-synuclein, TDP-43, and prions are briefly described in the sections on the respective diseases. Finally, one section is dedicated to cerebral multimorbidity, and a view on currently emerging neuropathological methods is given.

scholarly journals A toxic subset of soluble α-synuclein species in dementia with Lewy body

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Diana L Castillo-Carranza
Keyword(s):  
Cerebral Cortex ◽  
Lewy Body ◽  
Dementia With Lewy Bodies ◽  
Dementia With Lewy Body ◽  
Lewy Bodies

This scientific commentary refers to ‘Analysis of α-synuclein species enriched from cerebral cortex of humans with sporadic dementia with Lewy bodies’, by Sanderson et al. (https://doi.org/10.1093/braincomms/fcaa010).

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