scholarly journals The Effect of GBA Mutations and APOE Polymorphisms on Dementia with Lewy Bodies in Ashkenazi Jews

2021 ◽  
pp. 1-9
Author(s):  
Tamara Shiner ◽  
Anat Mirelman ◽  
Yevgenia Rosenblum ◽  
Gitit Kavé ◽  
Mali Gana Weisz ◽  
...  
Keyword(s):  
Dementia With Lewy Bodies ◽  
Rating Scale ◽  
Age Of Onset ◽  
Lewy Bodies ◽  
Clinical Impact ◽  
Motor Dysfunction ◽  
Ashkenazi Jews ◽  
Gba Gene ◽  
E4 Allele ◽  
Gba Mutations

Background: Glucocerebrosidase (GBA) gene mutations and APOE polymorphisms are common in dementia with Lewy bodies (DLB), however their clinical impact is only partially elucidated. Objective: To explore the clinical impact of mutations in the GBA gene and APOE polymorphisms separately and in combination, in a cohort of Ashkenazi Jewish (AJ) patients with DLB. Methods: One hundred consecutively recruited AJ patients with clinically diagnosed DLB underwent genotyping for GBA mutations and APOE polymorphisms, and performed cognitive and motor clinical assessments. Results: Thirty-two (32%) patients with DLB were carriers of GBA mutations and 33 (33%) carried an APOE ɛ4 allele. GBA mutation carriers had a younger age of onset (mean [SD] age, 67.2 years [8.9] versus 71.97 [5.91]; p = 0.03), poorer cognition as assessed by the Mini-Mental State Examination (21.41 [6.9] versus 23.97 [5.18]; p <  0.005), and more severe parkinsonism as assessed with the Unified Parkinson’s Disease Rating Scale motor part III (34.41 [13.49] versus 28.38 [11.21]; p = 0.01) compared to non-carriers. There were statistically significant interactions between the two genetic factors, so that patients who carried both a mild GBA mutation and the APOE ɛ4 allele (n = 9) had more severe cognitive (p = 0.048) and motor dysfunction (p = 0.037). Conclusion: We found a high frequency of both GBA mutations and the APOE ɛ4 allele among AJ patients with DLB, both of which have distinct effects on the clinical disease phenotype, separately and in combination.

scholarly journals High Frequency of GBA Gene Mutations in Dementia With Lewy Bodies Among Ashkenazi Jews

2016 ◽  
Vol 73 (12) ◽  
pp. 1448 ◽  
Author(s):  
Tamara Shiner ◽  
Anat Mirelman ◽  
Mali Gana Weisz ◽  
Anat Bar-Shira ◽  
Elissa Ash ◽  
...  
Keyword(s):  
High Frequency ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Gene Mutations ◽  
Ashkenazi Jews ◽  
Gba Gene

scholarly journals Traumatic Brain Injury and Age of Onset of Dementia with Lewy Bodies

2018 ◽  
Vol 66 (2) ◽  
pp. 717-723 ◽  
Author(s):  
Trung P. Nguyen ◽  
Jeff Schaffert ◽  
Christian LoBue ◽  
Kyle B. Womack ◽  
John Hart ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Dementia With Lewy Bodies ◽  
Age Of Onset ◽  
Lewy Bodies

scholarly journals Effects of Donepezil on Extrapyramidal Symptoms in Patients with Dementia with Lewy Bodies: A Secondary Pooled Analysis of Two Randomized-Controlled and Two Open-Label Long-Term Extension Studies

2015 ◽  
Vol 40 (3-4) ◽  
pp. 186-198 ◽  
Author(s):  
Etsuro Mori ◽  
Manabu Ikeda ◽  
Masaki Nakagawa ◽  
Hideaki Miyagishi ◽  
Hideo Yamaguchi ◽  
...  
Keyword(s):  
Dementia With Lewy Bodies ◽  
Rating Scale ◽  
Multivariate Logistic Regression Analysis ◽  
Lewy Bodies ◽  
Pooled Analysis ◽  
Extrapyramidal Symptoms ◽  
Open Label ◽  
Predisposing Factor ◽  
Baseline Severity

Background/Aims: The aim of this study was to clarify the effects of donepezil on extrapyramidal symptoms in patients with dementia with Lewy bodies (DLB). Methods: Using pooled datasets from phase 2 and 3, 12-week randomized, placebo-controlled trials (RCT, n = 281) and 52-week open-label long-term extension trials (OLE, n = 241) of donepezil in DLB, the effects of donepezil on the incidence of extrapyramidal adverse events (AEs) and on the Unified Parkinson's Disease Rating Scale (UPDRS) part III were assessed, and potential baseline factors affecting the AEs were explored. Results: The RCT analysis did not show significant differences between the placebo and active (3, 5, and 10 mg donepezil) groups in extrapyramidal AE incidence (3.8 and 6.5%, p = 0.569) and change in the UPDRS (mean ± SD: -0.2 ± 4.3 and -0.6 ± 6.5, p = 0.562). In the OLE analysis (5 and 10 mg donepezil), the incidence did not increase chronologically; all AEs leading to a dose reduction or discontinuation except one were relieved. The UPDRS was unchanged for 52 weeks. An exploratory multivariate logistic regression analysis of the RCTs revealed that donepezil treatment was not a significant factor affecting the AEs. Baseline severity of parkinsonism was a predisposing factor for worsening of parkinsonism without significant interactions between donepezil and baseline severity. Conclusion: DLB can safely be treated with donepezil without relevant worsening of extrapyramidal symptoms, but treatment requires careful attention to symptom progression when administered to patients with relatively severe parkinsonism.

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.

scholarly journals Clinical and Cognitive Phenotype of Mild Cognitive Impairment Evolving to Dementia with Lewy Bodies

2015 ◽  
Vol 5 (3) ◽  
pp. 442-449 ◽  
Author(s):  
Annachiara Cagnin ◽  
Cinzia Bussè ◽  
Simona Gardini ◽  
Nela Jelcic ◽  
Caterina Guzzo ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Visual Attention ◽  
Dementia With Lewy Bodies ◽  
Rating Scale ◽  
Lewy Bodies ◽  
Object Perception ◽  
Visual Object ◽  
Visual Stream ◽  
Extrapyramidal Signs

Objective: The aim of this study was to determine which characteristics could better distinguish dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) at the mild cognitive impairment (MCI) stage, with particular emphasis on visual space and object perception abilities. Methods: Fifty-three patients with mild cognitive deficits that were eventually diagnosed with probable DLB (MCI-DLB: n = 25) and AD (MCI-AD: n = 28) at a 3-year follow-up were retrospectively studied. At the first visit, the patients underwent cognitive assessment including the Qualitative Scoring Mini Mental State Examination Pentagon Test and the Visual Object and Space Perception Battery. The Neuropsychiatric Inventory Questionnaire, Unified Parkinson's Disease Rating Scale (UPDRS) and questionnaires for cognitive fluctuations and sleep disorders were also administered. Results: The best clinical predictor of DLB was the presence of soft extrapyramidal signs (mean UPDRS score: 4.04 ± 5.9) detected in 72% of patients, followed by REM sleep behavior disorder (60%) and fluctuations (60%). Wrong performances in the pentagon's number of angles were obtained in 44% of DLB and 3.7% of AD patients and correlated with speed of visual attention. Executive functions, visual attention and visuospatial abilities were worse in DLB, while verbal episodic memory impairment was greater in AD. Deficits in the visual-perceptual domain were present in both MCI-DLB and AD. Conclusions: Poor performance in the pentagon's number of angles is specific of DLB and correlates with speed of visual attention. The dorsal visual stream seems specifically more impaired in MCI-DLB with respect to the ventral visual stream, the latter being involved in both DLB and AD. These cognitive features, associated with subtle extrapyramidal signs, should alert clinicians to a diagnostic hypothesis of DLB.

GBA Mutations Are Associated With Earlier Onset and Male Sex in Dementia With Lewy Bodies

2016 ◽  
Vol 31 (7) ◽  
pp. 1066-1070 ◽  
Author(s):  
Ana Gámez-Valero ◽  
Patricia Prada-Dacasa ◽  
Cristina Santos ◽  
Cristina Adame-Castillo ◽  
Jaume Campdelacreu ◽  
...  
Keyword(s):  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Male Sex ◽  
Gba Mutations

More Severe Functional Impairment in Dementia With Lewy Bodies Than Alzheimer Disease Is Related to Extrapyramidal Motor Dysfunction

2006 ◽  
Vol 14 (7) ◽  
pp. 582-588 ◽  
Author(s):  
Ian G. McKeith ◽  
Elise Rowan ◽  
Kristina Askew ◽  
Anitha Naidu ◽  
Louise Allan ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Functional Impairment ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Motor Dysfunction ◽  
Extrapyramidal Motor

scholarly journals [18F]-AV-1451 binding in the substantia nigra as a marker of neuromelanin in lewy body diseases

2021 ◽  
Author(s):  
Elijah Mak ◽  
Antonina Kouli ◽  
Negin Holland ◽  
Nicolas Nicastro ◽  
George Savulich ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Lewy Body ◽  
Dementia With Lewy Bodies ◽  
Disease Duration ◽  
Rating Scale ◽  
Surrogate Marker ◽  
Lewy Bodies ◽  
Lewy Body Diseases

Abstract While [18F]-AV-1451 was developed as a positron emission tomography (PET) radiotracer with high affinity for hyperphosphorylated tau, it has been proposed that loss of “off-target” [18F]-AV-1451 binding to neuromelanin in the substantia nigra could be a surrogate marker of Lewy body diseases. [18F]-AV-1451 binding was measured in the substantia nigra of patients with Parkinson’s disease (n = 35), dementia with Lewy bodies (n = 10) and separate control groups (n = 37; n = 14). Associations with motor symptoms, cognition, and disease duration were evaluated using linear regression models. The dementia with Lewy bodies group had significantly reduced substantia nigra [18F]-AV-1451 binding compared to controls after adjusting for age (p &lt; 0.05). However, there were no significant differences in substantia nigra [18F]-AV-1451 binding between Parkinson’s disease and controls. Substantia nigra [18F]-AV-1451 binding was not associated with age, disease duration, Movement Disorders Society—Unified Parkinson’s Disease Rating Scale and cognitive scores in dementia with Lewy bodies and Parkinson’s disease groups. Despite the reduction of substantia nigra [18F]-AV-1451 binding in dementia with Lewy bodies, these findings suggest that substantia nigra [18F]-AV-1451 binding has no value as a diagnostic marker in early Parkinson’s disease. Further investigations in longitudinal cohorts are warranted.

scholarly journals Neural Stem Cells Rescue Cognitive and Motor Dysfunction in a Transgenic Model of Dementia with Lewy Bodies through a BDNF-Dependent Mechanism

2015 ◽  
Vol 5 (5) ◽  
pp. 791-804 ◽  
Author(s):  
Natalie R.S. Goldberg ◽  
Jacqueline Caesar ◽  
Ashley Park ◽  
Shawn Sedgh ◽  
Gilana Finogenov ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Motor Dysfunction ◽  
Transgenic Model ◽  
Dependent Mechanism
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