scholarly journals Genetics Contributes to Concomitant Pathology and Clinical Presentation in Dementia with Lewy Bodies

2021 ◽  
pp. 1-11
Author(s):  
Sven J. van der Lee ◽  
Inger van Steenoven ◽  
Marleen van de Beek ◽  
Niccolo Tési ◽  
Iris E. Jansen ◽  
...  
Keyword(s):  
Dementia With Lewy Bodies ◽  
Mini Mental State Examination ◽  
Disease Duration ◽  
Age At Onset ◽  
Lewy Bodies ◽  
Risk Scores ◽  
Clinical Measures ◽  
Core Symptoms ◽  
State Examination

Background: Dementia with Lewy bodies (DLB) is a complex, progressive neurodegenerative disease with considerable phenotypic, pathological, and genetic heterogeneity. Objective: We tested if genetic variants in part explain the heterogeneity in DLB. Methods: We tested the effects of variants previously associated with DLB (near APOE, GBA, and SNCA) and polygenic risk scores for Alzheimer’s disease (AD-PRS) and Parkinson’s disease (PD-PRS). We studied 190 probable DLB patients from the Alzheimer’s dementia Cohort and compared them to 2,552 control subjects. The p-tau/Aβ 1–42 ratio in cerebrospinal fluid was used as in vivo proxy to separate DLB cases into DLB with concomitant AD pathology (DLB-AD) or DLB without AD (DLB-pure). We studied the clinical measures age, Mini-Mental State Examination (MMSE), and the presence of core symptoms at diagnosis and disease duration. Results: We found that all studied genetic factors significantly associated with DLB risk (all-DLB). Second, we stratified the DLB patients by the presence of concomitant AD pathology and found that APOE ɛ4 and the AD-PRS associated specifically with DLB-AD, but less with DLB-pure. In addition, the GBA p.E365K variant showed strong associated with DLB-pure and less with DLB-AD. Last, we studied the clinical measures and found that APOE ɛ4 associated with reduced MMSE, higher odds to have fluctuations and a shorter disease duration. In addition, the GBA p.E365K variant reduced the age at onset by 5.7 years, but the other variants and the PRS did not associate with clinical features. Conclusion: These finding increase our understanding of the pathological and clinical heterogeneity in DLB.

Long-Term Use of Rivastigmine in Patients With Dementia With Lewy Bodies: An Open-Label Trial

2001 ◽  
Vol 13 (2) ◽  
pp. 199-205 ◽  
Author(s):  
Janet Grace ◽  
Sarah Daniel ◽  
Timothy Stevens ◽  
K. K. Shankar ◽  
Zuzanna Walker ◽  
...  
Keyword(s):  
Dementia With Lewy Bodies ◽  
Mini Mental State Examination ◽  
Neuropsychiatric Symptoms ◽  
Lewy Bodies ◽  
Neuropsychiatric Inventory ◽  
Short Term ◽  
Open Label ◽  
Open Label Trial ◽  
State Examination

Patients with dementia with lewy bodies (DLB) have progressive deficits in cognition, parkinsonism, and neuropsychiatric symptoms. Cholinesterase inhibitors have been used to ameliorate cognitive decline and neuropsychiatric symptoms in short-term trials. In this study, patients with DLB were treated with rivastigmine up to 96 weeks. Improvement from baseline was seen in cognitive function as measured by the Mini-Mental State Examination (MMSE), and neuropsychiatric symptoms as measured by the Neuropsychiatric Inventory (NPI) over the first 24 weeks of treatment. By 96 weeks, neither the MMSE scores nor the NPI scores were significantly worse than at baseline.

Montreal Cognitive Assessment and Mini-Mental State Examination performance in patients with mild-to-moderate dementia with Lewy bodies, Alzheimer's disease, and normal participants in Taiwan

2013 ◽  
Vol 25 (11) ◽  
pp. 1839-1848 ◽  
Author(s):  
Carol Sheei-Meei Wang ◽  
Ming-Chyi Pai ◽  
Pai-Lien Chen ◽  
Nien-Tsen Hou ◽  
Pei-Fang Chien ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mental State ◽  
Cognitive Assessment ◽  
Dementia With Lewy Bodies ◽  
Mini Mental State Examination ◽  
Lewy Bodies ◽  
Montreal Cognitive Assessment ◽  
Operating Characteristics ◽  
State Examination

ABSTRACTBackground:The aim of this study was to examine and test the sensitivity, specificity, and threshold scores of the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) and determine those that best correspond to a clinical diagnosis of dementia with Lewy bodies (DLB).Methods:Sixty-seven Alzheimer's disease (AD), 36 DLB, and 62 healthy participants without dementia (NC), aged 60 to 90, were enrolled. All three groups took the MoCA and MMSE tests at the same time. The Cochran–Mantel–Haenszel tests and receiver operating characteristics curve analysis were used to compare the different neuropsychological test results among the groups.Results:The cut-off point of the MoCA for AD was 21/22 with a sensitivity of 95.5% and a specificity of 82.3% (area under the curve (AUC): 0.945), and the cut-off point for DLB was 22/23 with a sensitivity of 91.7% and a specificity of 80.6% (AUC: 0.932). For the MMSE, the cut-off points for AD and for DLB from NC were all 24/25, with a sensitivity of 88.1% and a specificity of 85.5% for AD (AUC: 0.92), and a sensitivity of 77.8% and a specificity of 85.5% for DLB (AUC: 0.895). After controlling sex, age, and education, AD and DLB had lower scores in all MoCA subscales than the NC group (p < 0.05), except for the orientation and naming in DLB. In addition, AD had a lower score in the MoCA orientation (p = 0.03) and short-term memory (p = 0.02) than did DLB.Conclusions:The MoCA is a more sensitive instrument than the MMSE to screen AD or DLB patients from non-dementia cases.

scholarly journals Mini-Mental State Examination: Avaliação dos Novos Dados Normativos no Rastreio e Diagnóstico do Défice Cognitivo

2016 ◽  
Vol 29 (4) ◽  
pp. 240 ◽  
Author(s):  
Isabel Santana ◽  
Diana Duro ◽  
Raquel Lemos ◽  
Vanessa Costa ◽  
Miguel Pereira ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Mental State ◽  
Dementia With Lewy Bodies ◽  
Normative Data ◽  
Mini Mental State Examination ◽  
Lewy Bodies ◽  
State Examination

<p><strong>Introduction:</strong> The Mini-Mental State Examination is the most commonly used cognitive screening test. In Portugal, the cut-off scores are defined according to literacy groups, but different proposals have been recommended by more representative studies. We therefore propose to confirm the influence of demographical variables, such as age and education, in the subject’s performance; evaluating the discriminant ability of the new normative data; and to further examine the diagnostic acuity of the validated cut-off scoring for mild cognitive impairment and for the most prevalent types of dementia.<br /><strong>Material and Methods:</strong> Our study includes 1 441 educated subjects, divided into seven subgroups: Mild cognitive impairment, Alzheimer’s disease, frontotemporal dementia, vascular dementia, dementia with Lewy bodies, community-controls and memory clinic-controls.<br /><strong>Results:</strong> Altogether age and education explain 10.4% of the Mini-Mental State Examination results variance, with both variables contributing significantly to the results’ prediction. The diagnostic acuity based on the most recent normative data was always higher than the one obtained through the validation cut-off scoring, revealing an overall excellent specificity (superior to 90%) and different sensitivity values: excellent for mild Alzheimer’s disease (91%), good for dementia with Lewy Bodies (78%) and low for mild cognitive impairment (65%), frontotemporal dementia and vascular dementia (55%).<br /><strong>Discussion and Conclusions:</strong> The performance on the Mini-Mental State Examination is influenced by age and education, supporting the use of normative data that consider those variables. With this approach, the Mini-Mental State Examination could be a sensitive and specific instrument for the Alzheimer’s disease screening among all healthcare levels. Nevertheless, its diagnostic acuity is limited in other conditions frequently seen in memory clinics, such as Mild Cognitive Impairment and other types of dementia.</p>

Dementia With Lewy Bodies Treated With Rivastigmine: Effects on Cognition, Neuropsychiatric Symptoms, and Sleep

2001 ◽  
Vol 13 (3) ◽  
pp. 277-288 ◽  
Author(s):  
Lara E. Maclean ◽  
Chris C. Collins ◽  
E. Jane Byrne
Keyword(s):  
Dementia With Lewy Bodies ◽  
Mini Mental State Examination ◽  
Psychiatric Symptoms ◽  
Neuropsychiatric Symptoms ◽  
Case Series ◽  
Lewy Bodies ◽  
Symptomatic Treatment ◽  
Additional Information ◽  
Dementia Syndrome ◽  
State Examination

Dementia with Lewy bodies (DLB) is a common cause of the dementia syndrome. Symptomatic treatment of the fluctuating cognition, visual hallucinations, and sleep distrubance that characterize this condition is challenging; neuroleptics are relatively contraindicated. We describe eight patients fulfilling the consensus diagnostic criteria for probable DLB who were treated with rivastigmine. Clinical features rated were: cognition by the Modified Mini-Mental State Examination (3MS); and behavioral and psychiatric symptoms by the Neuropsychiatric Inventory (NPI). Additional information was obtained from family and nursing reports. Seven patients showed resolution or improvement in cognition and neuropsychiatric symptoms as demonstrated by improvement in their 3MS and NPI scores. They also became more independent in mobility and activities of daily living, and the majority returned to live in their own home. Of the seven patients with sleep disruption, six improved. One case had no improvement in his symptomatology and the rivastigmine was stopped. Outcomes in this case series suggest that rivastigmine is well tolerated in clinical practice.

Dementia with Lewy bodies—associated ß-synuclein mutations V70M and P123H cause mutation-specific neuropathological lesions

2021 ◽  
Author(s):  
Maryna Psol ◽  
Sofia Guerin Darvas ◽  
Kristian Leite ◽  
Sameehan U Mahajani ◽  
Mathias Bähr ◽  
...  
Keyword(s):  
Neuronal Network ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Sporadic Case ◽  
Network Activity ◽  
Proteinase K ◽  
Neuronal Network Activity ◽  
Distinct Disease

Abstract ß-Synuclein (ß-Syn) has long been considered to be an attenuator for the neuropathological effects caused by the Parkinson’s disease-related α-Synuclein (α-Syn) protein. However, recent studies demonstrated that overabundant ß-Syn can form aggregates and induce neurodegeneration in CNS neurons in vitro and in vivo, albeit at a slower pace as compared to α-Syn. Here we demonstrate that ß-Syn mutants V70M, detected in a sporadic case of Dementia with Lewy Bodies (DLB), and P123H, detected in a familial case of DLB, robustly aggravate the neurotoxic potential of ß-Syn. Intriguingly, the two mutations trigger mutually exclusive pathways. ß-Syn V70M enhances morphological mitochondrial deterioration and degeneration of dopaminergic and non-dopaminergic neurons, but has no influence on neuronal network activity. Conversely, ß-Syn P123H silences neuronal network activity, but does not aggravate neurodegeneration. ß-Syn WT, V70M and P123H formed proteinase K (PK) resistant intracellular fibrils within neurons, albeit with less stable C-termini as compared to α-Syn. Under cell free conditions, ß-Syn V70M demonstrated a much slower pace of fibril formation as compared to WT ß-Syn, and P123H fibrils present with a unique phenotype characterized by large numbers of short, truncated fibrils. Thus, it is possible that V70M and P123H cause structural alterations in ß-Syn, that are linked to their distinct neuropathological profiles. The extent of the lesions caused by these neuropathological profiles is almost identical to that of overabundant α-Syn, and thus likely to be directly involved into etiology of DLB. Over all, this study provides insights into distinct disease mechanisms caused by mutations of ß-Syn.

P2-191: IN VIVO MEASUREMENT OF CHOLINERGIC BASAL FOREBRAIN ATROPHY IN DEMENTIA WITH LEWY BODIES

2014 ◽  
Vol 10 ◽  
pp. P541-P541
Author(s):  
Michel J. Grothe ◽  
Christina Schuster ◽  
Florian Bauer ◽  
Johannes Prudlo ◽  
Stefan Teipel
Keyword(s):  
Basal Forebrain ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
In Vivo Measurement ◽  
Cholinergic Basal Forebrain

Single-subject SPM FDG-PET patterns predict risk of dementia progression in Parkinson disease

Neurology ◽  
2018 ◽  
Vol 90 (12) ◽  
pp. e1029-e1037 ◽  
Author(s):  
Andrea Pilotto ◽  
Enrico Premi ◽  
Silvia Paola Caminiti ◽  
Luca Presotto ◽  
Rosanna Turrone ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Fdg Pet ◽  
Cognitive Assessment ◽  
Disease Duration ◽  
Age At Onset ◽  
Statistical Parametric Mapping ◽  
Lewy Bodies ◽  
Single Subject ◽  
Incident Dementia

ObjectiveTo evaluate the statistical parametric mapping (SPM) procedure for fluorodeoxyglucose (FDG)-PET imaging as a possible single-subject marker of progression to dementia in Parkinson disease (PD).MethodsFifty-four consecutive patients with PD without dementia (age at onset of 59.9 ± 10.1 years, disease duration of 5.3 ± 3.4 years) entered the study. The patients underwent an extensive motor and cognitive assessment and a single-subject FDG-PET SPM evaluation at baseline. A 4-year follow-up provided disease progression and dementia diagnosis.ResultsThe FDG-PET SPM was evaluated by 2 expert raters allowing the identification of a “typical PD pattern” in 29 patients, whereas 25 patients presented with “atypical patterns,” namely, dementia with Lewy bodies (DLB)-like (n = 12), Alzheimer disease (AD)-like (n = 6), corticobasal syndrome (CBS)-like (n = 5), and frontotemporal dementia (FTD)-like (n = 2). At 4-year follow-up, 13 patients, all showing atypical brain metabolic patterns at baseline, progressed to dementia (PD dementia). The DLB- and AD-like SPM patterns were the best predictor for incident dementia (p < 0.005, sensitivity 85%, specificity 88%), independently from demographics or cognitive baseline classification.ConclusionsThis study suggests that FDG-PET SPM at the single-subject level might help in identifying patients with PD at risk of developing dementia.

In vivo Prevalence of Alzheimer Biomarkers in Dementia with Lewy Bodies

2019 ◽  
Vol 47 (4-6) ◽  
pp. 289-296
Author(s):  
George P. Paraskevas ◽  
Anastasia Bougea ◽  
Vasilios C. Constantinides ◽  
Mara Bourbouli ◽  
Olga Petropoulou ◽  
...  
Keyword(s):  
Dementia With Lewy Bodies ◽  
Lewy Bodies
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