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Background Increasing evidence supports the use of plasma biomarkers of amyloid, tau, neurodegeneration, and neuroinflammation for diagnosis of dementia. However, their performance for positive and differential diagnosis of dementia with Lewy bodies (DLB) in clinical settings is still uncertain. Methods We conducted a retrospective biomarker study in two tertiary memory centers, Paris Lariboisière and CM2RR Strasbourg, France, enrolling patients with DLB ( n  = 104), Alzheimer’s disease (AD, n  = 76), and neurological controls (NC, n  = 27). Measured biomarkers included plasma Aβ40/Aβ42 ratio, p-tau181, NfL, and GFAP using SIMOA and plasma YKL-40 and sTREM2 using ELISA. DLB patients with available CSF analysis ( n  = 90) were stratified according to their CSF Aβ profile. Results DLB patients displayed modified plasma Aβ ratio, p-tau181, and GFAP levels compared with NC and modified plasma Aβ ratio, p-tau181, GFAP, NfL, and sTREM2 levels compared with AD patients. Plasma p-tau181 best differentiated DLB from AD patients (ROC analysis, area under the curve [AUC] = 0.80) and NC (AUC = 0.78), and combining biomarkers did not improve diagnosis performance. Plasma p-tau181 was the best standalone biomarker to differentiate amyloid-positive from amyloid-negative DLB cases (AUC = 0.75) and was associated with cognitive status in the DLB group. Combining plasma Aβ ratio, p-tau181 and NfL increased performance to identify amyloid copathology (AUC = 0.79). Principal component analysis identified different segregation patterns of biomarkers in the DLB and AD groups. Conclusions Amyloid, tau, neurodegeneration and neuroinflammation plasma biomarkers are modified in DLB, albeit with moderate diagnosis performance. Plasma p-tau181 can contribute to identify Aβ copathology in DLB.

Background In dementia with Lewy bodies (DLB), autonomic and neurosensory disorders can precede neurocognitive symptoms by several years. Improving knowledge of these symptoms is essential to avoid associated complications and could reveal potential diagnostic biomarkers and shed light on the pathophysiological mechanisms involved in the early stages of the disease. Methods Within the AlphaLewyMA cohort, 142 probable DLB patients at the mild cognitive impairment or dementia stages were screened for 10 autonomic and three neurosensory disorders, at 0, 6, 12, 18, 24, 36, 48, 60, 72, 84 and 96 months of follow-up, using a standardized questionnaire and a test for neurogenic orthostatic hypotension. We described the prevalence and evolution over time of these disorders. To explore their neuroanatomical correlates, we performed whole-brain voxel-based morphometry (VBM) analyses on grey matter volumes in a subsample of 116 patients with MRI data. Results The mean age was 71, and 51% were men. Reports of autonomic and neurosensory disorders were very common in our main sample. As some fluctuated during follow-up, repeated screening had a major impact on their prevalence, with 95.7% of the patients declaring an autonomic disorder at least once during the follow-up and 76.8% a neurosensory disorder. The six most frequent symptoms over the follow-up were rhinorrhoea (79.3%), dry mouth (73.3%), sexual dysfunction (70.6%), neurogenic orthostatic hypotension (68.9%), urinary dysfunction (68.0%) and constipation (67.2%). In VBM analysis, dryness (whether ocular, nasal or oral) and severe taste disorders were associated with lower grey matter volumes in the left insula and in the left putamen and caudate nucleus, respectively. Conclusion Reports of autonomic and neurosensory disorders were very common and some seemed to fluctuate, highlighting the need for regular, systematic screening. Among these disorders, several symptoms little studied so far in DLB turned out to be the most frequently reported by our patients (rhinorrhoea, dry mouth and sexual dysfunction) and could provide interesting clues for diagnosis. VBM analysis may support an involvement of the insula and certain basal ganglia in dryness-type symptoms and taste disorders. Further prospective studies combining self-reporting and objective measures are needed to refine our results.

Background Dementia with Lewy bodies (DLB) is characterized by insular atrophy, which occurs at the early stage of the disease. Damage to the insula has been associated with disorders reflecting impairments of the most fundamental components of the self, such as anosognosia, which is a frequently reported symptom in patients with Lewy bodies (LB). The purpose of this study was to investigate modifications of the self-concept (SC), another component of the self, and to identify neuroanatomical correlates, in prodromal to mild DLB. Methods Twenty patients with prodromal to mild DLB were selected to participate in this exploratory study along with 20 healthy control subjects matched in terms of age, gender, and level of education. The Twenty Statements Test (TST) was used to assess the SC. Behavioral performances were compared between LB patients and control subjects. Three-dimensional magnetic resonance images (MRI) were acquired for all participants and correlational analyses were performed using voxel-based morphometry (VBM) in whole brain and using a mask for the insula. Results The behavioral results on the TST showed significantly impaired performances in LB patients in comparison with control subjects ( p  < .0001). Correlational analyses using VBM revealed positive correlations between the TST and grey matter volume within insular cortex, right supplementary motor area, bilateral inferior temporal gyri, right inferior frontal gyrus, and left lingual gyrus, using a threshold of p  = .001 uncorrected, including total intracranial volume (TIV), age, and MMSE as nuisance covariates. Additionally, correlational analysis using a mask for the insula revealed positive correlation with grey matter volume within bilateral insular cortex, using a threshold of p  = .005. Conclusions The behavioral results confirm the existence of SC impairments in LB patients from the prodromal stage of the disease, compared to matched healthy controls. As we expected, VBM analyses revealed involvement of the insula, among that of other brain regions, already known to be involved in other self-components. While this study is exploratory, our findings provide important insights regarding the involvement of the insula within the self, confirming the insula as a core region of the self-networks, including for high-order self-representations such as the SC.

In digital communication, synchronization between transmitter and receiver is essential for ensuring proper system performance. Error in the receiver symbol time sampling can significantly increase the bit error rate to unacceptable levels. In this paper, we propose a multilayer radial basis function neural network symbol-timing recovery (MRBFNN-STR). The proposed solution has been implemented for a 64-QAM (quadrature and amplitude modulation) system. Results show that the MRBFNN-STR improves the modulation error ratio up to 3.4 dB and reduces the bit error rate by almost one order of magnitude for 100 ppm (part per million) clock offset and signal to noise ratios above 25 dB compared to the classic widely used Gardner-Farrow’s approach. The MRBFNN is able to follow the system dynamics and to generalize, presenting good performance even when under operational situations not presented during the training phase (different clock offset, signal to noise ratio, etc.) and with lower-order modulation schemes, such as 32-QAM, 16-QAM, and QPSK (quadrature phase shift keying), without retraining. Due to the parallel nature of the MRBFNN architecture and the reduced complexity required for inference, it can be efficiently implemented in hardware and easily integrated into communication receivers, representing a feasible solution for receiver time synchronization.

Background Increasing evidence supports the use of plasma biomarkers of amyloid, tau, neurodegeneration and neuroinflammation for diagnosis of dementia. However, their performance for positive and differential diagnosis of dementia with Lewy bodies (DLB) in clinical settings is still uncertain. Method We conducted a retrospective biomarker study in two tertiary memory centers, Paris Lariboisière and CM2RR Strasbourg, France, enrolling patients with DLB (n=104), Alzheimer’s disease (AD, n=76) and neurological controls (NC, n=27). Measured biomarkers included plasma Aβ ratio, p‐tau181, NfL and GFAP using SIMOA and plasma YKL‐40 and sTREM2 using ELISA. DLB patients with available CSF analysis (n=90) were stratified according to their CSF Aβ profile. Results DLB patients displayed altered plasma Aβ ratio, p‐tau181 and GFAP levels compared with NC and altered plasma Aβ ratio, p‐tau181, GFAP, NfL and sTREM2 levels compared with AD patients (Figure 1, a‐f). Plasma p‐tau181 best differentiated DLB from AD patients (ROC analysis, area under the curve [AUC]=0.80) and NC (AUC=0.78) and combining biomarkers did not improve diagnosis performance. Plasma p‐tau181 was the best standalone biomarker to differentiate amyloid‐positive from amyloid‐negative cases (AUC=0.75) and was associated with cognitive status. Combining plasma Aβ ratio, p‐tau181 and NfL increased performance to identify amyloid copathology (AUC=0.79). Principal component analysis identified different segregation patterns of plasma biomarkers in AD and DLB groups (Figure 1, g‐h). Conclusion Amyloid, tau, neurodegeneration and neuroinflammation plasma biomarkers are modified in DLB, albeit with moderate diagnosis performance. Plasma p‐tau181 has potential contribute to identify Aβ copathology in DLB.

ApoE4 as a risk factor for dementia with Lewy bodies (DLB) is still an issue. We sought to determine the involvement of ApoE4 according to different clinical parameters in our cohort of patients from Strasbourg, France. ApoE genotyping was performed on the AlphaLewyMA cohort. In this cohort, 197 patients were genotyped: 105 DLB patients, 37 Alzheimer’s disease (AD) patients, 29 patients with AD/DLB comorbidity, and 26 control subjects (CS). The groups of patients were also classified according to the stage of evolution of the disease: prodromal or demented. We analyzed other parameters in relation to ApoE4 status, such as years of education (YOE) and Alzheimer CSF biomarkers. We observed a higher proportion of ApoE4 carriers in the AD (51.4%) and AD/DLB (72.4%) groups compared to the DLB (25.7%) and CS (11.5%) groups ( p  < 0.0001). We found a correlation between age at disease onset and YOE in the AD group ( p  = 0.039) but not in the DLB group ( p  = 0.056). Interestingly, in the DLB group, the subgroup of patients with high YOE (≥ 11) had significantly more patients with ApoE4 than the subgroup with low YOE (< 11). AD biomarkers did not seem to be impacted by the presence of ApoE4 , except for Aβ42: DLB ApoE4 -positive demented patients showed a more marked Aβ42 decrease. ApoE4 does not appear to be a risk factor for “pure” DLB patients. These results suggest a strong link between ApoE4 and amyloidopathy and consequently with AD. Trial registration: AlphaLewyMa, Identifier: NCT01876459, date of registration: June 12, 2013.

Spectrum sensing is one of the major challenges for commercial development of cognitive radio systems, since the detection of the presence of a primary user is a complex task that requires high reliability. This work proposes a signal classifier capable of detecting and identifying a primary user signal on a given channel of the radio spectrum. The proposed approach combines eigen-decomposition techniques and neural networks not only to decide about the presence of a primary user, but also to identify the primary user signal type, a feature that is not encountered in the current approaches proposed in literature. Besides the advantage of identifying the primary user type, the proposed method also considerably reduces the computational cost of the detection process. The proposed classification method has been applied to the development of five primary user signal Classification Modules, which includes wireless microphone, orthogonal frequency-division multiplexing and Digital Video Broadcasting-Terrestrial signals. The results show that the proposed classifier correctly detects and identifies the primary users, even under low signal to noise ratio and multipath scenarios.

Background Isolated subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) are the prodromal phases of dementia with Lewy bodies (DLB). MEMENTO is a nationwide study of patients with SCI and MCI with clinic, neuropsychology, biology, and brain imaging data. We aimed to compare SCI and MCI patients with symptoms of prodromal DLB to others in this study at baseline. Methods Participants of the French MEMENTO cohort study were recruited for either SCI or MCI. Among them, 892 were included in the Lewy sub-study, designed to search specifically for symptoms of DLB. Probable prodromal DLB diagnosis (pro-DLB group) was done using a two-criteria cutoff score among the four core clinical features of DLB. This Pro-DLB group was compared to two other groups at baseline: one without any core symptoms (NS group) and the one with one core symptom (1S group). A comprehensive cognitive battery, questionnaires on behavior, neurovegetative and neurosensory symptoms, brain 3D volumetric MRI, CSF, FDG PET, and amyloid PET were done. Results The pro-DLB group comprised 148 patients (16.6%). This group showed more multidomain (59.8%) MCI with slower processing speed and a higher proportion of patients with depression, anxiety, apathy, constipation, rhinorrhea, sicca syndrome, and photophobia, compared to the NS group. The pro-DLB group had isolated lower P-Tau in the CSF (not significant after adjustments for confounders) and on brain MRI widening of sulci including fronto-insular, occipital, and olfactory sulci (FDR corrected), when compared to the NS group. Evolution to dementia was not different between the three groups over a median follow-up of 2.6 years. Conclusions Patients with symptoms of prodromal DLB are cognitively slower, with more behavioral disorders, autonomic symptoms, and photophobia. The occipital, fronto-insular, and olfactory bulb involvement on brain MRI was consistent with symptoms and known neuropathology. The next step will be to study the clinical, biological, and imaging evolution of these patients. Trial registration Clinicaltrials.gov , NCT01926249

Dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) are often associated with depressive symptoms from the prodromal stage. The aim of the present study was to investigate the neuroanatomical correlates of depression in prodromal to mild DLB patients compared with AD patients. Eighty-three DLB patients, 37 AD patients, and 18 healthy volunteers were enrolled in this study. Depression was evaluated with the Mini International Neuropsychiatric Interview (MINI), French version 5.0.0. T1-weighted three-dimensional anatomical images were acquired for all participants. Regression and comparison analyses were conducted using a whole-brain voxel-based morphometry (VBM) approach on the grey matter volume (GMV). DLB patients presented a significantly higher mean MINI score than AD patients ( p  = 0.004), 30.1% of DLB patients had clinical depression, and 56.6% had a history of depression, while 0% of AD patients had clinical depression and 29.7% had a history of depression. VBM regression analyses revealed negative correlations between the MINI score and the GMV of right prefrontal regions in DLB patients ( p  < 0.001, uncorrected). Comparison analyses between DLB patients taking and those not taking an antidepressant mainly highlighted a decreased GMV in the bilateral middle/inferior temporal gyrus ( p  < 0.001, uncorrected) in treated DLB patients. In line with the literature, our behavioral analyses revealed higher depression scores in DLB patients than in AD patients. We also showed that depressive symptoms in DLB are associated with decreased GMV in right prefrontal regions. Treated DLB patients with long-standing depression would be more likely to experience GMV loss in the bilateral middle/inferior temporal cortex. These findings should be taken into account when managing DLB patients.

INTRODUCTION The cognitive and neuroimaging evolution during dementia with Lewy bodies (DLB) from the prodromal phase (Pro‐DLB; subjective cognitive impairment [SCI] to mild cognitive impairment [MCI]) according to amyloid beta (Aβ) status is poorly understood. METHODS The decline of Lewy‐Memento patients with SCI or MCI was compared according to Aβ status across four groups: Pro‐DLB, prodromal Alzheimer's disease (Pro‐AD), Pro‐DLB+AD, and a group without prodromal DLB and AD (no symptoms [NS]). We observed the evolution of cognitive, functional, quality of life measures, brain volumetry, and metabolism on fluorodeoxyglucose positron emission tomography. RESULTS In the Pro‐DLB and Pro‐DLB+AD groups, Aβ+ patients had more cognitive and functional decline than the Aβ– patients. In the Pro‐AD and NS groups, Aβ+ patients had more functional decline. Aβ+ Pro‐AD showed a greater volume decline of the brain (left insula). DISCUSSION The presence of amyloid lesions worsens very prodromal DLB patients over time, both cognitively and functionally, but without increasing atrophy. Highlights Patients at a very prodromal stage, subjective cognitive impairment or mild cognitive impairment, had a clinical diagnosis of either prodromal Alzheimer's disease (Pro‐AD), prodromal dementia with Lewy bodies (Pro‐DLB), Pro‐DLB+AD, or no diagnosis. Amyloid beta positive (Aβ+) patients had more functional decline, whatever the group. Aβ+ DLB patients (Pro‐DLB and Pro‐DLB+AD) had more global cognitive (Mini‐Mental State Examination) decline. Aβ+ Pro‐AD patients showed a greater volume decline of the left insula.