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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., (© 2024. The Author(s).)

Objectives: We have previously demonstrated difficulties in written production in dementia with Lewy bodies (DLB) patients. We now aim to determine the neural correlates of writing production in DLB, combining clinical data and structural MRI measures., Method: Sixteen prodromal to mild DLB patients were selected to participate in the study. The GREMOTS test was used to assess writing production. Using three-dimensional T1 brain MRI images, correlations between the GREMOTS test and grey matter (GM) volume were performed using voxel-based morphometry (VBM; SPM12, XjView and Matlab R2021b softwares)., Results: VBM analysis (p < 0.001, uncorrected) revealed a positive and significant correlation between both left anterior insula and left supramarginal gyrus GM volumes and DLB patients' ability to write logatoms using the phonological route. The handwriting deficit was negatively and significantly correlated to the supplementary motor area. The parkinsonism-like characteristics of agraphia were negatively and significantly correlated with both right anterior and right posterior cerebellum GM volumes. Our study also revealed a negative and significant correlation between grammatical spelling impairments and an area of the orbitofrontal gyrus, and a negative and significant correlation between supramarginal gyrus and general slowness in dictation tasks., Conclusion: Writing disorders in early DLB patients appears to be GM decreases in several brain regions, such as the left anterior insula, the left supramaginal gyrus, as well as two areas of the right cerebellum., (© 2024 John Wiley & Sons Ltd.)

Dementia with Lewy bodies (DLB) patients show few significant macroscopic structural changes, especially at the early stages of the disease, making quantitative MRI especially interesting to explore more subtle changes that are not detectable by conventional volumetric techniques. Microstructural alterations have been reported in DLB at the dementia stage, but no study to date was conducted in prodromal patients. Here, quantitative MRI data were collected from 46 DLB prodromal patients and 20 healthy elderly subjects, who also underwent a detailed clinical examination including the Mayo Clinic Fluctuation Scale. We conducted voxel-wise between-group comparisons in diffusion tensor imaging (DTI) metrics and in R2* mapping, along with a multivariate analysis combining the two modalities. We highlighted multiple grey matter and white matter microstructural changes in DLB patients at the prodromal stage, compared to control subjects. Our multivariate analysis identified three distinct regional patterns of DTI and R2* changes (anterior, anteromedial, posterior) in DLB patients, that could reflect different neuropathological processes across brain regions. We also observed an association between R2* alterations in the thalamus, and the severity of fluctuations, in the DLB group. These preliminary findings are promising and require future investigations to better understand the biological underpinnings of microstructural alterations., (© 2021 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

We investigated whether cerebrovascular disease contributes to neurodegeneration and clinical phenotype in dementia with Lewy bodies (DLB). Regional cortical thickness and subcortical gray matter volumes were estimated from structural magnetic resonance imaging (MRI) in 165 DLB patients. Cortical and subcortical infarcts were recorded and white matter hyperintensities (WMHs) were assessed. Subcortical only infarcts were more frequent (13.3%) than cortical only infarcts (3.1%) or both subcortical and cortical infarcts (2.4%). Infarcts, irrespective of type, were associated with WMHs. A higher WMH volume was associated with thinner orbitofrontal, retrosplenial, and posterior cingulate cortices, smaller thalamus and pallidum, and larger caudate volume. A higher WMH volume was associated with the presence of visual hallucinations and lower global cognitive performance, and tended to be associated with the absence of probable rapid eye movement sleep behavior disorder. Presence of infarcts was associated with the absence of parkinsonism. We conclude that cerebrovascular disease is associated with gray matter neurodegeneration in patients with probable DLB, which may have implications for the multifactorial treatment of probable DLB., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To determine the prevalence, localization and associations of cerebral microbleeds (CMB) in dementia with Lewy bodies (DLB) with its core clinical symptoms and cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD). We hypothesize DLB patients with CMB have increased amyloid burden compared to those without CMB, which could also translate into clinical differences., Methods: Retrospective cross-sectional analysis from the AlphaLewyMA study (https://clinicaltrials.gov/ct2/show/NCT01876459). Patients underwent a standardized protocol of brain MRI including 3D T1, 3D FLAIR and T2* sequences, and CSF analysis of AD biomarkers. CMB and white matter hyperintensities (WMHs) were visually assessed in prodromal and mild demented (DLB, N = 91) and AD (AD, N = 67) patients., Results: CMB prevalence did not differ among DLB and AD (24.2% vs. 37.3%; p = 0.081). CMB were mainly distributed in lobar topographies in both DLB (74%) and AD (89%). CMB in DLB was not associated with global cognitive performance, executive functioning, speed of information processing, or AD CSF biomarkers. Similarly, there was no difference regarding specific clinical symptoms: fluctuations, psychotic phenomena, sleep behavior disorder and Parkinsonism between DLB patients with and without CMB. AD patients with CMB had increased burden of WMH compared to those without (2.1 ± 0.86 vs. 1.4 ± 0.89; p = 0.005), according to Fazekas scale, whereas no significant difference was observed in DLB patients (1.68 ± 0.95 vs. 1.42 ± 0.91; p = 0.25)., Conclusion: CMB were equally prevalent with similar topographic distribution in both DLB and AD patients. CMB was not associated with CSF AD biomarkers or core clinical symptoms in DLB., (© 2020 John Wiley & Sons Ltd.)

Background: Fluctuations are one of the core clinical features characterizing dementia with Lewy bodies (DLB). They represent a determining factor for its diagnosis and strongly impact the quality of life of patients and their caregivers. However, the neural correlates of this complex symptom remain poorly understood. This study aimed to investigate the structural and functional changes in DLB patients, compared to Alzheimer's disease (AD) patients and healthy elderly subjects, and their potential links with fluctuations., Methods: Structural and resting-state functional MRI data were collected from 92 DLB patients, 70 AD patients, and 22 control subjects, who also underwent a detailed clinical examination including the Mayo Clinic Fluctuation Scale. Gray matter volume changes were analyzed using whole-brain voxel-based morphometry, and resting-state functional connectivity was investigated using a seed-based analysis, with regions of interest corresponding to the main nodes of the salience network (SN), frontoparietal network (FPN), dorsal attention network (DAN), and default mode network (DMN)., Results: At the structural level, fluctuation scores in DLB patients did not relate to the atrophy of insular, temporal, and frontal regions typically found in this pathology, but instead showed a weak correlation with more subtle volume reductions in different regions of the cholinergic system. At the functional level, the DLB group was characterized by a decreased connectivity within the SN and attentional networks, while the AD group showed decreases within the SN and DMN. In addition, higher fluctuation scores in DLB patients were correlated to a greater connectivity of the SN with the DAN and left thalamus, along with a decreased connectivity between the SN and DMN, and between the right thalamus and both the FPN and DMN., Conclusions: Functional connectivity changes, rather than significant gray matter loss, could play an important role in the emergence of fluctuations in DLB. Notably, fluctuations in DLB patients appeared to be related to a disturbed external functional connectivity of the SN, which may lead to less relevant transitions between different cognitive states in response to internal and environmental stimuli. Our results also suggest that the thalamus could be a key region for the occurrence of this symptom.

Background: Cortical and subcortical cognitive impairments are usually found in dementia with Lewy bodies (DLB). Roughly, they comprise visuo-constructive/executive function and attention/processing speed impairments, whereas memory would remain relatively spared. In this study, we focused on the neuro-anatomical substrates of attention and processing speed, which is still poorly understood. For the purpose of the study, we examined the correlations between behavioral scores measuring the speed of processing and the degree of cerebral atrophy in patients with prodromal to moderate DLB., Methods: Ninety-three prodromal to moderate DLB patients (mean MMSE = 25.5) were selected to participate in the study as well as 28 healthy elderly subjects (mean MMSE = 28.9), matched in terms of age and educational level. The Trail Making Test A (TMTA) and the Digit Symbol Substitution Test (DSST) were used to assess attention and processing speed. Behavioral performances were compared between patients and healthy control subjects. Three-dimensional MRI images were acquired for all participants, and correlational analyses were performed in the patient group using voxel-based morphometry (VBM)., Results: The behavioral results on both the TMTA (p = .026) and the DSST (p < .001) showed significantly impaired performances in patients in comparison with control subjects. In addition, correlational analyses using VBM revealed for the TMTA negative correlations in the caudate nucleus (left cluster peak significant at .05 FWE corrected), the putamen, the left thalamus, and the subthalamic nuclei (p < .05 FDR corrected). Some positive correlations associated with the DSST were found in the right inferior frontal gyrus, the left thalamus, and the left cerebellum (p < .001 uncorrected)., Conclusions: The behavioral results are in line with the literature on the DLB cognitive profile and confirm the existence of attention and processing speed impairment. Interestingly, VBM analysis revealed the involvement of the basal ganglia, in particular, the left caudate nucleus, which is part of the attention cerebral network, suggesting an important role of this structure for attentional processing speed. This also suggests the clinical implication of damage in this region relatively early in the course of the disease.

Diffuse atrophy including the insula was previously demonstrated in dementia with Lewy bodies (DLB) patients but little is known about the prodromal stage of DLB (pro-DLB). In this prospective study, we used SPM8-DARTEL to measure gray matter (GM) and white matter (WM) atrophy in pro-DLB patients (n = 54), prodromal Alzheimer's disease (pro-AD) patients (n = 16), DLB patients at the stage of dementia (mild-DLB) (n = 15), and Alzheimer's disease patients at the stage of dementia (mild-AD) (n = 28), and compared them with healthy elderly controls (HC, n = 22). Diminished GM volumes were found in bilateral insula in pro-DLB patients, a trend to significance in right hippocampus and parahippocampal gyrus in pro-AD patients, in left insula in mild-DLB patients, and in medial temporal lobes and insula in mild-AD patients. The comparison between prodromal groups did not showed any differences. The comparison between groups with dementia revealed atrophy around the left middle temporal gyrus in mild-AD patients. Reduced WM volume was observed in mild-DLB in the pons. The insula seems to be a key region in DLB as early as the prodromal stage. MRI studies looking at perfusion, and functional and anatomical connectivity are now needed to better understand the role of this region in DLB.

Abstract 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