Neuroanatomical substrates of depression in dementia with Lewy bodies and Alzheimer's disease.

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.

Who am I with my Lewy bodies? The insula as a core region of the self-concept networks.

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.

Neural basis of writing in prodromal to mild dementia with lewy bodies.

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.

Involvement of ApoE4 in dementia with Lewy bodies in the prodromal and demented stages: evaluation of the Strasbourg cohort.

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 Aß42: DLB ApoE4-positive demented patients showed a more marked Aß42 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.

Neural correlates of photophobia in prodromal and mild dementia with Lewy bodies.

BACKGROUND AND OBJECTIVES: Photophobia is a sensory disturbance provoked by light. Little is known about the association between photophobia and dementia with Lewy bodies (DLB). In this study, we aimed to identify the frequency and the neural basis of photophobia in prodromal and mild DLB. METHODS: One hundred and thirteen DLB patients, 53 Alzheimer's disease (AD) patients, 20 AD and DLB patients, 31 patients with other neurocognitive diseases (including prodromal and mild demented patients), and 31 healthy elderly controls were included in this case-control study. Photophobia was systematically looked for and compared between groups. Among a selection of 77 DLB patients, we used voxel-based morphometry (VBM) to compare those with and those without photophobia (gray matter volume; SPM12, XjView, and Matlab R2021b software). RESULTS: The frequency of photophobia was higher in the DLB group (47.3%) than in the other groups (p = 0.002). The photophobia questionnaire score was higher in the DLB group than in the AD group (p = 0.001). Comparison between DLB patients with and those without photophobia showed decreased gray matter in the photophobia subgroup, in the right precentral cortex, in the eyelid motor region of Penfield's homunculus (p = 0.007, family-wise error [FWE] corrected). CONCLUSIONS: Photophobia is a quite frequent symptom of prodromal and mild DLB. The neural basis of photophobia in DLB involves the right precentral cortex, which could have a role in the decrease of cerebral excitability, but also the motricity of the eyelids.

Memory Outcome in Prodromal and Mild Dementia with Lewy Bodies and Alzheimer's Disease: A Longitudinal Study.

BACKGROUND: Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are likely to induce memory impairments from the prodromal stage but, to our knowledge, no longitudinal study of these patients' memory profile has been conducted to date. OBJECTIVE: The aim of our study was to describe the characteristics and the evolution of the long-term memory profile of patients with prodromal and mild DLB and AD. METHODS: We collected verbal (RL/RI-16) and visual (DMS48) memory scores from 91 DLB patients, 28 AD patients, 15 patients with both conditions (DLB/AD), and 18 healthy control subjects at their inclusion visit and at 12, 24, and 48 months. RESULTS: On the RL/RI-16, DLB patients performed better than AD patients in terms of total recall (p < 0.001), delayed total recall (p < 0.001), recognition (p = 0.031), and loss of information over time (p = 0.023). On the DMS48, differences between these two groups were not significant (p > 0.05). Longitudinally, the memory performance of DLB patients was stable over 48 months, unlike that of AD patients. CONCLUSION: Four indicators were relevant to distinguish between DLB and AD patients in terms of memory performance: DLB patients benefitted greatly from semantic cueing, their recognition and consolidation abilities were well-preserved, and both their verbal and visual memory performance remained remarkably stable over four years. However, no performance differences between DLB and AD patients were found regarding visual memory, either qualitatively (memory profile) or quantitatively (severity of impairment), indicating the lesser relevance of this test in distinguishing between these two diseases.

Me, Myself and My Insula: An Oasis in the Forefront of Self-Consciousness.

The insula is a multiconnected brain region that centralizes a wide range of information, from the most internal bodily states, such as interoception, to high-order processes, such as knowledge about oneself. Therefore, the insula would be a core region involved in the self networks. Over the past decades, the question of the self has been extensively explored, highlighting differences in the descriptions of the various components but also similarities in the global structure of the self. Indeed, most of the researchers consider that the self comprises a phenomenological part and a conceptual part, in the present moment or extending over time. However, the anatomical substrates of the self, and more specifically the link between the insula and the self, remain unclear. We conducted a narrative review to better understand the relationship between the insula and the self and how anatomical and functional damages to the insular cortex can impact the self in various conditions. Our work revealed that the insula is involved in the most primitive levels of the present self and could consequently impact the self extended in time, namely autobiographical memory. Across different pathologies, we propose that insular damage could engender a global collapse of the self.

Cerebral and cognitive modifications in retired professional soccer players: TC-FOOT protocol, a transverse analytical study.

INTRODUCTION: Soccer is the most popular sport in the world. This contact sport carries the risk of exposure to repeated head impacts in the form of subconcussions, defined as minimal brain injuries following head impact, with no symptom of concussion. While it has been suggested that exposure to repetitive subconcussive events can result in long-term neurophysiological modifications, and the later development of chronic traumatic encephalopathy, the consequences of these repeated impacts remain controversial and largely unexplored in the context of soccer players. METHODS AND ANALYSIS: This is a prospective, single-centre, exposure/non-exposure, transverse study assessing the MRI and neuropsychological abnormalities in professional retired soccer players exposed to subconcussive impacts, compared with high-level athletes not exposed to head impacts. The primary outcome corresponds to the results of MRI by advanced MRI techniques (diffusion tensor, cerebral perfusion, functional MRI, cerebral volumetry and cortical thickness, spectroscopy, susceptibility imaging). Secondary outcomes are the results of the neuropsychological tests: number of errors and time to complete tests. We hypothesise that repeated subconcussive impacts could lead to morphological lesions and impact on soccer players' cognitive skills in the long term. ETHICS AND DISSEMINATION: Ethics approval has been obtained and the study was approved by the Comité de Protection des Personnes (CPP) No 2021-A01169-32. Study findings will be disseminated by publication in a high-impact international journal. Results will be presented at national and international imaging meetings. TRIAL REGISTRATION NUMBER: NCT04903015.

Prodromal characteristics of dementia with Lewy bodies: baseline results of the MEMENTO memory clinics nationwide cohort.

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.

Does culture shape our understanding of others' thoughts and emotions? An investigation across 12 countries.

Measures of social cognition have now become central in neuropsychology, being essential for early and differential diagnoses, follow-up, and rehabilitation in a wide range of conditions. With the scientific world becoming increasingly interconnected, international neuropsychological and medical collaborations are burgeoning to tackle the global challenges that are mental health conditions. These initiatives commonly merge data across a diversity of populations and countries, while ignoring their specificity. OBJECTIVE: In this context, we aimed to estimate the influence of participants' nationality on social cognition evaluation. This issue is of particular importance as most cognitive tasks are developed in highly specific contexts, not representative of that encountered by the world's population. METHOD: Through a large international study across 18 sites, neuropsychologists assessed core aspects of social cognition in 587 participants from 12 countries using traditional and widely used tasks. RESULTS: Age, gender, and education were found to impact measures of mentalizing and emotion recognition. After controlling for these factors, differences between countries accounted for more than 20% of the variance on both measures. Importantly, it was possible to isolate participants' nationality from potential translation issues, which classically constitute a major limitation. CONCLUSIONS: Overall, these findings highlight the need for important methodological shifts to better represent social cognition in both fundamental research and clinical practice, especially within emerging international networks and consortia. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Therapeutic trials and Dementia with Lewy bodies: a systematic review of the literature.

BACKGROUND: Cognitive diseases with Lewy bodies occur in two forms: dementia with Lewy bodies (DLB) and Parkinsonian dementia (PD), which follows the evolution of Parkinson disease. There is currently no curative treatment for these cognitive diseases with Lewy bodies. Therapeutic trials in DLB are rare, due to the fact that the disease has only recently been described and the first international diagnostic criteria have only recently been published (1996). METHOD: This article proposes a synthesis of the therapeutic trials carried out into DLB in the last five years, including PD patients, using the Clinicaltrials.gov and Pubmed.gov databases. RESULTS: We identified 35 therapeutic trials on ClinicalTrials.gov and 14 on PubMed. In line with our temporal criteria, 21 trials were analysed. Of the 11 completed trials with reported results, two drugs showed positive results: two trials with zonisamide (phases 2 and 3) showed improvements in Parkinsonian syndrome and one trial with neflamapimod (phase 2) showed improvements in cognition and walking. CONCLUSION: In recent years, there has been an increase in therapeutic research into DLB, which is consistent with the prevalence of this disease - approximately 200,000 patients in France. Compared to other cognitive neurodegenerative diseases, therapeutic research is largely insufficient, although the proportion of positive trials is significant. Effective treatment to modify the course of the disease would have significant consequences for patients and their relatives.

[Therapeutic trials in dementia with Lewy bodies: a systematic review of the literature]. / Les essais thérapeutiques dans la maladie à corps de Lewy : revue systématique de la littérature.

BACKGROUND: Cognitive diseases with Lewy bodies occur in two forms: dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), which follows the progression of Parkinson's disease. There is currently no curative treatment for these cognitive diseases with Lewy bodies. Therapeutic trials in DLB are rare, due to the recent description of the disease as well as its first international diagnostic criteria (1996). METHOD: This article proposes a synthesis of the therapeutic trials carried out in DLB in the last 5 years, including PDD patients with DLB patients, using the Clinicaltrials.gov and Pubmed.gov databases. RESULTS: We identified 35 therapeutic trials on Clinical Trials and 14 on PubMed. According to our temporal criteria, 21 trials were analyzed. Among the 11 completed trials with reported results, two molecules showed positive results: two trials with zonisamide (phase 2 and 3) showed a gain on parkinsonism and one trial with neflamapimod (phase 2) a gain on cognition and walking. CONCLUSION: In recent years, there has been an increase in the therapeutic research effort in DLB, which is consistent with the prevalence of this disease - approximately 200,000 patients in France. Compared to other cognitive neurodegenerative diseases, therapeutic research is largely insufficient, whereas the proportion of positive trials is important. An effective disease modifying would have strong consequences for the patient and the relatives.

The hippocampal region is necessary for text comprehension and memorization: a combined VBM/DTI study in neuropsychological patients.

According to the Construction-Integration model (Kintsch 1988; Kintsch 1998), two forms of representation are activated during the reading and the comprehension of a text: 1) the text base, which includes semantic propositions and 2) the situation model, corresponding to the integration of the information contained in the text to the memories and knowledge of the reader. Functional neuroimaging studies in healthy subjects have shown that the text base is underpinned by frontal regions and lateral temporal regions whereas the situation model would rather depend on the posterior cingulate cortex, the precuneus and other regions depending on the dimension studied. However, the brain regions highlighted so far were only involved in comprehension and not necessary for this cognitive ability. For the first time, we explored the brain structures necessary to understand texts using a combined VBM/DTI approach in neuropsychological patients with whom we obtained comprehension scores (text base and situation model) after the reading of narrative texts. To our great surprise and contrary to our hypotheses, which were based on the results of functional neuroimaging studies, our own results show that it is the hippocampal region that is necessary to activate and memorize/remember the text base and the situation model. The highlighting of a link between the integrity of a portion of the uncinate fasciculus which is well known to play a role in semantic processing and the performance scores of the text base suggests that the hippocampal region is necessary not only for the retrieval of the text base and of the situation model thanks to episodic memory, but also for the activation of the text base during the reading and the comprehension of a text.

Differential diagnostic value of total alpha-synuclein assay in the cerebrospinal fluid between Alzheimer's disease and dementia with Lewy bodies from the prodromal stage.

BACKGROUND: Several studies have investigated the value of alpha-synuclein assay in the cerebrospinal fluid (CSF) of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) patients in the differential diagnosis of these two pathologies. However, very few studies have focused on this assay in AD and DLB patients at the MCI stage. METHODS: All patients were enrolled under a hospital clinical research protocol from the tertiary Memory Clinic (CM2R) of Alsace, France, by an experienced team of clinicians. A total of 166 patients were included in this study: 21 control subjects (CS), 51 patients with DLB at the prodromal stage (pro-DLB), 16 patients with DLB at the demented stage (DLB-d), 33 AD patients at the prodromal stage (pro-AD), 32 AD patients at the demented stage (AD-d), and 13 patients with mixed pathology (AD+DLB). CSF levels of total alpha-synuclein were assessed using a commercial enzyme-linked immunosorbent assay (ELISA) for alpha-synuclein (AJ Roboscreen). Alzheimer's biomarkers (t-Tau, P-Tau, Aß42, and Aß40) were also measured. RESULTS: The alpha-synuclein assays showed a significant difference between the AD and DLB groups. Total alpha-synuclein levels were significantly higher in AD patients than in DLB patients. However, the ROC curves show a moderate discriminating power between AD and DLB (AUC = 0.78) which does not improve the discriminating power of the combination of Alzheimer biomarkers (AUC = 0.95 with or without alpha-synuclein). Interestingly, the levels appeared to be altered from the prodromal stage in both AD and DLB. CONCLUSIONS: The modification of total alpha-synuclein levels in the CSF of patients occurs early, from the prodromal stage. The adding of alpha-synuclein total to the combination of Alzheimer's biomarker does not improve the differential diagnosis between AD and DLB. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01876459 (AlphaLewyMa).

The insula, a grey matter of tastes: a volumetric MRI study in dementia with Lewy bodies.

BACKGROUND: Despite the growing number of discoveries during the past decades about its functions, the insula remains a mysterious 'island'. In addition to its involvement in basic functions such as gustation and interoception, the insular cortex is now considered a key region for integrated functions such as emotion/motivation processing, decision-making and self-consciousness. We hypothesized that this structure, standing at the crossroads of such functions, could ground personal tastes in general, beyond food preferences and aesthetic judgements. Given that dementia with Lewy bodies is characterized by a focal atrophy within the insular cortex from the early stages, this condition provides an opportunity to test such a hypothesis. METHODS: We developed a questionnaire to assess potential changes in personal tastes, submitted it to a cohort of 23 patients with early-stage dementia with Lewy bodies and compared their questionnaire results to those of 20 age-matched healthy controls. Furthermore, we performed a global and regional neuroimaging study to test for a potential correlation between the patients' scores for changes in personal tastes and their insular cortex volumes. RESULTS: Our results indicate that the patients presented significant changes in personal tastes compared to the controls, in both food and non-food domains. Moreover, imaging analyses confirmed the involvement of the insular cortex atrophy in the changes in personal tastes using global analysis, and in both food and non-food domains using regional analysis. CONCLUSIONS: These results bring new insights into the role of the insula as a 'grey matter of tastes', this structure supporting personal preferences in general, beyond the food domain. The insular cortex could be involved through its role in motivational processes by the representation of subjective awareness of bodily states during the phenomenological experience of stimulus appraisal. However, we also argue that it could support the abstract representations of personal tastes as self-concepts, acutely exemplifying embodied cognition. Finally, the questionnaire on changes in tastes could constitute an interesting tool to help early diagnosis of dementia with Lewy bodies and to assess insular dysfunction more generally.

Pay attention to the basal ganglia: a volumetric study in early dementia with Lewy bodies.

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.

Memories defining the self in Alzheimer's disease.

There is a debate over the extent to which personal identity or the self is preserved in patients with Alzheimer's disease (AD). Autobiographical memory deficits at early stages of AD could contribute to altering patients' self. However, the nature of the relationship between autobiographical memory deficits and the self in AD has not been much investigated experimentally. In the present study, we aimed to investigate the integrative meaning of self-defining memories (SDMs) in early stages of AD and to analyse its relationship with the self-concept. The results showed that, when compared to the control group, AD patients less frequently extracted meaning from their SDMs and the meaning was less frequently tied to the self. Patients exhibited some altered aspects of the self-concept (i.e., complexity and strength), though some other components still persisted (i.e., valence and certainty). Correlation analyses showed that the impaired integrative meaning in the AD group was correlated with some changes in self-concept. We suggest that integrative meaning may act as a bridge between autobiographical memories and the self-concept, with reduced integration abilities appearing as a potential mechanism for the deterioration of the self-concept in AD.

Cognitive profile in prodromal disease (dementia) with Lewy bodies.

This paper reviews findings on cognition in prodromal dementia with Lewy bodies (DLB). The issue of differential diagnosis between DLB and Alzheimer's disease (AD) on the one hand, and Parkinson's disease (PD) on the other hand, at prodromal stages of the diseases is discussed. The cognitive profile of prodromal DLB is also evaluated in terms of cognitive deficits and « cognitive weaknesses ¼ (low performances although in normal range). Findings suggest that visuo-constructive tests and verbal fluency are particularly relevant to dfferentiate DLB from AD. A similar finding is evident when comparing prodromal DLB and PD. Attentional, executive and visuo-constructive tests appear to be the best predictor of DLB. Moreover, investigation of the cognitive profile in prodromal DLB highlights that cognitive difficulties are diffuse. Yet it appears that difficulties in cortical visual abilities and executive functions are prominent and likely to account, at least partially, for cognitive disturbances observed in neuropsychological tests assessing other cognitive functions.

Insular cognitive impairment at the early stage of dementia with Lewy bodies: a preliminary study.

BACKGROUND: The anterior part of the insula appears atrophied in the early stage of dementia with Lewy bodies (DLB) whereas it is not the case in early Alzheimer's disease (AD). OBJECTIVE: The objective of this study was to develop neuropsychological markers supposed to reflect insular dysfunction, which would facilitate early diagnosis of DLB, namely in comparison to AD. METHODS: Twelve patients with DLB, 12 patients with AD, all at the stage of Mild cognitive impairment (MCI) or mild dementia, as well as 10 Controls subjects (CS) participated in the study. Cognitive functions supposedly related to the insula were evaluated with a battery of tests: a facial expression recognition test, a test assessing the feeling of disgust with images, a test evaluating idioms' comprehension, an empathy questionnaire and a questionnaire screening for disgusting behaviors. RESULTS: Compared to AD patients and CS, DLB patients experienced less disgust when they were shown disgusting images, whereas their ability to recognize emotional expression of disgust appeared to be preserved. Furthermore, DLB patients seemed less empathetic than AD patients. Finally, compared to CS, DLB patients were less effective to provide an intuitive decision about idioms' signification since they needed significantly more time to answer. CONCLUSION: This preliminary study suggests the existence of a potential « insular cognitive impairment ¼ profile in DLB at the early stage. These results provide interesting leads to develop tools facilitating the differential diagnosis of DLB and AD.

Henry, where have you lost your Self?

The Self is a complex construct encompassing distinct components, including episodic and semantic autobiographical memory, the Self-concept, and the subjective sense of Self, which highest level consists of Self-awareness. The neuro-anatomical correlates are complex, and it is debated as to whether a common region could support these different components of the Self, with a particular interest for the cortical midline structures and the medial prefrontal cortex (MPFC). Alzheimer's disease (AD) constitutes an interesting model for the study of Self as autobiographical memory typically deteriorates as the disease progresses. Here, we report the unexpected case of Henry, a patient with MCI due to AD who was unable to produce any personal autobiographical memories, nor describe his Self-concept, had a poor personal semantic memory, and disclosed unusual anosognosia for this stage of the disease. His cognitive performance was compared to a group of matched AD patients and a group of healthy controls confirming that the main components of his Self were degraded. We hypothesized that it was due to a marked atrophy within the cortical midline, as visually assessed on his MRI. We further elucidated these findings through Voxel-based morphometry analysis, which confirmed a significant atrophy of the MPFC that was specific to this patient. Moreover, this revealed significant atrophy within the bilateral insular cortex. Given the stage of the disease, the degradation of the Self is unlikely to be accounted for by deficient mnemonic processes, especially as the presence of discrete temporal atrophy was noted. We suggest that this specific pattern of MPFC and insular atrophy is responsible for the systematic collapse of the patient's Self, through the breakdown of the subjective sense of Self, which is proposed as a prerequisite to all other components, according to the model proposed by Prebble, Addis, and Tippett (2013).