Diagnostic value of CSF chromogranin A to discriminate between Alzheimer's disease and dementia with Lewy bodies.

BACKGROUND: Chromogranin A (CgA) seems to be involved in the pathophysiology of different neurodegenerative pathologies such as Alzheimer's disease (AD) and dementia with Lewy Bodies (DLB). CgA is present in the aggregates of amyloid plaques and in Lewy bodies but CgA also has a function in neuroinflammatory processes via microglia. Our objective was to determine if there is a difference in the CgA concentration in the cerebrospinal fluid (CSF) of AD and DLB patients and whether the CgA concentration can discriminate between the two diseases. METHODS: Using the previously described AlphaLewyMA cohort, we included 117 patients with a CSF CgA assay: 15 control subjects (CS group), 64 DLB patients, 17 AD patients and 21 patients with both AD and probable DLB criteria (AD/DLB group). CgA concentration was assessed using the MSD platform. RESULTS: CSF CgA was increased in the AD and AD/DLB groups compared with the DLB group (p = 0.0006 between AD and DLB, p = 0.0013 between AD/DLB and DLB). No significant difference in CgA concentration was found between DLB and CS. ROC curve analysis showed an area under the curve of 0.791 between AD and DLB. CgA concentrations were correlated with t-Tau and P-Tau regardless of the pathology (for Tau: p = 0.022 for AD; p < 0.0001 for DLB; p = 0.004 for AD/DLB; for P-Tau: p = 0.032 for AD; p < 0.0001 for DLB; p = 0.0009 for AD/DLB). Aß42 was positively correlated with CgA in the DLB group but not in the AD and AD/DLB groups (for DLB: p < 0.0001; for AD: p = 0.57; for AD/DLB: p = 0.58). CONCLUSIONS: CSF CgA concentrations are increased in AD but not in DLB and correlate with P-Tau and Tau whatever the disease. These results suggest a link between tauopathy/neurodegeneration and CgA.

Sex differences in brain atrophy in dementia with Lewy bodies.

INTRODUCTION: Sex influences neurodegeneration, but it has been poorly investigated in dementia with Lewy bodies (DLB). We investigated sex differences in brain atrophy in DLB using magnetic resonance imaging (MRI). METHODS: We included 436 patients from the European-DLB consortium and the Mayo Clinic. Sex differences and sex-by-age interactions were assessed through visual atrophy rating scales (n = 327; 73 ± 8 years, 62% males) and automated estimations of regional gray matter volume and cortical thickness (n = 165; 69 ± 9 years, 72% males). RESULTS: We found a higher likelihood of frontal atrophy and smaller volumes in six cortical regions in males and thinner olfactory cortices in females. There were significant sex-by-age interactions in volume (six regions) and cortical thickness (seven regions) across the entire cortex. DISCUSSION: We demonstrate that males have more widespread cortical atrophy at younger ages, but differences tend to disappear with increasing age, with males and females converging around the age of 75. HIGHLIGHTS: Male DLB patients had higher odds for frontal atrophy on radiological visual rating scales. Male DLB patients displayed a widespread pattern of cortical gray matter alterations on automated methods. Sex differences in gray matter measures in DLB tended to disappear with increasing age.

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.

Association of cerebral microbleeds with cerebrospinal fluid Alzheimer-biomarkers and clinical symptoms in early dementia with Lewy bodies.

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.

Environmental exposure to phthalates and dementia with Lewy bodies: contribution of metabolomics.

BACKGROUND: In neurodegenerative diseases, alongside genetic factors, the possible intervention of environmental factors in the pathogenesis is increasingly being considered. In particular, recent evidence suggests the intervention of a pesticide-like xenobiotic in the initiation of disease with Lewy bodies (DLB). OBJECTIVES: To test for the presence of pesticides or other xenobiotics in the cerebrospinal fluid (CSF) of patients with DLB. METHODS: A total of 45 patients were included in this study: 16 patients with DLB at the prodromal stage, 8 patients with DLB at the demented stage, 8 patients with Alzheimer's disease (AD) at the prodromal stage and 13 patients with AD at the demented stage. CSF was obtained by lumbar puncture and analysed by liquid chromatography-mass spectrometry. RESULTS: Among the compounds detected in greater abundance in the CSF of patients with DLB compared with patients with AD, only one had a xenobiotic profile potentially related to the pathophysiology of DLB. After normalisation and scaling, bis(2-ethylhexyl) phthalate was more abundant in the CSF of patients with DLB (whole cohort: 2.7-fold abundant in DLB, p=0.031; patients with dementia: 3.8-fold abundant in DLB, p=0.001). CONCLUSIONS: This study is the first reported presence of a phthalate in the CSF of patients with DLB. This molecule, which is widely distributed in the environment and enters the body orally, nasally and transdermally, was first introduced in the 1920s as a plasticizer. Thereafter, the first cases of DLB were described in the 1960s and 1970s. These observations suggest that phthalates may be involved in the pathophysiology of DLB.

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.

Cerebrospinal fluid Alzheimer biomarkers can be useful for discriminating dementia with Lewy bodies from Alzheimer's disease at the prodromal stage.

BACKGROUND: Differential diagnosis between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) is not straightforward, especially in the early stages of disease. We compared AD biomarkers (phospho-Tau181, total-Tau, Aß42 and Aß40) in cerebrospinal fluid (CSF) of patients with DLB and AD, focusing especially on the prodromal stage. METHODS: A total of 1221 CSF were collected in different memory centres (ePLM network) in France and analysed retrospectively. Samples were obtained from patients with prodromal DLB (pro-DLB; n=57), DLB dementia (DLB-d; n=154), prodromal AD (pro-AD; n=132) and AD dementia (n=783), and control subjects (CS; n=95). These centres use the same diagnostic procedure and criteria to evaluate the patients. RESULTS: In patients with pro-DLB, CSF Aß42 levels appeared much less disrupted than in patients at the demented stage (DLB-d) (P<0.05 CS>pro-DLB; P<0.001 CS>DLB-d). On average, Aß40 levels in patients with DLB (pro-DLB and DLB-d) were much below those in patients with pro-AD (P<0.001 DLB groups

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.

Neuroimaging of autobiographical memory in dementia with Lewy bodies: a story of insula.

Although deficits in learning and retrieving new information are well characterized in dementia with Lewy bodies, autobiographical memory has never been explored in this disease. Yet, autobiographical memory impairments are a pervasive feature of dementia, well characterized in other neurodegenerative diseases. Moreover, autobiographical memory corresponds to an extension over time of the self, which we hypothesize is altered in dementia with Lewy bodies and impairment of which could be linked to the insular atrophy occurring from an early stage of the disease. In this study, we sought to characterize autobiographical memory impairments and explore their neural correlates in dementia with Lewy bodies, on the assumption that insular damage could impact the self, including its most elaborate components, such as autobiographical memory. Twenty patients with prodromal to mild dementia with Lewy bodies were selected to participate in this exploratory study along with 20 healthy control subjects. The Autobiographical Interview was used to assess autobiographical memory. Performances were compared between patients and control subjects, and an analysis across life periods and recall conditions was performed. 3D magnetic resonance images were acquired for all participants, and correlational analyses were performed in the patient group using voxel-based morphometry. The behavioural results of the Autobiographical Interview showed that autobiographical memory performances were significantly impaired in dementia with Lewy body patients compared to control subjects in a temporally ungraded manner, for both the free recall and the specific probe conditions (P < 0.0001), though with greater improvement after probing in the patient group. Furthermore, autobiographical memory impairments were correlated with grey matter volume within right insular cortex, temporoparietal junction, precuneus, putamen, left temporal cortex, bilateral parahippocampus and cerebellum, using a threshold of P = 0.005 uncorrected. The behavioural results confirm the existence of temporally ungraded autobiographical memory impairments in dementia with Lewy bodies, from the early stage of the disease. As we expected, neuroimaging analysis revealed a role for the insula and the precuneus in autobiographical memory retrieval, two regions associated with elementary aspects of the self, among other brain regions classically associated with autobiographical memory, such as medial temporal lobe and temporoparietal junction. Our findings provide important insights regarding the involvement of the insula in the self and suggest that insular damage could lead to a global collapse of the self, including its more elaborated components, such as autobiographical memory.

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.

Plasma biomarkers of amyloid, tau, axonal, and neuroinflammation pathologies in dementia with Lewy bodies.

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 Aß40/Aß42 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 Aß profile. RESULTS: DLB patients displayed modified plasma Aß ratio, p-tau181, and GFAP levels compared with NC and modified plasma Aß 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 Aß 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 Aß copathology in DLB.

Dementia with Lewy bodies and gait neural basis: a cross-sectional study.

BACKGROUND: Dementia with Lewy Bodies (DLB) is responsible for cognitive-behavioural disorders but also for gait disorders. The latter are thought to be related to parkinsonism, but the neural bases of these disorders are not well known, especially in the early stages. The aim of this study was to investigate by volumetric Magnetic Resonance Imaging the neuronal basis of gait disorders in DLB patients, compared to Healthy Elderly Controls and Alzheimer's Disease patients. METHODS: Clinical examination with motor assessment including 10-meter walking speed, one-leg balance and Timed Up and Go test, a comprehensive neuropsychological evaluation and 3D brain Magnetic Resonance Imaging were performed on 84 DLB patients, 39 Alzheimer's Disease patients and 22 Healthy Elderly Controls. We used Statistical Parametric Mapping 12 to perform a one-sample t-test to investigate the correlation between each gait score and gray matter volume (P ≤ 0.05 corrected for family-wise error). RESULTS: We found a correlation for DLB patients between walking speed and gray matter decrease (P < 0.05, corrected for family-wise error) in caudate nuclei, anterior cingulate cortex, mid-cingulate cortex, hippocampi, supplementary motor area, right cerebellar cortex and left parietal operculum. We found no correlation with Timed Up and Go test and one-leg balance. CONCLUSION: Gait disorders are underpinned by certain classical regions such as the cerebellum and the supplementary motor area. Our results suggest there may be a motivational and emotional component of voluntary gait in DLB subjects, underpinned by the cingulate cortex, a spatial orientation component, underpinned by hippocampi and suggest the involvement of brain processing speed and parkinsonism, underpinned by the caudate nuclei. TRIAL REGISTRATION: The study protocol has been registered on ClinicalTrials.gov. (NCT01876459) on June 12, 2013.

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.

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.

Transient epileptic amnesia: a retrospective cohort study of 127 cases, including CSF amyloid and tau features.

BACKGROUND: Transient epileptic amnesia (TEA) is a late-onset epilepsy syndrome encompassing transient iterative amnesias and interictal cognitive impairment, two features that overlap with incipient neurodegenerative dementias. We, therefore, examined the yield of CSF amyloid and tau biomarkers in TEA. METHODS: In this retrospective study, 127 TEA patients with unremarkable imaging findings were divided into 2 groups, namely, CSF (n = 71) and no-CSF (n = 56). Both were compared for demographics; medical history; baseline neurological, cognitive, and behavioral features; baseline mesial temporal lobe atrophy; and cognitive follow-up at a median of 13 months. CSF samples were examined for amyloid ß-42 peptide as well as phospho-tau and total-tau levels. RESULTS: At baseline, the CSF-TEA group had significantly (p < 0.01) more frequent mild parkinsonism (42.9% vs. 20%) and cognitive concerns (31% vs. 10.7%), a more blunted sense of smell (34.3% vs. 9.4%), a lower baseline MMSE score (27 vs. 28.9), a more frequent amnestic mild cognitive impairment profile (69% vs. 42.6%), and more atrophic hippocampal changes. At follow-up, the CSF-TEA group had significantly (p < 0.01) lower MMSE scores (27.8 vs. 28.9). CSF analyses revealed amyloid and/or tau changes in 27 patients (38%), including an Alzheimer's disease (AD) profile in 17 (24%). CONCLUSIONS: This study shows a good diagnostic value of CSF sampling in a specific population of TEA with characteristics suggestive of incipient degenerative diseases (i.e., red flags). It argues for TEA being the inaugurating feature in some cases of AD. More broadly, our results suggest an etiological heterogeneity in TEA.

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.

MRI data-driven clustering reveals different subtypes of Dementia with Lewy bodies.

Dementia with Lewy bodies (DLB) is a neurodegenerative disorder with a wide heterogeneity of symptoms, which suggests the existence of different subtypes. We used data-driven analysis of magnetic resonance imaging (MRI) data to investigate DLB subtypes. We included 165 DLB from the Mayo Clinic and 3 centers from the European DLB consortium and performed a hierarchical cluster analysis to identify subtypes based on gray matter (GM) volumes. To characterize the subtypes, we used demographic and clinical data, as well as ß-amyloid, tau, and cerebrovascular biomarkers at baseline, and cognitive decline over three years. We identified 3 subtypes: an older subtype with reduced cortical GM volumes, worse cognition, and faster cognitive decline (n = 49, 30%); a subtype with low GM volumes in fronto-occipital regions (n = 76, 46%); and a subtype of younger patients with the highest cortical GM volumes, proportionally lower GM volumes in basal ganglia and the highest frequency of cognitive fluctuations (n = 40, 24%). This study shows the existence of MRI subtypes in DLB, which may have implications for clinical workout, research, and therapeutic decisions.

Asthma as a cause of persistent dyspnea in treated myasthenia gravis patients.

AIMS: The aim of this study was to evaluate the proportion of patients with treated myasthenia gravis (MG) who present with dyspnea not related to MG. METHODS: We analyzed the files of 63 consecutive adult patients with treated MG and persistent dyspnea who had been referred to our Pulmonary Function Test (PFT) Department between 2000 and 2010. RESULTS: We observed that asthma was the first cause of MG-unrelated dyspnea in MG patients, with 9 patients (14%) presenting with asthma-related PFT abnormalities. Six patients had asthma for several years before developing MG, and 3 patients (4%) developed asthma a few months after MG was diagnosed, suggesting a non-coincidental association between the two conditions. In all 3 cases, asthma appeared in elderly patients with severe late-onset AchR-Ab- positive MG, treated with pyridostigmine and corticosteroids and/or intravenous immunoglobulins. In all 3 patients, ß(2)-adrenergic agonist treatment allowed only partial control of dyspnea. In one case, respiratory symptoms were alleviated when pyridostigmine dosage was reduced. CONCLUSIONS: Patients with treated MG and persistent dyspnea should be investigated for asthma using PFT before being diagnosed with refractory MG. If asthma is diagnosed, a bronchodilator treatment should be instituted and a reduction in pyridostigmine dosage should be proposed.

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.