Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 45
Filter
1.
Rev Infirm ; 73(300): 37-39, 2024 Apr.
Article in French | MEDLINE | ID: mdl-38644001

ABSTRACT

Cognitive disorders can have significant repercussions on the quality of care and daily life for patients. We have developed a new tool specifically designed for nursing practice to identify these problems in patients with brain tumors. The Cognitive Impairment Assessment Questionnaire for nursing practice is an objective, quick and easy-to-administer tool that is readily accepted by patients.


Subject(s)
Cognition Disorders , Humans , Surveys and Questionnaires , Cognition Disorders/diagnosis , Cognition Disorders/nursing , Nursing Assessment/methods , Brain Neoplasms/nursing
2.
Alzheimers Dement ; 19(12): 5700-5718, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37422285

ABSTRACT

INTRODUCTION: This study aims to examine whether physical activity moderates the association between biomarkers of brain pathologies and dementia risk. METHODS: From the Memento cohort, we analyzed 1044 patients with mild cognitive impairment, aged 60 and older. Self-reported physical activity was assessed using the International Physical Activity Questionnaire. Biomarkers of brain pathologies comprised medial temporal lobe atrophy (MTA), white matter lesions, and plasma amyloid beta (Aß)42/40 and phosphorylated tau181. Association between physical activity and risk of developing dementia over 5 years of follow-up, and interactions with biomarkers of brain pathologies were tested. RESULTS: Physical activity moderated the association between MTA and plasma Aß42/40 level and increased dementia risk. Compared to participants with low physical activity, associations of both MTA and plasma Aß42/40 on dementia risk were attenuated in participants with high physical activity. DISCUSSION: Although reverse causality cannot be excluded, this work suggests that physical activity may contribute to cognitive reserve. HIGHLIGHTS: Physical activity is an interesting modifiable target for dementia prevention. Physical activity may moderate the impact of brain pathology on dementia risk. Medial temporal lobe atrophy and plasma amyloid beta 42/40 ratio were associated with increased dementia risk especially in those with low level of physical activity.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Dementia , Humans , Middle Aged , Aged , Dementia/complications , Amyloid beta-Peptides , Magnetic Resonance Imaging , Disease Progression , Cognitive Dysfunction/pathology , Biomarkers , Brain/pathology , Atrophy/pathology , Alzheimer Disease/pathology , tau Proteins
3.
Alzheimers Res Ther ; 14(1): 96, 2022 07 19.
Article in English | MEDLINE | ID: mdl-35854388

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.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Lewy Body Disease , Alzheimer Disease/diagnosis , Cognitive Dysfunction/diagnostic imaging , Cohort Studies , Humans , Lewy Body Disease/diagnostic imaging , Photophobia , Prodromal Symptoms
4.
Neurology ; 99(12): 511-515, 2022 Sep 20.
Article in English | MEDLINE | ID: mdl-35851255

ABSTRACT

OBJECTIVES: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is a promising treatment in relapsing B-cell lymphoma but is frequently associated with acute neurotoxicity. Neurologic long-term safety has not been thoroughly assessed. METHODS: All patients with consecutive refractory lymphoma admitted in our center for CAR T-cell therapy underwent neurologic examination, extensive neuropsychological assessment, and brain MRI (except 1 patient) and completed self-administrated questionnaires at baseline. The patients who remained disease-free at 2 years were re-evaluated similarly. All neurologic assessments were conducted by senior neurologists. RESULTS: None of the 19 disease-free patients developed new neurologic deficits or MRI changes when compared with baseline. There was no difference in cognitive performances before and 2 years after, even for the 11 patients who had developed acute neurotoxicity after CAR T cells. In self-questionnaire assessments, cognitive complaint was stable, reported by 32% of the patients at 2 years. We observed a reduction in HADS anxiety scores 2 years after treatment when compared with baseline (median score: 7/21 vs 4/21, p = 0.01). DISCUSSION: In conclusion, no significant neurocognitive or neurologic disorders were observed in this cohort of patients, 2 years after treatment with anti-CD19 CAR T cells.


Subject(s)
Immunotherapy, Adoptive , Lymphoma, B-Cell , Receptors, Chimeric Antigen , Adaptor Proteins, Signal Transducing , Antigens, CD19 , Cell- and Tissue-Based Therapy , Humans , Lymphoma, B-Cell/therapy , Neoplasm Recurrence, Local , Receptors, Antigen, T-Cell , Receptors, Chimeric Antigen/therapeutic use , T-Lymphocytes
5.
Alzheimers Res Ther ; 14(1): 68, 2022 05 18.
Article in English | MEDLINE | ID: mdl-35585559

ABSTRACT

BACKGROUND: This work aimed to investigate the potential pathways involved in the association between social and lifestyle factors, biomarkers of Alzheimer's disease and related dementia (ADRD), and cognition. METHODS: The authors studied 2323 participants from the Memento study, a French nationwide clinical cohort. Social and lifestyle factors were education level, current household incomes, physical activity, leisure activities, and social network from which two continuous latent variables were computed: an early to midlife (EML) and a latelife (LL) indicator. Brain magnetic resonance imaging (MRI), lumbar puncture, and amyloid-positron emission tomography (PET) were used to define three latent variables: neurodegeneration, small vessel disease (SVD), and AD pathology. Cognitive function was defined as the underlying factor of a latent variable with four cognitive tests. Structural equation models were used to evaluate cross-sectional pathways between social and lifestyle factors and cognition. RESULTS: Participants' mean age was 70.9 years old, 62% were women, 28% were apolipoprotein-ε4 carriers, and 59% had a Clinical Dementia Rating (CDR) score of 0.5. Higher early to midlife social indicator was only directly associated with better cognitive function (direct ß = 0.364 (0.322; 0.405), with no indirect pathway through ADRD biomarkers (total ß = 0.392 (0.351; 0.429)). In addition to a direct effect on cognition (direct ß = 0.076 (0.033; 0.118)), the association between latelife lifestyle indicator and cognition was also mostly mediated by an indirect effect through lower neurodegeneration (indirect ß = 0.066 (0.042; 0.090) and direct ß = - 0.116 (- 0.153; - 0.079)), but not through AD pathology nor SVD. CONCLUSIONS: Early to midlife social factors are directly associated with higher cognitive functions. Latelife lifestyle factors may help preserve cognitive functions through lower neurodegeneration.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Vascular Diseases , Aged , Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Biomarkers , Cognition , Cognitive Dysfunction/metabolism , Cross-Sectional Studies , Female , Humans , Life Style , Magnetic Resonance Imaging , Male , Positron-Emission Tomography
6.
J Int Neuropsychol Soc ; 28(5): 483-493, 2022 05.
Article in English | MEDLINE | ID: mdl-34027851

ABSTRACT

OBJECTIVE: To compare the administration of neuropsychological tests by teleneuropsychology (TeleNP) and face to face (F-F) in order to determine the feasibility and reliability of TeleNP. METHOD: At the inclusion visit, all participants underwent a traditional F-F neuropsychological assessment as part of their standard care. Four months after inclusion, they were randomized to undergo an additional neuropsychological assessment either by F-F administration or by TeleNP. RESULTS: A total of 150 adults with cognitive complaints, but with no major cognitive or sensorial impairment were included. At 4 months, 69 participants were randomized in the F-F arm and 71 in TeleNP arm (10 lost in the follow-up). The overall satisfaction was high: 87.1% in the TeleNP arm were "very satisfied", and 82.9% indicated no preference between F-F and TeleNP. In agreement with previous data from the literature, neuropsychological assessments gave similar results across both administration conditions for a large majority of tests [Mini-Mental State Examination (MMSE), Free and Cued Selective Reminding Test (FCSRT) French version, Mahieux gestural praxis battery, Frontal Assessment Battery (FAB), time of completion of the Trail making Test (TMT) A and B, number of errors of the TMT B, Rey complex figure test, categorical et phonological verbal fluency tests] and minor differences for others [80-picture naming test (DO-80), FAB, Digit Span forward and backward and number of errors in the TMT A]. CONCLUSIONS: TeleNP is a promising method to be able to test patients as an alternative to F-F condition. Before this procedure can be generalized, it is now necessary to standardize the adaptation of certain tests and to test them in populations with more significant cognitive disorders.


Subject(s)
Cognition Disorders , Videoconferencing , Adult , Cognition Disorders/diagnosis , Humans , Neuropsychological Tests , Reproducibility of Results
7.
J Alzheimers Dis ; 84(4): 1461-1471, 2021.
Article in English | MEDLINE | ID: mdl-34690140

ABSTRACT

BACKGROUND: The TNI-93 is a quick memory test designed for all patients regardless of their education level. A significant proportion of patients with Alzheimer's disease (AD) are illiterate or poorly educated, and only a few memory tests are adapted for these patients. OBJECTIVE: In this study we aimed at assessing the diagnostic value of the TNI-93 for diagnosis of patients with biologically confirmed amyloid status. METHODS: We included all patients who had an analysis of AD cerebrospinal fluid biomarkers, a neuropsychological assessment including a TNI-93 and an anatomical brain imaging at Avicenne Hospital between January 2009 and November 2019. We compared the TNI-93 scores in patients with amyloid abnormalities (A+) and patients without amyloid abnormalities (A-) according to the AT(N) diagnostic criteria. RESULTS: 108 patients were included (mean age: 66.9±8.5 years old, mean education level: 8.9±5.2 years). Patients from the A + group (N= 80) were significantly more impaired than patients from the A- group (N= 28) on immediate recall (A+: 5.9±2.8; A-: 7.4±2.6; p = 0.001), free recall (A+: 3.5±2.7; A-: 5.9±2.8; p ≤ 0.001), total recall (A+: 5.7±3.5; A-:7.8±2.8; p ≤ 0.001), and on number of intrusions during the recall phase (A+: 1±1.8; A-: 0.1±0.3; p = 0.002). ROC curves revealed that the best scores to discriminate A + from A- patients were immediate recall (Area under curve (AUC): 0.70), number of encoding trials (AUC: 0.73), free recall (AUC: 0.74), and total recall (AUC: 0.74). CONCLUSION: The TNI-93's immediate, free, and total recalls are valuable tools for the 39 diagnosis of AD.


Subject(s)
Alzheimer Disease/diagnosis , Amyloid , Mental Recall/physiology , Neuropsychological Tests/statistics & numerical data , Aged , Amyloid/cerebrospinal fluid , Amyloid/metabolism , Biomarkers/cerebrospinal fluid , Brain/metabolism , Female , Humans , Literacy , Male , Positron-Emission Tomography , Retrospective Studies
8.
Neurooncol Adv ; 3(1): vdab078, 2021.
Article in English | MEDLINE | ID: mdl-34396128

ABSTRACT

BACKGROUND: Little is known about diffuse glioma patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). METHODS: We performed a descriptive and retrospective analysis of 41 diffuse glioma patients with symptomatic SARS-CoV2 infection during the first wave of the COVID-19 pandemic. RESULTS: Confusion with or without fever was the most common neurological symptom (32%) supporting SARS-CoV2 testing in glioma patients with acute and unexplained confusion. Sixteen patients (39%) died after a median delay of 13 days. While multiple clinical, biological, and pathological features, COVID-19- or diffuse glioma-related, at hospital admission appeared to have a pejorative prognostic impact, none was significantly associated with death. Oncological treatments were interrupted at COVID-19 diagnosis and re-initiated with a median delay of 30 days after the end of COVID-19 symptoms. CONCLUSIONS: Interestingly, our retrospective study describes for the first time the characteristics of a cohort of diffuse glioma patients with symptomatic COVID-19. Diffuse glioma patients with poorly symptomatic COVID-19 did not come to the attention of physicians and were not enrolled in the study skewing the denominator for prognostic analysis. Further studies are warranted to specify prognosis of overall population of diffuse glioma patients with COVID-19, including asymptomatic patients, and interactions of prognostic factors of both COVID-19 and diffuse gliomas.

9.
Neurology ; 97(8): e836-e848, 2021 08 24.
Article in English | MEDLINE | ID: mdl-34210821

ABSTRACT

OBJECTIVE: To assess the role of biomarkers of Alzheimer disease (AD), neurodegeneration, and small vessel disease (SVD) as mediators in the association between diabetes mellitus and cognition. METHODS: The study sample was derived from MEMENTO, a cohort of French adults recruited in memory clinics and screened for either isolated subjective cognitive complaints or mild cognitive impairment. Diabetes was defined based on blood glucose assessment, use of antidiabetic agent, or self-report. We used structural equation modeling to assess whether latent variables of AD pathology (PET mean amyloid uptake, Aß42/Aß40 ratio, and CSF phosphorylated tau), SVD (white matter hyperintensities volume and visual grading), and neurodegeneration (mean cortical thickness, brain parenchymal fraction, hippocampal volume, and mean fluorodeoxyglucose uptake) mediate the association between diabetes and a latent variable of cognition (5 neuropsychological tests), adjusting for potential confounders. RESULTS: There were 254 (11.1%) participants with diabetes among 2,288 participants (median age 71.6 years; 61.8% women). The association between diabetes and lower cognition was significantly mediated by higher neurodegeneration (standardized indirect effect: -0.061, 95% confidence interval: -0.089, -0.032), but not mediated by SVD and AD markers. Results were similar when considering latent variables of memory or executive functioning. CONCLUSION: In a large clinical cohort in the elderly, diabetes is associated with lower cognition through neurodegeneration, independently of SVD and AD biomarkers.


Subject(s)
Alzheimer Disease/diagnosis , Cerebral Small Vessel Diseases/diagnosis , Cognitive Dysfunction/diagnosis , Diabetes Mellitus/diagnosis , Nerve Degeneration/diagnosis , Aged , Aged, 80 and over , Alzheimer Disease/epidemiology , Alzheimer Disease/metabolism , Alzheimer Disease/physiopathology , Amyloid beta-Peptides/cerebrospinal fluid , Biomarkers , Cerebral Small Vessel Diseases/epidemiology , Cerebral Small Vessel Diseases/metabolism , Cerebral Small Vessel Diseases/physiopathology , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/physiopathology , Cohort Studies , Comorbidity , Diabetes Mellitus/epidemiology , Diabetes Mellitus/metabolism , Diabetes Mellitus/physiopathology , Female , France/epidemiology , Humans , Magnetic Resonance Imaging , Male , Nerve Degeneration/epidemiology , Nerve Degeneration/metabolism , Nerve Degeneration/physiopathology , Neuropsychological Tests , Positron-Emission Tomography
10.
Harmful Algae ; 102: 101733, 2021 02.
Article in English | MEDLINE | ID: mdl-33875174

ABSTRACT

In France, REPHY (Observation and Surveillance Network for Phytoplankton and Hydrology in coastal waters) and REPHYTOX (Monitoring Network for Phycotoxins in marine organisms) have been contributing to long-term time series on ocean health for more than 30 years. The aim of this paper is to describe these networks and to highlight their key results. Over the last 20 years, phytoplankton flora analysis on French coasts from the Channel to Mediterranean has shown that the five "emblematic" taxa are Chaetoceros, Skeletonema, Cryptophyceae, Leptocylindrus and Pseudo-nitzschia. The latter, together with the taxa of interest Dinophysis + Phalacroma, Alexandrium, and Karenia, have been consistently recorded along the entire French coastline. However, when taking into account frequency of occurrence some taxa exhibit more distinct geographical distributions. In particular, the occurrence of Phaeocystis appeared to be strongly specific to the northern coasts of the Channel. French coasts have been regularly affected since the 1980s by the presence of toxins in bivalve molluscs, leading to bans on fishing and sale of shellfish during periods of varying duration. Three categories of toxins were involved. PST and AST were absent from the French coasts, respectively before 1988 and 2000. DST (Diarrheic Shellfish Toxins) have affected many areas along the whole coast every year since 1987. For PST (Paralytic Shellfish Toxins), only a few areas have been affected, sometimes sporadically, since 1988 in the Channel, 1993 in the Atlantic, and 1998 in the Mediterranean. Many areas have been impacted since 2000 by AST (Amnesic Shellfish Toxins) episodes, mainly affecting scallops in the Channel and on Atlantic coasts. The patterns of change of shellfish toxicity episodes showed no real trend in any province over the entire period 1987-2018.


Subject(s)
Phytoplankton , Shellfish Poisoning , Animals , France , Marine Toxins , Shellfish/analysis
11.
Harmful Algae ; 102: 101976, 2021 02.
Article in English | MEDLINE | ID: mdl-33875184

ABSTRACT

The IOC-ICES-PICES Harmful Algal Event Database (HAEDAT) was used to describe the diversity and spatiotemporal distribution of harmful algal events along the Atlantic margin of Europe from 1987 - 2018. The majority of events recorded are caused by Diarrhetic Shellfish Toxins (DSTs). These events are recorded annually over a wide geographic area from southern Spain to northern Scotland and Iceland, and are responsible for annual closures of many shellfish harvesting areas. The dominant causative dinoflagellates, members of the morphospecies 'Dinophysis acuminata complex' and D. acuta, are common in the waters of the majority of countries affected. There are regional differences in the causative species associated with PST events; the coasts of Spain and Portugal with the dinoflagellates Alexandrium minutum and Gymnodinium catenatum, north west France/south west England/south Ireland with A. minutum, and Scotland/Faroe Islands/Iceland with A. catenella. This can influence the duration and spatial scale of PST events as well as the toxicity of shellfish. The diatom Pseudo-nitzschia australis is the most widespread Domoic Acid (DA) producer, with records coming from Spain, Portugal, France, Ireland and the UK. Amnesic Shellfish Toxins (ASTs) have caused prolonged closures for the scallop fishing industry due to the slow depuration rate of DA. Amendments to EU shellfish hygiene regulations introduced between 2002 and 2005 facilitated end-product testing and sale of adductor muscle. This reduced the impact of ASTs on the scallop fishing industry and thus the number of recorded HAEDAT events. Azaspiracids (AZAs) are the most recent toxin group responsible for events to be characterised in the ICES area. Events associated with AZAs have a discrete distribution with the majority recorded along the west coast of Ireland. Ciguatera Poisoning (CP) has been an emerging issue in the Canary Islands and Madeira since 2004. The majority of aquaculture and wild fish mortality events are associated with blooms of the dinoflagellate Karenia mikimotoi and raphidophyte Heterosigma akashiwo. Such fish killing events occur infrequently yet can cause significant mortalities. Interannual variability was observed in the annual number of HAEDAT areas with events associated with individual shellfish toxin groups. HABs represent a continued risk for the aquaculture industry along the Atlantic margin of Europe and should be accounted for when considering expansion of the industry or operational shifts to offshore areas.


Subject(s)
Harmful Algal Bloom , Animals , England , Europe , France , Ireland , Portugal , Scotland , Spain
12.
Neuro Oncol ; 23(9): 1569-1575, 2021 09 01.
Article in English | MEDLINE | ID: mdl-33822183

ABSTRACT

BACKGROUND: Chimeric antigen receptor-modified T (CAR T) cells are profoundly changing the standard of care in B-cell malignancies. This new therapeutic class induces a significant number of acute neurotoxicity, but data regarding mid- and long-term neurological safety are scarce. We evaluated mid-term neurological safety, with special emphasis on cognitive functions, in a series of adults treated with CAR T cells. METHODS: Patients treated in a single center with CD19-targeted CAR T cells for a relapsing B-cell lymphoma were prospectively followed up by neurologists. Before CAR T-cell infusion, all patients underwent neurological examinations with neuropsychological testing and filled out questionnaires assessing anxiety, depression, and cognitive complaints. Patients surviving without tumor progression were re-evaluated similarly, 6-12 months later. RESULTS: In this prospective cohort of 56 consecutive adult patients treated with CAR T cells, 27 were eligible for mid-term evaluation (median time 7.6 months). Twelve patients developed an acute and reversible neurotoxicity with median duration time of 5.5 days. In all patients, neurological examination on mid-term evaluation was similar to baseline. In self-assessment questionnaires, 63% of patients reported clinically meaningful anxiety, depression, or cognitive difficulties at baseline, a number reduced to 44% at the time of mid-term evaluation. On cognitive assessments, no significant deterioration was found when compared to baseline, in any cognitive functions assessed (verbal and visual memory, executive functions, language, and praxis), even in patients who developed acute neurotoxicity. CONCLUSION: In this cohort of patients treated with CD19-targeted CAR T cells, we found no evidence for neurological or cognitive toxicity, 6-12 months after treatment.


Subject(s)
Lymphoma, B-Cell , Receptors, Chimeric Antigen , Antigens, CD19 , Humans , Immunotherapy, Adoptive , Lymphoma, B-Cell/therapy , Prospective Studies , T-Lymphocytes
13.
Article in English | MEDLINE | ID: mdl-37359131

ABSTRACT

Global trends in the occurrence, toxicity and risk posed by harmful algal blooms to natural systems, human health and coastal economies are poorly constrained, but are widely thought to be increasing due to climate change and nutrient pollution. Here, we conduct a statistical analysis on a global dataset extracted from the Harmful Algae Event Database and Ocean Biodiversity Information System for the period 1985-2018 to investigate temporal trends in the frequency and distribution of marine harmful algal blooms. We find no uniform global trend in the number of harmful algal events and their distribution over time, once data were adjusted for regional variations in monitoring effort. Varying and contrasting regional trends were driven by differences in bloom species, type and emergent impacts. Our findings suggest that intensified monitoring efforts associated with increased aquaculture production are responsible for the perceived increase in harmful algae events and that there is no empirical support for broad statements regarding increasing global trends. Instead, trends need to be considered regionally and at the species level.

14.
Sci Rep ; 10(1): 18997, 2020 11 04.
Article in English | MEDLINE | ID: mdl-33149178

ABSTRACT

Chimeric antigen receptor-modified T (CAR T) cell therapy is a highly promising treatment for haematological malignancies but is frequently associated with cytokine release syndrome and neurotoxicity. Between July 2018 and July 2019, all patients treated with CD19-targeted CAR T-cell therapy for relapsing lymphoma were followed-up longitudinally to describe neurological symptoms and their evolution over time. Four different French centres participated and 84 patients (median age 59 years, 31% females) were included. Neurotoxicity, defined as the presence of at least one neurological symptom appearing after treatment infusion, was reported in 43% of the patients. The median time to onset was 7 days after infusion with a median duration of 6 days. More than half of the patients (64%) had grade 1-2 severity and 34% had grade 3-4. CRS was observed in 80% of all patients. The most frequent neurological symptoms were cognitive signs, being severe in 36%, and were equally distributed between language disorders and cognitive disorders without language impairment. Non-pyramidal motor disorders, severe in 11%, were reported in 42% of the patients. Elevation of C-reactive protein (CRP) within 4 days after treatment was significantly correlated with the occurrence of grade 3-4 neurotoxicity. Although sometimes severe, neurotoxicity was almost always reversible. The efficacy of steroids and antiepileptic drugs remains unproven in the management of neurotoxicity. Neurotoxicity associated with CAR T-cell therapies occurs in more than 40% of patients. The clinical pattern is heterogeneous but cognitive disorders (not limited to language disorders) and, to a minor degree, non-pyramidal motor disorders, appeared as a signature of severe neurotoxicity.


Subject(s)
Immunotherapy, Adoptive/adverse effects , Lymphoma, B-Cell/therapy , Neurotoxicity Syndromes/epidemiology , Receptors, Antigen, T-Cell/metabolism , Adult , Aged , C-Reactive Protein/metabolism , Female , Humans , Lymphoma, B-Cell/metabolism , Male , Middle Aged , Neurotoxicity Syndromes/metabolism , Prospective Studies , Severity of Illness Index , Survival Analysis , Treatment Outcome
15.
Alzheimers Dement (Amst) ; 12(1): e12066, 2020.
Article in English | MEDLINE | ID: mdl-32775598

ABSTRACT

OBJECTIVE: To assess progression of semantic loss in early stages of cognitive decline using semantic and letter fluency performance, and its relation with Alzheimer's disease (AD)-specific neurodegeneration using longitudinal multimodal neuroimaging measures. METHODS: Change in verbal fluency was analyzed among 2261 non-demented individuals with a follow-up diagnosis of no mild cognitive impairment (MCI), amnestic MCI (aMCI), non-amnestic MCI (naMCI), or incident dementia, using linear mixed models across 4 years of follow-up, and relations with magnetic resonance imaging (MRI; n = 1536) and 18F-fluorodeoxyglucose brain positron emission tomography (18F-FDG-PET) imaging (n = 756) using linear regression models across 2 years of follow-up. RESULTS: Semantic fluency declined-fastest in those at higher risk for AD (apolipoprotein E [APOE] e4 carriers, Clinical Dementia Rating score of .5, aMCI, or incident dementia)-while letter fluency did not except for those with incident dementia. Lower baseline semantic fluency was associated with an increase in white matter hyperintensities and total mean cortical thinning over time, and regionally with less hippocampal volume as well as more cortical thinning and reduced 18F-FDG-PET uptake in the inferior parietal lobule, entorhinal cortex, isthmus cingulate, and precuneus-posterior cingulate area. In contrast, baseline letter fluency was not associated with change in total nor regional neurodegeneration. Whole-brain neurodegeneration over time was associated with faster decline in both fluencies, while AD-specific regions were associated with a faster rate of decline in semantic but not letter fluency. INTERPRETATION: This study provides strong evidence of distinctive degeneration of semantic abilities early on in relation to both cognitive decline and AD-specific neurodegeneration.

16.
J Immunother Cancer ; 8(2)2020 07.
Article in English | MEDLINE | ID: mdl-32747471

ABSTRACT

Immune-checkpoint inhibitors (ICIs) targeting cytotoxic T lymphocyte-associated antigen-4 and programmed cell death ligand-1) are associated with several immune-related neurological disorders. Cases of meningitis related to ICIs are poorly described in literature and probably underestimated. Several guidelines are available for the acute management of these adverse events, but the safety of resuming ICIs in these patients remains unclear. We conducted a retrospective case series of immune-related meningitis associated with ICIs that occurred between October 1 2015 and October 31 2019 in two centers: Saint-Louis and Cochin hospitals, Paris, France. Diagnosis was defined by a (1) high count of lymphocytes (>8 cells/mm3) and/or high level of proteins (>0.45 g/L) without bacteria/virus or tumor cells detection, in cerebrospinal fluid and (2) normal brain and spine imaging. Patients were followed-up for at least 6 months from the meningitis onset. Seven cases of immune-related meningitis are here reported. Median delay of meningitis occurrence after ICIs onset was 9 days. Steroid treatment was introduced in four patients at a dose of 1 mg/kg (prednisone), allowing a complete recovery within 2 weeks. The other three patients spontaneously improved within 3 weeks. Given the favorable outcome, ICIs were reintroduced in all patients. The rechallenge was well tolerated and no patients experienced meningitis recurrence. In conclusion, in our series, the clinical course was favorable and steroids were not always required. Resuming ICIs in these patients appeared safe and can thus be considered in case of isolated meningitis. However, a careful analysis of the risk/benefit ratio should be done on a case-by-case basis.


Subject(s)
Immune Checkpoint Inhibitors/therapeutic use , Melanoma/drug therapy , Meningitis/chemically induced , Adult , Aged , Female , Humans , Immune Checkpoint Inhibitors/pharmacology , Male , Melanoma/pathology , Meningitis/pathology , Middle Aged
17.
Neurosci Biobehav Rev ; 107: 602-614, 2019 12.
Article in English | MEDLINE | ID: mdl-31553925

ABSTRACT

A number of neurotoxicity associated with oncological treatments has been reported in non-central nervous system cancers. An expert group presents the state of the art and a guide to help the choice of appropriated tools to assess patient cognition in studies on oncology and neurobehavior in animal models. In addition, current cognitive rehabilitation programs currently under evaluation are also discussed. Cognitive assessments in oncology depend on the research question, study design, cognitive domains, patients' characteristics, psychometric properties of the tests, and whether the tests are supervised or not by a neuropsychologist. Batteries of electronic tests can be proposed, but several of them are characterized by weak psychometric developments. In order to improve the comprehension on the impact of cancer treatments on cognition, new animal models are in development, and would in the future include non-human primate models. By bringing together the skills and practices of oncologists, neurologists, neuropsychologists, neuroscientists, we propose a series of specific tools and tests that accompany the cognitive management of non-CNS cancer patients.


Subject(s)
Cognitive Dysfunction/etiology , Neoplasms/complications , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/therapy , Humans , Neoplasms/psychology , Neoplasms/therapy
18.
J Clin Exp Neuropsychol ; 41(10): 1060-1073, 2019 12.
Article in English | MEDLINE | ID: mdl-31394979

ABSTRACT

Introduction: Music is increasingly used to improve cognition in clinical settings. However, it remains unclear whether its use as a mnemonic strategy is effective in Alzheimer's disease (AD). The present study aimed at determining whether a musical mnemonic might mitigate patients' learning of new verbal information and at exploring the effect of factors such as retention delay and emotional valence of the musical excerpt used. Method: 13 patients with AD and 26 healthy comparisons (HC) with a low musical expertise were included. They learned texts about everyday life themes that were either set to familiar instrumental music, which was positively- or negatively-valenced, or spoken only. Immediate and delayed recalls (after 10 min and 24 hours) were measured. Results: Main results showed that (i) HC demonstrated better verbal episodic memory performance than participants with AD; (ii) participants with AD encoded texts paired with positively-valenced music better than texts paired with negatively-valenced music; (iii) participants with AD recalled sung texts better than spoken texts (after 10 min and 24 hours), regardless of musical valence while HC displayed better recall for texts paired with positively-valenced music. Conclusions: Musical mnemonics may help people with AD learn verbal information that relates to their daily life, regardless the musical expertise of the patients. This result gives promising clinical insights showing that music processing is robust to brain damage in AD. Possible hypotheses explaining the effectiveness of musical mnemonics in AD regardless the musical valence are discussed (e.g., different processing between musical and spoken conditions; disappearance of the positivity bias and implications with respect to the underlying socio-emotional selectivity theory).


Subject(s)
Alzheimer Disease/psychology , Memory, Episodic , Mental Recall/physiology , Music Therapy/methods , Music/psychology , Aged , Aged, 80 and over , Cognition/physiology , Emotions/physiology , Female , Health Status , Humans , Male , Middle Aged , Neuropsychological Tests
19.
Am J Alzheimers Dis Other Demen ; 34(7-8): 469-477, 2019.
Article in English | MEDLINE | ID: mdl-30827122

ABSTRACT

Few neuropsychological tests are available to assess executive dysfunction in low-educated and multicultural populations. To address this issue, the TFA-93, a switching verbal fluency test to assess cognitive flexibility, was administered to 70 healthy controls, 57 patients with a clinical diagnosis of Alzheimer's disease, and 21 with a clinical diagnosis of a neurodegenerative disease associated with frontal disorders. Most of the participants were low-educated and nonnative French speakers. The TFA-93 comprises 2 categorical fluency tasks (animals and fruits) and a fluency task in which participants have to switch between animals and fruits. Correct responses and errors were collected, and a flexibility index expressed the switching cost. Results showed that correct responses were lower, and the switching cost was greater in both patient groups. In low-educated and multicultural populations, the TFA-93 seems to be a good alternative to assess flexibility compared to the standard neuropsychological tools based on academic abilities.


Subject(s)
Alzheimer Disease/diagnosis , Executive Function/physiology , Neurodegenerative Diseases/diagnosis , Neuropsychological Tests/standards , Aged , Aged, 80 and over , Alzheimer Disease/physiopathology , Cultural Diversity , Educational Status , Female , France , Humans , Male , Middle Aged , Neurodegenerative Diseases/physiopathology
20.
J Alzheimers Dis ; 64(3): 889-897, 2018.
Article in English | MEDLINE | ID: mdl-29966201

ABSTRACT

BACKGROUND: CSF Alzheimer's disease (AD) biomarkers allow classifying individuals based on their levels of amyloid and neurodegeneration pathologies. OBJECTIVE: To investigate the distribution of AD biomarker profiles from patients suffering from cognitive disorders. METHODS: We analyzed 3001 patients with cognitive disorders and referred by 18 French memory clinics located in and around Paris. Patients were classified as normal, amyloidosis (A+/N-), amyloidosis and neurodegeneration (A+/N+) or suspected non-AD pathophysiology (SNAP), according to their CSF levels of biomarkers. Analysis were performed for the overall population and stratified by gender, age quintiles, and Mini-Mental State Examination (MMSE) score quintiles. Results were compared to previous findings in cohorts of healthy elderly adults. RESULTS: 37% of the sample were classified as A+/N+, 22% were classified A+/N-, and 15% as SNAP. The A+/N+ profile was associated with female gender, advanced age, and lower MMSE score, while the A+/N-profile was observed more frequently in men and the distribution was stable across age and MMSE. The SNAP profile showed no association with gender or age, was less frequent in patients with lower MMSE, and had a lower repartition than the one previously reported in asymptomatic populations. CONCLUSIONS: While A+/N+ patients had the clinical characteristics typically observed in AD, A+/N-patients had a different epidemiological pattern (higher frequency in men, no association with advanced age or lower MMSE). The SNAP profile was less frequent than previously reported in the general elderly population, suggesting that this profile is not a frequent cause of memory impairment in this population.


Subject(s)
Biomarkers/cerebrospinal fluid , Cognition Disorders/cerebrospinal fluid , Aged , Aged, 80 and over , Amyloid beta-Peptides/cerebrospinal fluid , Amyloidosis/cerebrospinal fluid , Disease Progression , Female , France , Humans , Longitudinal Studies , Male , Middle Aged , tau Proteins/cerebrospinal fluid
SELECTION OF CITATIONS
SEARCH DETAIL
...