RESUMO
Despite a growing literature, experiments directly related to attachment are still needed. We explored brain processes involved in two aspects of attachment, distress and comfort. Seventy-eight healthy adult males with different attachment styles (secure, avoidant, and anxious) viewed distress, comfort, complicity-joy and neutral images (picture database BAPS-Adult) in an fMRI block design. ROIs from the modules described in the functional Neuro-Anatomical Model of Attachment (Long et al. 2020) were studied. Secure participants used more co- and self-regulation strategies and exhibited a higher activation of the reward network in distress and comfort viewing, than insecure participants. Avoidant participants showed the lower brain activations. Their approach and reward modules were the least activated in distress and comfort. Anxious participants presented both higher activations of the approach and aversion modules during complicity-joy. In addition, comfort and complicity-joy were processed differently according to attachment styles and should be differentiated among positive stimuli to disentangle attachment processes.
RESUMO
Microduplications of the 17q21.31 chromosomal region encompassing the MAPT gene, which encodes the Tau protein, were identified in patients with a progressive disorder initially characterized by severe memory impairment with or without behavioral changes that can clinically mimic Alzheimer disease. The unique neuropathological report showed a primary tauopathy, which could not be unanimously classified in a given known subtype, showing both 4R- and 3R-tau inclusions, mainly within temporal cortical subregions and basal ganglia, without amyloid deposits. Recently, two subjects harboring the same duplication were reported with an atypical extrapyramidal syndrome and gait disorder. To decipher the phenotypic spectrum associated with MAPT duplications, we studied ten carriers from nine families, including two novel unrelated probands, gathering clinical (n = 10), cerebrospinal fluid (n = 6), MRI (n = 8), dopamine transporter scan (n = 4), functional (n = 5), amyloid (n = 3) and Tau-tracer (n = 2) PET imaging data as well as neuropathological examination (n = 4). Ages at onset ranged from 37 to 57 years, with prominent episodic memory impairment in 8/10 patients, associated with behavioral changes in four, while two patients showed atypical extrapyramidal syndrome with gait disorder at presentation, including one with associated cognitive deficits. Amyloid imaging was negative but Tau imaging showed significant deposits mainly in both mesiotemporal cortex. Dopaminergic denervation was found in 4/4 patients, including three without extrapyramidal symptoms. Neuropathological examination exclusively showed Tau-immunoreactive lesions. Distribution, aspect and 4R/3R tau aggregates composition suggested a spectrum from predominantly 3R, mainly cortical deposits well correlating with cognitive and behavioral changes, to predominantly 4R deposits, mainly in the basal ganglia and midbrain, in patients with prominent extrapyramidal syndrome. Finally, we performed in vitro seeding experiments in HEK-biosensor cells. Morphological features of aggregates induced by homogenates of three MAPT duplication carriers showed dense/granular ratios graduating between those induced by homogenates of a Pick disease and a progressive supranuclear palsy cases. These results suggest that MAPT duplication causes a primary tauopathy associated with diverse clinical and neuropathological features.
Assuntos
Encéfalo/patologia , Tauopatias/patologia , Proteínas tau/metabolismo , Adulto , Idade de Início , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Feminino , Heterozigoto , Humanos , Corpos de Inclusão/patologia , Masculino , Pessoa de Meia-Idade , Tauopatias/metabolismo , Proteínas tau/genéticaRESUMO
BACKGROUND: Some students have neurodevelopmental disorders that might affect their academic and professional careers if they are not identified and addressed by specific pedagogic adaptations. The objective of this work was to describe medical teachers' opinions of students with neurodevelopmental disorders and their management of these students. METHODS: An anonymous cross-sectional electronic survey was performed to describe medical teachers' opinions about the impact of neurodevelopmental disorders on the student's life and on the medical teachers' management. aThe survey was created, including visual analogic scales and free text, to assess teachers' opinions from identification and assessment of neurodevelopemental burden on students and teachers, to their own knowledge about neurodevelopemental disorders and the specific pedagogic management available. The survey was sent to 175 medical teachers in 2019, of whom 67 responded. Quantitative descriptive statistics and qualitative analysis of free text were reported. RESULTS: Many medical teachers report having encountered students who might have had neurodevelopmental disorders (dyspraxia 33%; dyslexia 46%; autism spectrum disorders 68%; attention deficit hyperactivity disorders 75%). Impact on students and on teachers was considered as important (mean VAS score for impact over 60/100 for all syndromes except for dyspraxia). Medical teachers' self-reported knowledge about neurodevelopmental disorders (mean VAS score 43.9/100) and available pedagogical adaptations (mean VAS score 19.0/100) was limited. The teachers were concerned about ethical issues (mean VAS score 72.2/100) but were interested in receiving specialized training (mean VAS score 64.4/100). CONCLUSION: Medical teachers feel unprepared to manage students with neurodevelopmental disorders. They would be interested in specific training and procedures about the pedagogic management of these students.
Assuntos
Docentes , Estudantes , Atitude , Estudos Transversais , Humanos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Cognitive impairment is common in patients with PD. Core markers of Alzheimer's dementia have been related also to PD dementia, but no disease-specific signature to predict PD dementia exists to date. OBJECTIVES: The aim of this study was to investigate CSF markers associated with cognition in early PD. METHODS: A high-throughput suspension bead array examined 216 proteins in CSF of 74 PD patients in the AETIONOMY project. Cognitive function was assessed with Repeatable Battery for the Assessment of the Neuropsychological Status, Montreal Cognitive Assessment, and Mini-Mental State Examination. RESULTS: Of 69 patients with complete data, 34 had high (≥90) and 35 had low Repeatable Battery for the Assessment of the Neuropsychological Status total score (<90). Of 14 proteins in CSF that differed in levels between groups, increased kininogen-1, validated with several antibodies, was independently associated with lower Repeatable Battery for the Assessment of the Neuropsychological Status and Montreal Cognitive Assessment scores after adjustment for confounders. CONCLUSIONS: Kininogen-1 levels in CSF may serve as a marker of cognitive impairment in PD. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Assuntos
Transtornos Cognitivos , Disfunção Cognitiva , Doença de Parkinson , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Disfunção Cognitiva/etiologia , Humanos , Cininogênios , Testes de Estado Mental e Demência , Testes Neuropsicológicos , Doença de Parkinson/complicaçõesRESUMO
INTRODUCTION: Cognitive impairment is frequent in persons with multiple sclerosis (PwMS) and can impact on activities of daily living. The capacity to differentiate real changes from background statistical noise induced by human, instrumentational, and environmental variations inherent to the evaluation would improve cognitive assessments. OBJECTIVE: To assess the short-term reproducibility of cognitive tests in non-multiple sclerosis (non-MS) persons and PwMS. METHODS: Sixty-two PwMS and 19 non-MS persons performed 2 measurements, 1 week apart, of the Symbol Digit Modalities Test (SDMT) and phonological and semantic verbal fluency. Test-retest reliability was evaluated by the intraclass correlation coefficients (ICC) and agreement by standard error of measurement (SEM) and minimum detectable change (MDC). RESULTS: The reliability of the cognitive variables studied had moderate to high ICC values (ICC > 0.8) in both populations. The threshold to consider a significant cognitive modification evaluated by SEM and MDC was lower in PwMS compared with non-MS persons. CONCLUSIONS: SDMT and verbal fluency have good short-term reproducibility in PwMS. Specific SEM and MDC cutoffs based on the same design of evaluation (especially retest timing) and to the targeted pathological population (MS vs. healthy) should systematically be used to consider cognitive modification as significant in research protocol as well as in clinical practice.
Assuntos
Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Esclerose Múltipla/complicações , Testes Neuropsicológicos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/psicologia , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: To estimate the prevalence of amyloid positivity, defined by positron emission tomography (PET)/cerebrospinal fluid (CSF) biomarkers and/or neuropathological examination, in primary progressive aphasia (PPA) variants. METHODS: We conducted a meta-analysis with individual participant data from 1,251 patients diagnosed with PPA (including logopenic [lvPPA, n = 443], nonfluent [nfvPPA, n = 333], semantic [svPPA, n = 401], and mixed/unclassifiable [n = 74] variants of PPA) from 36 centers, with a measure of amyloid-ß pathology (CSF [n = 600], PET [n = 366], and/or autopsy [n = 378]) available. The estimated prevalence of amyloid positivity according to PPA variant, age, and apolipoprotein E (ApoE) ε4 status was determined using generalized estimating equation models. RESULTS: Amyloid-ß positivity was more prevalent in lvPPA (86%) than in nfvPPA (20%) or svPPA (16%; p < 0.001). Prevalence of amyloid-ß positivity increased with age in nfvPPA (from 10% at age 50 years to 27% at age 80 years, p < 0.01) and svPPA (from 6% at age 50 years to 32% at age 80 years, p < 0.001), but not in lvPPA (p = 0.94). Across PPA variants, ApoE ε4 carriers were more often amyloid-ß positive (58.0%) than noncarriers (35.0%, p < 0.001). Autopsy data revealed Alzheimer disease pathology as the most common pathologic diagnosis in lvPPA (76%), frontotemporal lobar degeneration-TDP-43 in svPPA (80%), and frontotemporal lobar degeneration-TDP-43/tau in nfvPPA (64%). INTERPRETATION: This study shows that the current PPA classification system helps to predict underlying pathology across different cohorts and clinical settings, and suggests that age and ApoE genotype should be considered when interpreting amyloid-ß biomarkers in PPA patients. Ann Neurol 2018;84:737-748.
Assuntos
Peptídeos beta-Amiloides , Afasia Primária Progressiva/patologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Afasia Primária Progressiva/genética , Apolipoproteínas E/genética , Encéfalo/patologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
BACKGROUND: In the nineteenth century, Jean Martin Charcot explained functional neurological disorder (formerly called conversion disorder) as a "psychodynamic" lesion. Numerous advances in neuroimaging have permitted identification of the neural underpinnings of this disorder. CASE PRESENTATION: Herein we describe a case of functional neurological disorder (FND) with initial left sensorimotor deficit, in-coordinated limb movements, neglect, clouded consciousness, slurred speech and a semiology of visual impairment. A single photon emission computed tomography (SPECT) showed a right thalamic hypoperfusion, which is rather concordant with the initial semiology. Later, the semiology changed, presenting with a predominantly neurovisual complex presentation. The second SPECT showed no more thalamic abnormalities but an hypoperfusion in the right temporo-occipital junction, right inferior parietal lobe and left superior frontal lobe, which is also rather concordant with the changing semiology. CONCLUSIONS: This case illustrates the evolving neuroimaging patterns of FND but also the concordance between semiology and neuroimaging findings in FND supporting Charcot's theory of "dynamic lesion".
Assuntos
Encéfalo , Transtorno Conversivo , Neuroimagem , Tomografia Computadorizada de Emissão de Fóton Único , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Transtorno Conversivo/diagnóstico por imagem , Transtorno Conversivo/fisiopatologia , HumanosRESUMO
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 groupsAssuntos
Doença de Alzheimer/líquido cefalorraquidiano
, Doença de Alzheimer/diagnóstico
, Doença por Corpos de Lewy/líquido cefalorraquidiano
, Doença por Corpos de Lewy/diagnóstico
, Sintomas Prodrômicos
, Idoso
, Peptídeos beta-Amiloides/líquido cefalorraquidiano
, Biomarcadores/líquido cefalorraquidiano
, Estudos de Casos e Controles
, Diagnóstico Diferencial
, Feminino
, Humanos
, Masculino
, Pessoa de Meia-Idade
, Fragmentos de Peptídeos/líquido cefalorraquidiano
, Estudos Retrospectivos
, Proteínas tau/líquido cefalorraquidiano
RESUMO
OBJECTIVE: Two methods using exercise and body cooling could influence the well-being of patients with multiple sclerosis (PwMS). The aim of this study was to determine whether wearing a cooling vest during a physical training program could increase the cognitive and physical capacities and quality of life in PwMS. METHODS: Eighteen PwMS (49.6 ± 8 years; Expanded Disability Status Score 5.0 ± 1.0) were randomly assigned to a cooling or control group. PwMS underwent a 7-week physical training program. In the cooling group, PwMS wore a cooling vest during each training session, whereas in the control group, PwMS wore a cotton T-shirt. Before and after the training program, both groups completed the Isaacs Set Test (IST), Trail Making Test A-B (TMT A-B), SEP-59, Multidimensional Fatigue Inventory and performed a 6-minute walk test (6MWT). RESULTS: The cooling group showed significantly (p < 0.05) improved performance for IST, TMT A and 6MWT. Their emotional well-being and cognitive functions investigated in SEP-59 were significantly (p < 0.05) improved, and general and physical fatigue significantly (p < 0.05) decreased. CONCLUSIONS: This physical training program combined with a cooling strategy could have a significant positive influence on both cognitive and physical performances, perceived fatigue and emotional well-being in heat-sensitive PwMS.
Assuntos
Exercício Físico , Hipotermia Induzida/métodos , Esclerose Múltipla/reabilitação , Adulto , Cognição , Temperatura Baixa , Fadiga , Feminino , Humanos , Hipotermia Induzida/instrumentação , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Qualidade de VidaRESUMO
BACKGROUND: Gait impairment is one of the most disabling symptoms in people with multiple sclerosis (PwMS). Fampridine, has demonstrated a positive effect on gait speed in PwMS after 14 days of treatment but the long-term effects have not yet been demonstrated. This study reviews the long-term effects of fampridine on gait in PwMS. SUMMARY: This systematic review was conducted according to the PRISMA statement. Studies were considered long term if treatment exceeded 28 days. From the 498 studies identified, 18 (2,200 patients) fulfilled all eligibility criteria. Only 3 studies followed-up patients for >1 year and one of these showed a non-significant improvement in the gait speed. Key Messages: Fampridine seems to be beneficial at improving gait speed in PwMS in the long term. Further long-term studies are needed on related gait and functional parameters.
Assuntos
4-Aminopiridina/uso terapêutico , Transtornos Neurológicos da Marcha/tratamento farmacológico , Marcha/efeitos dos fármacos , Esclerose Múltipla/complicações , Bloqueadores dos Canais de Potássio/uso terapêutico , Adulto , Feminino , Transtornos Neurológicos da Marcha/etiologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: A classification framework for posterior cortical atrophy (PCA) is proposed to improve the uniformity of definition of the syndrome in a variety of research settings. METHODS: Consensus statements about PCA were developed through a detailed literature review, the formation of an international multidisciplinary working party which convened on four occasions, and a Web-based quantitative survey regarding symptom frequency and the conceptualization of PCA. RESULTS: A three-level classification framework for PCA is described comprising both syndrome- and disease-level descriptions. Classification level 1 (PCA) defines the core clinical, cognitive, and neuroimaging features and exclusion criteria of the clinico-radiological syndrome. Classification level 2 (PCA-pure, PCA-plus) establishes whether, in addition to the core PCA syndrome, the core features of any other neurodegenerative syndromes are present. Classification level 3 (PCA attributable to AD [PCA-AD], Lewy body disease [PCA-LBD], corticobasal degeneration [PCA-CBD], prion disease [PCA-prion]) provides a more formal determination of the underlying cause of the PCA syndrome, based on available pathophysiological biomarker evidence. The issue of additional syndrome-level descriptors is discussed in relation to the challenges of defining stages of syndrome severity and characterizing phenotypic heterogeneity within the PCA spectrum. DISCUSSION: There was strong agreement regarding the definition of the core clinico-radiological syndrome, meaning that the current consensus statement should be regarded as a refinement, development, and extension of previous single-center PCA criteria rather than any wholesale alteration or redescription of the syndrome. The framework and terminology may facilitate the interpretation of research data across studies, be applicable across a broad range of research scenarios (e.g., behavioral interventions, pharmacological trials), and provide a foundation for future collaborative work.
Assuntos
Encefalopatias/classificação , Encéfalo/diagnóstico por imagem , Encefalopatias/diagnóstico por imagem , Encefalopatias/fisiopatologia , Encefalopatias/psicologia , HumanosRESUMO
The vast majority of people experience musical imagery, the sensation of reliving a song in absence of any external stimulation. Internal perception of a song can be deliberate and effortful, but also may occur involuntarily and spontaneously. Moreover, musical imagery is also involuntarily used for automatically completing missing parts of music or lyrics from a familiar song. The aim of our study was to explore the onset of musical imagery dynamics that leads to the automatic completion of missing lyrics. High-density electroencephalography was used to record the cerebral activity of twenty healthy volunteers while they were passively listening to unfamiliar songs, very familiar songs, and songs previously listened to for two weeks. Silent gaps inserted into these songs elicited a series of neural activations encompassing perceptual, attentional and cognitive mechanisms (range 100-500ms). Familiarity and learning effects emerged as early as 100ms and lasted 400ms after silence occurred. Although participants reported more easily mentally imagining lyrics in familiar rather than passively learnt songs, the onset of neural mechanisms and the power spectrum underlying musical imagery were similar for both types of songs. This study offers new insights into the musical imagery dynamics evoked by gaps of silence and on the role of familiarity and learning processes in the generation of these dynamics. The automatic and effortless method presented here is a potentially useful tool to understand failure in the familiarity and learning processes of pathological populations.
Assuntos
Percepção Auditiva/fisiologia , Córtex Cerebral/fisiologia , Eletroencefalografia/métodos , Potenciais Evocados/fisiologia , Imaginação/fisiologia , Aprendizagem/fisiologia , Música/psicologia , Poesia como Assunto , Reconhecimento Psicológico/fisiologia , Adulto , Feminino , Humanos , MasculinoRESUMO
Inherited white matter diseases are rare and heterogeneous disorders usually encountered in infancy. Adult-onset forms are increasingly recognized. Our objectives were to determine relative frequencies of genetic leukoencephalopathies in a cohort of adult-onset patients and to evaluate the effectiveness of a systematic diagnostic approach. Inclusion criteria of this retrospective study were: (i) symmetrical involvement of white matter on the first available brain MRI; (ii) age of onset above 16 years. Patients with acquired diseases were excluded. Magnetic resonance imaging analysis identified three groups (vascular, cavitary and non-vascular/non-cavitary) in which distinct genetic and/or biochemical testing were realized. One hundred and fifty-four patients (male/female = 60/94) with adult-onset leukoencephalopathies were identified. Mean age of onset was 38.6 years. In the vascular group, 41/55 patients (75%) finally had a diagnosis [including CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, n = 32) and COL4A1 mutation, n = 7]. In the cavitary group, 13/17 (76%) patients had a diagnosis of EIF2B-related disorder. In the third group (n = 82), a systematic biological screening allowed a diagnosis in 23 patients (28%) and oriented direct genetic screening identified 21 additional diseases (25.6%). Adult-onset genetic leukoencephalopathies are a rare but probably underestimated entity. Our study confirms the use of a magnetic resonance imaging-based classification with a final diagnosis rate of 64% (98/154) cases.
Assuntos
Leucoencefalopatias/genética , Leucoencefalopatias/patologia , Adolescente , Adulto , Idade de Início , Idoso , Transtornos Cerebrovasculares/genética , Transtornos Cerebrovasculares/patologia , Feminino , França , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Substância Branca/patologia , Adulto JovemRESUMO
BACKGROUND: ANO10 mutations have recently been reported in autosomal recessive cerebellar ataxia type 3 (ARCA3). The objective of this study was to describe the phenotype of 2 siblings with compound heterozygous ANO10 mutations and progressive cerebellar ataxia, epilepsy, and cognitive impairment. A porencephalic cyst was also described in one of them and a coenzyme Q10 deficiency in the other one. METHODS: We performed neurological, neuropsychological, electromyographic, electroencephalic and MRI examinations in 2 siblings with compound heterozygous ANO10 mutations. RESULTS: We reported for the first time the neuropsychological profile of 2 ARCA3 patients showing an adult-onset executive and attentional syndrome. Both presented epilepsy. One of them presented a porencephalic cyst. CONCLUSION: These results suggest that executive and attentional disorders are impaired in ANO10 mutation. In addition, epilepsy and porencephalic cysts were also described in our ARCA3 patients, the cyst thus expanding the clinical phenotype of ARCA3 patients due to ANO10 mutation.
Assuntos
Cistos do Sistema Nervoso Central/genética , Ataxia Cerebelar/complicações , Ataxia Cerebelar/genética , Ataxia Cerebelar/patologia , Disfunção Cognitiva/genética , Epilepsia/genética , Proteínas de Membrana/genética , Adolescente , Adulto , Anoctaminas , Cistos do Sistema Nervoso Central/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Mutação , FenótipoRESUMO
BACKGROUND/AIMS: High frequency repetitive transcranial magnetic stimulation (hf-rTMS) improves language skills in Alzheimer's disease (AD). We report the use of hf-rTMS in a patient with logopenic primary progressive aphasia (LPPA) due to AD. METHOD: hf-rTMS was applied to the left dorsolateral prefrontal cortex of a LPPA patient. Cerebral perfusion, neuropsychological and linguistic performances were evaluated before and 1 month after hf-rTMS. RESULTS: The tolerance was good. Improvements on linguistic (fluency, naming, lesser paraphasia) and cognitive skills (Mini Mental State Examination, verbal memory free recall, speed processing) and cerebral perfusion were observed. CONCLUSION: hf-rTMS can be used in LPPA patients. A procognitive effect persisting several weeks after stimulation in LPPA patients was suggested and should therefore be evaluated in a clinical trial as an adjunctive therapeutic tool.
Assuntos
Afasia Primária Progressiva/terapia , Estimulação Magnética Transcraniana/métodos , Idoso , Afasia Primária Progressiva/diagnóstico , Cognição/fisiologia , Feminino , Humanos , Testes Neuropsicológicos , Resultado do TratamentoRESUMO
INTRODUCTION: The genetics underlying posterior cortical atrophy (PCA), typically a rare variant of Alzheimer's disease (AD), remain uncertain. METHODS: We genotyped 302 PCA patients from 11 centers, calculated risk at 24 loci for AD/DLB and performed an exploratory genome-wide association study. RESULTS: We confirm that variation in/near APOE/TOMM40 (P = 6 × 10(-14)) alters PCA risk, but with smaller effect than for typical AD (PCA: odds ratio [OR] = 2.03, typical AD: OR = 2.83, P = .0007). We found evidence for risk in/near CR1 (P = 7 × 10(-4)), ABCA7 (P = .02) and BIN1 (P = .04). ORs at variants near INPP5D and NME8 did not overlap between PCA and typical AD. Exploratory genome-wide association studies confirmed APOE and identified three novel loci: rs76854344 near CNTNAP5 (P = 8 × 10(-10) OR = 1.9 [1.5-2.3]); rs72907046 near FAM46A (P = 1 × 10(-9) OR = 3.2 [2.1-4.9]); and rs2525776 near SEMA3C (P = 1 × 10(-8), OR = 3.3 [2.1-5.1]). DISCUSSION: We provide evidence for genetic risk factors specifically related to PCA. We identify three candidate loci that, if replicated, may provide insights into selective vulnerability and phenotypic diversity in AD.
Assuntos
Doença de Alzheimer/genética , Moléculas de Adesão Celular Neuronais/genética , Córtex Cerebral/patologia , Predisposição Genética para Doença/genética , Proteínas/genética , Semaforinas/genética , Fatores Etários , Idoso , Doença de Alzheimer/complicações , Apolipoproteínas E/genética , Atrofia/etiologia , Feminino , Estudos de Associação Genética , Humanos , Masculino , Proteínas de Membrana Transportadoras/genética , Pessoa de Meia-Idade , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Polimorfismo de Nucleotídeo Único/genética , Polinucleotídeo Adenililtransferase , Receptores de Complemento 3b/genética , Fatores de RiscoRESUMO
The cerebrospinal fluid levels of amyloid beta 1-42 (Aß1-42), total tau and tau phosphorylated at threonine 181 (ptau181) are well established biomarkers of cerebral amyloid pathology and tau related neurodegeneration, two hallmarks of Alzheimer's disease. These biomarkers can help to improve diagnostic accuracy and consequent decisions on counseling, support, and therapy of patients with mild cognitive impairment and dementia. The use of biomarkers is part of the proposed new criteria of AD diagnosis. It may be particularly helpful in cases of atypical clinical presentation and uncertain diagnosis, and if an important benefit for the patient is expected. The ongoing development of new biomarkers based on less or non-invasive procedures will allow for a larger use of biomarkers to improve the diagnosis of cognitive impairment.
Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Doença de Alzheimer/terapia , Biomarcadores/líquido cefalorraquidiano , Terapia Cognitivo-Comportamental/métodos , Diagnóstico Diferencial , Diagnóstico Precoce , Humanos , Valor Preditivo dos Testes , Sensibilidade e EspecificidadeRESUMO
We describe the case of a patient with pure verbal palinacousis and perseveration of inner speech after a right inferior temporal lesion. The superior temporal lobe, including the superior temporal sulcus and the interhemispheric connection between the 2 superior temporal lobes, explored by tractography, were preserved. These regions are involved in voice processing, verbal short-term memory and inner speech. It can then be hypothesised that abnormal activity in this network has occurred. Palinacousis and 'palinendophonia', a term proposed for this symptom not previously reported, may be due to common cognitive processes disorders involved in both voice hearing and inner speech.
Assuntos
Encefalite por Herpes Simples/complicações , Ilusões/etiologia , Lobo Temporal/patologia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND/AIMS: Fampridine is sometimes reported to improve cognition and especially the information-processing speed. Motor improvement might be a confounding factor. The aim of this study was to evaluate the effects of fampridine on verbal fluencies in patients with multiple sclerosis (MS). METHODS: Fifty MS patients were included in a prospective monocentric open label trial with a mean Expanded Disability Status Scale of 5.3 ± 1.1. Assessments of verbal phonological and semantic fluencies were repeated twice (within 1 week) before fampridine treatment and twice after fampridine treatment in order to have the maximal practice effect. Gait velocity and fatigue (visual analogical scale) were also assessed. Distribution into gait responders, gait non-responders, fluency responders and fluency non-responders, was described. RESULTS: Verbal fluencies were significantly higher after fampridine treatment. No correlation was observed between phonological fluency improvement and semantic fluency improvement. Gait responders and gait non-responders did not present significant differences in verbal fluency performance and fatigue score. No correlation between gait velocity improvement and fatigue improvement compared with verbal fluency improvement was observed. CONCLUSION: Our results suggest that fampridine could have a selective procognitive effect on phonological fluency in MS, even in the gait non-responder patients.
Assuntos
4-Aminopiridina/uso terapêutico , Transtornos Cognitivos/tratamento farmacológico , Apraxia da Marcha/tratamento farmacológico , Esclerose Múltipla/tratamento farmacológico , Distúrbios da Fala/tratamento farmacológico , Medida da Produção da Fala , Comportamento Verbal/efeitos dos fármacos , Adulto , Avaliação da Deficiência , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
OBJECTIVE: The study aims to assess mnesic performances of patients, following a head injury with pericerebral hematoma, according to the size of the hematoma. METHODS: Cognitive performances of a group of 25 patients with large (≥10 mm) pericerebral hematomas were compared with those of a matched group of 25 patients with small (<10 mm) ones and a matched group of patient with moderate-severe traumatic brain injury with no pericerebral hematoma. RESULTS: Executive function and information processing speed were not significantly different. Mnesic performances of the large hematomas group were more impaired: cuing effect (63.5 vs. 80% and 83%; p = 0.002; x03B7;2 = 0.183) and total recall (37.5/48 vs. 43.2 and 44.2; p = 0.022; x03B7;2 = 0.65) of the Free and Cued Recall Test. CONCLUSION: Memory of those in the large hematomas group was impaired with probable storage/consolidation disorders. To identify specific cognitive disorders resulting from large hematomas, it is justified to systematically screen these disorders and to adapt their management.