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1.
Mol Psychiatry ; 17(9): 875-9, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22472873

ABSTRACT

Performing exome sequencing in 14 autosomal dominant early-onset Alzheimer disease (ADEOAD) index cases without mutation on known genes (amyloid precursor protein (APP), presenilin1 (PSEN1) and presenilin2 (PSEN2)), we found that in five patients, the SORL1 gene harbored unknown nonsense (n=1) or missense (n=4) mutations. These mutations were not retrieved in 1500 controls of same ethnic origin. In a replication sample, including 15 ADEOAD cases, 2 unknown non-synonymous mutations (1 missense, 1 nonsense) were retrieved, thus yielding to a total of 7/29 unknown mutations in the combined sample. Using in silico predictions, we conclude that these seven private mutations are likely to have a pathogenic effect. SORL1 encodes the Sortilin-related receptor LR11/SorLA, a protein involved in the control of amyloid beta peptide production. Our results suggest that besides the involvement of the APP and PSEN genes, further genetic heterogeneity, involving another gene of the same pathway is present in ADEOAD.


Subject(s)
Alzheimer Disease/genetics , Codon, Nonsense/genetics , LDL-Receptor Related Proteins/genetics , Membrane Transport Proteins/genetics , Mutation, Missense/genetics , Aged , Case-Control Studies , Exome/genetics , Female , Genetic Predisposition to Disease/genetics , Genetic Predisposition to Disease/psychology , Humans , Male
2.
Rev Neurol (Paris) ; 168(6-7): 471-82, 2012 Jun.
Article in French | MEDLINE | ID: mdl-22579080

ABSTRACT

BACKGROUND: Criteria for the clinical diagnosis of Alzheimer's disease (AD) were established in 1984, and they needed to be updated and revised, in vue of the scientific knowledge acquired over the last decades. METHODS: The National Institute on Aging (NIA) and the Alzheimer's Association (AA) sponsored a series of advisory round table meetings to establish a revision of diagnostic and research criteria for AD. The workgroups reviewed the biomarker, epidemiological, and neuropsychological evidence, and proposed conceptual frameworks as well as operational research criteria based on the prevailing scientific evidence to date. RESULTS: Three preclinical stages of AD were proposed: asymptomatic amyloidosis, asymptomatic amyloidosis+neurodegeneration, amyloidosis+neurodegeneration+subtle cognitive decline. The preclinical workgroup developed recommendations to determine the factors, which best predict the risk of progression from normal cognition to mild cognitive impairment (MCI) and AD dementia. It is necessary to refine these models with longitudinal clinical research studies. The workgroups on MCI and AD dementia sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. The symptomatic predementia phase of AD was referred to as MCI due to AD. Core clinical and cognitive criteria of MCI were proposed, the final set of criteria for MCI due to AD has four levels of certainty, depending on the presence and nature of the biomarker findings. Criteria for all-cause dementia and for AD dementia were presented. Dementia caused by AD were classified in: probable AD dementia, possible AD dementia, and probable or possible AD dementia with evidence of the AD pathophysiological process, for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis. CONCLUSIONS: In the revised criteria, a conceptual distinction is made between AD pathophysiological processes and clinically observable syndromes. The core clinical criteria of the recommendations regarding MCI due to AD and AD dementia are intended to guide diagnosis in the clinical setting whereas the recommendations of the preclinical AD workgroup are intended purely for research purposes and do not have any clinical implications. Considerable work is needed to validate the criteria that use biomarkers and to standardize biomarker analysis for use in community settings.


Subject(s)
Alzheimer Disease/diagnosis , Cognitive Dysfunction/diagnosis , Dementia/diagnosis , Aged , Alzheimer Disease/psychology , Amyloidosis/diagnosis , Biomarkers , Cognitive Dysfunction/psychology , Dementia/psychology , Disease Progression , Humans , Neurodegenerative Diseases/diagnosis , Neurodegenerative Diseases/psychology , Reference Standards
3.
Rev Neurol (Paris) ; 168(2): 161-9, 2012 Feb.
Article in French | MEDLINE | ID: mdl-22104064

ABSTRACT

OBJECTIVE: The aim of the study was to compare the profiles of patients with young (age≤65 years) and late (age>65 years) onset of dementia in a memory clinic of a Memory Referral Center in Lyons (France), for the year 2008. METHODS: A total of 746 demented patients were evaluated using clinical, neuropsychological and imaging information. For each patient, diagnoses of the dementing disorder used clinical criteria at the first visit. We examined the distribution of patients diagnosis and differences in sex and education between the young-onset dementia (YOD) and the late-onset dementia (LOD) groups. RESULTS: From a total of 746 registered demented patients (300 men, 446 women), there were 91 patients (12.2%) with YOD (from 36.5 to 65 years) and 655 patients with LOD (from 66 to 92 years). Among the 91 YOD patients, the most frequent causes were Mild Cognitive Impairment (MCI) (18.7%), then Alzheimer's disease (AD), frontotemporal dementia and posterior cortical atrophy (14.3% each), followed by progressive aphasia (11.0%), dementia with Lewy bodies (DLD) (9.9%), semantic dementia (8.8%), other causes (3.3%), vascular dementia (2.2%), undetermined dementia (2.2%), AD+cerebrovascular disease (1.1%). Among the 655 LOD patients, AD was the most frequent cause of dementia (57.4%). Referred cases by a specialist doctor were 50.5% in the YOD group and 12.7% in the LOD group (P<0.0001). In the ACP group, 68.4% patients began before 65 years. CONCLUSION: The number of YOD in our memory clinic was four-fold the number of expected patients in France. The characteristics of the Referral Center explain the high frequency of rare dementia such as progressive aphasia (5.2% of overall number), semantic dementia (3.6%) and posterior cortical atrophy (2.5%).


Subject(s)
Dementia/diagnosis , Dementia/epidemiology , Dementia/etiology , Referral and Consultation/statistics & numerical data , Adult , Age of Onset , Aged , Ambulatory Care Facilities/organization & administration , Dementia/classification , Female , France/epidemiology , Humans , Male , Memory Disorders/diagnosis , Middle Aged , Neurology/methods , Neurology/organization & administration , Neurology/statistics & numerical data , Retrospective Studies , Socioeconomic Factors
4.
Rev Neurol (Paris) ; 167(6-7): 485-94, 2011.
Article in French | MEDLINE | ID: mdl-21429543

ABSTRACT

INTRODUCTION: Posterior cortical atrophy (PCA) is a clinical neurodegenerative syndrome associated with atrophy in parieto-occipital cortices, and characterized by prominent disorders of higher visual processing, affecting both dorsal and ventral streams. METHODS: We used a questionnaire (Q-ACP) specifically designed to assess visual and praxis dysfunctions in PCA. The Q-ACP contains 32 items (combined in 12 domains) aimed at describing everyday deficiencies that patients or caregivers notice about visual and gestural domains. It was administered to 34 patients with PCA (MMSE = 20.0 ± 5.1) which were compared with 17 patients with Alzheimer's disease (AD) (MMSE = 23.4 ± 1.9) and 31 normal controls (MMSE = 28.9 ± 1.1). RESULTS: Q-ACP of PCA patients (18.4 ± 5.3) was significantly greater than those of AD patients (2.7 ± 2.0) or normal controls (0.97 ± 1.6), and revealed disproportionate deficits on questions of visuospatial ability. Q-ACP was comparable in right (18.5 ± 4.3) and left (18.2 ± 6.8) PCA patients (p = 0.88). There was a negative correlation between MMSE and Q-ACP in PCA patients (r = -0.36; p = 0.045), but not in AD patients (r = -0.21; p = 0.42). When only the 22 PCA patients with MMSE equal or greater than 20 were considered, their Q-ACP score (17.2 ± 5.3) remained significantly greater than those of AD patients and normal controls (p = 0.0001). Controls had difficulties for only 12 of the 32 questions, and AD patients for 20 questions, whereas each of the 32 questions could be abnormal in the PCA group. The less often reported difficulties by PCA patients were for more easily reading small than big letters (14.7 %) whereas the most frequently impaired questions were for spatial and apractic agraphia (88.2 % for each question). Of the 12 domains of Q-ACP, all were impaired in PCA patients, 11 in AD patients and seven in controls. CONCLUSION: Q-ACP is a useful tool for assessing visual and praxis everyday difficulties of patients with PCA. These difficulties are rarely observed in normal aged controls or patients with mild AD.


Subject(s)
Cerebral Cortex/pathology , Gestures , Neurodegenerative Diseases/psychology , Surveys and Questionnaires , Visual Perception/physiology , Aged , Agraphia/etiology , Agraphia/psychology , Alzheimer Disease/psychology , Atrophy/psychology , Caregivers , Demography , Female , Functional Laterality/physiology , Humans , Male , Middle Aged , Neuropsychological Tests , Psychomotor Performance/physiology , Reading , Space Perception/physiology
5.
Encephale ; 37(2): 127-32, 2011 Apr.
Article in French | MEDLINE | ID: mdl-21482230

ABSTRACT

OBJECTIVES: Patients with major depression (MD) express frequent memory complaints leading to consultations in memory clinics. The 5-word test (5WT) is a verbal memory test with semantic cueing, which has shown its sensitivity and its specificity in identifying patients with Alzheimer's disease (AD). Our objective was to evaluate memory performances of aged patients with MD compared with controls and AD patients. METHODS: Characteristics of the 5WT were investigated in a sample of 37 patients with MD (66.8±7.5 years) compared with 36 normal controls (67.3±6.8 years) and 35 mild AD patients (67.5±6.1 years). RESULTS: Duration of depression was 15.3±11.5 years. Memory complaints of MD patients were ancient (4.6±5.5 years) and severe (McNair memory questionnaire=47.6±20.7). The Total score of MD patients did not differ from controls but was greater than those of AD patients. Learning and Memory scores of MD patients were significantly lower than those of controls and significantly greater than those of AD patients. Forgetting rate between Learning and Memory scores was more important in AD (72.4%) than in controls (2.8%) and MD (13.6%). No intrusions were recorded in controls, three MD patients each made one intrusion, whereas 80% of AD patients made between one to six intrusions (mainly during cued delayed recall). Receiver operating characteristic curves determined the most significant cut-off scores of the Total score. It appeared easy to discriminate AD patients from controls (cut-off=9, sensitivity=94.3%, specificity=100%) or MD patients (cut-off=8, sensitivity=88.5%, specificity=89.2%) whereas it was more difficult to discriminate MD patients from controls (cut-off=10, specificity=88.9%, sensitivity=37.8%). DISCUSSION: MD patients had significant difficulties with the 5WT as compared to controls, without being of the magnitude of those observed in AD patients. CONCLUSION: The 5WT allows a reliable evaluation of memory in MD patients. The presence of true memory deficits with the 5WT could not be ascribed to depression but to other pathological conditions. Consequently, further memory testing should be conducted.


Subject(s)
Alzheimer Disease/diagnosis , Depressive Disorder, Major/diagnosis , Mental Recall , Neuropsychological Tests/statistics & numerical data , Verbal Learning , Aged , Alzheimer Disease/psychology , Chronic Disease , Cues , Depressive Disorder, Major/psychology , Female , Humans , Male , Memory, Short-Term , Middle Aged , Psychometrics/statistics & numerical data , Reference Values , Reproducibility of Results , Retention, Psychology , Semantics
6.
Rev Neurol (Paris) ; 166(8-9): 711-20, 2010.
Article in French | MEDLINE | ID: mdl-20399477

ABSTRACT

INTRODUCTION: The five-word test (5WT) is a serial verbal memory test with semantic cuing. It is proposed to rapidly evaluate memory of aging people and has previously shown its sensitivity and its specificity in identifying patients with AD. It measures the efficacy of free and cued recalls during a procedure of immediate and delayed recalls. METHODS: The 5WT was compared in a group of 202 normal subjects and a group of 302 mild AD patients (MMS of 20 or more) aged from 60 to 92 years, in three age classes (60 years, 70 years, 80 years). Nine scores were measured (Total Score, Total Weighted Score, Free Immediate Recall, Learning Score=total of Immediate Recalls, Free Delayed Recall, Memory Score=total of Delayed Recalls, Forgetting Rate, Percentage of Immediate Cuing, Percentage of Delayed Cuing) as well as the presence of intrusions. For each age class, Receiver Operating Characteristic curves determined the most significant cut-off scores. RESULTS: For each score of the 5WT, AD patients differed significantly from controls. The cut-off scores were not the same according to age. For the Total Score, the cut-off scores were 10 (60 years), 9 (70 years) and 8 (80 years), whereas the cut-off scores of the Total Weighted Score were 17 (60 years), 16 (70 years) and 14 (80 years). As suggested by Cowppli-Bony et al. (2005), the Total Weighted Score (which gives a higher coefficient to free recalls) was better than the Total Score for discriminating mild AD. The 5WT is useful to discriminate normal controls and mild AD patients. Normal aged subjects displayed good encoding, efficient stocking and consolidation (few forgetting, efficient cued recall), intrusions were rare. Mild AD patients were characterized by weak encoding of words and severe deficit for stocking and consolidation (important forgetting, impaired cued recall), they made numerous intrusions. This psychometric profile is characteristic of the amnestic hippocampal syndrome found in AD. CONCLUSION: The 5WT is a simple and reliable test for investigating memory in elderly people above 60 years old. According to age, different cut-offs are needed for the Total Score and the Total Weighted Score, the latter appearing more discriminating than the Total Score for the diagnosis of mild AD. It is also interesting to evaluate the presence of intrusions. Lastly, it is important to consider the forgetting rate (between Learning and Memory Scores) in order to confirm the presence of a hippocampal amnesia.


Subject(s)
Alzheimer Disease/diagnosis , Memory Disorders/diagnosis , Neuropsychological Tests , Severity of Illness Index , Aged , Aged, 80 and over , Aging/psychology , Cognition Disorders/diagnosis , Cues , Female , Hippocampus/physiopathology , Humans , Male , Memory Disorders/physiopathology , Mental Recall , Middle Aged , Socioeconomic Factors , Verbal Learning
7.
Rev Neurol (Paris) ; 166(6-7): 584-93, 2010.
Article in French | MEDLINE | ID: mdl-20226490

ABSTRACT

INTRODUCTION: The Rapid BAttery of Denomination (BARD) is a short 10-item naming test derived from the 60-item Boston Naming Test. It is easily performed in less than 15 seconds by normal controls independently of age, gender and education (Croisile, 2005,2007,2008). Our aim was to evaluate the BARD in various conditions seen in a memory clinic. PATIENTS AND METHODS: The BARD was used in 382 normal subjects (165 men and 217 women, aged from 20 to 97 years) and 1004 patients attending a memory clinic. Three groups of 505 patients with Alzheimer's disease (AD) were compared: mild patients (n=402), moderate patients (n=84) and moderately severe patients (n=19). The BARD was also used in 499 patients with a Mini Mental Status (MMSE)>or=20: 173 patients with amnestic Mild Cognitive Impairment (aMCI), 56 patients with frontotemporal dementia (FTD), 41 patients with Lewy Body dementia (LBD), 36 patients with nonfluent primary progressive aphasia (NFPPA), 27 patients with semantic dementia (SD), 16 patients with posterior cortical atrophy (PCA), 150 patients with anxiety or depression (ADD). RESULTS: The performance of the patients was not affected by age, gender or education. aMCI had a score of 9.97+/-0.18, ADD a score of 9.97+/-0.2. A mild anomia was observed in three groups: mild AD (9.78+/-0.5), FTD (9.79+/-0.65) et LBD (9.98+/-0.16). A more pronounced anomia was present in moderate AD (9.10+/-1.06), moderately severe AD (8.05+/-1.27), PCA (8.12+/-3.28) and NFPPA (8.44+/-1.61). The anomia was severe in SD (5.85+/-2.46). The 10 items were perfectly named by 98 % of ADD, 96.53 % of aMCI, 82.09 % of mild AD, 87.5 % of FTD patients, 97.56 % of LBD patients, 68.75 % of PCA patients, but only 45.24 % moderate AD, 5.26 % of moderately severe AD, 27.78 % of NFPPA, and 3.7 % of SD. In the patients with MMS>or=20, Anova showed that the BARD scores of the ADD, aMCI, mild AD, FTD and LBD groups were significantly greater than the BARD scores of NFPPA, SD and PCA. PCA and NFPPA groups did not differ for BARD scores whereas they were significantly better than SD. A ROC curve comparing the 822 mild anomic patients (AD, FTD, LBD, aMCI, ADD) with the 79 more anomic patients (NFPPA, SD, PCA) showed that for a BARD score of 10, sensitivity was 72.2 %, specificity was 89.2 %, and 87.7 % of the patients were correctly classified. CONCLUSION: The BARD is a quick and useful tool for identifying naming disorders in a memory clinic. In patients with MMSE>or=20, making one error at the BARD is highly abnormal and significantly characteristic of cognitive disorders: the more frequent the errors are, the more probable is the presence of a visual agnosia (PCA), an aphasia (NFPPA), or a semantic disorder (SD).


Subject(s)
Anomia/diagnosis , Dementia/psychology , Language Tests , Names , Neuropsychological Tests , Severity of Illness Index , Adult , Aged , Aged, 80 and over , Alzheimer Disease/psychology , Ambulatory Care Facilities , Anomia/psychology , Aphasia/psychology , Cognition Disorders/psychology , Female , Humans , Male , Middle Aged , ROC Curve
8.
Rev Neurol (Paris) ; 165(3): 256-62, 2009 Mar.
Article in French | MEDLINE | ID: mdl-19124140

ABSTRACT

INTRODUCTION: Posterior cortical atrophy (PCA) is a clinically and radiologically defined syndrome, in which predominant symptoms focus on higher visual dysfunction with progressive course and association with cortical atrophy or hypometabolism that predominates in the posterior part of the hemispheres. Homonymous hemianopia (HH) has rarely been described in this syndrome. METHODS: We report on six patients (four females, two males, aged 63 to 80) referred for visual disorder which led to demonstration of HH using perimetry testing. These patients were followed for 1 to 5 years after discovery of HH. Brain imaging with MRI or CT scan was obtained in the six cases and a SPECT scan was performed in four cases. RESULTS: HH was left-sided in four cases and right-sided in two cases. Associated symptoms related to higher visual dysfunction were simultagnosia, alone or as part of a full Balint's syndrome, alexia, constructional apraxia, dressing apraxia, visual form agnosia, prosopagnosia and hemispatial neglect. These symptoms were mild at onset but invariably worsened with disease progression. Dementia eventually developed in all cases. The clinical diagnosis was probable Alzheimer's disease in five cases and corticobasal degeneration in one case. Radiology showed posterior cortex atrophy in all cases as well as reduced cerebral blood flow in the same region, with an asymmetrical pattern compatible with the side of HH. CONCLUSION: Elementary cortical lesions in PCA can develop mainly in the associative visual areas and even in the primary visual area, resulting in HH. HH has rarely been documented in PCA, but its prevalence would probably be higher if systematic search was conducted. Apparently isolated HH of insidious onset should suggest PCA and lead to neuropsychological testing and search for discrete atrophic changes of the posterior cortex on MRI as well as for metabolic alterations with SPECT or PET.


Subject(s)
Cerebral Cortex/pathology , Hemianopsia/pathology , Aged , Aged, 80 and over , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/pathology , Atrophy , Cerebral Cortex/diagnostic imaging , Dementia/etiology , Disease Progression , Female , Hemianopsia/diagnostic imaging , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Positron-Emission Tomography , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray Computed
9.
Rev Neurol (Paris) ; 163(3): 323-33, 2007 Mar.
Article in French | MEDLINE | ID: mdl-17404519

ABSTRACT

INTRODUCTION: The 5-word test (5WT) is a serial verbal memory test with semantic cuing. It allows to estimate cued learning, free recall, and cued recall of 5 words during immediate and delayed recalls (5 min later). The 5WT is proposed to rapidly evaluate memory of aging people. It has shown its sensitivity and its specificity in identifying patients with Alzheimer's disease (AD). OBSERVATIONS: We report the constitution of a sample of 191 French speaking normal subjects, aged from 50 to 90 years, in four age classes (50 years, 60 years, 70 years, 80 years) and three education levels. Total Score, Total Weighted Score, Free Delayed Recall, Delayed Recalls Total (memory score), and Free Recalls Total appear to be the best scores to appreciate the memory performance of the normal subjects. A Total Score of 10 was obtained in 74.9 p.cent of the subjects. No immediate nor delayed intrusions were recorded. In spite of the absence of an explicit consign, the recalled words were often ordered as they were in the list. CONCLUSION: The 5WT is a simple and reliable test for investigating memory in elderly people above 50 years old.


Subject(s)
Memory, Short-Term , Mental Recall , Verbal Learning , Aged , Aged, 80 and over , Aging , Educational Status , Humans , Memory Disorders/epidemiology , Middle Aged , Reference Values , Reproducibility of Results
10.
Arch Neurol ; 49(9): 971-6, 1992 Sep.
Article in English | MEDLINE | ID: mdl-1520089

ABSTRACT

We report a case of slowly progressive amusia and aprosody in association with orofacial and eyelid apraxias. The patient was independent in daily living activities. Insight, judgment, and behavior were intact. Her language was normal, and she demonstrated no limb, dressing, or constructional apraxia. She had no prosopagnosia, no visuospatial disturbances, and no memory impairment. Imaging studies (computed tomography, magnetic resonance imaging, single photon emission computed tomography) indicated a selective disorder of the right frontal and temporal regions. Review of the literature shows an increasing number of reports of this degenerative syndrome affecting the left dominant hemisphere and language areas, whereas cases of the syndrome affecting the right hemisphere are rare. To our knowledge, this is the first case in which aprosody and amusia were associated with a focal cortical degeneration.


Subject(s)
Language Disorders/diagnosis , Music , Speech Disorders/diagnosis , Brain/blood supply , Brain/diagnostic imaging , Brain/pathology , Female , Humans , Language Disorders/pathology , Language Tests , Magnetic Resonance Imaging , Middle Aged , Regional Blood Flow , Speech Disorders/pathology , Tomography, Emission-Computed
11.
Neurology ; 43(2): 301-5, 1993 Feb.
Article in English | MEDLINE | ID: mdl-8437693

ABSTRACT

Preclinical research suggests that piracetam (a nootropic drug) may improve cognitive functions, but previous studies have failed to demonstrate a clear benefit for the treatment of Alzheimer's disease (AD). We report a 1-year, double-blind, placebo-controlled, parallel-group study with a high dose of piracetam (8 g/d per os) in 33 ambulant patients with early probable AD. Thirty subjects completed the 1-year study. No improvement occurred in either group, but our results support the hypothesis that long-term administration of high doses of piracetam might slow the progression of cognitive deterioration in patients with AD. The most significant differences concerned the recall of pictures series and recent incident and remote memory. The drug was well-tolerated.


Subject(s)
Alzheimer Disease/drug therapy , Piracetam/administration & dosage , Aged , Aged, 80 and over , Alzheimer Disease/psychology , Analysis of Variance , Double-Blind Method , Female , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Time Factors
12.
Eur J Cancer ; 32A(1): 69-71, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8695244

ABSTRACT

A phase II study was conducted in order to determine the feasibility and toxicity of cisplatin combined with the nitrosourea fotemustine in central nervous system metastases from non-small cell lung cancer. 31 chemotherapy-naïve patients were included between November 1990 and April 1993. Computed tomography scan-documented tumour regression in brain metastases was observed in 7 of the 25 evaluable patients, but only 4 of these (16%) lasted more than 4 weeks. In 2 of these 4 patients, the response on central nervous system metastases was considered as complete. The median duration of response was 20.5 weeks and the median survival was 16 weeks overall and 28.5 weeks for responding patients. The limiting toxicity of this regimen was haematological. 2 patients died from infectious pneumonitis while in neutropenia. Treatment delays due to haematological toxicity occurred in 57% of patients. Despite the rather encouraging response rate, such toxicity appears too high when compared to the overall bad prognosis of this population of patients. Cranial radiotherapy remains the standard treatment in this setting and should only be compared in the future to less aggressive schedules.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Neoplasms/drug therapy , Brain Neoplasms/secondary , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/secondary , Lung Neoplasms/pathology , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Cisplatin/adverse effects , Female , Hematologic Diseases/chemically induced , Humans , Male , Middle Aged , Nitrosourea Compounds/administration & dosage , Nitrosourea Compounds/adverse effects , Organophosphorus Compounds/administration & dosage , Organophosphorus Compounds/adverse effects , Survival Rate
13.
J Neurol Sci ; 166(2): 141-51, 1999 Jul 01.
Article in English | MEDLINE | ID: mdl-10475108

ABSTRACT

The contribution of striatal (caudate nucleus-putamen) dopaminergic deficiency to the severity of motor signs is well established in Parkinson's disease (PD), while its role in the occurrence of cognitive and mood changes remains unresolved. We therefore measured in 27 non-demented PD patients and 10 age-matched controls striatal uptake of [18F]-6-fluoro-L-Dopa (F-Dopa) with PET, and mood (Beck depression), memory (Grober-Buschke), frontal executive functions (verbal fluency and Wisconsin card sorting), and attentional processing of sensory stimuli (N2-P3 auditory event-related potentials--ERPs). Locomotor disability of patients was assessed by Hoehn and Yahr score and Unified Parkinson's Disease Rating Scale (UPDRS). ANOVA showed that memory, but neither frontal lobe functions nor ERPs, was significantly altered in PD patients, whereas indices of depression were found only in advanced PD. The F-Dopa rate constant Ki was significantly reduced in the striatum, more in putamen than caudate nucleus, and inversely correlated with disease duration. A significant inverse correlation was found between both putamen and caudate nucleus Ki and Hoehn and Yahr score, and between putamen--but not caudate nucleus Ki --and UPDRS motor score. Principal components analysis (PCA) of PD patients Ki values and mood, cognitive and ERP parameters gave a three-factor solution. Variables contributing to factor 1 were memory score and N2-P3 ERP latencies, those to factor 2 were striatal Ki values, and those to factor 3 frontal executive performances. Depression did not segregate with any variable. Our findings suggest that unlike locomotor disability, cognitive abilities and mood state of non-demented PD patients are for the most part unrelated to striatal dopaminergic depletion and may result from dysfunction of extra-striatal dopaminergic or from non-dopaminergic systems.


Subject(s)
Caudate Nucleus/physiopathology , Dopamine Agents/pharmacology , Levodopa/pharmacokinetics , Motor Skills Disorders/physiopathology , Parkinson Disease/physiopathology , Putamen/physiopathology , Adult , Affect/physiology , Aged , Analysis of Variance , Case-Control Studies , Caudate Nucleus/diagnostic imaging , Caudate Nucleus/metabolism , Cognition/physiology , Event-Related Potentials, P300 , Female , Humans , Male , Middle Aged , Parkinson Disease/diagnostic imaging , Parkinson Disease/metabolism , Putamen/diagnostic imaging , Putamen/metabolism , Tomography, Emission-Computed
14.
Clin Neurol Neurosurg ; 91(4): 325-7, 1989.
Article in English | MEDLINE | ID: mdl-2555093

ABSTRACT

A 76-year-old man suddenly presented with loss of motivation for speaking. He had no aphasia, depression or dementia, but he did not want to speak with other people. CT scan showed hypodensities, presumably lacunes, mainly in the anterior limb of the two internal capsules. Global behavioral changes with loss of self psychic activation have been reported, but in our patient the disturbance was restricted to oral language. The role of activating cortico-subcortical loops is discussed.


Subject(s)
Cerebral Infarction/complications , Language Disorders/etiology , Motivation , Aged , Cerebral Infarction/diagnostic imaging , Humans , Male , Tomography, X-Ray Computed
15.
Brain Lang ; 54(3): 361-87, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8866054

ABSTRACT

Written and oral spelling were compared in 33 patients with Alzheimer's disease (AD) and 25 control subjects. AD patients had poorer spelling results which were influenced by orthographic difficulty and word frequency, but not by grammatical word class. Lexical spelling was also more deteriorated than phonological spelling. Moreover, oral spelling was more impaired than written spelling in AD patients, whereas no difference was present between oral and written spelling of controls. Analysis of spelling errors showed that, for controls, errors were predominantly phonologically accurate in both spelling tasks. Significantly, AD patients produced more phonologically accurate than inaccurate errors in written spelling, whereas these errors did not differ in oral spelling. In contrast to controls who produced more constant than variable responses in oral and written spelling, AD patients made more variable responses (words correctly spelled in one task but incorrectly in the other) and they showed many instances of variable errors (different misspellings from one spelling task to the other). Two stepwise regression procedures showed that written misspellings were specifically correlated with language impairment, whereas oral spelling errors were correlated with attentional and language disorders. These results suggest that AD increases the attentional demands of oral spelling process as compared to written spelling. This dissociation argues, either for a unique Graphemic Buffer in which oral spelling requires more attentional resources than written spelling or for the hypothesis of separate buffers for oral and written spelling.


Subject(s)
Alzheimer Disease/physiopathology , Speech , Writing , Aged , Brain/physiopathology , Cognition Disorders/diagnosis , Female , Humans , Male , Neuropsychological Tests
16.
Brain Lang ; 53(1): 1-19, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8722896

ABSTRACT

Oral and written picture descriptions were compared in 22 patients with Alzheimer's disease (AD) and 24 healthy elderly subjects. AD patients had a significant reduction of all word categories, which, similarly to controls, was more pronounced in written than in oral texts. They also reported fewer information units than controls, but without task difference. At the syntactic level, written descriptions of AD subjects were characterized by a diminution of subordinate clauses and a reduction of functors. More grammatical errors were present in written descriptions by AD and control subjects. AD and control groups produced an equivalent number of semantic errors in both tasks. However, in oral description, AD patients had more word-finding difficulties. In sum, AD descriptions were always shorter and less informative than control texts. Additionally, written descriptions of AD patients appeared shorter and more syntactically simplified than, but as informative as oral descriptions. Whereas no phonemic paraphasias were observed in either group, AD patients produced many more graphemic paragraphias than controls produced. Furthermore, written descriptions had more irrelevant semantic intrusions. Thus, as compared to oral descriptions, written texts appeared to be a more reliable test of semantic and linguistics difficulties in AD.


Subject(s)
Alzheimer Disease/complications , Language Disorders/etiology , Aged , Female , Humans , Language Disorders/diagnosis , Male , Middle Aged , Semantics , Writing
17.
Rev Neurol (Paris) ; 145(10): 720-4, 1989.
Article in French | MEDLINE | ID: mdl-2814154

ABSTRACT

Pure agraphia is a disorder of written language without aphasia, alexia or apraxia. Its existence has long been disputed. We report 2 cases due to a left parietal hematoma. In the first patient, with a deep precuneate lesion, agraphia included disorders in handwriting and orthographic problems in copying or writing from dictation with the two hands. The second patient, with a lesion of the postero-inferior part of the left angular gyrus, made errors in choice and combination of letters during dictation, whereas these same letters were well-written and copying was normal. The first cases of pure agraphia were ascribed to frontal lesions and then confusional states. Current opinion tends to implicate parietal lesions of various types: superior or inferior, internal or external. Findings in the present 2 cases and those reported indicate that pure parietal agraphia is heterogeneous.


Subject(s)
Agraphia/etiology , Cerebral Hemorrhage/complications , Hematoma/complications , Parietal Lobe/physiopathology , Aged , Agraphia/diagnostic imaging , Agraphia/physiopathology , Brain Diseases/complications , Brain Diseases/diagnostic imaging , Brain Diseases/physiopathology , Cerebral Hemorrhage/diagnostic imaging , Hematoma/diagnostic imaging , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Parietal Lobe/diagnostic imaging , Tomography, X-Ray Computed
18.
Rev Neurol (Paris) ; 146(5): 338-44, 1990.
Article in French | MEDLINE | ID: mdl-2196653

ABSTRACT

Three clinical cases are reported, resulting in apathy, uninterest, flattened affect and lack of initiative for usual daily activities. Intellectual performances were normal and there was no depression. This syndrome was reversible when patients were stimulated. Stereotyped behaviors resembling compulsions were frequent. One of the patients presented with prolonged akinetic episodes reversible by verbal stimulation. CT and MRI showed bilateral lesions, mainly in and around the head of the caudate nucleus. Such behavioral disorders have been termed psychic akinesia or athymhormia syndrome, suggesting that the patients suffered from a loss of drive and motivation. The lesions involved bilaterally the globus pallidus, the striatum or the frontal lobe. Recently, anatomical findings have shown several circuits through the basal ganglia additional to the motor circuit. The caudate nucleus receives inputs from the prefrontal and limbic cortex. These inputs are transmitted to the globus pallidus, then to the thalamus and ultimately return to the dorsolateral prefrontal, lateral orbitofrontal and anterior cingulate areas. Lesions in any part of these cortico-subcortical loops may be responsible for a dramatic behavioral syndrome, emphasizing their functional specificity in drive. However, a procedural learning impairment in neostriatal dysfunction could possibly explain the disorders observed in our patients.


Subject(s)
Caudate Nucleus , Psychomotor Disorders/etiology , Brain Diseases/complications , Brain Diseases/physiopathology , Caudate Nucleus/blood supply , Caudate Nucleus/physiopathology , Cerebral Hemorrhage/complications , Cerebral Infarction/complications , Female , Hematoma/complications , Humans , Male , Middle Aged , Psychomotor Disorders/physiopathology
19.
Rev Neurol (Paris) ; 159(11): 1009-15, 2003 Nov.
Article in French | MEDLINE | ID: mdl-14710021

ABSTRACT

It may be difficult to distinguish between a primary progressive aphasia at a very mild stage from the beginning of Alzheimer's disease (AD). However, this may be achieved by carrying out simple neuro-psychological tests. Nine non-fluent PPA (NFPPA) and 76 AD patients with comparable MMSE as well as 58 control subjects were evaluated using simple tests: MMSE, fluency, apraxia, naming, digital span, story memory, 5 words memory test. NFPPA patients had significantly impaired functions during the semantic category fluency and naming tests as compared to AD patients, whereas they showed a better delayed recall of the 5 words and story memory tests. As compared to AD, MMSE of NFPPA patients was also better in the time orientation and word recall sub-tests, although inferior in words repetition and language items. Thus, with comparable MMSE, NFPPA patients have more lexico-semantic difficulties, but a better delayed verbal memory than AD patients. These simple tests easily confirm the language impairment of NFPPA patients as opposed to the mnestic difficulties of AD, even at very early stages of these pathologies.


Subject(s)
Aphasia, Broca/diagnosis , Adult , Aged , Aged, 80 and over , Alzheimer Disease/diagnosis , Cognition Disorders/diagnosis , Diagnosis, Differential , Disease Progression , Female , Humans , Male , Middle Aged , Severity of Illness Index , Wechsler Scales
20.
Rev Neurol (Paris) ; 151(6-7): 416-9, 1995.
Article in French | MEDLINE | ID: mdl-7481408

ABSTRACT

A 71 year-old hypertensive right-handed man presented a small intracerebral haematoma limited to the left subthalamic nucleus that resulted in right hemiballismus and a neurobehavioral disinhibition syndrome. The latter associated logorrhoea and euphoria, but there was no frontal signs nor mental confusion. The patient kept full insight into his mental change, that contrasted with his prior personality. Hemiballismus and the manic-like state resolved within 2 months. This case and some others from the literature illustrated that a focal lesion in the basal ganglia could result in manic-like affective change, and that a relation did exist between hyperkinetic syndrome and euphoria. Our case contrasted with most of the published cases of neurobevioral changes following basal ganglia discrete lesions, expressing as hypokinesia, apathy and loss of motivation. With reference to the functional circuits linking the frontal cortex and the basal ganglia, as described by Alexander, this syndrome of combined disinhibition of motricity, speech and affect could involve either the lateral orbito-frontal or the anterior cingulate loops, more especially the indirect pathways travelling through the subthalamic nucleus, lesion of which is known to disinhibit thalamo-cortical activity.


Subject(s)
Cerebral Hemorrhage/complications , Chorea/complications , Hematoma/complications , Mood Disorders/etiology , Speech Disorders/etiology , Aged , Brain/physiopathology , Cerebral Cortex/physiopathology , Cerebrovascular Circulation , Humans , Male , Thalamic Nuclei
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