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M Benoit

Publications and source records attributed to M Benoit.

At least 19 recordsLinked to original sources

99mTc-HMPAO and 99mTc-ECD brain uptake correlates of verbal memory in Alzheimer's disease.

AIM: Technetium-99m hexamethylpropylene amine oxime ((99m)Tc-HMPAO) and technetium-99m N,N-1,2-ethylene diylbis-Lcysteine diethyl ester dihydrochloride ((99m)Tc-ECD) SPECT are widely used in Dementia Clinics for early and differential diagnosis. They have been shown to perform differently in Alzheimer's disease (AD), but the impact of such differences on both research and clinical work is unknown. We investigated the differences between the 2 compounds in research work by assessing correlation between performance on a verbal memory task and cerebral perfusion in 2 matched groups of AD patients. METHODS: Nineteen pairs of patients with mild to moderate AD undergoing SPECT with either 99mTc-HMPAO or (99m)Tc-ECD were retrospectively selected in a Memory Clinic. Patients were matched for sex, age (+/-3 years) and the Mini-Mental State Examination score (+/-2 points) with a case-control procedure, thus obtaining 2 well-matched groups. The score on the Grober-Buschke selective reminding test (SRT) was correlated with SPECT in each group by means of statistical parametric mapping 99 (height threshold: P<0.01). RESULTS: (99m)Tc-HMPAO SPECT yielded 3 significant correlation clusters involving inferior and middle frontal gyri, para-hippocampal gyrus and putamen in the right hemisphere; the middle and superior temporal gyri, insula and claustrum in the left hemisphere. (99m)Tc-ECD gave a significant cluster of correlation in left postcentral gyrus and inferior parietal lobule. CONCLUSION: (99m)Tc-HMPAO SPECT correlation sites seem more consistent than (99m)Tc-ECD ones with the neurophysiological models of verbal memory, as designed both in normal individuals and in pathological conditions. The demonstration of such relevant differences introduces a source of variability among studies performed with either of the 2 compounds, which must be considered when interpreting results.

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Lack of initiative and interest in Alzheimer's disease: a single photon emission computed tomography study.

Apathy is defined as a lack of motivation. The aim of this study was to investigate the relation between two major dimensions of apathy (lack of initiative and lack of interest) and brain perfusion. in patients with Alzheimer's disease (AD). Brain perfusion was measured by single photon emission tomography (SPECT). Thirty-one AD patients were included. Lack of initiative and interest were assessed with the Apathy Inventory. Nineteen AD subjects presented a lack of initiative and interest pathological score whereas 12 AD subjects did not. The lack of initiative and interest score correlated significantly with the right frontal and the right inferior temporal lobes. The AD patients with lack of initiative and interest showed a significantly lower perfusion in the right anterior cingulate than the AD patients without lack of initiative and interest. These results derive from rather small subgroups of patients but have the interest to dismantle the complementary aspects of emotion and motivation in apathy and suggest that the latter one is more related to cingulate area.

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[Behavioral and psychological symptoms in dementia: description and management].

Behavioral and Psychological Symptoms in Dementia (BPSD) are, beside cognitive disorders, major features of Alzheimer's disease and related disorders. Diagnosis is important to enhance our knowledge of the pathophysiology of dementia and of their functional consequences for patients and caregivers. Pharmacological and non-pharmacological management of dementia depends to a large extent on the presence of BPSD. A committee of geriatricians, neurologists and psychiatrists specialized in dementia (THEMA 2) has promoted an epidemiological, diagnostic and therapeutic update in this field. This work was based on the BPSD Consensus Conference Report edited in 2000 by the International Psychogeriatric Association. This report was updated with the most recent literature reports, and was adapted to the French environment. This paper is a synthesis of this meeting, validated and corrected by the entire Thema 2 group.

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Long-acting risperidone in stable patients with schizoaffective disorder.

Oral and long-acting risperidone has been shown to be effective for acute and maintenance treatment of patients with schizoaffective disorders. The present analysis investigated the efficacy and tolerability of direct transition from other antipsychotics to risperidone long-acting injectable in patients with schizoaffective disorder. Patients aged > or = 18 years with schizoaffective disorder (DSM-IV), who required a change of medication, received risperidone long-acting injectable 25 mg (increased to 37.5 or 50 mg, if necessary) every 2 weeks for 6 months. The analysis included 249 patients (47% male; mean age 43 years), of whom 74% completed the 6-month study. Mean scores for the total Positive and Negative Syndrome Scale (PANSS) and all three subscales were significantly reduced from baseline to week 4 (p < 0.001), with further improvements until treatment endpoint. Significant improvements from baseline to endpoint were seen in the mood symptom domains of anxiety/depression (10.4+/-4.1 vs 8.7+/-3.9) and uncontrolled hostility/excitement (7.6+/-3.6 vs 6.9+/-3.8). Mean Global Assessment of Function (GAF) score improved significantly from 59.4+/-15.6 at baseline to 66.4+/-17.7 (p < 0.001) at endpoint. Of 87 patients hospitalized at baseline, 67% were discharged at endpoint. Both quality of life (SF-36) and satisfaction with treatment were improved significantly at endpoint. Total ESRS scores fell progressively throughout the study, and the reduction was already statistically significant (p < 0.001) at 4 weeks. Small but statistically significant (p < 0.001) mean shifts of 1.8% were seen in body weight and Body Mass Index (BMI). Patients with schizoaffective disorder derived several benefits from a change to risperidone long-acting injectable, including reductions in psychiatric symptoms (particularly the mood symptom domains) and a reduction in the severity of drug-induced neurological movement disorders.

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Nutritional status assessment during Alzheimer's disease: results after one year (the REAL French Study Group).

OBJECTIVES: Weight loss and malnutrition are frequent and serious complications of Alzheimer's disease. The aim of the present article was to describe the cognitive and behavioural characteristics of the test population within the frame of the PHRC REAL.FR cohort (for Réseau sur la Maladie d'Alzheimer Français), depending on their nutritional state, and to consider their evolution one year after the original inclusion. METHOD: The study population' stratification was done in three groups according to their Mini Nutritional Assessment (MNA) score: malnutrition group (MNA < 17.5), at risk of malnutrition group (MNA 17.5-23.5), and normal nutritional status group (MNA > or = 23.5). 561 patients were evaluated at inclusion time, 393 at one year. The evaluation included the following scales: Mini Nutritional Assessment (MNA), Mini Mental State Examination (MMSE), Activities Daily Living (ADL), Instrumental Activities Daily Living (IADL), Neuro Psychiatric Inventory (NPI) and Zarit scale (ZARIT). Comparison and descriptive analysis for each MNA group at baseline and at one year has been performed. RESULTS: at baseline, the well-nourished and the malnutrition risk groups are significantly different concerning age, IADL and NPI; the well-nourished and undernutrition groups are different concerning MMSE, NPI and Zarit; the malnutrition risk and undernutrition groups are only different concerning NPI. At one year, the well-nourished and the malnutrition risk and undernutrition groups are different concerning one lonely variable, the NPI, in a significant way. The comparison of the three groups between baseline and one-year evaluation demonstrate for the well-nourished group an aggravation of MMSE, ADL, IADL, NPI, for the malnutrition risk group of MMSE and IADL, and for the undernutrition group of MMSE, IADL and NPI. CONCLUSION: Among the patients suffering from Alzheimer's disease, the most malnutritioned worsen highly on cognitive and functional capacities. Furthermore, the nutritional aggravation seems strongly linked to behavioural disorders aggravation. The improvement of those disorders has therefore to be part of every improvement strategy applied to the nutritional status of the demented patients.

Activities of Daily Living↗

One-year longitudinal evaluation of neuropsychiatric symptoms in Alzheimer's disease. The REAL.FR Study.

Behavioral and Psychological Symptoms are major and frequent manifestations of Alzheimer's Disease (AD). The aim of the present study was to evaluate neuropsychiatric symptoms in the PHRC REAL.FR cohort (for Réseau sur la maladie d'Alzheimer Français) after one year of evolution. Four hundred and eighty two patients with mild and moderate AD were assessed. A majority of them had significant symptoms at inclusion (85.3 % of subjects with mild AD, 89.7% of patients with a moderate AD). Patients with mild AD had a significant increase of the Neuropsychiatric Inventory (NPI) frequency x severity scores for apathy and aberrant motor behavior. Patients with moderate AD had a significant increase of NPI disinhibition, aberrant motor behavior and sleep disorders scores. The variation of NPI total score at one year correlated positively with change in Zarit's caregiver burden score, independently of global cognitive evolution. After one year, a group of 54 patients were institutionalized in nursing home or long term care unit. When compared to non institutionalized patients, the institutionalized group was characterized at base line by a lower MMSE score, a higher Zarit caregiver burden score, and a higher NPI agitation and disinhibition scores.

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Predictive factors of rate of loss of autonomy in Alzheimer's disease patients. A prospective study of the REAL.FR Cohort.

Alzheimer's disease is characterised by a progressive loss of autonomy in activities of daily living. Many patients lose this autonomy rapidly with dramatic consequences for the patients and their relatives, and for health and social services. The aim of this study was to determine, in a large French cohort of community-living Alzheimer patients (REAL.FR), the factors underpinning different rates of loss of autonomy. Six hundred and eighty seven patients were recruited to this French cohort. Autonomy in activities of daily living was estimated with the IADL scale (Lawton). Patients were divided into three groups according to loss of autonomy during the first one-year follow-up period. Patients with a decrease in the IADL score had worse ADAS-cog score (Alzheimer's Disease Assessment Scale, cognitive subscale), Mini-Mental State Examination (MMSE), and Clinical Dementia Rating Scale scores. Up to a point, a marked decrease in the IADL score was less frequent among patients with a better ADAS-cog score (p < 0.10, bilateral test). At one-year evaluation, patients with a marked decline in autonomy were characterised by a greater decrease in Mini-Mental State score, faster progression of behavioural disturbance, and more hospitalisations. Further prospective studies, using established models, are needed to isolate the factors associated with a high rate of loss of autonomy in activities of daily living in Alzheimer patients.

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Brain perfusion correlates of the apathy inventory dimensions of Alzheimer's disease.

BACKGROUND: Apathy is defined as a lack of motivation in behavior, cognition and affect. This syndrome is frequent in various neuropsychiatric diseases but little is known about its pathophysiology. OBJECTIVES: The aim of this study was to investigate the metabolic correlates of the behavioral, cognitive and emotional, aspects of apathy in Alzheimer's disease (AD). METHOD: Thirty AD patients were included. Lack of initiative, lack of interest and of emotional blunting were assessed with the Apathy Inventory (IA), a tool designed to provide a separate assessment of the behavioral, cognitive and emotional, aspects of apathy. Brain perfusion was measured by (99m)Tc-labeled bicisate (ECD) single photon emission tomography. RESULTS: The Statistical Parametric Mapping software provides negative correlation between IA total score and brain perfusion in left and right superior orbito-frontal gyrus, and to a lesser extent in left middle frontal gyrus (BA10). Lack of initiative score was negatively correlated with perfusion in right anterior cingulate cortex. Lack of interest score was negatively correlated with perfusion in right middle orbitofrontal gyrus). Emotional blunting score correlated negatively with in left superior dorsolateral prefrontal cortex activity. CONCLUSION: These results underline that the cognitive, behavioral and affective components of motivation are mediated by different fronto-sub-cortical circuits and are differently lateralized. In particular, left prefrontal hypoperfusion is involved in emotional blunting, as it was often demonstrated in depressive disorders. These distinct components of apathy may be targeted by different therapeutic means, in which dopaminergic enhancement might play a major role.

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Molecular resolution of cell adhesion forces.

Recently, AFM-based force spectroscopy has been used to quantify single-molecule adhesion forces on living ameboid cells. Force spectroscopy was used to measure the rupture forces of single receptor-ligand bonds which can occur rapidly between the cell types used, a metastasising B16 melanoma cell and a vascular bEnd.3 endothelial cell. Parameters which influence the critical experimental conditions are discussed to discriminate between multiple bond ruptures and single bonds. Under physiological conditions of temperature and pH the force measurements show an average rupture force of 33 pN (SD = 12 pN) for single bonds. Single-molecule force spectroscopy will be very useful to study the regulation of cell adhesion on a molecular level in normal processes, such as leukocyte homing, and in major human disorders, including tumor metastasis, autoimmune diseases and atherosclerosis.

Journal Article↗

A force-based protein biochip.

A parallel assay for the quantification of single-molecule binding forces was developed based on differential unbinding force measurements where ligand-receptor interactions are compared with the unzipping forces of DNA hybrids. Using the DNA zippers as molecular force sensors, the efficient discrimination between specific and nonspecific interactions was demonstrated for small molecules binding to specific receptors, as well as for protein-protein interactions on protein arrays. Finally, an antibody sandwich assay with different capture antibodies on one chip surface and with the detection antibodies linked to a congruent surface via the DNA zippers was used to capture and quantify a recombinant hepatitis C antigen from solution. In this case, the DNA zippers enable not only discrimination between specific and nonspecific binding, but also allow for the local application of detection antibodies, thereby eliminating false-positive results caused by cross-reactive antibodies and nonspecific binding.

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Long-term results of intrathoracic chemohyperthermia (ITCH) for the treatment of pleural malignancies.

There is no standard treatment for patients with pleural malignancies. The aim of this prospective study was to investigate the toxicity and long-term results of a multimodality treatment consisting of surgery and intrathoracic chemohyperthermia (ITCH) for the treatment of patients with pleural malignancies. From January 1990 to August 2000, 24 patients with mesothelioma (n=17), fibrosarcoma (n=3), pleural adenocarcinoma (n=3) and thymoma (n=1) were included. The mesothelioma stages were T1 or T2 in 10 cases, and T3 or T4 in seven cases. After cytoreductive surgery, ITCH was carried out for over 60 min, at inflow temperatures less than 45 degrees C, either with mitomycin C (n=7) or cisplatin (n=5) or both (n=12). One patient died from major thoracic air leaks after major decortication and pleurectomy. Seven patients had complications, one pleural clotting necessitating reoperation. After a median follow-up of 89 months, the overall 1-year and 5-year survival rates were 74 and 27%, respectively. For T1 and T2 mesothelioma patients, the median survival was 41.3 months, and for T3 and T4 tumours, it was 4.5 months (P=0.001). The fibrosarcoma patients are alive with no evidence of recurrence at 24, 43 and 54 months. In the conclusion, the combination of surgery with ITCH with mitomycin and/or cisplatin is relatively safe. This procedure may offer unexpected long-term survival in a selected group of patients (T1 and T2 mesothelioma patients and fibrosarcoma patients).

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Role of behavioural disturbance in the loss of autonomy for activities of daily living in Alzheimer patients.

BACKGROUND: Cognitive impairment is associated with functional impairment in patients with Alzheimer's disease (AD). Behavioural disturbance is very common in these patients. Nevertheless, there has been very little research into the relations between behavioural disturbance and functional status in AD. The purpose of this study is to investigate the relationship between behavioural disturbance and functional status after taking account of cognitive impairment. MATERIAL AND METHODS: 579 patients were prospectively evaluated at 16 French hospitals, all referents for AD, and were diagnosed with possible or probable AD. These patients were assessed with NeuroPsychiatric Inventory (NPI), cognitive subscales of the Alzheimer's Disease Assessment Scale (ADAS-cog), Clinical Dementia Rating scale (CDR) and Instrumental Activities of Daily Living scale (IADL). RESULTS: The number of men with available data for IADL total score was too small to make any analysis. 'Group A' gathered 256 women for whom the relation between autonomy for Activities of Daily Living (ADL) and the other variables were determined. 'Group B', pooled 85 women for whom relations found were verified. Linear regression was used for the analysis. With age, cognitive impairment allows us to explain best (38%) the loss of autonomy for ADL. CONCLUSION: The role of behavioural disturbances in the loss of autonomy for ADL was not determinant in our study, whereas cognitive impairment and age were better able to determine the loss of autonomy for ADL. Further study is needed to explain the decline of functional status in AD patients.

Activities of Daily Living↗

[Nutritional status and Alzheimer's disease: preliminary results of the REAL.FR study].

Weight loss is common in elderly people with dementia, particularly those with Alzheimer' disease (AD), and feeding difficulties are major issues in their care in the later stages of the disease. In this study (REAL FR for Réseau sur la maladie d'Alzheimer Français) we prospectively used the Mini Nutritional Assessment (MNA) to examine the nutritional status of 479 subjects. Three groups of patients were studied: group 1 = 22 patients with undernutrition (MNA = 17), group 2 = 166 patients with risk of undernutrition (17 < MNA < 24), and group 3 = 291 patients without undernutrition (MNA = 24). Correlations with behavioral and psychological signs and symptoms of dementia (Neuropsychiatric Inventory NPI), with caregiver distress (Zarit), and with the Mini Mental State Examination (MMSE) were studied. Undernutrition is more frequently associated with low MMSE (p < 0.001), high behavioural disturbances (p < 0.001) and high distress of caregivers (p < 0.001). Risk of undernutrition is also associated with NPI (p < 0.001) and Zarit (p < 0.001). These first results in a French cohort of patients with AD underline the importance of the evaluation of nutritional status and finally the follow-up of eating behavior, cognitive status and the quality of life of the caregivers.

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[Behavioral and psychologic symptoms in Alzheimer's disease: results of the REAL.FR study].

Behavioral and Psychological Signs and Symptoms of Dementia (BPSD) are important manifestations of Alzheimer's Disease (AD) and other forms of dementia, because they are associate with care-giver distress, increase the likelihood of institutionalization, and may be associated with more rapid cognitive decline In this study (REAL.FR for Réseau sur la maladie d'Alzheimer Français) we prospectively used the Neuropsychiatric Inventory NPI to examine BPSD. 255 AD patients with a Mini-Mental State Examination (MMSE) score between 11 and 20 and 244 AD patients with a MMSE between 21 and 30 were examined. Factor analysis was carried out leading to three different syndromes according to the level of cognitive impairment. BPSD were detected in 92.5% of the patients with a MMSE between 11 and 20, and in 84% of the patients with a MMSE between 21 and 30. Apathy was the most common abnormality, followed by anxiety and dysphoria. These results in a French cohort of patients with AD underline the importance of the evaluation and finally of the treatment of BPSD.

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The apathy inventory: assessment of apathy and awareness in Alzheimer's disease, Parkinson's disease and mild cognitive impairment.

OBJECTIVE: This study was designed to establish the validity and reliability of the apathy inventory (IA), a rating scale for global assessment of apathy and separate assessment of emotional blunting, lack of initiative, and lack of interest. METHOD: Information for the IA can be obtained from the patient or from a caregiver. We evaluated 115 subjects using the IA, consisting of 19 healthy elderly subjects, 24 patients with Mild Cognitive Impairment (MCI), 12 subjects with Parkinson's disease (PD) and 60 subjects with Alzheimer's disease (AD). RESULTS: Internal consistency, item reliability, and between-rater reliability were high. A test-retest reliability study demonstrated that caregiver responses to IA questions were stable over short intervals. A concurrent validity study showed that the IA assesses apathy as effectively as the Neuro Psychiatric Inventory apathy domain. In the caregiver-based evaluation, AD subjects had significantly higher scores than controls, both for global apathy score and for the lack of interest dimension. When the AD patients were subdivided according to diagnostic criteria for apathy, apathetic patients had significantly higher scores than non apathetic patients. With the patient-based evaluations, no differences were found among the AD, MCI and control groups. The scores in the patient-based evaluations were only higher for the PD group versus the control subjects. The results also indicated that AD patients had poor awareness of their emotional blunting and lack of initiative. CONCLUSIONS: The IA is a reliable method for assessing in demented and non-demented elderly subjects several dimensions of the apathetic syndrome, and also the subject's awareness of these symptoms.

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Perfusion brain SPECT and statistical parametric mapping analysis indicate that apathy is a cingulate syndrome: a study in Alzheimer's disease and nondemented patients.

Apathy is the most frequent behavioral symptom in Alzheimer's disease and is also frequently reported in other brain organic disorders occurring in the elderly. Based on the literature, we hypothesized that apathy was related to an anterior cingulate hypofunction. Forty-one subjects were studied. According to ICD 10 diagnostic criteria, 28 patients had Alzheimer dementia (demented: diagnostic group 1), and 13 had organic personality disorders or mild cognitive impairment not attributable to dementia (nondemented: diagnostic group 2). Apathy was evaluated by the Neuro-Psychiatric Inventory. As a result each diagnostic group was divided into two symptomatic subgroups: apathetic or nonapathetic. Brain perfusion was measured by (99m)Tc-labeled bicisate (ECD) brain SPECT and the images were compared using Statistical Parametric Mapping (SPM96). We began by comparing apathetic vs nonapathetic patients, whatever their diagnostic group (whole population), then analyzed them within each group. Twenty-one subjects were apathetic (14 in group 1 and 7 in group 2) and 20 were not (14 in group 1 and 6 in group 2). For the whole population, the Z map showed a significant decrease in ECD uptake for the apathetic patients in the anterior cingulate (P < 0.002) bilaterally. This area was also identified as hypoactive by SPM analysis in the demented (P < 0.035) and in the nondemented (P < 0.02) apathetic patient groups. Finally, conjunction analysis indicated that the anterior cingulate was the common hypoactive structure of the two apathetic subgroups (Z = 4.35, P < 0.0009). These results point to a close relationship between apathy and the anterior cingulate region.

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