Clinique de Psychiatrie et de Psychologie Médicale Pole des Neurosciences Cliniques 30 avenue de La Voie Romaine BP 69 06002 NICE cedex 1 - France
benoit.m@chu-nice.fr
MD and DES Psychiatry (1994 - University of Nice Sophia-Antipolis - France) PhD ( 2001 - University Claude Bernard - Lyon I - France) Associate professor in adult psychiatry - CHU Nice - France
Abstract: INTRODUCTION: Child and adolescent catatonia has been poorly investigated. Moreover, diagnosis criteria only exist for adult psychiatry, and there are no therapeutic guidelines. The aim of this paper is to describe the case of a 14-year-old girl presenting an overlap between psychogenic and neuroleptic induced catatonia, acute treatment and ten year's follow-up. CASE REPORT: A 14-year-old Caucasian French girl, Elsa, was admitted in February 1998 to a University adolescent mental health center with an acute psychotic disorder. She showed agitation, impulsivity (sudden engagement in inappropriate behaviour), paranoid delusions, visual and auditory hallucinations, diurnal and nocturnal urinary incontinence, lack of self-care, inadequate food intake because of fear of poisoning, and vomiting after meals leading to rapid weight loss of 5kg. Clinical examination, laboratory tests, EEG and RMI were normal. Toxicological tests were negative. Her IQ, assessed six months before admission, was in the dull average range (70-75). Elsa was treated with loxapine 150mg per day for one week without improvement and this was then replaced by haloperidol 30mg per day. One week after the start of haloperidol her agitation, impulsivity, and hallucinatory symptoms decreased. Twenty four days after loxapine introduction and 17 days after the haloperidol, her condition deteriorated rapidly over less than 48hours. She exhibited immobility, minimal response to stimuli, staring and catalepsy with waxy flexibility. The diagnosis of catatonia was established. Examination revealed tremulous extremities, tachychardia (110pm) and apyrexia. Creatine phosphokinase levels were 106 UI/l (normal range 0-250). Human immunodeficiency virus, hepatitis, listeria and Lyme serology were negative. Cerebrospinal fluid analysis was normal. Haloperidol was stopped and intravenous clonazepam 5mg/kg was begun. It was not possible to obtain signed consent from the two parents for Electroconvulsive therapy. The patient was transferred to a pediatric intensive care unit. The treatment was standard parenteral nutrition, nursing, intravenous clonazepam 0.05mg/kg, with regular attendance by a child psychiatrist. Elsa stayed three weeks in this condition. She then began to notice the child psychiatrist, and a few days later she was able to carry out simple requests. Elsa was transferred to an adolescent psychiatric unit. As soon as she could eat by herself again, carbamazepine 400mg per day was begun. Her agitation reduced at a carbamazepine level of 7mg/l. One month later her condition was stable. However, language difficulties persisted for a further six months. One year after the episode she scored 66 on a repeat IQ test and her RMI was normal. She exhibited no significant residual symptoms except some cognitive impairment. She integrated into a special education facility. These attempts to stop the carbamazepine were followed by depressed mood, aggressiveness and impulsivity; carbamazepine was finally stopped successfully after seven years. Ten years later, Elsa is the mother of two young children and is able to take care of them. She has never had a relapse of her psychotic disorder or catatonic state. DISCUSSION: The etiopathogenic diagnosis is problematic. Some indices in the familial history may suggest a traumatic event. But one to the total residual amnesia it was never confirmed, and traumatic catatonia are extremely rare. Normal CPK levels, with autonomic disturbance limited to tachycardia and the lack of resolution after discontinuance of medication, argues against a diagnosis of neuroleptic malignant syndrome (NMS). But CPK levels are non specific, and NMS without pyrexia has been described. The occurrence of the catatonic syndrome 21 days after the first dose of a neuroleptic could be diagnostic. This case involved a non organic catatonic psychosis followed by neuroleptic induced catatonia. Catatonia is described as a risk factor for the development of NMS and some consider NMS to be a variant of malignant catatonia. The interest of this report is (1) it reinforces the need to be cautious before prescribing neuroleptics in adolescents presenting with symptoms of catatonia; (2) the complete recovery from catatonia after treatment with intensive care and more than three weeks of intravenous clonazepam without the use of ECT and (3) the effectiveness of carbamazepine over a long period of follow-up. Although trials on carbamazepine in catatonia are published, there are no data available for the control of residual symptoms or the long term prognosis, especially in child and adolescent psychiatry.
Abstract: OBJECTIVE: To determine the role of persistent apathy in rapid loss of autonomy in Instrumental Activities of Daily Living (IADL) in women with Alzheimer s disease (AD), taking into account the grade of cognitive decline. METHODS: The study was conducted on 272 women from the French REAL cohort. At inclusion patients had a Mini-Mental State Examination (MMSE) score between 10-26. A rapid functional decline was defined as a yearly drop of 4 points or more on the 14-point IADL Lawton scale. Persistent apathy was defined as a frequency score equal to 3 or 4 on the Neuro-Psychiatric Inventory at the three consecutive 6-monthly assessments. RESULTS: 27.6% of women had rapid functional decline in 1 year and 22.1% of them had persistent apathy. A logistic regression analysis showed that, in addition to cognitive decline, persistent apathy plays a role in rapid functional decline in 1 year. For example, for a 3-point decline in MMSE in 1 year, the probability of a rapid loss in IADL is 0.45 for women with persistent apathy compared with 0.28 for those without persistent apathy. CONCLUSIONS: In this study, a rapid loss in IADL score was partly explained by persistent apathy.
Abstract: There is wide acknowledgement that apathy is an important behavioural syndrome in Alzheimer's disease and in various neuropsychiatric disorders. In light of recent research and the renewed interest in the correlates and impacts of apathy, and in its treatments, it is important to develop criteria for apathy that will be widely accepted, have clear operational steps, and that will be easily applied in practice and research settings. Meeting these needs is the focus of the task force work reported here. The task force includes members of the Association Française de Psychiatrie Biologique, the European Psychiatric Association, the European Alzheimer's Disease Consortium and experts from Europe, Australia and North America. An advanced draft was discussed at the consensus meeting (during the EPA conference in April 7th 2008) and a final agreement reached concerning operational definitions and hierarchy of the criteria. Apathy is defined as a disorder of motivation that persists over time and should meet the following requirements. Firstly, the core feature of apathy, diminished motivation, must be present for at least four weeks; secondly two of the three dimensions of apathy (reduced goal-directed behaviour, goal-directed cognitive activity, and emotions) must also be present; thirdly there should be identifiable functional impairments attributable to the apathy. Finally, exclusion criteria are specified to exclude symptoms and states that mimic apathy.
Abstract: BACKGROUND: Apathy and depression are the most common neuropsychiatric features in Alzheimer's disease (AD). The clinical and functional specific correlates of these syndromes are not well known independently from cognitive deficits and other behavioral disturbances. MATERIAL AND METHODS: Six hundred and eighty-six patients diagnosed with possible or probable AD were included in a prospective multicenter study (REAL-FR). They had an assessment of their cognitive and functional status. Neuropsychiatric symptoms were assessed with the Neuropsychiatric Inventory (NPI) and caregiver's burden was measured with Zarit's Burden Scale. RESULTS: A majority of patients at any stage of the disease presented with one or several behavioral and psychological disturbances. Apathy concerned 43% of patients and, with or without depression, was associated with more pronounced deficits in global cognition, everyday life and instrumental abilities, nutritional status and with a higher burden level. A high level of psychotropic prescription, especially with antidepressant, was observed in patients with apathy. In a multivariate analysis taking into account the cognitive and functional variables of AD, apathy and depression were the only significant predictors of psychotropic prescription. CONCLUSION: Some negative neuropsychiatric symptoms such as apathy and depression have a specific relation with functional and therapeutic outcomes of AD, independently from cognitive status. Further studies are needed to establish if apathy represents a particularly severe phenotype of AD.
Abstract: OBJECTIVES: The aim of the present study was to stress the relationship between neuropsychiatric symptoms and most particularly apathy and striatal dopamine uptake in patients with Alzheimer's disease (AD) or dementia with Lewy body (DLB). PATIENTS AND METHODS: Twenty-two patients (AD n=14; DLB n=8) were included. All patients had neuropsychological and behavioral examination including Mini Mental Test Examination (MMSE), Neuropsychiatric Inventory (NPI), and UPDRS for the motor activity assessment. Apathy dimensions, emotional blunting, lack of initiative and lack of interest were assessed using the Apathy Inventory (AI). Dopamine transporter (DAT) striatal uptake was assessed using (123)I-FP-CIT (DaTSCAN) SPECT. Quantitative measurements were obtained in 3D using a method which compensates for physical detection biases including partial volume effect. RESULTS: We observed a correlation between DAT uptake and NPI's domains only for apathy. More specifically using the AI, lack of initiative significantly correlated with bilateral putamen DAT uptake. Using partial correlation coefficients controlling for the UPDRS score, the correlation remained significant between lack of initiative and right and left putamen DAT uptake. CONCLUSION: These results demonstrate a relationship between apathy and DAT levels independent from motor activity. They suggest that the patients with neurodegenerative diseases presenting with apathy are characterized by some degree of dopaminergic neuronal loss.
Abstract: The European Dementia Consensus Network (EDCON) is a special project of the Madariaga Foundation located in Brussels. The Madariaga Foundation seeks to facilitate collaboration between European countries and between the public and private sector. This paper will review the differences in the definitions of Severe Dementia and summarise the EDCON consensus on their implications for management. EDCON recommends that:--The attributes of the person suffering from dementia should be given as much attention (and are as important for care) as the severity of cognitive decline in dementia;--The dementia syndrome (particularly in it's severe form) is inadequately defined by criteria which only includes the domain of cognition;--Physical, legal, social and cultural factors defining the environment of patients and their families should be carefully examined and that the results of this examination should be used in conjunction with the results of the somatic and psychiatric assessment in planning care and placement of the patient;--patients with severe dementia should have access to palliative care; - family members should be included in the care plans for those with severe dementia who are in institutional care.
Abstract: OBJECTIVE: Apathy is one of the most common behavioral symptoms in mild cognitive impairment (MCI). The aim of the authors' study was to examine the influence of the apathy dimensions, i.e., emotional blunting, lack of initiative, and lack of interest, on the risk of developing of Alzheimer disease (AD) in patients with MCI. DESIGN: Longitudinal study. SETTING: Fourteen French memory clinics. PARTICIPANTS: Apathy was assessed in 214 MCI patients. The main endpoint considered was the development of AD during the 3-year follow-up. MEASUREMENTS: The neuropsychiatric evaluation included the Goldberg anxiety scale and the Montgomery and Asberg Depression Rating Scale; apathy was assessed with the Apathy Inventory. RESULTS: After 3 years, 59 patients (27.2%) had developed AD. The risk of conversion to AD was significantly higher for patients with lack of interest. Using Cox analyses, controlling for age, gender and education, the difference between survival curves was significant for lack of interest. CONCLUSIONS: Lack of interest, a mild behavioral sign, could be an indicator of potential decline in MCI patients and underlines the importance of checking the cognitive status of these patients.
Abstract: 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.
Abstract: 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.
Abstract: OBJECTIVE: To evaluate the relation between apathy and development of dementia in patients with amnestic mild cognitive impairment (MCI). METHODS: Two hundred and fifty-one French-speaking outpatients fulfilling the criteria of amnestic MCI were enrolled. Apathy was assessed with the Apathy Inventory (IA). Neuropsychiatric evaluation also included the Goldberg anxiety scale and the Montgomery and Asberg Depressive Rating Scale (MADRS). The main end point considered after a 1-year follow-up was the development of dementia of Alzheimer type (DAT). RESULTS: At baseline there were 86 (39.8%) subjects presenting at least one symptom of apathy among the 216 included in analysis. After a 1-year follow-up, 22 patients developed DAT. Of the patients with apathy at baseline 13 (15.1%) developed DAT in comparison with 9 (6.9%) of the non-apathetic patients. At the 1-year follow-up, patients developing DAT had a significantly higher frequency of apathetic symptoms (91.7%) than patients without DAT (26.9%). CONCLUSION: Taking into account that apathy is one of the most frequently observed neuropsychiatric symptoms in MCI and in DAT the present study suggests that patients with MCI and apathy should be more closely observed.
Abstract: OBJECTIVE: To investigate the neuropsychological characteristics of patients diagnosed with mild cognitive impairment (MCI) with and without apathy. METHODS: A cohort of 245 MCI patients (mean age = 72 +/- 5.5 years; mean MMSE = 27.5 +/- 1.3) was divided into two subgroups according to their Apathy Inventory score and underwent an extensive neuropsychological battery. RESULTS: There were 94 (38.4%) patients with and 151 (61.6%) patients without apathy. At baseline the apathetic subgroup had a significantly lower total score on the free and cued selective reminding test (FCSR). Furthermore, the apathetic subgroup showed a significant deterioration in FCSR total recall score between baseline and the 1-year assessment. In conclusion, the presence of apathy in MCI patients is not associated with frontal task performance but with a higher degree of memory impairment.
Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: Behavioral and psychological symptoms in dementia (BPSD) are, beside cognitive disorders, major features of Alzheimer's disease and related disorders. Their diagnosis is important to enhance our knowledge of the pathophysiology of dementia and of their functional consequences on patient and caregivers. Pharmacological and non-pharmacological management of dementia depend on a large extent on the presence of BPSD.
Abstract: 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.
Abstract: Apathy is defined as a lack of motivation in behaviour, cognition and affect. The aim of this article is to evaluate, in Alzheimer's disease (AD), the frequency of apathy and its relations with depressive symptoms and neuroanatomical correlates. We present the results of 3 French studies: the evaluation of behavioural symptoms in 499 AD subjects; the evaluation of depression and apathy in 128 AD subjects; a single photon computed tomography study (SPECT) performed in 31 AD subjects.
Abstract: DEPRESSION IN THE ELDERLY SUBJECT: Depression is diagnosed to a varying extent in the elderly. In subjects with Alzheimer's disease, the most specific signs involve mood disorders, loss of energy, a feeling of hopelessness, and sometimes body discomfort or pain. DEFINITION OF APATHY: Apathy is defined as a loss of motivation, expressed by a loss of interest in activities, lack of productivity, loss of will and initiative, as well as limited affective response to positive or negative elements. TWO DIFFERENT SYNDROMES: The differential diagnosis is difficult, but studies have demonstrated that depression and apathy are two relatively different syndromes, which may be intertwined. Lack of volition and initiative are suggestive of apathy. Neuropsychology, particularly the capacity to divide attention, may be useful. FUNCTIONAL CONSEQUENCES: Apathy and depression both have functional effects which may accelerate institutionalization (altered capacity for initiative, adaptation to the environment). FUNCTIONAL ANATOMY AND NEUROCHEMICAL CONSEQUENCES: Apathy and to a lesser degree depression, involve prefrontal cortical areas. Involvement of the prefrontal pathways is a common feature of apathy and depression, but the other pathways are affected specifically. Cholinesterase inhibitors and selective serotonine reuptake inhibitors as well as serotoninergic antidepressants have been found to be effective for certain components of apathy.
Abstract: 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.
Abstract: BACKGROUND: Impulsivity (I) and anxiety (A) were hypothesized to be crucial clinical features in adolescents with at-risk behavior. We therefore classified them into sub-groups according to these two major dimensions. The study examined the relevance of these groups by describing their major diagnoses and behavioral characteristics. METHODS: During a 1-year period, all in-patients consecutively admitted for at-risk behavior, except those with a previous psychotropic treatment and/or schizophrenic disorders, were rated for anxiety and impulsivity, and categorized into four groups: impulsive and anxious (IA), impulsive and non-anxious (Ia), non-impulsive and anxious (iA), non-impulsive and non-anxious (ia). We assessed the main behavioral disturbances (suicide attempt, carving, violence, delinquency, substance abuse, and eating disorder) and the main current axis I disorder in each sub-group. RESULTS: A total of 69 patients were included. In the IA group 62% exhibited hypomanic episodes and 87% recurrent suicide attempts. In the Ia group all exhibited conduct disorders, 93% were males, 80% delinquents, and 100% violent with others. Both groups reported a high percentage of cannabis use (67%). The iA group exhibited anorexia nervosa (73%) with a major depressive episode. The ia patients were mainly non-violent, first suicide attempts with low risk. LIMITATIONS: Long-term data are needed to assess the stability of these groups. CONCLUSIONS: We found that sub-typing adolescents with at-risk behavior into four groups according to their level of anxiety and impulsivity was highly predictive of being suicidal with mood disorders (AI), delinquent with conduct disorder (Ia), anorectic or depressed (Ai), and with substance abuse associated only to impulsivity. It is likely that this sub-typing of patients may be useful for prevention and therapeutics. The impulsive-anxious group (IA) appears closely related to the soft bipolar spectrum. A replication and follow-up data are now needed.
Abstract: Alzheimer's disease (AD) is clinically characterized by cognitive symptoms that, in combination with behavioral disturbances, significantly interfere with activities of daily living. These behavioral disorders contribute to the clinical heterogeneity of the disease and probably express different pathophysiological processes. Apathy is one of the most frequent behavioral disorders in AD. The aim of this study was to evaluate brain perfusion of AD patients with and without apathy (as determined by the Neuropsychiatric Inventory) compared with that in healthy elderly subjects. A total of 15 AD patients without apathy (AD/NA; mean age 76.6) and 15 AD patients with apathy (AD/A; mean age 77.6) were studied. Brain perfusion was measured by 99mTc-labeled bicisate (ECD) single-photon emission tomography (ECD SPECT). The images of the two AD subgroups were compared by means of statistical parametric mapping (SPM 99) to corresponding images of 11 healthy elderly control subjects (obtained from the Society of Nuclear Medicine database). Compared with the healthy elderly subjects, the apathy-free AD subgroup had significantly lower perfusion of inferior temporal regions (left fusiform gyrus, left parahippocampal area) and occipital regions (left gyrus lingualis). The apathy subgroup had significantly decreased perfusion of the left anterior cingulate, the right inferior and medial gyrus frontalis, the left orbitofrontal gyrus and the right gyrus lingualis. The differences in the brain areas with reduced perfusion between the apathy-free subjects (mainly the posterior regions) and the apathetic subjects (mainly the anterior regions) indicate that behavioral disorders such as apathy participate in the heterogeneity of brain perfusion in AD.
Abstract: 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.
Abstract: 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.
Abstract: Fundamental and therapeutic research in Alzheimer's disease (AD) focused for a long time exclusively on cognitive aspects. However, AD also frequently involves complex disorders of affect and behavior, which are currently grouped under the heading 'behavioral and psychological signs and symptoms of dementia' (BPSSD). Several rating tools have been developed over the years on the basis of a variety of source data. Some are derived from psychiatric practise or have specifically been developed for dementia, such as the Neuropsychiatric Inventory (NPI). In this study we prospectively used the NPI to examine BPSSD. Sixty-three French patients (mean age 74.7 years, SD 7.9) with a Mini-Mental State Examination (MMSE) score higher than 10 were examined. BPPSD were detected by NPI in 95. 2% of the patients. Anxiety was the most common abnormality (65.1%), followed by apathy and dysphoria (58.7%). The highest frequency x severity NPI score was observed for apathy. In order to identify the relationship between regional cerebral perfusion and apathy, 20 of these AD patients underwent a technetium-99m-bicisate SPECT protocol within the same week as the NPI evaluation. The mean age of this population was 74.4 years (SD 5.3) and the mean MMSE score was 21 (SD 4.1). The apathy NPI score was correlated with right cingulate deficit whereas the highest correlation for the MMSE was with the left temporoparietal area. This stresses the interest to focus on SPECT imaging of AD patients not only in the posterior areas. CopyrightCopyright 1999S.KargerAG,Basel
Abstract: The aim of this study was to determine whether schizophrenic patients' impairment in semantic verbal fluency tasks is due to difficulties in organizing their search or, in other words, in organizing output in terms of clusters of meaningfully related words. Consecutive association of words belonging to subcategories of the semantic task was defined as semantic clustering. A categorical verbal fluency task was first administered to 100 healthy subjects and then to 22 schizophrenic patients and 22 healthy subjects matched for sex, age and education. In the normal population, semantic clustering was found to be involved in word generation. A large number of semantic clusters indicated efficient organization of semantic knowledge and led to better word production. Schizophrenic patients showed impaired verbal fluency and generated a smaller number of semantic clusters than the control subjects. These findings point to a defect in self-initiation of semantic categorization in schizophrenia.
Abstract: There is a general agreement that schizophrenia is an heterogeneous disorder and cognitive performances could be an interesting feature in order to allow a better description of specific subtypes. The aim of this study was: 1) to describe clinical and neuropsychological performances of 45 DSM IV schizophrenic patients divided in two groups according to their performances in verbal fluency task; 2) to compare each group with the performances of healthy subjects matched for sex, age and education. METHOD: The differentiation criteria was the total number of words generated during 3 formal and 3 semantic fluency tasks. Data were analysed using a disjoint clustering procedure with Euclidean distance. A two cluster solution was considered optimal. Cluster S1 includes 21 schizophrenic subjects defined as low performer (range: 40-83, mean 66.7). Cluster S2 includes 24 schizophrenic subjects (range: 87-158, mean 102.8). All schizophrenic patients were clinically evaluated with SANS, SAPS and a psychosocial aptitude rating scale (PARS). Patients and controls were assessed with the following battery: verbal fluency, Trail making test A & B, Stroop test, Brown Peterson paradigm for evaluation of working memory. RESULTS: Patients with low verbal fluency had significantly higher scores at the SANS and PARS. Furthermore, the low performers (cluster S1) were differentiated from those with better performances (cluster S2) by significantly poorer results in all neuropsychological tests. Comparison with healthy subjects indicated that cluster S1 patients also had significantly poorer results in all neuropsychological tests. Relative to their 24 controls cluster S2 patients performances was lower in all measures excepted in one subscore of the Stroop test and in the number of cluster produced. This later result could indicate that some capacities for willed intention were preserved in this group and that the alteration in verbal fluency performances were better explained by impairment of the other cognitive processes. DISCUSSION: These findings point out that: 1) use of performance in cognitive executive task such as verbal fluency is a possible criteria in order to separate different types of schizophrenic patients; 2) in the two groups of schizophrenic subjects, various processes defects underline cognitive performances indicating the presence of different neurobiological dysfunctioning.
Abstract: Fifteen nondemented subjects with memory complaints underwent serial single photon emission computed tomography (SPECT) studies with technetium-99m-d, l-hexamethyl-propylene amine oxime (HMPAO) as tracer. Scans were carried out under a baseline conditions and during the learning phase of the Memory Efficiency Profile (MEP), a combined visual perception and memory task developed by Rey. Results indicate a positive correlation between activation, as indexed by HMPAO uptake, and neuropsychological assessment. Right temporal activation was correlated with MEP immediate recall. The right cerebellum was correlated with both MEP immediate and delayed recall. This study suggests that SPECT can show cortical activation during cognitive performance in subjects with mild memory impairment.
