Christophe Arbus

Subthalamic nucleus stimulation in severe obsessive-compulsive disorder.

BACKGROUND Severe, refractory obsessive-compulsive disorder (OCD) is a disabling condition. Stimulation of the subthalamic nucleus, a procedure that is already validated for the treatment of movement disorders, has been proposed as a therapeutic option. METHODS In this 10-month, crossover, double-blind, multicenter study assessing the efficacy and safety of stimulation of the subthalamic nucleus, we randomly assigned eight patients with highly refractory OCD to undergo active stimulation of the subthalamic nucleus followed by sham stimulation and eight to undergo sham stimulation followed by active stimulation. The primary outcome measure was the severity of OCD, as assessed by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), at the end of two 3-month periods. General psychopathologic findings, functioning, and tolerance were assessed with the use of standardized psychiatric scales, the Global Assessment of Functioning (GAF) scale, and neuropsychological tests. RESULTS After active stimulation of the subthalamic nucleus, the Y-BOCS score (on a scale from 0 to 40, with lower scores indicating less severe symptoms) was significantly lower than the score after sham stimulation (mean [+/-SD], 19+/-8 vs. 28+/-7; P=0.01), and the GAF score (on a scale from 1 to 90, with higher scores indicating higher levels of functioning) was significantly higher (56+/-14 vs. 43+/-8, P=0.005). The ratings of neuropsychological measures, depression, and anxiety were not modified by stimulation. There were 15 serious adverse events overall, including 1 intracerebral hemorrhage and 2 infections; there were also 23 nonserious adverse events. CONCLUSIONS These preliminary findings suggest that stimulation of the subthalamic nucleus may reduce the symptoms of severe forms of OCD but is associated with a substantial risk of serious adverse events. (ClinicalTrials.gov number, NCT00169377.)

Predictive Value of Rapid Decline in Mini Mental State Examination in Clinical Practice for Prognosis in Alzheimer’s Disease

Background: Given the poorer prognosis of Alzheimer’s disease (AD) patients with rapid cognitive decline (RCD), there is a need for a clinical assessment tool to detect these patients. Objective: To investigate if there is a Mini Mental State Examination (MMSE) threshold of decline during 6 months of follow-up which predicts a worse disease progression at the 2-year follow-up. Then, to propose a feasible definition of RCD for routine clinical practice. Methods: Data from 565 community-dwelling AD patients recruited in a multi-centre prospective observational study were assessed. All patients had MMSE scores between 10 and 26 at inclusion and were followed up 6-monthly using a standardised clinical assessment. Patients were classified as rapid and non-rapid decliners according to 2 MMSE decline thresholds tested: ≧3 points and ≧4 points for decline over the first 6 months of the study. Worse disease outcome was defined as attainment of 1 of 4 clinical end points 18 months later: institutionalisation, death, increased physical dependence or worsening of behavioural and psychological symptoms. Results: 135 patients (23.9%) lost ≧3 points during the first 6 months of follow-up in the MMSE score and 77 patients (13.6%) lost ≧4 points. Patients with moderate disease and a loss of ≧4 points showed a significantly increased risk of mortality (HR = 5.6, 95% CI 2.0–15.9) and institutionalisation (HR = 3.8, 95% CI 1.8–8.1) at the 2-year follow-up. The same MMSE threshold was associated with a higher risk of physical decline (HR = 1.6, 95% CI 1.2–2.3). Conclusion: The loss of ≧4 points in MMSE during the first 6 months of follow-up seems to be a predictor of worse clinical course, and thus it could be used to define the category of AD patients presenting a RCD.

Rapid cognitive decline in Alzheimer’s disease. Consensus paper

The rate of cognitive decline in Alzheimer’s disease (AD) varies considerably between individuals, with some subjects showing substantial deterioration and others showing little or no change over the course of the disease. These wide variations support the relatively new concept of Rapid Cognitive Decline (RCD). Patients with an accelerated rate of cognitive decline have showed to present a worse evolution in terms of mortality, loss of autonomy and institutionalisation. The conclusions from RCD studies conducted in the past years remain very heterogeneous and sometimes contradictory. This is possibly due to methodological differences, mainly the different “a priori” definitions of RCD used to identify rapid decliners. Consequently of this, there is considerable variation in reported frequency of patients with RCD which may vary from 9.5% to 54%. The lack of both consensus definition and consensual clinical assessment tools is one of the major barriers for establishing an appropriated management of rapid decliners in clinical practice. Presently, management of rapid decliners in AD remains to be a challenge waiting to better know predictive factors of a RCD. To date no specific guidelines exist to follow-up or to treat patients with this condition. This consensus paper proposes the loss of 3 points or greater in Mini-Mental State Examination (MMSE) during six months as an empirical definition of rapid cognitive decline to be used in routine medical practice and to be relevant for clinical-decision making in patients with mild to moderately-severe AD.

An overview of the use of music therapy in the context of Alzheimer's disease: A report of a French expert group

Objectives: The aim of this overview is to present the developments of music therapy in France, its techniques, mechanisms and principal indications, mainly in the context of Alzheimers disease. Methods: An international review of the literature on music therapy applied to Alzheimers disease was conducted using the principal scientific search engines. A work group of experts in music therapy and psychosocial techniques then considered the different points highlighted in the review of literature and discussed them. Results and Discussion: Clinical and neurophysiological studies have enlightened some positive benefits of music in providing support for people with Alzheimers disease or related disorders. Music therapy acts mainly through emotional and psycho-physiological pathways. It includes a series of techniques that can respond to targeted therapeutic objectives. Some studies have shown that music therapy reduces anxiety, alleviates periods of depression and aggressive behaviour and thus significantly improves mood, communication and autonomy of patients. Conclusion: Psychosocial interventions, such as music therapy, can contribute to maintain or rehabilitate functional cognitive and sensory abilities, as well as emotional and social skills and to reduce the severity of some behavioural disorders.

Deep brain stimulation of the subthalamic nucleus improves pain in Parkinson's disease

BACKGROUND In Parkinsons disease (PD), chronic pain is a common symptom which markedly affects the quality of life. Some physiological arguments proposed that Deep Brain Stimulation of the Subthalamic Nucleus (STN-DBS) could improve pain in PD. METHODS We investigated in 58 PD patients the effect of STN-DBS on pain using the short McGill Pain Questionnaire and other pain parameters such as the Bodily discomfort subscore of the Parkinsons disease Questionnaire 39 and the Unified Parkinsons Disease Rating Scale section II (UPDRS II) item 17. RESULTS All pain scores were significantly improved 12 months after STN-DBS. This improvement was not correlated with motor improvement, depression scores or L-Dopa reduction. CONCLUSIONS STN-DBS induced a substantial beneficial effect on pain in PD, independently of its motor effects and mood status of patients.

Neuronal activity correlated with checking behaviour in the subthalamic nucleus of patients with obsessive–compulsive disorder

Doubt, and its behavioural correlate, checking, is a normal phenomenon of human cognition that is dramatically exacerbated in obsessive-compulsive disorder. We recently showed that deep brain stimulation in the associative-limbic area of the subthalamic nucleus, a central core of the basal ganglia, improved obsessive-compulsive disorder. To understand the physiological bases of symptoms in such patients, we recorded the activity of individual neurons in the therapeutic target during surgery while subjects performed a cognitive task that gave them the possibility of unrestricted repetitive checking after they had made a choice. We postulated that the activity of neurons in this region could be influenced by doubt and checking behaviour. Among the 63/87 task-related neurons recorded in 10 patients, 60% responded to various combinations of instructions, delay, movement or feedback, thus highlighting their role in the integration of different types of information. In addition, task-related activity directed towards decision-making increased during trials with checking in comparison with those without checking. These results suggest that the associative-limbic subthalamic nucleus plays a role in doubt-related repetitive thoughts. Overall, our results not only provide new insight into the role of the subthalamic nucleus in human cognition but also support the fact that subthalamic nucleus modulation by deep brain stimulation reduced compulsive behaviour in patients with obsessive-compulsive disorder.

Antidepressant use in Alzheimer's disease patients: results of the REAL.FR cohort

BACKGROUND Psychotropic medication is widely prescribed in clinical practice for the management of behavioral and psychological symptoms of dementia (BPSD) in Alzheimers disease (AD). However, there have been few pharmaco-epidemiological studies or studies conducted in a natural setting on the real use of antidepressants in AD. The aim of this survey was to assess the prevalence of antidepressant use in AD and to identify the clinical factors associated with antidepressant prescription. METHODS REAL.FR is a four-year, prospective, multi-center study. Baseline data including demographic characteristics, clinical variables and drug intake were obtained. Depressive symptoms were determined using the Neuropsychiatric Inventory (NPI). RESULTS A total of 686 AD patients were included. Antidepressant treatment was prescribed for 34.8% of patients. Clinically significant depressive symptoms (NPI >or= 4) were observed in 20.5% of the total population. Although depressed subjects were significantly more likely to be treated with antidepressants than non-depressed subjects (p<0.0001), only 60% of depressed subjects overall were prescribed an antidepressant. In multivariate analysis, clinically significant depressive symptoms were associated with antidepressant prescription although this result was only observed in subjects without a previous history of depression. CONCLUSIONS The available data on antidepressant efficacy in BPSD other than depression (in particular, agitation, aggression and, occasionally, psychotic symptoms) do not influence prescription choices. Depressive symptoms may be taken more seriously in the absence of a previous history of depression, leading to increased antidepressant prescription rates in individuals presenting with depression for the first time.

Peritraumatic distress predicts posttraumatic stress symptoms in older people

In a recent publication of the International Journal of Geriatric Psychiatry, Chung et al. (2009) found that 35% of older people were suffering from posttraumatic stress disorder (PTSD) after a fall. However, they found no predictive factors for the development of PTSD. We would like to report the preliminary results of a study carried out with the main objective of assessing the predictive power of peritraumatic reactions in older adults. Peritraumatic distress, a measure of the intensity of DSM-IV PTSD criteria A2, indexes ‘fear, helplessness, and horror’ as well as other reactions experienced during or immediately after trauma exposure while peritraumatic dissociation refers to alterations in the experience of time, place, and persons. Older adults were enrolled in the study from the emergency department (ED) of Toulouse and Bordeaux University Hospitals. The study was approved by the institutional ethical committee of the Toulouse University Hospital. Eligible adults (age >65 years, French speaking) were admitted to the ED after either a road traffic accident or a violent assault. Exclusion criteria comprised mental retardation, prior psychiatric disorder, Mini Mental State Examination score <28, or a life-threatening condition. During the recruitment period, 34 participants were enrolled in the study and were assessed within 1 week of ED admission. Twenty-five of these subjects (73.5%) completed a second assessment 1 month after admission. Peritraumatic reactions were assessed at baseline and PTSD symptoms at 1 month. The Peritraumatic Distress Inventory (PDI) was used to assess distress at the time of the traumatic event. The PDI is composed of 13 selfreport items scored on a 5-point scale, with higher total scores indicating increased distress (range: 0–52) (Brunet et al., 2001). Peritraumatic dissociation was assessed using the Peritraumatic Dissociative Experiences Questionnaire (PDEQ). The PDEQ is a 10-item self-report questionnaire, with each item scored on a 5point scale and higher total scores indicating increased dissociation (range: 10–50) (Birmes et al., 2005). The primary outcome measure was PTSD symptoms measured using the Clinician-Administered PTSD Scale (CAPS). The CAPS provides a total symptom severity score (range: 0–136) with higher scores indicating an increased level of PTSD symptoms (Blake et al., 1995). Clinical and sociodemographic data were collected from medical charts and are reported in Table 1. Five (20%) participants met the criteria for PTSD at 1 month. Pearson’s correlation analyses revealed that 1-month CAPS score was not significantly correlated with gender or age. It was, however, significantly associated with baseline PDI score (r1⁄4 0.60, p< 0.01) and PDEQ score (r1⁄4 0.41, p< 0.05). Multiple regression analysis was then performed to assess the ability of peritraumatic variables (PDI and PDEQ) to predict 1-month PTSD symptoms. Due to the small sample size, all other independent variables were excluded from the analysis. The model identified PDI score as the only significant peritraumatic predictor of 1-month PTSD symptoms (b1⁄4 0.78, p< 0.01) and predicted 32.2% of the total variance. Our results do not replicate those of Chung et al. (2009) concerning the association between PTSD symptoms and gender or age. This discrepancy might be explained by the small sample size. Nevertheless, the main original finding from this study is that peritraumatic distress is a significant predictor of acute PTSD symptoms 1 month after trauma in older adults. Similar to results in younger adults, increased distress at the time of a trauma predicts increased levels of PTSD symptoms in elderly subjects. Previous research has highlighted the association between peritraumatic dissociation and the development of PTSD symptoms in adults (Lensvelt-Mulders et al., 2008). Our study confirms these results but suggests that peritraumatic distress might be a better predictor than dissociation in older adults. There are several limitations to our study. The small sample size and low number of PTSD cases limited the analysis to symptoms only. Furthermore, assessing PTSD symptoms 1month posttraumamight be too early and the impact of peritraumatic distress and dissociation on long-term symptoms remains to be explored.

Health management of older persons with chronically medicated psychotic disorders: the results of a survey in France

BACKGROUND The medical care of elderly patients with psychotic disorders is a matter of major concern. The aim of the study was to investigate health conditions and treatment of elderly patients with psychotic disorders in France. METHODS The SAGE (Schizophrenia AGEd) study (observational, cross-sectional) was a survey conducted among 123 physicians in France, regarding prescriptions of antipsychotic drugs in elderly patients (≥60 years) suffering from psychotic disorders. The survey was based on a questionnaire addressing the mental and somatic health management of the patients. RESULTS Data from 930 patients (mean age: 70.4 years) were collected. Most patients (58.5%) suffered from schizophrenia, 20.8% had delusional disorder and 20.6% hallucinatory chronic psychosis (very-late-onset schizophrenia-like psychosis). 70.8% of them were outpatients, while 29.2% were inpatients. The severity of psychotic symptoms was assessed in 97.8% of patients, but cognitive function was only evaluated in 41.6%. Some 46.5% of patients were treated with atypical antipsychotics alone, 36.2% with classical antipsychotics alone and 17.3% received a combination of both, atypical and classical antipsychotics; 36.3% patients were given antiparkinsonian medication, of whom only 17.8% as preventive treatment; 51.1% of patients had somatic comorbidities, particularly cardiovascular disorders (34.0%). Evaluation of renal and/or liver function to adjust the dose of treatment was done in only 32.1% of patients. Over the previous 12 months, almost half of the patients had had no ECG, glycemia or creatininemia investigated and HDL-cholesterol and triglycerides were available for less than one-third of them. CONCLUSIONS Antipsychotic and antiparkinsonian drug prescriptions in French aged psychotic patients follow only partially the clinical guidelines and recommendations of consensus conferences. Moreover, cognitive, cardiac and metabolic aspects are not fully managed as expected.

The prevalence of clinically significant depressive symptoms in Alzheimer's disease : relationship with other psychological and behavioural symptoms

An increasingly literature is available on depression and depressive symptoms in Alzheimer’s disease (AD). The hypotheses explaining the occurrence of depression in AD (dAD) may be considered according to four main axes: an emotional reaction to cognitive decline, a recurrence of previous episodes of depression in the adult, vascular aetiology (vascular depression) or the neurodegenerative process which is itself causing the depressive symptoms (Lee and Lyketsos, 2003). We can estimate the dAD prevalence at around 20–40% (Arbus et al., 2003). The aim of this study is to evaluate the prevalence, associated factors and clinical correlates of depressive symptoms in AD in a sample of subjects living at home with a caregiver, and recruited through the French national network on AD (REAL.FR). The REAL.FR cohort has been described in detail in a previous article (Gillette-Guyonnet et al., 2003). Our work is a cross-sectional study. Data collected included sociodemographic data, medical and surgical history, evaluation of physical disability using the Activities of Daily Living (ADL) scale, assessment of cognitive functions with the MMSE and the ADASCog, assessment of the patient’s behavioural and psychological symptoms of dementia (BPSD) using the Neuro-Psychiatric Inventory (NPI) scale, evaluation of nutritional state by the Mini Nutritional Assessment (MNA) and evaluation of the severity stage of the dementia using the Clinical Dementia Rating (CDR) scale. Measurement of the caregiver’s subjective burden was assessed by the Zarit scale. A total of 686 subjects were enrolled. The mean age of subjects was 77.86 6.82 years. Mean scores forMMSE, the ADL scale and the total NPI were respectively 20.01 4.23; 5.43 0.90 and 15.31 15.29. There were 20.5% subjects showing clinically significant depressive symptoms (NPI 4). In comparison with the group of non-depressed subjects (NPI< 4), this subjectsweremore often women (p1⁄4 0.014), had a lower MMSE (p1⁄4 0.003), were more at risk of malnutrition (p< 0.0001) and were less often treated with a specific treatment for AD (p1⁄4 0.040). In these subjects, a personal history of depression was over-represented (p< 0.0001) and they were more often treated with antidepressants (p< 0.0001). Caregiver burden was higher in this group (p< 0.0001). Table 1 shows the correlations existing between depressive symptoms and the various neuropsychiatric symptoms. The significance threshold of 4 was retained for each BPSD. Apathy was the disorder most often seen among patients with depressive symptoms (60%), followed by anxiety (56%). Delusions and hallucinations were significantly more common in depressed subjects but in considerably lower proportions than the other disorders cited above (17% and 6.3%, respectively). A strong statistical association between depressive symptoms and anxiety is found [Odds Ratio (OR): 6.95; 95% Confidence Intervals (CI): 4.60–10.51] as well as, between depressive symptoms and irritability (OR: 3.34; 95% CI: 2.20–5.06). After multivariate logistic regression model that included gender, age and CDR score, the association between depressive symptoms and others BPSD still remained significant except for exaltation. Our study confirm that depressive symptoms are common in AD and are clinically significant in 20% of subjects. Depressed subjects showed other BPSD than depressive symptoms and their severity was more marked. In the context of evaluation of the BPSD with the NPI, the symptoms most common among patients with depressive symptoms were apathy, followed by anxiety, irritability and aggressiveness. Psychotic disorders were more common than in subjects whose INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY