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Does subthalamic nucleus stimulation induce apathy in Parkinson's disease?

BACKGROUND: Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) has been shown to significantly improve motor symptoms in advanced Parkinson's disease (PD). Only few studies, however, have focused on the non-motor effects of DBS. METHODS: A consecutive series of 15 patients was assessed three months before (M-3), then three months (M3) and six months (M6) after surgery. Mean (+/- SD) age at surgery was 59.7 (7.6). Mean disease duration at surgery was 12.2 (2.8) years. The Mini International Neuropsychiatric Inventory was used to assess psychiatric disorders three months before surgery. Depression was evaluated using Montgomery and Asberg Rating Scale (MADRS). Anxiety was evaluated using the AMDP system (Association for Methodology and Documentation in Psychiatry). Apathy was particularly evaluated using the Apathy Evaluation Scale (AES) and the Starkstein Scale. All these scales were performed at every evaluation. RESULTS: Apathy worsened at M3 and M6 after STN-DBS in comparison with the preoperative evaluation: the AES mean score was significantly impaired between the preoperative (38.4+/-7.1) and both the postoperative M3 (44.6+/-9.5, p = 0.003) and M6 scores (46.0+/-10.9, p = 0.013). Significant worsening of apathy was confirmed using the Starkstein scale. There was no evidence of depression: the mean MADRS score did not differ before surgery (9.1+/-7.4) and at both M3 (8.6+/-8.2) and M6 (9.9+/-7.7) after STN-DBS. The anxiety level did not change between preoperative (9.4+/-9.2) and both M3 (5.5+/-4.5) and M6 (6.6+/-4.6) postoperative states. CONCLUSION: Although STN-DBS constitutes a therapeutic advance for severely disabled patients with Parkinson's disease, we should keep in mind that this surgical procedure may contribute to the inducing of apathy. Our observation raises the issue of the direct influence of STN- DBS on the limbic system by diffusion of stimulus to the medial limbic compartment of STN.

Aged↗

Reliability and validity of the Apathy Evaluation Scale.

This article presents evidence for the reliability and construct validity of the Apathy Evaluation Scale (AES). Conceptually, apathy is defined as lack of motivation not attributable to diminished level of consciousness, cognitive impairment, or emotional distress. Operationally, the AES treats apathy as a psychological dimension defined by simultaneous deficits in the overt behavioral, cognitive, and emotional concomitants of goal-directed behavior. Three versions of the AES (clinician, informant, and self-rated) were evaluated for 123 subjects, ages 53-85, meeting research criteria for right or left hemisphere stroke, probable Alzheimer's disease, major depression, or well elderly control. Multiple forms of reliability (internal consistency, test-retest, and interrater) were satisfactory. Several types of validity evidence are presented for each version of the scale, including the following: ability of the AES to discriminate between groups according to mean levels of apathy, discriminability of apathy ratings from standard measures of depression and anxiety, convergent validity between the three versions of the scale, and predictive validity measures derived from observing subjects' play with novelty toys and videogames. Guidelines for the administration of the AES are presented, along with suggestions for potential applications of the scale to clinical and research questions.

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Coping strategies in patients with acquired brain injury: relationships between coping, apathy, depression and lesion location.

Coping strategies in individuals suffering severe traumatic brain injury (TBI), cerebrovascular accidents (CVA), or hypoxic brain injury (HBI) were investigated in relation to apathy, depression, and lesion location. Seventy patients (27 with TBI, 30 with CVA, and 13 with HBI) filled in a coping questionnaire (COPE) and were evaluated with respect to apathy and depression. A comparison sample of 71 students also filled in COPE. Patients coping strategies were similar to the comparison group, but patients tended to display less differentiated coping styles. A factor analysis indicated two dimensions of coping in the patient sample; approach oriented and avoidance oriented coping. Approach and avoidance coping sum scores, based on subscales from the two factors, were positively correlated in the patient sample, but not in the comparison group. Lack of active approach oriented coping was associated with apathy, whereas avoidant coping was associated with depression. Coping styles were not related to lesion location. Apathy was related to subcortical and right hemisphere lesions. In bivariate analyses, depression was unrelated to lesion location, but, in a MANCOVA, avoidant coping, apathy and lesion location (left hemisphere lesions) contributed to the variance in positive depressive symptoms. The consistent relationships between coping strategies and neuropsychiatric symptoms were interpreted as two dimensions of adaptational behaviour: an active vs. passive dimension and a depression--distress-avoidance dimension.

Adaptation, Psychological↗

Selective serotonin reuptake inhibitor-induced apathy: a pediatric case series.

OBJECTIVES: Selective serotonin reuptake inhibitor (SSRI)-induced apathy is characterized by a lack of motivation that is not a result of sedation or symptoms of depression. This report describes two pediatric cases of SSRI-induced apathy, one of which is the first reported case in a child with a non-OCD (obsessive compulsive disorder) anxiety disorder. METHODS: The sample included 43 participants from the Johns Hopkins University site of the Research Units on Pediatric Psychopharmacology (RUPP) study of fluvoxamine in pediatric anxiety disorders. Data were reviewed for adverse events of at least moderate severity or that required a slowing of drug titration during the protocol; fluvoxamine blood levels were examined. RESULTS: Two (2) cases of apathy were identified (5%), 1 in a 9-year-old child and the other in a 16-year-old adolescent; neither had depressive illness. Similarities to existing reports included: Lack of insight, delayed onset, dose dependency, and reversibility with SSRI dose reduction or discontinuation. Plasma fluvoxamine levels were 459 ng/mL and 87 ng/mL, representing, respectively, the 90th percentile and 50th percentile, of the blood level sample groups at the time of apathy presentation (weeks 8 and 24). The 16-year-old also exhibited cooccurring disinhibition symptoms. CONCLUSIONS: Educating patients and families, and close monitoring by clinicians for symptoms of SSRI-induced apathy, are important to limit the impact of this reversible adverse event on compliance and quality of life.

Adolescent↗

Does bilateral stimulation of the subthalamic nucleus aggravate apathy in Parkinson's disease?

OBJECTIVE: High frequency stimulation of the subthalamic nucleus (STN) dramatically decreases motor disability in patients with Parkinson"s disease (PD), but has been reported to aggravate apathy. The aim of this study was to analyse the effect of STN stimulation on motivation and reward sensitivity in a consecutive series of PD patients. METHODS: Apathy and reward sensitivity (Apathy Scale, Stimulus-Reward Learning, Reversal, Extinction, and Gambling tasks) were assessed in 18 PD patients treated by bilateral STN stimulation ("on" and "off" conditions) compared with 23 matched patients undergoing long term treatment with levodopa ("on" and "off" conditions). RESULTS: Apathy decreased under both STN stimulation and levodopa treatment, whereas explicit and implicit stimulus reward learning was unchanged. CONCLUSIONS: Bilateral STN stimulation in PD patients does not necessarily have a negative effect on motivation and reward sensitivity and can even improve apathy provided patients have been appropriately selected for neurosurgery.

Antiparkinson Agents↗

Cognitive impairment related to apathy in early Huntington's disease.

OBJECTIVE: To investigate the relationships between cognitive impairment and apathy in patients with early Huntington's disease (HD) and to further explore the influence of depression on the outcome of cognitive changes associated with apathy. METHODS: We included 36 early HD patients, among them 20 were apathetic (HDA) and 16 were not (HDnA). The two groups were matched by age, education and severity of disease. Cognitive functions were evaluated by a comprehensive neuropsychological battery that measures memory, attention, executive function, language and visuospatial abilities. RESULTS: The HDA patients had significantly lower scores on memory, attention and executive function tests when compared with the HDnA patients (p values <0.05). We compared the performance of patients with (50%) and without depression on cognitive tasks and showed that depression per se did not influence performance. Finally, the results demonstrate that interactions between apathy and motor disturbance have a significant effect on cognitive impairment in HD. DISCUSSION: The presence of apathy is associated with more severe deficits of attention, executive function and episodic memory in early HD patients. Furthermore, the findings suggest that depression has little or no effect on cognitive deficits. Finally, apathy increased in parallel with both motor and cognitive dysfunction.

Adult↗

Apathy is not depression.

If depression is associated with apathy, then they should be expressed together in different dementia syndromes and should co-occur at varying levels of disease severity. The authors performed a cross-sectional comparison of neuropsychiatric symptoms in 30 Alzheimer's disease, 28 frontotemporal dementia, 40 Parkinson's disease, 34 Huntington's disease, and 22 progressive supranuclear palsy patients, using a standardized rating scale (the Neuropsychiatric Inventory). Apathy did not correlate with depression in the combined sample; apathy (r = -0.40, P < 0.0001), but not depression, correlated with lower cognitive function as measured by the Mini-Mental State Examination. The relationship of apathy to depression also varied across diagnostic groups. Apathy is a specific neuropsychiatric syndrome that is distinct from depression. Distinguishing these two syndromes has therapeutic implications.

Adult↗

Apathy, depression, and cognitive performance in HIV-1 infection.

The authors examined the relationship between apathy, depression, and cognitive performance in 48 HIV-1-seropositive and 21 seronegative (control) subjects, using reaction time (RT) and working memory tasks. Apathy, but not depression, was associated with working memory deficits among HIV-seropositive subjects. The cognitive-affective component of the Beck Depression Inventory (BDI), but not apathy, was associated with slowing and decreased accuracy on a choice RT task. The BDI cognitive-affective component was more closely associated than the BDI somatic component with both RT slowing and apathy. Results suggest that prominent symptoms of apathy, independent of depression, may be an important indicator of CNS involvement in HIV infection. Total BDI scores showed a less consistent relationship with neurocognitive performance, suggesting that somatic symptomatology is diagnostically ambiguous among HIV-infected subjects.

AIDS Dementia Complex↗

Relationships among apathy, depression, and cognitive impairment in HIV/AIDS.

This study was designed to determine whether apathy is associated with neurocognitive symptoms and/or depressive symptoms in HIV/AIDS and also whether apathy is associated with patient expectancies about antiretroviral medication adherence. Seventy-five HIV+ homosexual men and 58 HIV+ women were assessed for depressive disorders and symptoms. Neuropsychological tests measured attention, concentration, learning, memory, executive function, and psychomotor speed. Other measures included Marin's Apathy Evaluation Scale, the Adherence Determinants Questionnaire, CD4 cell count, and HIV RNA viral load. Apathy was consistently related to depression and unrelated to neuropsychological impairment. Patient expectancies regarding medication adherence were unrelated to apathy when the analysis was controlled for depressive symptoms.

Adult↗

A comparison of self-report and caregiver assessment of depression, apathy, and irritability in Huntington's disease.

The natural history of psychiatric syndromes associated with Huntington's disease (HD) remains unclear, and longitudinal studies of symptoms such as depression, apathy, and irritability are required to better understand the progression and role of these syndromes and their effect on disability. Self-administered scales such as the Beck Depression Inventory (BDI) may be useful to document changes in symptoms over time, but the validity of self-report may be questionable with the inevitable progression of cognitive deficits. An alternative to the patient's self-report would be assessments by the caregiver. The authors assessed interrater agreement between patient self-assessment and caregiver assessment of patients status for the presence of depressed mood using the BDI and apathy and irritability using an apathy and irritability scale. Agreement between these scales across strata of cognitive status was also examined. Interrater agreement varied from moderate to good for the BDI, depending on patient cognitive status. Agreement for the apathy scores was low for patients with poor cognition and fair in patients with better cognition. Irritability scale agreement was fair at best and was the worst in patients with the most intact cognition. Caregiver assessment of patients' moods and apathy may be an acceptable alternative to patient self-report as patients' cognitive status worsens.

Adult↗

Apathy and executive function in depressed elderly.

Apathy and executive cognitive dysfunction (ECD) are important though conceptually different aspects of late-life depression. The primary objective of this study was to evaluate the relationship of apathy to ECD. The authors also evaluated the relationship of apathy and ECD to global cognitive impairment and word generation. Fifty-two elderly subjects with major depression and MMSE scores of 15 or greater were evaluated with apathy-related items from the Hamilton rating scale for depression (ApHRSD), the Executive Interview (EXIT), the Dementia Rating Scale (DRS), and the Controlled Oral Word Association test (COWA). ApHRSD scores were not significantly correlated with any of these variables. EXIT scores were correlated significantly with DRS and COWA. The results suggest that apathy and ECD may be independent of each other in some samples of elderly with late-life depression. Correlations may have been reduced by low variance for the variables of interest and by psychometric limitations of the ApHRSD.

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[A study of gender difference in student apathy].

This study attempted to construct Male Apathy Inventory (MAI), Female Apathy Inventory (FAI), and Obsession Scale (OS), and investigate the relations among apathy, obsession, self-consciousness, and self-image. Forty-seven original items for MAI and FAI, 13 original items for OS, Sugawara's self-consciousness scale (1984), and Murase and Murase's self-image scale (1966) were administered to 508 university students. Principal component analysis and factor analysis were used to select 24, 32, and 9 items for MAI, FAI, OS, respectively. Students high on OS tended to be higher on private self-consciousness, and male students who were low on both apathy and obsession had the lowest public self-consciousness. Self-images of the students high on apathy tended to be negative. Also, high obsession scores seemed beneficial for the adjustment of female students.

Adult↗

[Apathy: a useful but limited concept].

In the nineties, Marin proposed to define apathy as a clinical syndrome due to a lack of motivation. The syndrome is characterized by a diminished goal-directed overt behaviors, a lack of interest or concern for social and personal activities and a lack of responsiveness to positive and negative events. Apathy is clearly distinct from depression and can be observed in many conditions, in healthy people as well as in psychiatric disorders such as depression or schizophrenia. It is very common in patients with brain lesions involving the frontal lobes, the right hemisphere, but also in degenerative diseases such as Alzheimer's disease. Motivation, considered as the source of apathy by Marin, is not a simple construct. It refers to a complex set of multiple affective and cognitive processes. However, it is considered, either in an energetic acception, as a single quantitative variable, a force which impulses action but not direct behavior or, in a more specific acception, as the factor which direct behavior towards specific actions. The description of apathy by Marin and the scales designed to its assessment, are based on the first acception. The term apathy is only descriptive, such as those of dysphasia or anosognosia. They do not allow to study the mechanisms underlying the motivation disorders, essential process for the management of apathetic patients. A tentative qualitative approach to assess motivation disorders is proposed, using a semi-structured interview. However, it should be stressed that motivation can not be directly assessed: motivation is a concept to explain some behavior disorders and an inference from the study of behavior.

Emotions↗

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.

Aged↗

Does abnormal neuronal excitability exist in myotonic dystrophy? II. Effects of the antiarrhythmic drug hydroquinidine on apathy and hypersomnia.

An abnormal neuronal excitability in myotonic dystrophy (MD) might contribute to psychomotor and behavioral disturbances of MD patients. To gain new insights into the pathophysiology of MD, we determined whether the antiarrhythmic drug hydroquinidine could ameliorate apathy and hypersomnia besides slow saccadic eye movements in these patients. The study was conducted in a randomized, placebo-controlled, double-blind, crossover manner. Ten ambulatory patients without contraindications to hydroquinidine administration were enrolled. Hydroquinidine (450 mg/day) or placebo was given orally for 6 weeks with a washout period of 6 weeks between treatments. Apathy was evaluated by means of the apathy evaluation scale (AES) and hypersomnia by a sleep diary. Two patients withdrew in the first week of active treatment because of nausea and epigastralgia. The drug significantly reduced AES scores and daily sleep time compared to placebo. Thus, hydroquinidine can ameliorate apathy and hypersomnia in MD. However, the possibility of proarrhythmia and the high frequency of cardiac disturbances in MD seriously limit the therapeutic perspective. The effects on eye movements are presented in a companion paper.

Anti-Arrhythmia Agents↗

Regional cerebral metabolism in early Alzheimer's disease with clinically significant apathy or depression.

BACKGROUND: Alzheimer's disease (AD) is clinically characterized by cognitive impairment and behavioral disturbances. The aim of the study was to identify regional alterations in brain function associated with neuropsychiatric symptoms in early AD. METHODS: Patients underwent measures of cerebral glucose metabolism applying positron emission tomography (PET) and (18)F-fluorodeoxyglucose. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory (NPI). Positron emission tomography images of patients suffering a neuropsychiatric symptom of clinical significance (NPI subscore for a specific item >/=4 points) were compared with the images of patients without the specific symptom under study (NPI subscore for a specific item = 0 points). RESULTS: A total of 53 patients with AD (Mini-Mental State Examination [MMSE] 22.5 +/- 2.94 points) entered the study. Of all symptoms, apathy and depression were most frequently encountered. The patient group with apathy (n = 17) revealed significant decreases in left orbitofrontal regions when compared with patients free of apathy. Depression of clinical significance (n = 10) was associated with hypometabolism in dorsolateral prefrontal regions. CONCLUSIONS: These findings support the notion that different functional circuits underlie apathy and depression in early AD.

Aged↗

Cutoff score on the apathy evaluation scale in subjects with traumatic brain injury.

This cross-sectional study was designed to determine a cutoff score on the Apathy Evaluation Scale (AES) that predicts a clinician's designation of a subject with TBI as apathetic or not. Forty-five outpatients with TBI completed the AES-S, and 37 family members, friends, or significant others filled out the AES-I. Three clinicians prospectively gave their impressions of the presence or absence of apathy and retrospectively chose the degree of apathy on a 7-point subjective rating scale. The data was analysed by logistic regression and Receiver Operating Characteristic (ROC) curve. Sensitivity and specificity were calculated. No cutoff score on the AES-S or AES-I was found to have reasonable sensitivity and specificity with respect to the ability to predict the clinician's designation of a subject as apathetic. The AES requires further study if it is to be used to measure apathy following TBI.

Adolescent↗

Behavioral and psychological symptoms in Alzheimer's disease. Relation between apathy and regional cerebral perfusion.

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

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