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Methylphenidate may treat apathy independent of depression.

OBJECTIVE: To report a case of apathy treated with methylphenidate in which improvement in apathy was independent of improvement of depression. CASE SUMMARY: A 47-year-old woman with a 20-year history of recurrent major depression was diagnosed as having significant apathy with lack of initiative and motivation. Over the course of a 4-week treatment regimen with methylphenidate, her apathy, as measured by the Apathy Evaluation Scale, improved, with her score decreasing from 57 to 31. During this period, her depression, as assessed by the 21-item Hamilton Rating Scale for Depression, remained unchanged. DISCUSSION: Our report of improvement of apathy with methylphenidate is consistent with other reports in the literature, although previous studies have not specifically used the rating scales to assess apathy. Even though this patient had experienced apathy for a long time, it had not been detected due to lack of direct questioning. In this case, as noted, the improvement of apathy was independent of improvement in depression. CONCLUSIONS: A high degree of suspicion and specific inquiry is required for identification of apathy. Once detected, methylphenidate may be beneficial in its treatment, a strategy that may work independently of augmentation of antidepressants.

Affective Symptoms↗

Cognitive correlates of apathy in traumatic brain injury.

OBJECTIVE: To investigate the relation between apathy and cognitive deficits in patients with severe traumatic brain injury (TBI). BACKGROUND: Apathy defined as reduced goal-directed behavior due to lack of motivation constitutes a major neuropsychiatric symptom following TBI. According to definition, apathy should not be associated with global cognitive reduction, but rather with specific areas of cognitive dysfunction. METHODS: results from the Apathy Evaluation Scale (AES) and a comprehensive neuropsychologic assessment were collected in up to 53 patients with severe TBI. Neuropsychologic tests were organized in the following seven areas of cognitive function: acquisition and memory, attention span, executive function, psychomotor speed, verbal skills, nonverbal skills, and motor speed. RESULTS: Apathy score was significantly correlated with reduced performance on acquisition and memory, psychomotor speed, and executive functions. A principal component analysis showed that these specific areas of cognitive functions clustered together with the cognitive dimension of apathy, not with behavioral or emotional aspects of apathy. CONCLUSIONS: Apathy is associated with specific cognitive deficits related to frontal lobe dysfunction. The results are in accordance with the definition of apathy and confirm apathy-cognitive function relationships reported in other neurologic populations.

Adolescent↗

Reduced daytime activity in patients with acquired brain damage and apathy: a study with ambulatory actigraphy.

PRIMARY OBJECTIVE: Apathy is difficult to assess in clinical practice. Ambulatory actigraphy was used with the aim to measure locomotor activity during the daytime as a correlate of self-initiated action in brain-damaged patients with apathy. RESEARCH DESIGN: Twenty-four patients with acquired brain damage and high levels of apathy or low levels of apathy as well as 12 healthy controls were investigated using a parallel group design. METHODS AND PROCEDURES: Apathy was diagnosed after clinical observation and evaluated with the apathy evaluation scale. Locomotor activity was measured with a wrist-worn actigraph over 3 days. RESULTS: High apathy patients showed significantly reduced locomotor activity and more episodes of inactivity (naps) during the daytime. Self-rated apathy correlated with daytime activity, nap frequency and cognitive (executive) deficits. CONCLUSIONS: Ambulatory actigraphy is a promising method to evaluate self-initiated action in patients with apathy.

Adult↗

Group differences in the relationship between apathy and depression.

The purpose of this study was to evaluate the discriminability of apathy and depression by determining whether the relationship of these two dimensions of behavior varies in different diagnostic groups. Using the authors' Apathy Evaluation Scale and the Hamilton Rating Scale for Depression, we rated 123 subjects, mean age 72 years, who met research criteria for healthy elderly controls, left or right hemisphere stroke, probable Alzheimer's disease, and major depression. Elevated apathy scores unassociated with elevated depression were most frequent in Alzheimer's disease and right hemisphere stroke, and also occurred in a small number of left hemisphere stroke and normal subjects. In major depression, apathy was associated with high depression scores, although a substantial number of major depressives showed elevated depression without elevated apathy. In left hemisphere stroke, probable Alzheimer's disease, and major depression, there were significant positive correlations between apathy and depression. The slope of the regression of apathy on depression was greatest in probable Alzheimer's disease and major depression. These results indicate that the relationship between apathy and depression differs across diagnostic groups and, thus, support the discriminability of apathy and depression.

Affective Symptoms↗

Apathy in schizophrenia: reduced frontal lobe volume and neuropsychological deficits.

OBJECTIVE: Apathy is a common negative symptom in schizophrenia. The authors investigated neuropsychological performance and regional brain volumes in schizophrenia patients with high versus low levels of apathy. METHOD: Schizophrenia patients with low apathy levels (N=18) and high apathy levels (N=20) and 12 healthy comparison subjects completed neuropsychological testing as well as magnetic resonance imaging scanning to obtain lobar volumes after total intracranial volume was controlled. RESULTS: The high apathy group scored lower than comparison subjects on rapid visuomotor sequencing and verbal learning/recall. The high apathy group had lower performance IQ scores than the low apathy and comparison groups. Only the high apathy group showed significantly reduced bilateral frontal lobe volumes relative to comparison subjects; both schizophrenia patient groups showed bilateral temporal lobe volume reductions. CONCLUSIONS: The present findings are consistent with studies in other disorders showing frontal lobe involvement in apathy.

Adult↗

Clinical, neuropsychological, and morphometric correlates of apathy in Parkinson's disease.

Apathy is a salient feature of various neuropsychiatric disorders, from depression to Alzheimer's disease. We formally assess its prevalence in idiopathic Parkinson's disease (PD) together with its clinical, neuropsychological, and morphometric correlates. Thirty patients with PD and 25 normal controls were assessed using an extensive neuropsychological battery and Marin's Apathy Scale; parkinsonian patients also underwent MRI scan, followed by linear measurement of various frontotemporal structures. Approximately 45% of the PD sample showed apathy. For comparison analysis, given the unimodal distribution of the apathy scores, the PD sample was divided into three groups on the basis of the apathy tertiles. All three PD groups had worse cognitive and depression scores than controls, whereas they did not differ in terms of demographic, neurological, general cognitive, or affective features. By contrast, a significant positive association was found between apathy scores and performance on tests of executive function. As regards the morphometric data, we failed to find any specific measure of frontotemporal atrophy correlating with the presence or severity of apathy. Thus, apathy seems to be a frequent and important companion of PD, in many cases probably due to a primary motivational impairment, possibly related to a frontosubcortical dysfunction.

Affect↗

Reduced prefrontal N-acetylaspartate in stroke patients with apathy.

BACKGROUND: Although substantial numbers of stroke patients suffer from apathy, its causes are still poorly understood. Previous studies suggest that dysfunction of the frontal lobes is implicated in the pathophysiology of motivation. Our aim was to investigate the association between proton magnetic resonance spectroscopy (H1-MRS) measurements in unaffected frontal lobes and apathy in a group of first-time stroke patients. METHODS: 31 patients with a first-time ischemic stroke located outside the frontal lobes and 20 healthy subjects were included in the study. The authors performed single voxel H1-MRS in order to measure the N-acetylaspartate/creatine (NAA)/Cr, glutamate+glutamine (Glx)/Cr, choline (Cho)/Cr and myo-inositol (mI)/Cr ratios in the frontal lobes. Patients were assessed between days 7 and 12 post stroke. Diagnosis of apathy was made on the basis of clinical observation, interview and Apathy Scale. RESULTS: 13 out of 31 patients (42%) demonstrated apathy. Patients with apathy had lower NAA/Cr ratios in the right frontal lobe than non-apathetic subjects. The patient group was divided into two subgroups: Those with left hemisphere strokes, and those with right hemisphere strokes. Of these subjects, significantly lowered NAA/Cr ratios were found in the right hemispheres of apathetic patients in the subgroup with left-sided brain lesions. CONCLUSIONS: These findings point to the association between apathy and frontal lobe integrity, suggest different reactions of the hemispheres and indicate that changes in the NAA/Cr ratio are related to the apathy.

Aged↗

Apathy predicts hedonic but not craving response to cocaine.

Cocaine-induced craving has been implicated in the maintenance of ongoing cocaine use and is presumed to be mediated by enhanced synaptic availability of monoamines, including dopamine. Apathy is a neuropsychiatric syndrome that is associated with hypodopaminergic functioning and is neurobiologically distinct from depression. Apathy has been observed to be prevalent during the initial phases of abstinence in cocaine-dependent individuals. In the current report, we sought to investigate the relationship between apathy, depression, and craving in response to an acute intravenous administration of cocaine. To this end, sixteen non-treatment seeking volunteers were evaluated. Following acute administration of cocaine (40 mg, IV), patients with low apathy scores exhibited increased craving, whereas patients with high apathy scores exhibited decreased craving. In addition, patients with high apathy scores exhibited increased ratings of the subjective measure of "High", suggesting that high apathy predicts a greater hedonic response in dependence. Self-reported ratings of depression did not account for the observed differences. The data reveal that cocaine-induced craving is not ubiquitous, and may not play a critical role in the maintenance of cocaine dependence. Overall, the findings suggest that apathy predicts hedonic but not craving response to cocaine.

Cocaine↗

Apathy syndrome in cocaine dependence.

The cocaine abstinence syndrome has been associated with a range of symptoms, including apathy and depression. Although initial studies reported high prevalence rates of 'apathy/amotivation' and depression, validated rating scales of apathy were not then available. Using a validated measure of apathy, we hypothesized that newly abstinent cocaine-dependent subjects would report increased apathy compared with non-cocaine-using control subjects. Furthermore, because apathy and depression are dissociable in other neuropsychiatric syndromes, we examined whether they were dissociable in recently abstinent cocaine-dependent subjects. Following 4 days of monitored abstinence, cocaine-dependent subjects (n=11) and non-drug-using control subjects (n=19) were administered standardized tests of apathy and depression. Cocaine-dependent subjects had elevated scores on the apathy rating scale compared with the control group, but the groups did not differ in ratings of depression. These data suggest that apathy is present during the initial phases of abstinence for a subset of cocaine-dependent individuals. This group may benefit from targeted pharmacological intervention.

Adult↗

Brain perfusion in Alzheimer's disease with and without apathy: a SPECT study with statistical parametric mapping analysis.

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.

Activities of Daily Living↗

Apathy and executive function in Alzheimer's disease.

Apathy is a common behavioral disturbance in patients with Alzheimer's disease (AD). Recent studies have linked the presence of apathy to alterations in frontal lobe functions, but few studies have explored the relationship using standard neuropsychological measures in patients with AD. We administered a comprehensive battery of neuropsychological tests and a behavior rating scale to 80 patients with AD. We explored the relationship of apathy to executive dysfunction. AD patients with apathy performed significantly worse on tests of executive function (WAIS-R Digit Symbol, Trail-Making, Stroop Color Interference Test) than AD patients without apathy. The presence of dysphoria did not modify these results and no significant relationships were found between tests of executive functions and dysphoria. Performance on executive measures as a group were effective in correctly classifying patients as apathetic or nonapathetic with 75% accuracy. Neuropsychological measures not dependent on executive functions were unrelated to apathy. Apathy is associated with executive dysfunction and not with other neuropsychological deficits. Apathy is distinct from dysphoria.

Aged↗

Apathy: Concept, Syndrome, Neural Mechanisms, and Treatment.

The essential meaning of apathy is lack of motivation. Criteria for diagnosing the syndrome of apathy and for distinguishing symptomatic and syndromal apathetic states are based on this definition, whereas assessment of apathy as a continuous variable is operationalized in the Apathy Evaluation Scale, which provides reliable and valid measures of diminished motivation in diverse clinical populations. The clinical utility of this formulation is shown by describing the causes, differential diagnosis, and treatment of apathy. The neural mechanisms of apathy are postulated to involve the brainstem and forebrain circuits that mediate goal-directed behavior. The functions of these circuits provide a model for understanding a provisional classification of apathy syndromes into cognitive, sensory, motor, and affective subtypes. This classification and its postulated neural basis has heuristic value for increasing our understanding of the disorders in which apathy is prominent.

Journal Article↗

Prevalence of apathy following head injury.

Although several studies have examined the demographics of mood disorders and personality changes following closed head injury (CHI), there are no studies that address the prevalence of apathy after CHI. Utilizing standardized evaluation tools, this study examines the prevalence of apathy in 83 consecutive patients seen in a neuropsychiatric clinic. A total of 10.84% had apathy without depression while an equal number were depressed without apathy; another 60% of patients exhibited both apathy and depression. Younger patients were more likely to be apathetic than older patients who were more likely to be depressed and apathetic. Patients with severe injury were more likely to exhibit apathy alone. Family members rated the patients higher on apathy scale. These findings suggest that apathy is a frequent symptom after head injury and may occur either alone or in association with depression.

Adolescent↗

A prospective longitudinal study of apathy in Alzheimer's disease.

BACKGROUND: Apathy and depression are the most frequent behavioural and psychiatric disorders in Alzheimer's disease, and may both have a negative impact on the progression of the illness. OBJECTIVES: To examine the clinical correlates of apathy in Alzheimer's disease (AD), and to determine whether apathy is a significant predictor of more rapid cognitive, functional and emotional decline. METHODS: Using a structured psychiatric evaluation, we examined a consecutive series of 354 subjects meeting clinical criteria for AD. Apathy was assessed by the Apathy Scale, and diagnosed using standardised criteria. Additional measurements included scales for depression, functional impairment, and global cognitive functions. A follow up evaluation was carried out in 247 patients (70% of the total sample) between 1 and 4 years after the baseline evaluation. RESULTS: Apathy was significantly associated with older age (p = 0.009), and a higher frequency of minor and major depression (p < 0.0001). Apathy at baseline was a significant predictor of depression at follow up (p = 0.01), and was associated with a faster cognitive (p = 0.0007) and functional decline (p = 0.006). CONCLUSIONS: Apathy in AD is a behavioural marker of a more aggressive dementia, characterised by a faster progression of cognitive, functional, and emotional impairment.

Aged↗

Impaired novelty processing in apathy after subcortical stroke.

BACKGROUND AND PURPOSE: Apathy is associated with decreased novelty-seeking behaviors and is a prevailing behavioral symptom after stroke affecting cortical and subcortical regions. We studied the relationship between apathetic state after subcortical stroke and neural orienting response to novel events using an event-related evoked potential (ERP) technique. METHODS: Twenty-nine patients with subcortical ischemic stroke were grouped according to whether they showed apathy or not. We analyzed apathy state scaled by the modified Starkstein apathy score and auditory P3 ERP components evoked by task-relevant target stimuli (target P3) and task-irrelevant novel stimuli (novelty P3). RESULTS: The apathetic group showed a significantly lower score of verbal fluency test and global cognitive function test compared with the nonapathetic group. The novelty P3 latency was significantly prolonged, and its amplitude was reduced over the frontal site in the apathy group. The apathy scale was correlated with the novelty P3 latency and amplitude at the frontal site. The target P3 measures were related to global cognitive function. CONCLUSIONS: The present study suggests that apathy after subcortical stroke is associated with impaired neural processing of novel events within the frontal-subcortical system and that the novelty P3 is a useful physiological measure for assessing apathy after stroke.

Affect↗

Dissociating apathy and depression in Parkinson disease.

OBJECTIVE: To examine the hypothesis that apathy is a core feature of Parkinson disease (PD) and that apathy can be dissociated from depression. METHODS: Eighty patients with PD and 20 patients with dystonia completed depression and apathy measures including the Marin Apathy Evaluation Scale (AES), Beck Depression Inventory (BDI), and Centers for Epidemiologic Studies-Depression Scale (CES-D). RESULTS: There was a significantly higher severity and frequency of apathy in PD (frequency = 51%, 41/80) than in dystonia (frequency = 20%, 4/20). Apathy in the absence of depression was frequent in PD and did not occur in dystonia (PD = 28.8%, dystonia = 0%). CONCLUSIONS: Patients with Parkinson disease (PD) experienced significantly higher frequency and severity of apathy when compared with patients with dystonia. Apathy may be a "core" feature of PD and occurs in the absence of depression.

Affective Symptoms↗

[Depression and apathy in Alzheimer's disease].

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.

Aged↗

Cerebral blood flow correlates of apathy in Alzheimer disease.

BACKGROUND: Apathy is a pervasive noncognitive neuropsychiatric disturbance in Alzheimer disease, which causes significant caregiver distress. The neuroanatomical substrate of apathy is not well understood. OBJECTIVE: To study the relationship between regional cerebral blood flow and the presence and severity of the personality disturbance, apathy, in individuals with Alzheimer disease. DESIGN: Analysis of the relationship between regional cerebral blood flow as measured by single photon emission computed tomography and severity of apathy as measured by the Neuropsychiatric Inventory using an analysis of variance design. We examined regional cerebral perfusion alterations as measured by xenon 133Xecalibrated technetium Tc 99m hexamethyl-propyleneamine-oxime single photon emission computed tomography in relation to the presence and severity of apathy. SETTING: The neurology clinics of the University of California, Los Angeles, UCLA School of Medicine, and Harbor-UCLA Medical Center. PARTICIPANTS: Thirty-one community-dwelling patients fulfilling National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association diagnostic criteria for probable Alzheimer disease who had a single photon computed tomographic scan performed within 3 months of administration of the Neuropsychiatric Inventory. RESULTS: The presence of apathy was associated with more severe prefrontal and anterior temporal dysfunction. These regional cerebral perfusion relationships with apathy were independent of cognitive decline except in the dorsolateral prefrontal cortex. CONCLUSIONS: These results demonstrate the association of apathetic syndromes with prefrontal and anterior temporal regional brain dysfunction and are consistent with similar findings previously reported in other disorders.

Aged↗