Improvement In Apathy Research Articles

Neuroanatomical correlates of apathy in late-life depression and antidepressant treatment response

BackgroundApathy is a prominent feature of geriatric depression that predicts poor clinical outcomes and hinders depression treatment. Yet little is known about the neurobiology and treatment of apathy in late-life depression. This study examined apathy prevalence in a clinical sample of depressed elderly, response of apathy to selective serotonin reuptake inhibitor (SSRI) treatment, and neuroanatomical correlates that distinguished responders from non-responders and healthy controls. MethodsParticipants included 45 non-demented, elderly with major depression and 43 elderly comparison individuals. After a 2-week single-blind placebo period, depressed participants received escitalopram 10mg daily for 12 weeks. The Apathy Evaluation Scale (AES) and 24-item Hamilton Depression Rating Scale (HDRS) were administered at baseline and 12 weeks. MRI scans were acquired at baseline for concurrent structural and diffusion tensor imaging of anterior cingulate gray matter and associated white matter tracts. Results35.5% of depressed patients suffered from apathy. This declined to 15.6% (p<0.1) following treatment, but 43% of initial sufferers continued to report significant apathy. Improvement of apathy with SSRI was independent of change in depression but correlated with larger left posterior subgenual cingulate volumes and greater fractional anisotropy of left uncinate fasciculi. LimitationsModest sample size, no placebo control, post-hoc secondary analysis, use of 1.5T MRI scanner ConclusionsWhile prevalent in geriatric depression, apathy is separable from depression with regards to medication response. Structural abnormalities of the posterior subgenual cingulate and uncinate fasciculus may perpetuate apathetic states by interfering with prefrontal cortical recruitment of limbic activity essential to motivated behavior.

Efficacy of pain treatment on mood syndrome in patients with dementia: a randomized clinical trial.

Depression is common in nursing home (NH) patients with dementia, and often clustered with anxiety and other mood symptoms. An association between pain and depressive symptoms has been reported, but the impact of pain management on depression and other mood symptoms has not been investigated. Secondary analyses of a cluster randomized clinical trial examine the response of dementia-related mood symptoms to a Stepwise Protocol of Treating Pain. Three-hundred fifty-two patients with moderate and severe dementia and significant behavioural disturbances, related to 60 clusters (i.e. clusters defined as single independent NH units) in 18 NHs of Western Norway, were included. All patients in the intervention group received individual daily pain treatment with paracetamol, extended release morphine, buprenorphine transdermal patch or pregabaline for 8 weeks, with additional follow-up assessment 4 weeks after completion of the intervention. Clusters randomized to control received usual treatment. A mood cluster consisting of depression, anxiety, sleep disorders, apathy and appetite items from the Neuropsychiatric Inventory-Nursing Home (NPI-NH) was the primary outcome. Analysed by Mann-Whitney U-tests, Stepwise Protocol of Treating Pain conferred significant benefit in treatment of the NPI-NH mood cluster (F = 13.4, df = 1;299, p < 0.001) and depression (F = 2.0, df = 1;301, p = 0.025). Further analyses highlighted improvements in apathy (F = 5.3, df = 1;300, p = 0.017), night-time behaviours (F = 3.1, df = 1;301, p = 0.050), and appetite items (F = 11.6, df = 1;301, p = 0.005), but not irritability (p = 0.092) and anxiety (p = 0.125). Mood symptoms including depression significantly improved with pain treatment, emphasizing the importance of more rigorous treatment of pain in agitated people with dementia. Findings have potentially immediate clinical relevance.

The relationship between change in apathy and changes in cognition and functional outcomes in currently non-depressed SSRI-treated patients with major depressive disorder

AimsApathy in the context of treated major depressive disorder (MDD) is a frequently observed phenomenon in clinical practice. This study aimed to assess the validity of the Rothschild Scale for Antidepressant Tachyphylaxis® (RSAT) and the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) for measuring apathy, and to assess the relationship between apathy and possible contributing factors, in patients with MDD and residual apathy in the absence of depressed mood. MethodsThe underlying structure and validity of the RSAT and CPFQ were assessed via factor analysis and correlation with the Apathy Evaluation Scale—Clinician rated version (AES-C) in 483 patients who had previously responded to treatment with a selective serotonin reuptake inhibitor. The relationship between apathy and contributing variables was investigated via structural equation modeling. Correlation and regression analyses were conducted to examine the relationship between the Sheehan Disability Scale (SDS) and the RSAT, CPFQ, and AES-C. ResultsThe RSAT and CPFQ were validated with the AES-C with respect to energy and motivation. The latent variable “Energy and Interest”, based on the energy, motivation, and interest items (RSAT and CPFQ), was a major contributing factor to apathy. Improvements in function (SDS) were significantly correlated with, and predicted by, improvements in apathy and cognitive and physical functioning (assessed by the RSAT, CPFQ, and AES-C). ConclusionsThese analyses provide further information on apathy and its assessment in the context of treated MDD. A better understanding of apathy will aid further investigation of this phenomenon and, ultimately, determination of the most appropriate approach for its clinical management.

Parkinsonian apathy responds to dopaminergic stimulation of D2/D3 receptors with piribedil

Apathy is one of the most common symptoms encountered in Parkinson's disease, and is defined as a lack of motivation accompanied by reduced goal-directed cognition, behaviour and emotional involvement. In a previous study we have described a delayed withdrawal syndrome after successful motor improvement related to subthalamic stimulation allowing for a major decrease in dopaminergic treatment. This withdrawal syndrome correlated with a diffuse mesolimbic dopaminergic denervation. To confirm our hypothesis of parkinsonian apathy being related to mesolimbic dopaminergic denervation, we performed a randomized controlled study using piribedil, a relatively selective D2/D3 dopamine agonist to treat parkinsonian apathy, using the model of postoperative apathy. A 12-week prospective, placebo-controlled, randomized, double-blinded trial was conducted in 37 patients with Parkinson's disease presenting with apathy (Starkstein Apathy Scale score > 14) following subthalamic nucleus stimulation. Patients received either piribedil up to 300 mg per day (n = 19) or placebo (n = 18) for 12 weeks. The primary end point was the improvement of apathy under treatment, as assessed by the reduction of the Starkstein Apathy Scale score in both treatment groups. Secondary end points included alleviation in depression (Beck Depression Inventory), anxiety (Beck Anxiety Inventory), improvement of quality of life (PDQ39) and anhedonia (Snaith-Hamilton Pleasure Scale). Exploratory endpoints consisted in changes of the Robert Inventory score and Hamilton depression scales. An intention to treat analysis of covariance analysis was performed to compare treatment effects (P < 0.05). The number of premature study dropouts was seven in the placebo and five in the piribedil groups, mostly related to intolerance to hypodopaminergic symptoms. At follow-up evaluation, the apathy score was reduced by 34.6% on piribedil versus 3.2% on placebo (P = 0.015). With piribedil, modifications in the Beck depression and anxiety scores were -19.8% and -22.8%, respectively versus +1.4% and -8.3% with placebo, without reaching significance level. Piribedil led to a trend towards improvement in quality of life (-16.2% versus +6.7% on placebo; P = 0.08) and anhedonia (-49% versus -5.6% on the placebo; P = 0.08). Apathy, assessed by the Robert Inventory score, improved by 46.6% on piribedil and worsened by 2.3% on placebo (P = 0.005). Depression, measured by the Hamilton score, improved in the piribedil group (P = 0.05). No significant side effects were observed. The present study provides a class II evidence of the efficacy of the dopamine agonist piribedil in the treatment of apathy in Parkinson's disease.

Improvement of Apathy After Levofloxacin Treatment

Apathy is common in various neurological conditions. A caregiver of a patient with normal pressure hydrocephalus and cognitive decline repeatedly reported improvement in apathy, social interaction, and ability to perform activities of daily living after treatment with levofloxacin for upper respiratory infections. We sought to determine whether this effect could be objectively supported and replicated outside the context of infection. An n-of-1 study was performed using 2 treatment and 2 nontreatment phases during an infection-free interval. Treatment arms consisted of 10-day courses of levofloxacin 500 mg daily. The evaluating investigator, caregiver, and patient were blind to treatment assignments. Measures included the Apathy Evaluation Scale (clinician and caregiver), Apathy Inventory (clinician and caregiver), Northwestern University Disability Scale, Disability Assessment for Dementia, and caregiver clinical global impression score. The patient had less apathy and disability during 2 periods of treatment with levofloxacin 500 mg daily compared with periods without levofloxacin treatment. Caregiver clinical global impression scores were significantly better during days on treatment compared with off treatment (P=0.0007). Evaluation of a single patient suggests that improvement in apathy may be a previously undescribed effect of levofloxacin. Further study is warranted.

Apathy in currently nondepressed patients treated with a SSRI for a major depressive episode: Outcomes following randomized switch to either duloxetine or escitalopram

Apathy in the context of treated major depressive disorder (MDD) is a common but understudied symptom. This multicenter, double-blind, randomized study investigated whether switching from a selective serotonin reuptake inhibitor (SSRI) to a serotonin-norepinephrine reuptake inhibitor (SNRI), compared with switching to another SSRI, improved apathy symptoms in patients who had been treated with a SSRI for MDD for ≥3 months, were no longer depressed (Montgomery-Åsberg Depression Rating Scale [MADRS] total score ≤15), and continued to have apathy (Apathy Evaluation Scale – Clinician rated version [AES-C] total score >30). Following 8 weeks of treatment, both the duloxetine (SNRI, 244 patients) and escitalopram (SSRI, 239 patients) groups significantly improved from baseline on the AES-C total score (least squares mean change [standard error]: duloxetine −13.9 [0.54]; escitalopram −13.5 [0.54], both P < 0.001), and on the secondary apathy, depression, and functional outcomes. There were no significant differences between the two groups on any measure, including AES-C total score (least squares mean difference [95% confidence interval]: −0.4 [−1.87 to 1.10], P = 0.612; primary objective). There was a significant within-group improvement in apathy in the subgroup who received escitalopram before and during the study. There were few differences in safety between the two groups. This study did not support the hypothesis that switching from a SSRI to a SNRI has a beneficial effect on apathy symptoms. However, given the study limitations, it is possible that more specific targeting of the noradrenergic pathway would be of benefit.

Physical and Cognitive Stimulation in Alzheimer Disease. The GAIA Project

Several data suggest that physical activity and cognitive stimulation have a positive effect on the quality of life (QoL) of people with Alzheimer's disease (AD), slowing the decline due to the disease. A pilot project was undertaken to assess the effect of cognitive stimulation, physical activity, and socialization on patients with AD and their informal caregiver's QoL and mood. Fourteen patients with AD were randomly divided into active treatment group and control group. At the end of treatment, a significant improvement in apathy, anxiety, depression, and QoL in the active treatment group was found. Considering caregivers, those of the active treatment group exhibited a significant improvement in their mood and in their perception of patients' QoL. This study provides evidence that a combined approach based on cognitive stimulation, physical activity, and socialization is a feasible tool to improve mood and QoL in patients with AD and their caregivers.

Use of Psychostimulants in Patients with Dementia

To review the efficacy and safety of psychostimulants for negative behavioral symptoms (ie, apathy, excessive daytime sedation) and cognition in patients with dementia. Literature was accessed through PubMed and MEDLINE (1966-June 2010), using the terms stimulant, psychostimulant, methylphenidate, dexmethylphenidate, amphetamine, dextroamphetamine, lisdexamfetamine, atomoxetine, modafinil, armodafinil, dementia, Alzheimer disease, vascular dementia, Lewy body dementia, mixed dementia, frontotemporal dementia, therapy, treatment, and therapeutic. Additional references identified from the initial search were reviewed. All relevant clinical trials published in English and involving primarily older adults with dementia were included. Case reports, review articles, and other preclinical literature were included as appropriate. Psychostimulants have been employed as a treatment for cognitive and behavioral symptoms in dementia for decades, but the literature has lagged behind this practice. Eight reports on use of psychostimulants as a treatment of apathy in dementia were reviewed. Methylphenidate was the most frequently studied medication and improvements in apathy were consistently noted; however, the magnitude and duration of effect remain unclear. Six studies examining the cognitive effects of a variety of psychostimulants in patients with dementia were reviewed; psychostimulants had little to no effect on cognition. A lack of studies exists to draw conclusions about the use of psychostimulants for the treatment of excessive daytime sedation in dementia. The possibility of psychostimulants to increase blood pressure; elevate heart rate; and lead to irritability, agitation, and psychosis makes careful patient selection critical, especially in older adults with severe cardiovascular disease or other underlying cardiac abnormalities. Based on limited studies, methylphenidate is a possible treatment for apathy in patients with dementia. Psychostimulants, as a group, do not appear to be broadly effective treatments for behavioral or cognitive symptoms of dementia. The potential utility of psychostimulants must be balanced with careful patient selection.

Methylphenidate for Apathy and Functional Status in Dementia of the Alzheimer Type

Apathy is the most common behavioral problem in persons with dementia of the Alzheimer type (DAT). Treatment of apathy in DAT is not systematically studied. The purpose of this study was to evaluate the response of apathy to methylphenidate treatment and to examine whether functional status improved. The authors conducted a 12-week open-labeled study with immediate release formulation of methylphenidate. Twenty-three patients with DAT scoring >40 on the Apathy Evaluation Scale (AES) were recruited. Repeated measures analysis of variance and correlation analysis were performed. None of the patients dropped out of the study because of adverse events. Significant improvement in apathy was noted during 12 weeks. Significant improvement was also noted in depression, Mini-Mental State Examination score, and functional status. There was no correlation between changes in the AES and depression scores. Methylphenidate was well tolerated in these patients with DAT. Apathy improved with the use of methylphenidate.

Apathy Due to Cerebrovascular Accidents Successfully Treated With Methylphenidate: A Case Series

Apathy Due to Cerebrovascular Accidents Successfully Treated With Methylphenidate: A Case Series

Treatment of Apathy With Methylphenidate

Treatment of Apathy With Methylphenidate

Treatment of Apathy With Methylphenidate

Apathy is a common condition that transcends psychiatric diagnoses. Its treatment is not well studied. The authors present four cases of apathy treated with a regimen of methylphenidate. Significant improvement in apathy and its sub-domains (motivation, novelty, and persistence) were noted.

Methylphenidate May Treat Apathy Independent of Depression

To report a case of apathy treated with methylphenidate in which improvement in apathy was independent of improvement of depression. 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. 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. 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.

Metabolic Patterns Associated With the Clinical Response to Galantamine Therapy

Regional brain correlates of treatment with cholinesterase inhibitors in those with Alzheimer disease are unknown. To map brain metabolism associated with the treatment response to galantamine with fludeoxyglucose F 18 positron emission tomography in patients with Alzheimer disease. This is a hypothesis-driven, prospective, open-label study of 19 patients with mild to moderate Alzheimer disease examined before and after treatment with the cholinesterase inhibitor galantamine. Clinical examinations included the cognitive portion of the Alzheimer Disease Assessment Scale, the Mini-Mental State Examination, and the Neuropsychiatric Inventory. Imaging was performed using fludeoxyglucose F 18 positron emission tomography. The positron emission tomographic data, registered to a probabilistic anatomical atlas, were subjected to a voxel-based analysis of 3 subgroups: total patient analysis, cognitive analysis, and behavioral analysis. Subvolume thresholding corrected random lobar noise to produce 3-dimensional significance maps. The total group analysis showed an increase in left caudate metabolism with no significant change in clinical outcomes for the total group with treatment. Subgroup analysis of cognitive and behavioral responders demonstrated a significant activation of a striatal-thalamofrontal network with galantamine treatment that was not present in patients whose condition worsened or was unchanged by therapy. In cognitive subgroups, change in left anterior cingulate metabolism significantly correlated with change in the cognitive portion of the Alzheimer Disease Assessment Scale (r = 0.70, P = .02); in behavioral subgroups, right cingulate metabolic change significantly correlated with improvement in depression and right ventral putamen metabolic change with improvement in apathy (r = 0.63, P<.05 for both). Cognitive and behavioral responders to galantamine therapy show clinically related improvements in prefrontal network metabolism along with thalamic activation.