Poststroke Depression: An Update.

The presence of neuropsychiatric disorders after stroke has been recognized for more than 100 years, but controlled systematic studies did not begin until the 1970s. The most clinically important advances, however, have been in the treatment and prevention of poststroke depression (PSD). Recent meta-analyses of randomized controlled trials (RCTs) for the treatment of PSD have demonstrated the efficacy of antidepressants. Similarly, RCTs for the prevention of PSD have shown that antidepressants significantly decrease the incidence of PSD compared with placebo. Early treatment of PSD with antidepressants also appears to enhance both physical and cognitive recovery from stroke and may increase survival up to 10 years. Genetic and epigenetic variations, white matter disease, cerebrovascular deregulation, altered neuroplasticity, and changes in glutamate neurotransmission may be relevant etiological factors.

Intensive aphasia therapy improves low mood in fluent post-stroke aphasia: Evidence from a case-controlled study.

Introduction: Depressive symptoms are a major drawback of aphasia, negatively impacting on functional outcomes. In a previous study, Intensive Language-Action Therapy (ILAT) was effective in improving depression and low mood in persons with chronic non-fluent aphasia. We present a proof-of-concept case-control study that evaluates language and mood outcomes amongst persons with fluent post-stroke aphasia.Participants: Thirteen Spanish speaking persons with fluent aphasia due to chronic stroke lesions in the left hemisphere participated in the study.Intervention: Five participants (intervention group) received ILAT for 3 h/day during two consecutive weeks, for an overall of 30 h, and 8 participants (control group) entered a waiting-list no-treatment arm.Results: The main finding was that participants receiving active treatment showed significant improvements on depression and aphasia severity scores, whereas no significant changes were found in the control group.Conclusions: The implementation of ILAT was efficient in improving clinical language deficits in people with fluent aphasia and contributes to improvement in mood after therapy.Trial registration: EUDRACT (2008-008481-12).

Design and validation of a new instrument to assess fear of falling in Parkinson's disease.

BACKGROUND: Fear of falling may be significantly associated with falls in Parkinson's disease (PD) and may have a negative impact on quality of life. Nevertheless, there are no valid and reliable tools to examine this condition in PD. The objective of this study was to design and determine the psychometric attributes of an instrument to assess fear of falling in PD. METHODS: A prospective 1-year, 2-phase study was conducted to validate the Fear of Falling Scale, a self-assessed instrument for assessing fear of falling in PD. During phase 1, we designed a scale to measure the severity of fear of falling and determine its baseline psychometric characteristics, whereas phase 2 was a 1-year follow-up study to assess the frequency of falls and other clinical factors linked to fear of falling. Convergent and discriminant validity were assessed against the Fear of Falling Measure and the Starkstein Apathy Scale, respectively. RESULTS: The Fear of Falling Scale showed high internal consistency, test-retest reliability, and strong convergent and discriminant validity. There was a significant association between fear of falling score and the presence of both generalized anxiety disorder and major depression, poor balance-related motor ability, increased nonmotor symptoms of PD, more severe impairments in activities of daily living, and increased motor fluctuations. Finally, generalized anxiety disorder was a significant predictor of number of falls during a 12-month follow-up period. CONCLUSIONS: The Fear of Falling Scale is a valid and reliable instrument to assess fear of falling in PD. Fear of falling in PD is associated with specific psychiatric and motor disorders and is significantly related to the performance of balance-related motor functions. © 2019 International Parkinson and Movement Disorder Society.

Modified Mindfulness-Based Cognitive Therapy for Depressive Symptoms in Parkinson's Disease: a Pilot Trial.

BACKGROUND: Mindfulness-based cognitive therapy (MBCT) has evidence of efficacy in a range of populations, but few studies to date have reported on MBCT for treatment of anxious and depressive symptoms in Parkinson's disease (PD). AIMS: The aim of this study was to examine the efficacy of modified MBCT in reducing symptoms of anxiety and depression and improving quality of life in PD. METHOD: Thirty-six individuals with PD were randomly assigned to either modified MBCT or a waitlist control. Changes in symptoms of anxiety, depression and quality of life were compared at group level using generalized linear mixed models and at individual level using reliable change analysis. RESULTS: At post-treatment, there was a significant reduction in depressive symptoms for people undertaking modified MBCT at both group and individual levels compared with controls. There was no significant effect on anxiety or quality of life at the group level, although significantly more people had reliable improvement in anxiety after modified MBCT than after waitlist. Significantly more waitlist participants had reliable deterioration in symptoms of anxiety and depression than those completing modified MBCT. Most participants stayed engaged in modified MBCT, with only three drop-outs. DISCUSSION: This proof-of-concept study demonstrates the potential efficacy of modified MBCT as a treatment for depressive symptoms in Parkinson's disease and suggests further research is warranted.

Dementia onset, incidence and risk in type 2 diabetes: a matched cohort study with the Fremantle Diabetes Study Phase I.

AIMS/HYPOTHESIS: The study aimed to assess the incidence, age of onset, survival and relative hazard of dementia in well-categorised community-based patients with type 2 diabetes compared with a matched cohort of individuals without diabetes. METHODS: A longitudinal observational study was undertaken involving 1291 participants with type 2 diabetes from the Fremantle Diabetes Study and 5159 matched residents without documented diabetes. Linkage with health-related databases was used to detect incident dementia. Relative hazards were assessed using both cause-specific and subdistribution proportional hazards models. RESULTS: During 13.8 ± 5.8 years of follow-up, incident dementia occurred in 13.9% and 12.4% of the groups of participants with and without diabetes, respectively (p = 0.15). With type 2 diabetes, the incidence of dementia was higher (incidence rate ratio [IRR] 1.28, 95% CI 1.08, 1.51), as was the competing risk of death (IRR 1.50, 95% CI 1.38, 1.64). The ages when dementia was first recorded and when death with dementia occurred were both earlier with diabetes, by 1.7 (95% CI 0.6, 2.9) and 2.3 (95% CI 1.1, 3.6) years, respectively (both p ≤ 0.004). Type 2 diabetes was associated with an adjusted subdistribution HR of 1.18 (95% CI 1.00, 1.39), and a cause-specific HR of 1.51 (95% CI 1.27, 1.78) for all-cause dementia. CONCLUSIONS/INTERPRETATION: Type 2 diabetes is associated with an increased incidence of dementia, and dementia onset occurs at a younger age. The relative hazards of both dementia and premature mortality are increased and, as a consequence, the increased risk of dementia in type 2 diabetes is not as marked as suggested by cause-specific HRs.

Modeling anxiety in Parkinson's disease.

BACKGROUND: The aim of this work was to construct a model for anxiety in PD and compare the relative contributions of PD-specific and -nonspecific general population risk factors for anxiety in this model. METHODS: Structural equation modeling of associations of risk factors with the anxiety outcome using a cross-sectional data set of 342 patients with PD were used. RESULTS: A model with acceptable to good fit was generated that explained 65% of the variance in anxiety scores. A previous history of depression and the severity of the depressive symptoms scored on the Hamilton Depression Rating Scale were the only nonspecific variables with a direct effect on anxiety. The presence of motor fluctuations and disease-related decline in activities of daily living were PD-specific markers of anxiety. Nonspecific risk factors had a greater influence in the model than PD-specific risk factors. Standardized regression coefficients suggested that the Hamilton Depression Rating Scale score was the most important contributor to the variation in anxiety. A post-hoc analysis showed that the effects of the following variables on anxiety levels were fully mediated by depression: sex; family history of depression; previous history of anxiety; cognitive status; difficulties in non-disease-specific activities of daily living; and severity of motor signs. CONCLUSION: In this cross-sectional study, we showed that nonspecific general population risk factors are more important markers for anxiety than PD-specific risk factors. Depression was the most prominent marker. PD-specific markers for anxiety appear to be more situational and related to off periods and disease-specific disturbances of activities of daily living.

Comorbid Anxiety and Depression and Their Impact on Cardiovascular Disease in Type 2 Diabetes: The Fremantle Diabetes Study Phase II.

BACKGROUND: The aims were to determine whether anxious depression, defined by latent class analysis (LCA), predicts cardiovascular outcomes in type 2 diabetes and to compare the predictive power of anxious depression with Diagnostic & Statistical Manual Versions IV and 5 (DSM-IV/5) categories of depression and generalized anxiety disorder (GAD). METHODS: Prospective observational study of 1,337 type 2 participants. Baseline assessment with the 9-item Patient Health Questionnaire and the GAD Scale; LCA-defined groups with minor or major anxious depression based on anxiety and depression symptoms. Cox modeling used to compare the independent impact of: (1) LCA anxious depression, (2) DSM-IV/5 depression, (3) GAD on incident cardiovascular events and deaths after 4 years. RESULTS: LCA minor and major anxious depression was present in 21.9 and 7.8% of participants, respectively, DSM-IV/5 minor and major depression in 6.2 and 6.1%, respectively, and GAD in 4.8%. There were 110 deaths, 31 cardiovascular deaths, and 199 participants had incident cardiovascular events. In adjusted models, minor anxious depression (Hazard ratio (95% confidence intervals): 1.70 (1.15-2.50)) and major anxious depression (1.90 (1.11-3.25)) predicted incident cardiovascular events and major anxious depression also predicted cardiovascular mortality (4.32 (1.35-13.86)). By comparison, incident cardiovascular events were predicted by DSM-IV/5 major depression (2.10 (1.22-3.62)) only and cardiovascular mortality was predicted by both DSM-IV/5 major depression (3.56 (1.03-12.35)) and GAD (5.92 (1.84-19.08)). CONCLUSIONS: LCA-defined anxious depression is more common than DSM-IV/5 categories and is a strong predictor of cardiovascular outcomes in type 2 diabetes. These data suggest that this diagnostic scheme has predictive validity and clinical relevance.

Amygdala Volumetric Change Following Psychotherapy for Posttraumatic Stress Disorder.

The authors investigated the impact of eye movement desensitization and reprocessing (EMDR) and prolonged exposure (PE) on the volumes of the amygdala and hippocampus, structures known to be important in fear conditioning, in 20 patients with posttraumatic stress disorder (PTSD). Patients were randomly allocated to either EMDR or PE. Volumes were assessed before and after treatment via magnetic resonance imaging (MRI). Both groups showed significant improvements in PTSD symptoms. Left amygdala mean volume increased significantly following EMDR treatment only. No significant volumetric changes were found for the hippocampus.

A Randomized, Placebo-Controlled, Double-Blind Efficacy Study of Nefiracetam to Treat Poststroke Apathy.

BACKGROUND: To evaluate the efficacy of treatment with nefiracetam compared to placebo in poststroke apathy. METHODS: A parallel group, randomized, placebo-controlled, double-blind two-center trial in patients with recent stroke and apathy was conducted in 2 tertiary teaching hospitals in Perth, Western Australia, between March 2010 and October 2014. Consenting patients hospitalized with stroke were screened for participation at the time of hospitalization and, if diagnosed with apathy 8-36 weeks later, they were randomized to 12 weeks of 900 mg/day nefiracetam or placebo. The primary efficacy parameter was change in apathy at 12 weeks defined by the 14-item Apathy Scale (AS). RESULTS: Of 2514 patients screened, only 377 (15%) were eligible for the study after the first screening, 233 declined further participation, and 144 were assessed for apathy at 8-36 weeks post stroke to confirm eligibility. Twenty patients out of 106 with a complete psychiatric assessment had apathy (19%). Of this sample, 13 patients were randomized. Overall, the AS score decreased by a mean of 7.0 points (95% CI = -14.6 to .6), but there was no significant between-group difference at week 12 (mean paired t-tests, P > .14). CONCLUSIONS: Treatment with nefiracetam did not prove to be more efficacious than placebo in ameliorating apathy in stroke. The main limitation was the very small sample randomized, highlighting the limitations of conducting drug trials for behavioral problems among stroke patients. Pharmacological studies of apathy in stroke will require a large multicenter study and a massive sample of patients.

Is the Parkinson Anxiety Scale comparable across raters?

The Parkinson Anxiety Scale is a new scale developed to measure anxiety severity in Parkinson's disease specifically. It consists of three dimensions: persistent anxiety, episodic anxiety, and avoidance behavior. This study aimed to assess the measurement properties of the scale while controlling for the rater (self- vs. clinician-rated) effect. The Parkinson Anxiety Scale was administered to a cross-sectional multicenter international sample of 362 Parkinson's disease patients. Both patients and clinicians rated the patient's anxiety independently. A many-facet Rasch model design was applied to estimate and remove the rater effect. The following measurement properties were assessed: fit to the Rasch model, unidimensionality, reliability, differential item functioning, item local independency, interrater reliability (self or clinician), and scale targeting. In addition, test-retest stability, construct validity, precision, and diagnostic properties of the Parkinson Anxiety Scale were also analyzed. A good fit to the Rasch model was obtained for Parkinson Anxiety Scale dimensions A and B, after the removal of one item and rescoring of the response scale for certain items, whereas dimension C showed marginal fit. Self versus clinician rating differences were of small magnitude, with patients reporting higher anxiety levels than clinicians. The linear measure for Parkinson Anxiety Scale dimensions A and B showed good convergent construct with other anxiety measures and good diagnostic properties. Parkinson Anxiety Scale modified dimensions A and B provide valid and reliable measures of anxiety in Parkinson's disease that are comparable across raters. Further studies are needed with dimension C.

Apathy in older patients with type 2 diabetes.

OBJECTIVE: To determine the prevalence, incidence, persistence, likely causes, and consequences of apathy in patients with Type 2 diabetes and to compare the prevalence with a healthy control sample. DESIGN: Cross-sectional comparison of diabetic and nondiabetic samples; longitudinal follow-up of diabetic sample. SETTING: Academic research department. PARTICIPANTS: Non-demented, older patients with long-standing Type 2 diabetes (N = 122) recruited from a community-based cohort study and 69 healthy volunteers. MEASUREMENTS: Clinical assessments of apathy and potential causative conditions, repeated in the diabetic sample after 16.7 ± 2.5 months. Informant rated symptoms from the 14-item Apathy Scale were used to generate apathy diagnoses based on standardized criteria. Cognition was assessed by Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR). RESULTS: The diabetic and comparison samples had the same age and MMSE scores, but the diabetic sample had a higher frequency of depression, cerebrovascular history, and cognitive deficits. Apathy was more prevalent in diabetes (diabetic 13.9% versus control sample 1.4%, p = 0.005) and was independently associated with CDR 0.5 status (OR [95% CI]: 3.66 [1.25-19.70]) and depression (8.48 [2.74-26.21]). In 108 diabetic patients who were followed up, incident apathy occurred in 7.4% of cases, and persisted in 50% of those with baseline apathy. Baseline apathy was independently associated with lnHbA1c levels (ß: 0.20, t = 2.29, df = 119, p = 0.024; model R(2) = 0.10) and incident/persistent apathy was associated with greater risk of cognitive decline (6.72 [1.19-37.87]). CONCLUSION: Apathy is a frequent neuropsychiatric syndrome in older patients with Type 2 diabetes, and is associated with poor glycaemic control and cognitive decline.

The impact of emotional distress on motor blocks and festination in Parkinson's disease.

Recent studies suggest that depression and anxiety in patients with Parkinson's disease may predispose them to freezing. Although festination is also frequent, the association with emotional disorders has not been examined. The aim of the authors was to clarify the association between freezing and festination with anxiety, depressive disorders, and emotional distress. The authors examined a consecutive series of 95 patients with Parkinson's disease using comprehensive psychiatric assessments and a new instrument specifically designed to assess the severity of freezing, festination, and emotional distress (Motor Blocks and Festination Scale). All patients were assessed with the Motor Blocks and Festination Scale, the Mini International Neuropsychiatric Interview, and scales to measure the severity of mood and anxiety disorders. A linear regression analysis showed that both motor blocks and festination were significantly associated with emotional distress and deficits on activities of daily living. Conversely, there was no significant association between motor blocks or festination and generalized anxiety disorder, panic disorder, agoraphobia, social phobia, or depression. Motor blocks and festination are significantly associated with emotional distress, but no significant associations were found with anxiety or affective disorders.

The Parkinson Anxiety Scale (PAS): development and validation of a new anxiety scale.

Existing anxiety rating scales have limited construct validity in patients with Parkinson's disease (PD). This study was undertaken to develop and validate a new anxiety rating scale, the Parkinson Anxiety Scale (PAS), that would overcome the limitations of existing scales. The general structure of the PAS was based on the outcome of a Delphi procedure. Item selection was based on a canonical correlation analysis and a Rasch analysis of items of the Hamilton Anxiety Rating Scale (HARS) and the Beck Anxiety Inventory (BAI) from a previously published study. Validation was done in a cross-sectional international multicenter study involving 362 patients with idiopathic PD. Patients underwent a single screening session in which the PAS was administered, along with the Hamilton Depression Rating Scale, the HARS, and the BAI. The Mini International Neuropsychiatric Interview was administered to establish Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnoses of anxiety and depressive disorders. The PAS is a 12-item observer or patient-rated scale with three subscales, for persistent, episodic anxiety and avoidance behavior. Properties for acceptability and reliability met predetermined criteria. The convergent and known groups validity was good. The scale has a satisfactory factorial structure. The area under the receiver operating characteristics curve and Youden index of the PAS are higher than that of existing anxiety rating scales. The PAS is a reliable and valid anxiety measure for use in PD patients. It is easy and brief to administer, and has better clinimetric properties than existing anxiety rating scales. The sensitivity to change of the PAS remains to be assessed.

Anxiety has specific syndromal profiles in Parkinson disease: a data-driven approach.

BACKGROUND: Anxiety symptoms are common in Parkinson disease (PD). Recent evidence suggests that anxiety syndromes as encountered in clinical practice may not correspond to the DSM-IV classification of anxiety disorders. OBJECTIVE: To examine the syndromal pattern of the anxiety spectrum in a large series of patients with PD, as determined with a data-driven approach using latent class analysis (LCA). METHODS: 342 patients with PD were recruited from referrals to movement disorders or psychiatry clinics at six tertiary centers. Participants were assessed with a structured psychiatric interview and specific scales rating the severity of anxiety, depression, cognition and parkinsonism. The main outcome measure was classes of patients with a specific syndromal profile of anxiety symptoms based on LCA. RESULTS: LCA identified four classes that were interpreted as "no anxiety or depression", "episodic anxiety without depression", "persistent anxiety with depression", and "both persistent and episodic anxiety with depression". Symptoms of persistent anxiety were almost invariably associated with symptoms of depression. There were significant differences between classes in terms of history of depression and anxiety, use of psychoactive medication, and on the Mentation and Complications sections of the Unified Parkinson Disease Rating Scale. CONCLUSIONS: Patients with PD show different syndromic profiles of anxiety that do not align with the symptom profiles represented by DSM-IV anxiety disorders and major depression. Accordingly, DSM-IV criteria for anxiety disorders may not be clinically useful in PD. The different classes identified here provide empirically validated phenotypes for future research.

Sertraline for anxiety in adults with a diagnosis of autism (STRATA): study protocol for a pragmatic, multicentre, double-blind, placebo-controlled randomised controlled trial.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to manage anxiety in adults with an autism diagnosis. However, their effectiveness and adverse effect profile in the autistic population are not well known. This trial aims to determine the effectiveness and cost-effectiveness of the SSRI sertraline in reducing symptoms of anxiety and improving quality of life in adults with a diagnosis of autism compared with placebo and to quantify any adverse effects. METHODS: STRATA is a two-parallel group, multi-centre, pragmatic, double-blind, randomised placebo-controlled trial with allocation at the level of the individual. It will be delivered through recruiting sites with autism services in 4 regional centres in the United Kingdom (UK) and 1 in Australia. Adults with an autism diagnosis and a Generalised Anxiety Disorder Assessment (GAD-7) score ≥ 10 at screening will be randomised 1:1 to either 25 mg sertraline or placebo, with subsequent flexible dose titration up to 200 mg. The primary outcome is GAD-7 scores at 16 weeks post-randomisation. Secondary outcomes include adverse effects, proportionate change in GAD-7 scores including 50% reduction, social anxiety, obsessive-compulsive symptoms, panic attacks, repetitive behaviours, meltdowns, depressive symptoms, composite depression and anxiety, functioning and disability and quality of life. Carer burden will be assessed in a linked carer sub-study. Outcome data will be collected using online/paper methods via video call, face-to-face or telephone according to participant preference at 16, 24 and 52 weeks post-randomisation, with brief safety checks and data collection at 1-2, 4, 8, 12 and 36 weeks. An economic evaluation to study the cost-effectiveness of sertraline vs placebo and a QuinteT Recruitment Intervention (QRI) to optimise recruitment and informed consent are embedded within the trial. Qualitative interviews at various times during the study will explore experiences of participating and taking the trial medication. DISCUSSION: Results from this study should help autistic adults and their clinicians make evidence-based decisions on the use of sertraline for managing anxiety in this population. TRIAL REGISTRATION: ISRCTN, ISRCTN15984604 . Registered on 08 February 2021. EudraCT 2019-004312-66. ANZCTR ACTRN12621000801819. Registered on 07 April 2021.

Clinical issues in the treatment of anxiety and depression in older adults with Parkinson's disease.

A significant proportion of persons affected by Parkinson's disease (PD) are over age 65 years. Mental health issues are often less a focus of treatment in this population than physical manifestations of the illness. Anxiety or depression alone, as well as comorbid depression and anxiety, are underrecognized in patients with PD and are associated with deleterious effects on physical and interpersonal functioning, negatively impacting quality of life and well-being. We offer a brief overview of salient clinical points with respect to assessment and treatment approaches to enhance efficacy of the treatment of mental health symptoms in older adults with PD. Cognitive behavior therapy involves the patient learning to overcome behavioral avoidance associated with anxiety and challenge unhelpful negative cognitions. It is suggested that cognitive behavior therapy is an effective approach to treatment of anxiety and depression in PD and should be offered as a treatment to patients.

The Clinical Relevance of Diabetes Distress versus Major Depression in Type 2 Diabetes: A Latent Class Analysis from the Fremantle Diabetes Study Phase II.

BACKGROUND: The nosological position and clinical relevance of the concept of diabetes distress (DD) are uncertain. The aim of this study was to use latent class analysis (LCA) to categorise classes of people with type 2 diabetes and to compare their characteristics. METHODS: Data from 662 participants in the longitudinal observational Fremantle Diabetes Study Phase II were analysed. LCA identified latent subgroups based on individual responses to the Patient Health Questionnaire-9, the Generalised Anxiety Disorder Scale, and the 5-item Problem Areas in Diabetes Scale. RESULTS: Four classes were identified: Class 1 (65.7%, no symptoms), Class 2 (14.0%, DD), Class 3 (12.6%, subsyndromal depression (SSD)), and Class 4 (7.6%, major depression (MD)). Multinomial regression analysis with Class 1 as reference showed significant associations between the DD class and Southern European and Asian ethnic background, HbA1c, and BMI. The SSD class was significantly associated with HbA1c, cerebrovascular disease, and coronary heart disease (CHD). The MD class had significant associations with age (inversely), Southern European ethnic background, HbA1c, BMI, and CHD. In conclusion, LCA identified a pure DD group comprising 14.0% of participants. The only variable uniquely associated with the DD class was Asian ethnic background. CONCLUSION: Although identification of DD may have some utility in assessing the psychological wellbeing of individuals with type 2 diabetes, it adds little to the assessment of depressive disorder and its significant clinical sequalae.

Donepezil alone and combined with intensive language-action therapy on depression and apathy in chronic post-stroke aphasia: A feasibility study.

This study explored the feasibility and effectiveness of a short-term (10-week) intervention trial using Donepezil administered alone and combined with intensive language action therapy (ILAT) for the treatment of apathy and depression in ten people with chronic post-stroke aphasia. Outcome measures were the Western Aphasia Battery and the Stroke Aphasia Depression Questionnaire-21. Structural magnetic resonance imaging and 18fluorodeoxyglucose positron emission tomography were acquired at baseline and after two endpoints (Donepezil alone and Donepezil-ILAT). The intervention was found to be feasible to implement. Large treatment effects were found. Donepezil alone and combined with ILAT reduced aphasia severity, while apathy and depression only improved with Donepezil-ILAT. Structural and functional neuroimaging data did not show conclusive results but provide hints for future research. Given these overall positive findings on feasibility, language and behavioral benefits, further studies in larger sample sizes and including a placebo-control group are indicated.

Apathy in Parkinson's disease: diagnostic and etiological dilemmas.

About one-third of patients with Parkinson's disease (PD) are diagnosed with apathy in cross-sectional studies. However, once patients with concomitant depression and dementia are excluded, the frequency of apathy drops to 5% to 10%. Several scales have been recommended to rate apathy in PD, but specific psychiatric interviews have not been developed, and recently proposed standardized diagnostic criteria are still in the validation process. Most studies assessing the association between subthalamic deep brain stimulation (STN-DBS) and apathy have reported a relative increase in the frequency and severity of apathy, although discrepant findings have also been reported. Several mechanisms to explain apathy in PD have been proposed, from dopaminergic imbalances in frontal-basal ganglia circuits to dysfunction of nondopaminergic circuits and the cingulate gyrus. Future studies should provide reliable and valid instruments to diagnose apathy in PD, and should examine the mechanism of apathy accounting for relevant confounders, such as depression and cognitive deficits, and important contextual factors. Finally, treatment for apathy in PD should not be restricted to psychoactive drugs, but should also include nonpharmacological techniques such as psychotherapy and occupational therapy.