Apathy In Parkinson's Disease Research Articles

Cross-Sectional and Longitudinal Association of Clinical and Neurocognitive Factors With Apathy in Patients With Parkinson Disease.

A robust understanding of the natural history of apathy in Parkinson disease (PD) is foundational for developing effective clinical management tools. However, large longitudinal studies are lacking while the literature is inconsistent about even cross-sectional associations. We aimed to determine the longitudinal predictors of apathy development in a large cohort of people with PD and its cross-sectional associations and trajectories over time, using sophisticated Bayesian modeling techniques. People with PD followed up in the longitudinal New Zealand Parkinson's progression project were included. Apathy was defined using the neuropsychiatric inventory subscale ≥4, and analyses were also repeated using a less stringent cutoff of ≥1. Both MoCA and comprehensive neuropsychological testing were used as appropriate to the model. Depression was assessed using the hospital anxiety and depression scale. Cross-sectional Bayesian regressions were conducted, and a multistate predictive model was used to identify factors that predict the initial onset of apathy in nonapathetic PD, while also accounting for the competing risk of death. The relationship between apathy presence and mortality was also investigated. Three hundred forty-six people with PD followed up for up to 14 years across a total of 1,392 sessions were included. Apathy occurrence did not vary significantly across the disease course (disease duration odds ratio [OR] = 0.55, [95% CI 0.28-1.12], affecting approximately 11% or 22% of people at any time depending on the NPI cutoff used. Its presence was associated with a significantly higher risk of death after controlling for all other factors (hazard ratio [HR] = 2.92 [1.50-5.66]). Lower cognition, higher depression levels, and greater motor severity predicted apathy development in those without motivational deficits (HR [cognition] = 0.66 [0.48-0.90], HR [depression] = 1.45 [1.04-2.02], HR [motor severity] = 1.37 [1.01-1.86]). Cognition and depression were also associated with apathy cross-sectionally, along with male sex and possibly lower dopaminergic therapy level, but apathy still occurred across the full spectrum of each variable (OR [cognition] = 0.58 [0.44-0.76], OR [depression] = 1.43 [1.04-1.97], OR [female sex] = 0.45 [0.22-0.92], and OR [levodopa equivalent dose] = 0.78 [0.59-1.04]. Apathy occurs across the PD time course and is associated with higher mortality. Depressive symptoms and cognitive impairment in particular predict its future development in those with normal motivation.

Greater Apathy Associated With Selective Serotonin Reuptake Inhibitor Use in Parkinson's Disease.

Apathy, a motivational disorder, is common in Parkinson's disease (PD) and often misdiagnosed as depression. Use of selective serotonin reuptake inhibitors (SSRIs) has been associated with increased apathy in adolescents and adults with depression. Based on observations that serotonin may downregulate dopaminergic systems, we examined the relationship between apathy and SSRI use in individuals with PD. Medications, mood/motivation scales, and clinical data were collected from a convenience sample of 400 individuals with PD. Depression and apathy were measured using the Beck Depression Inventory-II (BDI-Il) and the Apathy Scale (AS). Antidepressant medications were grouped by mechanism type. Of the 400 PD patients, 26% were on SSRIs. On standard mood/motivation scales, 38% of the sample exceeded clinical cut-offs for apathy and 28% for depression. Results of hierarchical regression analyses revealed that SSRIs were the only antidepressant that were significantly associated with higher apathy scores (β = .1, P = .02). Less education (β = -.1, P = .01) worse cognition (β = -.1, P = .01), and greater depressive symptoms (β = .5, P < .001) were also significant predictors of apathy. These findings suggest that use of SSRIs, but not other antidepressants, is associated with greater apathy in PD. Given the interactive relationship between serotonin and dopamine, the current findings highlight the importance of considering apathy when determining which antidepressants to prescribe to individuals with PD. Similarly, switching a SSRI for an alternative antidepressant in individuals with PD who are apathetic may be a potential treatment for apathy that needs further study.

Treatment of Apathy in Parkinson's Disease and Implications for Underlying Pathophysiology.

Apathy is a prevalent and highly debilitating non-motor symptom of Parkinson's disease (PD) that is often overlooked in clinical practice due to its subtle nature. This review aims to provide a comprehensive overview of the current evidence for the treatment of apathy in PD, highlighting recent advancements and emerging therapeutic avenues. In this review, we analyse a diverse array of treatment strategies for apathy in PD, including pharmacological interventions, non-pharmacological approaches, and emerging neuromodulation techniques. We evaluate the efficacy, safety, and limitations of established pharmacotherapies, such as dopaminergic agents, antidepressants, and cognitive enhancers. Additionally, we examine the promising role of non-pharmacological interventions, encompassing psychotherapies and behavioural interventions, in ameliorating apathetic symptoms. Furthermore, this review explores the effects of neuromodulation techniques on apathy, including the modulation of apathy via deep brain stimulation and emerging data on the potential influence of transcranial magnetic stimulation (TMS) on apathy in PD. Ultimately, a deeper understanding of effective treatment strategies for apathy has the potential to significantly improve the quality of life and overall well-being of individuals living with PD.

Impaired value-based decision-making in Parkinson's disease apathy.

Apathy is a common and disabling complication of Parkinson's disease characterized by reduced goal-directed behaviour. Several studies have reported dysfunction within prefrontal cortical regions and projections from brainstem nuclei whose neuromodulators include dopamine, serotonin and noradrenaline. Work in animal and human neuroscience have confirmed contributions of these neuromodulators on aspects of motivated decision-making. Specifically, these neuromodulators have overlapping contributions to encoding the value of decisions, and influence whether to explore alternative courses of action or persist in an existing strategy to achieve a rewarding goal. Building upon this work, we hypothesized that apathy in Parkinson's disease should be associated with an impairment in value-based learning. Using a four-armed restless bandit reinforcement learning task, we studied decision-making in 75 volunteers; 53 patients with Parkinson's disease, with and without clinical apathy, and 22 age-matched healthy control subjects. Patients with apathy exhibited impaired ability to choose the highest value bandit. Task performance predicted an individual patient's apathy severity measured using the Lille Apathy Rating Scale (R = -0.46, P < 0.001). Computational modelling of the patient's choices confirmed the apathy group made decisions that were indifferent to the learnt value of the options, consistent with previous reports of reward insensitivity. Further analysis demonstrated a shift away from exploiting the highest value option and a reduction in perseveration, which also correlated with apathy scores (R = -0.5, P < 0.001). We went on to acquire functional MRI in 59 volunteers; a group of 19 patients with and 20 without apathy and 20 age-matched controls performing the Restless Bandit Task. Analysis of the functional MRI signal at the point of reward feedback confirmed diminished signal within ventromedial prefrontal cortex in Parkinson's disease, which was more marked in apathy, but not predictive of their individual apathy severity. Using a model-based categorization of choice type, decisions to explore lower value bandits in the apathy group activated prefrontal cortex to a similar degree to the age-matched controls. In contrast, Parkinson's patients without apathy demonstrated significantly increased activation across a distributed thalamo-cortical network. Enhanced activity in the thalamus predicted individual apathy severity across both patient groups and exhibited functional connectivity with dorsal anterior cingulate cortex and anterior insula. Given that task performance in patients without apathy was no different to the age-matched control subjects, we interpret the recruitment of this network as a possible compensatory mechanism, which compensates against symptomatic manifestation of apathy in Parkinson's disease.

Treatment of apathy in Parkinson's disease: A bayesian network meta-analysis of randomised controlled trials

BackgroundApathy is an important but unrecognised aspect of Parkinson's disease (PD). The optimal therapeutic options for apathy remain unclear. Early recognition and treatment of apathy can reduce the significant burden of disease for patients and their caregivers. Here we conducted a meta-analysis to evaluate the comparative efficacy of different treatment modalities of apathy in PD (CRD42021292099). MethodsWe screened Medline, Embase, and PsycINFO databases for articles on therapies for apathy in PD. The outcome of interest is the reduction in apathy scores post-intervention and is measured by standardised mean differences (SMD) with 95% credible intervals (CrI). We included only randomised controlled trials examining interventions targeted at reducing apathy. ResultsNineteen studies involving 2372 patients were included in the quantitative analysis. The network meta-analysis found pharmacotherapy to be the most efficacious treatment, significantly better than brain stimulation (SMD -0.43, 95% CrI −0.78 to −0.07), exercise-based interventions (SMD -0.66, 95% CrI −1.25 to −0.08), supplements (SMD -0.33, 95% CrI −0.67 to 0), and placebo (SMD -0.38, 95% CrI −0.56 to −0.23). Subgroup analysis of pharmacotherapy versus placebo found similar efficacy of dopamine agonists (SMD -0.36, 95% CI -0.59 to −0.12, P = 0.003) and alternative medications (SMD -0.42, 95% CI -0.61 to −0.23, P < 0.001). The remaining comparisons and subgroup analyses did not demonstrate any significant treatment effects. ConclusionOur meta-analysis of randomised controlled trials showed that pharmacotherapy is the most efficacious treatment option, with dopamine agonists having similar efficacy as other medications. Further research is needed to determine the optimal management strategy.

Gait initiation in Parkinson's disease: comparison of timing and displacement during anticipatory postural adjustments as a function of motor severity and apathy in a large cohort

IntroductionGait initiation is preceded by three anticipatory postural adjustment (APA) phases. In Parkinson's disease (PD) generated force, displacement and timing during APA differ from healthy controls. APA might be influenced by disease status, weight or emotion. It is unknown how motor severity, disease duration or presence of apathy influences APA timing and displacement. MethodsWe included 99 people with PD and 50 healthy controls (HC) to perform five gait initiation trials following an auditory cue. Force plates measured timing and center of pressure (CoP) displacement during APA phases. ResultsTime to gait initiation (tGI) was higher in the PD group (p < 0.001, t = 2.74, 95%CI (0.008, 0.066)). The first two APA phases (APA1 and APA2a) lasted longer in PD (respectively p < 0.001, t = 3.87, 95%CI (0.091, 0.28) and p < 0.001, t = 4.1, 95%CI (0.031, 0.091)). Mean CoP displacement, variability in timing and displacement did not differ. A multiple regression model was used to determine if clinical variables were related to gait initiation parameters. tGI was predicted by age (p < 0.001) and weight (p = 0.005). The duration of APA1 was predicted by weight (p = 0.006) and APA2a by age (p < 0.001). Variability in duration of the locomotor phase (LOC) was predicted by age (p < 0.001). ConclusiontGI and initial APA phases are longer in PD than in HC. There are no significant differences in variability of timing or displacement between the two groups. Gait initiation parameters are independent of disease duration, motor severity, medication usage or apathy in PD. Our findings suggest that cueing does not speed up gait initiation but reduces variability.

Dimensions of apathy in Parkinson's disease.

Apathy is one of the most common neuropsychiatric manifestations in Parkinson's disease (PD). Recent proposals consider apathy as a multidimensional construct, which can manifest in behavioral, cognitive, emotional, and/or social dimensions. Apathy also overlaps conceptually and clinically with other non-motor comorbidities, particularly depression. Whether all of these dimensions are applicable to the apathetic syndrome experienced by people with PD is unclear. In the present study, we investigated the multidimensional pattern of apathy associated with PD, using the recently developed Apathy Motivation Index (AMI) which probes behavioral, emotional, and social apathy dimensions. We then examined the relationship between these dimensions and other features of PD commonly associated with apathy, including depression, anxiety, cognition, and motor state. A total of 211 participants were identified from the New Zealand Brain Research Institute (NZBRI) longitudinal PD cohort. One hundred eight patients and 45 controls completed the AMI, administered as an online questionnaire, and additional assessments including neuropsychiatric, neuropsychological, and motor scores. The pattern of dimensional apathy in PD was assessed using a repeated-measured analysis of variance, while simple linear regressions were performed to evaluate relationships between these dimensions and other variables. We found a significant interaction between group (PD versus control) and apathy subscale, driven mainly by higher levels of social and behavioral-but not emotional-apathy in those with PD. This result was strikingly similar to a previous study investigating social apathy in PD. Distinct patterns of dimensional apathy were associated with depression and anxiety, with social and behavioral apathy positively associated with depression, and emotional apathy negatively associated with anxiety. This work provides further evidence for a distinct pattern of apathy in people with PD in which deficits manifest in some-but not all-dimensions of motivated behavior. It emphasizes the importance of considering apathy as a multidimensional construct in clinical and research settings.

Semiology and determinants of apathy across neurodegenerative motor disorders: A comparison between amyotrophic lateral sclerosis, Parkinson's and Huntington's disease.

The semiology and determinants of apathy are largely unknown across amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Huntington's disease (HD), due to both motor and non-motor confounders. This study thus aimed at (1) profiling apathy in ALS, PD, and HD and (2) exploring its clinical determinants. Consecutive ALS (N = 99), PD (N = 73), and HD (N = 25) patients underwent a motor-free assessment of apathy (Dimensional Apathy Scale, DAS), global cognition, anxiety and depression. Function was assessed through disease-specific scales. The DAS was also completed by N = 101 healthy controls (HCs). Between-group comparisons on DAS scores were implemented by covarying for all applicable confounders. Predictive models on DAS scores were built through multiple, stepwise regressions. Parkinson's disease and HD, but not ALS, patients were more apathetic than HCs-with HD patients also selectively showing lower initiation and poorer goal-directed planning than HCs. Higher apathetic features were detected in PD and HD as compared to ALS. Education was a protective factor against apathy in ALS. Anxiety was a risk factor for global apathy in ALS, HD, and to a lesser extent, in PD, whereas, protective only toward affective disintegration in PD and ALS. Cognitive inefficiency was a risk factor toward apathy in both PD and ALS. Depression was a risk factor for executive-related apathy in PD. This study provides unprecedented insights into the heterogeneous semiology and determinants of apathy across ALS, PD, and HD via the DAS, in turn informing clinical practice and research.

Impaired interhemispheric synchrony in Parkinson's disease patients with apathy

BackgroundApathy is a common non-motor symptom in Parkinson's disease (PD), yet the neural mechanism remains unknown. It has been reported that the lateralization of dopamine levels is correlated with apathetic symptoms. We aimed to ascertain the role of lateralization in the neuropathogenesis of apathy in PD. MethodsTwenty-six apathetic PD patients (PD-A), twenty-seven nonapathetic PD patients (PD-NA), and twenty-three healthy controls (HCs) were recruited. All subjects underwent T1-weighted and resting state functional MRI scanning during OFF medication state. Voxel-mirrored Homotopic Connectivity (VMHC) and asymmetry voxel-based morphometry (asymmetry VBM) analysis were applied to detect the synchrony of homotopic connections between hemispheres and grey matter asymmetry index. ResultsCompared with both PD-NA and HCs groups, the PD-A group showed excessively decreased z-VMHC values in the nucleus accumbens (NAcc) and putamen. Additionally, both PD subgroups exhibited decreased z-VMHC values in the cerebellum lobule VIII compared with controls. However, no corresponding alteration in grey matter asymmetry index was found. Further, a negative correlation between the z-VMHC values of the NAcc and the Apathy Scale (AS) was confirmed in the PD-A group. Meanwhile, the same relationship was also confirmed between the putamen and AS. Notably, ROC curve analyses uncovered that the z-VMHC values of the NAcc and putamen could be a potential neuroimaging feature discerning apathetic PD patient, respectively. LimitationsThis is a cross-sectional study. ConclusionOur findings demonstrated that the asymmetric functional connectivity in the mesocorticolimbic and nigrostriatal systems might induce the pathophysiological mechanisms of apathy in PD.

Apathy Reflects Extra-Striatal Dopaminergic Degeneration in de novo Parkinson's Disease.

Apathy represents a core neuropsychiatric symptom in Parkinson's disease (PD). As there is currently no established effective treatment for apathy in PD, further investigating the biological origin of this symptom is needed to design novel therapeutic strategies. Among the multiple neurotransmitter alterations that have been associated with apathy, the involvement of extra-striatal dopaminergic degeneration remains to be fully explored. To investigate whether apathy in PD reflects increased dopaminergic degeneration extending beyond striatal regions. In the de novo PD cohort of the Parkinson's Progression Markers Initiative (PPMI), we performed whole-brain I123-Ioflupane Single Photon Emission Computed Tomography (DAT-SPECT) analyses to characterize cross-sectional and longitudinal differences in DAT uptake associated with the presence of apathy. We also assessed the relationship between apathy and cognition in this sample, as apathy has been suggested to herald cognitive decline. Apathetic PD patients (N = 70) had similar sociodemographic, clinical, and biomarker profiles compared to the non-apathetic group (N = 333) at baseline. However, apathy was associated with an increased risk of developing cognitive impairment after a four-year follow-up period (p = 0.006). Compared to non-apathetic patients, apathetic patients showed a widespread reduction of extra-striatal DAT uptake at baseline as well as an increased longitudinal loss of DAT uptake (corrected p < 0.05). Isolated apathy in PD is associated with extra-striatal dopaminergic degeneration. As this abnormal dopamine depletion was in turn related to cognitive performance, this might explain, at least partially, the increased risk of apathetic PD patients to develop cognitive impairment or dementia.

Olfaction and apathy in early idiopathic Parkinson's disease

BackgroundApathy remains a disabling symptom in Parkinson's disease (PD) with limited therapeutic success. Processing of emotions and smell share neuroanatomical and evolutionary pathways. ObjectivesTo explore the association of apathy with smell dysfunction (SD) in early PD. MethodsWe analyzed patients with de-novo PD, with follow-up of at least 5 years from the Parkinson's Progression Markers Initiative. SD and apathy were defined using University of Pennsylvania Smell Identification Test and MDS-UPDRS part 1A. Odds ratios were calculated between apathy and olfaction groups. Kaplan-Meier survival analysis was grouped by presence/ absence of smell dysfunction. The Log Rank test was used to compare time to apathy. ResultsWe found no association between presence of apathy in patients with and without SD (OR 1.01 [0.49–2.08]). There was no significant difference between PD patients with and without SD in time to apathy (p = 0.72). ConclusionsSD does not portend greater risk of apathy in PD.

Dopamine D3 Receptors: A Potential Target to Treat Motivational Deficits in Parkinson's Disease.

Parkinson's disease (PD), which is traditionally viewed as a motor disorder involving the degeneration of dopaminergic (DA) neurons, has recently been identified as a quintessential neuropsychiatric condition. Indeed, a plethora of non-motor symptoms may occur in PD, including apathy. Apathy can be defined as a lack of motivation or a deficit of goal-directed behaviors and results in a pathological decrease of self-initiated voluntary behavior. Apathy in PD appears to fluctuate with the DA state of the patients, suggesting a critical role of DA neurotransmission in the pathophysiology of this neuropsychiatric syndrome. Using a lesion-based approach, we developed a rodent model which exhibits specific alteration in the preparatory component of motivational processes, reminiscent to apathy in PD. We found a selective decrease of DA D3 receptors (D3R) expression in the dorsal striatum of lesioned rats. Next, we showed that inhibition of D3R neurotransmission in non-lesioned animals was sufficient to reproduce the motivational deficit observed in our model. Interestingly, we also found that pharmacologically targeting D3R efficiently reversed the motivational deficit induced by the lesion. Our findings, among other recent data, suggest a critical role of D3R in parkinsonian apathy and highlight this receptor as a promising target for treating motivational deficits.

Evolution of Apathy in Early Parkinson's Disease: A 4-Years Prospective Cohort Study.

Objective: We investigated the prevalence, evolution, associated factors, and risk factors of apathy in a cohort of patients with early-stage Parkinson's disease (PD), who underwent a 4-years prospective follow-up.Methods: This study included 188 patients with PD (baseline disease duration <3 years) who underwent an annual evaluation using the Lille Apathy Rating Scale (LARS). Based on the cut-off value of −21 observed on the LARS, patients were categorized as PD with and without apathy. The generalized estimating equations (GEE) model was utilized to determine the factors associated with apathy, and the Cox proportional-hazards regression model was used to determine the predictors of apathy.Results: Apathy increased from a baseline rate of 18.6–28.8% after 4 years; notably, this rate was not persistent across patients' visits. The LARS score was independently associated with the male sex (B 8.131, p = 0.009), low Frontal Assessment Battery (FAB) scores (B 0.567, p = 0.011), low attention scores on the Montreal Cognitive Assessment (MOCA) test (B 0.217, p = 0.026), high Hamilton Depression Rating Scale (HDRS) scores (B 1.362, p < 0.001), high Unified Parkinson's Disease Rating Scale (UPDRS) part III scores (B 1.147, p < 0.001), and prolonged follow-up time (B 1.785, p = 0.048). A high HDRS score was the only predictor of apathy in PD [hazard ratio (HR) 1.043, p = 0.026].Conclusions: The risk of apathy is higher in men with progressive PD accompanied by disease-specific motor and non-motor symptoms. Depression during early-stage PD is a primary risk factor for apathy in PD.

Abnormal Spontaneous Neural Activity in Parkinson's Disease With "pure" Apathy.

BackgroundApathy is one of the most common non-motor symptoms of Parkinson’s disease (PD). However, its pathophysiology remains unclear.MethodsWe analyzed resting-state functional magnetic resonance imaging (MRI) data acquired at a 3.0T MRI scanner using the amplitude of low-frequency fluctuation (ALFF) metric in 20 de novo, drug-naïve, non-demented PD patients with apathy (PD-A), 26 PD patients without apathy (PD-NA) without comorbidity of depressive or anxious symptoms, and 23 matched healthy control (HC) subjects.ResultsWe found that the ALFF decreased significantly in the bilateral nucleus accumbens, dorsal anterior cingulate cortex (ACC), and left dorsolateral prefrontal cortex in patients with PD-A compared to patients with PD-NA and HC subjects. Furthermore, apathy severity was negatively correlated with the ALFF in the bilateral nucleus accumbens and dorsal ACC in the pooled patients with PD.ConclusionThe present study characterized the functional pattern of changes in spontaneous neural activity in patients with PD-A. With the aim to better elucidate the pathophysiological mechanisms responsible for these changes, this study controlled for the potentially confounding effects of dopaminergic medication, depression, anxiety, and global cognitive impairment. The findings of the current study add to the literature by highlighting potential abnormalities in mesocorticolimbic pathways involved in the development of apathy in PD.

Alterations of regional homogeneity in Parkinson's disease with “pure” apathy: A resting-state fMRI study

BackgroundApathy is a prevalent and debilitating neuropsychiatric syndrome in Parkinson's disease (PD). However, its neural mechanisms are still unclear. MethodsForty-six de novo, drug-naïve, non-demented PD patients without depressive or anxious symptoms, of whom 26 were apathetic (PD-A) and 20 were not (PD-NA) according to the Apathy Scale (AS), and 23 matched healthy control (HC) subjects were enrolled in this study. The regional homogeneity (ReHo) approach based on resting-state functional MRI on a 3-T MR system was used to investigate apathy related local brain activity. ResultsCompared with both patients with PD-NA and HC subjects, patients with PD-A showed significantly lower ReHo values in the dorsal anterior cingulate cortex (ACC) and right caudate. Both the PD-A and PD-NA groups also demonstrated lower ReHo values in the right putamen compared to the HC group. Further correlation analyses revealed that AS scores were negatively correlated with the ReHo values in the dorsal ACC and right caudate in the pooled patients with PD. LimitationsThe present results are preliminary due to the small sample size in the study. ConclusionsThis study used ReHo for the first time to characterize “pure” apathy related regional spontaneous brain function within the frontostriatal circuits in PD. Our findings suggest that abnormal brain activity in the dorsal ACC and caudate may involve the pathological mechanisms of apathy in PD.

Detecting Apathy in Individuals with Parkinson's Disease: A Systematic Review.

Individuals experiencing apathy in Parkinson's disease (PD) have a lack of emotion and motivation. Apathy often overlaps with comorbidities such as depression, and is sometimes difficult to detect. To examine diagnostic accuracy of apathy-screening tools compared with a gold standard (clinician diagnosis) among adult outpatients with PD. A systematic review was conducted. Six research databases were searched to May 23, 2018. Diagnostic accuracy measures, including sensitivity and specificity were gathered. 1,007 full-text articles were reviewed with seven full-text articles included. The gold standard was considered a clinician diagnosis as apathy is not defined in the DSM/ICD. Diagnostic accuracy measures were reported for the Lille Apathy Rating Scale (LARS) both informant- and observer-rated, Unified Parkinson's Disease Rating Scale (UPDRS), Apathy Scale (AS), Apathy Evaluation Scale (AES), Non-Motor Symptoms Questionnaire (NMS-Q), and Dimensional Apathy Scale (DAS). The AES had the best reported sensitivity and specificity values, both 90%. The AS had the highest reported specificity at 100%, with 66% sensitivity. Pooled prevalence of apathy was 29.1% (95% CI 21.5%-36.6%). While 18 screening tools exist to screen for apathy in PD, only six have been validated against clinician diagnosis. The AES had the highest reported sensitivity and specificity and is a brief, easy to use tool. The AS was designed specifically for use in PD populations and has the highest reported specificity. Future research should focus on the development of an accepted gold standard, to further understand accuracy measures of all available apathy screening tools.

Apathy in Parkinson's disease with REM sleep behavior disorder

ObjectivesRapid eye movement (REM) sleep behavior disorder (RBD) in patients with Parkinson's disease (PD) is associated with increased risk of non-motor symptoms. However, the association between RBD and apathy in PD remains unclear. AimsTo compare the prevalence and severity of apathy symptoms in PD patients with RBD (PD-RBD+) and without (PD-RBD-). In addition, we explored the association between apathy, depressive symptoms and RBD, taking into consideration the concomitant influence of demographic, disease- and therapy-associated variables. MethodsSixty-four PD patients were evaluated with systematic motor (unified Parkinson's disease rating scale, UPDRS-III) and non-motor assessments. The diagnosis of RBD was based on the international consensus criteria using video-polysomnography. Apathy, sleepiness, depressive symptoms and cognitive performance were assessed using the Starkstein apathy (SAS, cut-off = 14), the Epworth sleepiness (ESS), the Hamilton depression (HAM-D, cut-off = 9) scales and the mini-mental state examination (MMSE), respectively. ResultsAmong 64 patients, 26 (40%) had RBD. In the PD-RBD+ group, apathy symptoms were more frequent (52% vs 42%) and more severe (14.3 ± 5.8 vs 11.2 ± 4.9, p < 0.05), especially in the females (17.3 ± 6.0 vs 11.4 ± 5.8 in males, p < 0.05) compared to the PD-RBD- group. A high percentage of patients, especially in the PD-RBD+ group (53%), had isolated apathy without increased depressive symptoms. Increased depressive symptoms were also more frequent (50% vs 20%) and more severe in the PD-RBD+ group. The two groups were comparable in respect to demographic and clinical characteristics. ConclusionsIn PD, RBD is associated with isolated apathy and increased severity of depressive symptoms, independent of medication, motor and other non-motor symptoms. Potential mechanisms underlying this association are discussed.

Clinical and demographic correlates of apathy in Parkinson's disease.

To better understand the demographic, neuropsychiatric, cognitive, and motor predictors of apathy in Parkinson's disease (PD). 112 participants (Mage = 68.53 years; Mdisease duration = 6.17years) were administered the Apathy Scale (AS), Beck Depression Inventory-II (BDI-II), Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Trail Making Test (TMT), Wechsler Adult Intelligence Scale-IV Matrix Reasoning subtest, letter (F-A-S) and category (Animals) fluency, and Hopkins Verbal Learning Test-Revised. Psychosis was assessed. A stepwise logistic regression analysis was performed to investigate the ability of demographic factors and clinical assessments to predict nonapathetic (AS ≤ 13) versus apathetic (AS > 13) group membership. The regression analysis yielded a robust model in which older age, less education, elevated BDI-II, current psychosis, higher MDS-UPDRS PartIII (motor score), and slower TMT-B performance predicted membership in the apathetic group, with a correct classification rate of 77.5% (Nagelkerke R2 = 0.48, p < .001). Depression (OR = 9.20, p < .001) and education (OR = 0.66, p = 0.002) contributed significantly to the overall model. A linear regression with AS score as the outcome variable was similar, but TMT-B additionally contributed significantly (p = 0.02) to the overall model, F(6, 86) = 12.02, p < .001, adjusted R2 = 0.42. Of the factors examined, depression, education, and executive functioning were the strongest correlates of apathy in PD. These results support the idea that common underlying frontosubcortical disruptions in this population contribute to apathy, depression, and executive dysfunction.

Altered EEG alpha and theta oscillations characterize apathy in Parkinson's disease during incentivized movement.

Apathy is a common non-motor symptom of Parkinson's disease (PD) that is difficult to quantify and poorly understood. Some studies have used incentivized motor tasks to assess apathy, as the condition is often associated with a reduction in motivated behavior. Normally event-related desynchronization, a reduction of power in specific frequency bands, is observed in the motor cortex during the peri-movement period. Also, alpha (8–12 Hz) and theta (4–7 Hz) oscillations are sensitive to rewards that are closely related to motivational states however these oscillations have not been widely investigated in relation to apathy in PD. Using EEG recordings, we investigated the neural oscillatory characteristics of apathy in PD during an incentivized motor task with interleaved rest periods. Apathetic and non-apathetic PD subjects on dopaminergic medication and healthy control subjects were instructed to squeeze a hand grip device for a monetary reward proportional to the subject's grip force and the monetary value attributed to that trial. Apathetic PD subjects exhibited higher alpha and theta powers in the pre-trial baseline rest period compared to non-apathetic PD subjects and healthy subjects. Further, we found that both resting power and relative power in alpha and theta bands during incentivized movement predicted PD subjects' apathy scores. Our results suggest that apathetic PD patients may need to overcome greater baseline alpha and theta oscillatory activity in order to facilitate incentivized movement. Clinically, resting alpha and theta power as well as alpha and theta event-related desynchronization during movement may serve as potential neural markers for apathy severity in PD.

Psychometric properties of apathy scales in Parkinson's disease: a systematic review.

Apathy is among the most prevalent neuropsychiatric symptom experienced in Parkinson's disease (PD) and can be assessed with a variety of scales. To identify which scale is most suitable for apathy assessment in PD, the psychometric properties of each scale and its sensitivity to change were analyzed. The methodological quality of the studies ranged from adequate to excellent. The Lille Apathy Rating Scale demonstrated consistently favorable psychometric properties and was used in two of four clinical trials found. The Starkstein Apathy Scale was the only other scale used in clinical trials. Further work is necessary to develop a gold standard for assessing apathy in PD.