Apathy Scale Research Articles

Virtual Group Music Therapy for Apathy in Parkinson's Disease: A Pilot Study.

To evaluate the effect of virtual group music therapy on apathy in people with Parkinson's disease (PD). Apathy affects 40% of people with PD, lacks effective therapies, and independently predicts poorer quality of life and greater caregiver burden. Music therapy is the clinical application of music to address a person's physical or emotional needs and is effective in treating apathy in dementia. People with idiopathic PD and apathy (Movement Disorders Society-Unified Parkinson's Disease Rating Scale, apathy item ≥ 2) and their caregivers participated in twelve, weekly virtual group music therapy sessions, with session attendance signifying adherence. Participants completed pre- and post-intervention assessments of apathy (Apathy Scale (AS)), quality of life (Parkinson's Disease Questionnaire-short form), functional ability (Schwab & England Activities of Daily Living Scale), depression (Beck Depression Inventory (BDI-II)), and cognition (Montreal Cognitive Assessment-Blind). Among secondary outcomes, we assessed caregiver burden (Zarit Burden Interview-short form) and strain (Multidimensional Caregiver Strain Index). Sixteen PD participants (93.8% men, mean age 68.3 ± 8.4years, median 6 years PD duration) and their caregivers (93.8% women, mean age 62.6 ± 11years) completed the study. All PD participants and 88% of caregivers were >70% adherent to the intervention. Apathy (AS, effect size = 0.767, P = 0.002) and depression (BDI-II, effect size = 0.542, P = 0.03) improved, with no change in caregiver measures. Group music therapy is an effective treatment for apathy in PD and may improve mood. The virtual format is a feasible alternative to in-person sessions with high adherence and satisfaction.

Apathy and Parkinson’s Disease Motor Phenotypes: A Preliminary Study (P6-11.014)

<h3>Objective:</h3> To investigate apathy characteristics across Parkinson’s Disease (PD) motor phenotypes using the Dimensional Apathy Scale (DAS). <h3>Background:</h3> Apathy is a common non-motor symptom of PD, characterized by decreased goal directed behavior. Apathy results in significant decline in functional abilities, caregiver burden, and increased costs of care. Motor phenotypes of PD are widely recognized (i.e., Postural Instability and Gait Difficulty [PIGD] and non-PIGD). It is unknown if distinct apathy profiles characterize motor PD phenotypes. DAS allows a multi-dimensional characterization of apathy (executive, emotional and cognitive/behavioral components) in addition to self-awareness. <h3>Design/Methods:</h3> Eighteen participants (9 women, mean age: 64.5±9.5 years) with PD were recruited at Baylor College of Medicine under an IRB approved protocol. Apathy was measured by the DAS (cut off = 28.5), completed by both, participants and caregivers. Participants were also assessed with the Movement Disorders Society’s-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and the Montreal Cognitive Assessment (MoCA). Analyses were performed for the whole cohort and clinical subgroups (PIGD and non-PIGD). Statistical analyses were done by GraphPad Prism version 9.0. <h3>Results:</h3> Seven participants were apathetic (PD-A) and 11 non-apathetic (PD-NA). There were no significant differences in age and MDS-UPDRS score between PD-A and PD-NA. The PD-A group had a significantly lower MoCA score (24.7±2.2 vs 27.4±2.5; p=0.03). In the whole cohort, there was a negative correlation between MoCA and total DAS score. DAS scores of participants and caregivers were correlated for the behavioral/cognitive and executive subscores but not for the emotional domain. Among those with PIGD-phenotype, 75% (3/4) had apathy versus 28.6% (4/14) among those with non-PIGD. <h3>Conclusions:</h3> The prevalence of apathy in the PIGD subtype was higher. Discrepancy of emotional DAS scores between participants and caregivers may suggest domain specific deficits on self-awareness. Future work in a larger population will focus on the characterization of apathy across PD subtypes. <b>Disclosure:</b> Mr. Lenka has nothing to disclose. Dr. Gazes has nothing to disclose. The institution of Dr. Vanegas-Arroyave has received research support from National Institutes of Health.

Impact of non-motor fluctuations on QOL in patients with Parkinson's disease.

Long-term levodopa treatment in patients with Parkinson's disease (PwPD) often causes motor fluctuations, which are known to affect their quality of life (QOL). These motor fluctuations may be accompanied by fluctuations in non-motor symptoms. There is no consensus on how non-motor fluctuations affect QOL. This was a single-center, retrospective study and included 375 patients with Parkinson's disease (PwPD) who visited the neurology outpatient department of Fukuoka University Hospital between July 2015 and June 2018. All patients were evaluated for age, sex, disease duration, body weight, and motor symptoms by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III, depression scale by the Zung self-rating depression scale, apathy scale, and cognitive function by the Japanese version of The Montreal Cognitive Assessment. A nine-item wearing-off questionnaire (WOQ-9) was used to assess the motor and non-motor fluctuations. QOL in PwPD was investigated using the eight-item Parkinson's Disease Questionnaire (PDQ-8). In total, 375 PwPD were enrolled and classified into three groups according to the presence or absence of motor and non-motor fluctuations. The first group included 98 (26.1%) patients with non-motor fluctuations (NFL group), the second group included 128 (34.1%) patients who presented with only motor fluctuations (MFL group), and the third group included 149 (39.7%) patients without fluctuations in motor or non-motor symptoms (NoFL group). Among them, the PDQ-8 SUM and SI were significantly higher in the NFL group than in the other groups (p < 0.005), implying that the NFL group had the poorest QOL among groups. Next, multivariable analysis showed that even one non-motor fluctuation was an independent factor that worsened QOL (p < 0.001). This study showed that PwPD with non-motor fluctuation had a lower QOL than those with no or only motor fluctuation. Moreover, the data showed that PDQ-8 scores were significantly reduced even with only one non-motor fluctuation.

Mental health outcomes in older breast cancer survivors: Five-year follow-up from the CLIMB study

BackgroundThere is a lack of information on mental health outcomes for the increasing older population. Therefore, the aim of the current study is to assess depressive symptoms, loneliness, and apathy in older patients with breast cancer within the first 5 years after diagnosis. MethodsWomen aged ≥70 years with early-stage breast cancer were included. Multivariate linear mixed models were used to assess longitudinal changes in symptoms of depression (according to the 15-item Geriatric Depression Scale), loneliness (according to the De Jong Gierveld Loneliness Scale) and apathy (according to the Starkstein Apathy Scale) over time at 3, 9, 15, 27 and 60 months follow-up. ResultsIn total, 299 patients were included (mean [standard deviation (SD)] age: 75.8 [5.2] years). At 3 months follow-up, shortly after the acute treatment, 10% of patients had significant depressive symptoms, while loneliness and apathy were present in 31% and 41% of all patients, respectively. Depression, loneliness and apathy scores showed no clinically relevant changes over time in the whole cohort. Patients who received adjuvant systemic therapies (i.e. endocrine therapy and/or chemotherapy and/or targeted therapy (trastuzumab)) had similar mental health outcomes as those who did not. However, frail patients had more symptoms (p < 0.001) and were more prone to develop depressive symptoms over time than non-frail patients (p = 0.002). DiscussionDepression, loneliness and apathy were frequently observed in older women with breast cancer and did not change over time. Patients who received adjuvant systemic therapies had similar mental health outcomes as those who did not. However, frail patients were at higher risk to experience these symptoms.

507 Apathy Following Bilateral Subthalamic Deep Brain Stimulation for Parkinson’s Disease: The INTREPID Randomized Controlled Trial

INTRODUCTION: Motivational disturbances including apathy have been reported following bilateral subthalamic deep brain stimulation (STN-DBS). Many studies suggest apathy is associated with dopaminergic denervation and can be unmasked by drug withdrawal and by aggressive drug tapering following surgery. Additionally, it is suspected that stimulation of the limbic-associative sub-regions of STN might serve as a catalyst, an independent cause, or possibly act synergistically with dopaminergic medication reduction. METHODS: INTREPID (NCT01839396) is a multi-center, prospective, double-blinded RCT. Participants with advanced Parkinson's disease (PD) received bilateral STN-DBS and completed a neuropsychological battery at screening (prior to DBS) and at follow up (12-months). Apathy was assessed using the Starkstein Apathy Scale (SAS). Demographic and clinical data including age, gender, disease duration, levodopa-equivalent daily dose (LEDD), and imaging correlates of DBS (including location and volume of stimulated tissue) were analyzed. RESULTS: There were a total of 160 subjects evaluated at 1-year following STN-DBS, 44 (27.5%) reported an improvement in apathy scores of at least 5-points, and 7 (4.4%) an improvement &gt;10 points. Eighteen (11.3%) participants had worsening apathy scores &gt;5 points, and 8 (5%) reported worsening &gt;10 points. Aggregation of stimulation field models (SFM) across the cohorts, indicated that worsening of apathy was associated with activation of limbic and associative areas of the STN. CONCLUSIONS: Bilateral STN-DBS in this prospective dataset revealed both improvement and worsening of apathy at 1-year follow-up visits. Further analysis of LEDD, dopamine agonist use, and volume of tissue activation may help us to understand the clinical factors underpinning apathy following DBS. Appropriate counseling preoperatively coupled with post-operative monitoring is important for setting expectations and for employing appropriate treatment when necessary.

The Differential Role of Executive Apathy in Alzheimer's Disease Dementia, Mild Cognitive Impairment and Healthy Cognitive Ageing.

The objective of the present work was to compare the levels of executive, emotional, and initiation apathy in individuals with mild cognitive impairment (MCI), mild Alzheimer's disease dementia (ADD), and cognitively intact healthy controls (HCs). Fifty-two patients with mild ADD, 40 individuals with MCI, and 37 cognitively intact individuals were included in the current study. The participants were consecutive visitors to the Outpatient Memory Clinic of "Nestor" Alzheimer's Center. The symptoms of apathy were measured with the dimensional apathy scale. Analyses showed that ADD patients had significantly higher degrees of executive, emotional, initiation, and overall apathy compared with both the MCI group and the HCs. Additionally, a significant difference was observed in the dimension of executive apathy between individuals with MCI and the HCs. In conclusion, the dimension of executive apathy was the most sensitive measure regarding the differentiation of individuals with mild ADD or MCI and HCs. Hence, detailed evaluation of executive apathy in older individuals referred to a memory clinic may provide useful information contributing to their diagnostic categorization and to the differentiation between neurocognitive disorders and healthy cognitive ageing.

Effect of cyborg-type robot Hybrid Assistive Limb on patients with severe walking disability in acute stroke: A randomized controlled study

ObjectivesTo investigate whether early gait training using Hybrid Assistive Limb (HAL) is feasible and improves walking and independency compared with conventional physical therapy (CPT) in patients with severe walking disability after stroke. MethodsWe conducted a single-center, randomized controlled study. Patients with first-ever stroke who had severe walking disability were included. All patients started gait training within 10 days post-stroke onset. Twenty-four patients were randomly assigned into HAL or CPT groups. Outcome measures were collected at three time points, at baseline, completion of 20 sessions of gait training (second assessment), and 3 months after the initiation of gait training. The primary outcomes were changes in motor sub-scores of the Functional Independence Measure or Functional Ambulation Category at the completion of the second assessment from baseline. ResultsTwenty-two patients (median age, 68 years; 12 patients in the HAL group and 10 patients in the CPT group) completed the study. There were no significant differences in primary outcomes. Apathy scale, one of the secondary outcomes, showed a decreasing trend in the HAL group (mean change of -3.8, 95% CI -8.14 to 0.475), and a slight increasing trend in the CPT group (mean change of 1.2, 95% CI -2.66 to 5.06) at the second assessment. Patients in the HAL group experienced no adverse events. ConclusionsEarly gait training in patients with severe walking disability after stroke using HAL was feasible. Walking ability and independency were not improved at the completion of 20 sessions of gait training.

Changes in Apathy, Depression, and Anxiety in Parkinson's Disease from before to during the COVID-19 Era.

Apathy, depression, and anxiety are common non-motor symptoms of Parkinson's disease (PD). Tracking the changes in such symptoms over time would be valuable not only to determine their natural course during the disease, but also to establish the effects of unusual historical events interacting with the natural course. Having collected data on apathy (Apathy Scale), depression (Beck Depression Inventory-II), and anxiety (Parkinson's Anxiety Scale) in a large sample of persons with PD (PwPD) before the beginning of the COVID-19 era, we followed up with these individuals to investigate the changes in their prevalence of apathy, depression, and anxiety across two timepoints (T1 and T2). Of the original 347 participants, 111 responded and provided complete data at T2. The data collection at T1, before COVID-19, occurred between 2017-2018. The data collection at T2 occurred in 2021 and included the same measures, with the addition of the Coronavirus Impact Scale to assess the effects of the pandemic on the individual participants. Over this period, there was a significant increase in apathy, but not in depression or anxiety. Anxiety and depression, but not apathy, were correlated with the impact of COVID-19.

Standardization of the Italian ALS-CBS™ Caregiver Behavioral Questionnaire.

The present investigation aimed at testing the psychometrics and diagnostics of the Italian version of the Caregiver Behavioral Questionnaire (CBQ) from the ALS Cognitive Behavioral Screen (ALS-CBS™), as well as its case-control discrimination, in a cohort of non-demented patients with ALS. The caregivers of N = 265 non-demented patients with ALS and N = 99 healthy controls (HCs) were administered the CBQ and the Edinburgh Cognitive and Behavioural ALS Screen-Carer Interview (ECAS-CI). For N = 98 patients, an in-depth behavioural/psychopathological assessment via the Frontal Behavioural Inventory (FBI), the Dimensional Apathy Scale (DAS), the State and Trait Anxiety Inventory-Form Y (STAI-Y), and the Beck Depression Inventory (BDI) was also available. Factorial and construct validity, internal reliability, and diagnostics against an abnormal ECAS-CI score were tested in patients. Case-control discrimination was explored through logistic regression. The CBQ was internally reliable (McDonald's ω = 0.90) and underpinned by a simple, unidimensional structure; it converged with ECAS-CI, FBI, and DAS scores and diverged from STAI-Y and BDI ones. A cutoff of ≤ 33 accurately detected abnormal ECAS-CI scores (AUC = 0.85), yielding optimal error- and information-based diagnostics. The CBQ was independent of demographic and disease-related variables and discriminated patients from HCs (p < 0.001). The Italian version of the CBQ from the ALS-CBS™ is a valid, reliable, diagnostically sound, and feasible screener for detecting frontotemporal-like behavioural changes in non-demented patients with ALS. Its adoption is thus recommended within clinical practice and research in the view of providing preliminary information on whether the administration of more extensive behavioural instruments is needed.

A nomogram based on iron metabolism can help identify apathy in patients with Parkinson's disease.

Apathy is common in Parkinson's disease (PD) but difficult to identify. Growing evidence suggests that abnormal iron metabolism is associated with apathy in PD. We aimed to investigate the clinical features and iron metabolism of apathetic patients with PD, and construct a nomogram for predicting apathy in PD. Data of 201 patients with PD were analyzed. Demographic data, Apathy Scale (AS) assessments, and serum iron metabolism parameters were obtained. Spearman correlations were used to assess relationships between AS scores and iron metabolism parameters, separately for male and female patients. Additionally, a nomograph for detecting apathetic patients with PD was built based on the results of logistic regression analysis. The serum transferrin (TRF, p < 0.0024) concentration and total iron binding capacity (TIBC, p < 0.0024) were lower in the apathetic group after Bonferroni correction, and they were negatively associated with AS scores in male participants with PD (TRF, r = -0.27, p = 0.010; TIBC, r = -0.259, p = 0.014). The nomogram was developed by incorporating the following five parameters: age, sex, serum iron concentration, TIBC and Hamilton Depression Rating Scale (HAMD) scores, which showed good discrimination and calibration, with a consistency index of 0.799 (95% confidence interval = 0.732-0.865). Abnormal iron metabolism may contribute to apathy in PD, especially among men. TIBC levels in combination with HAMD scores can be effectively used for the prediction of apathetic patients with PD.

Effect of Repetitive Transcranial Magnetic Stimulation on Long Coronavirus Disease 2019 with Fatigue and Cognitive Dysfunction.

There is no established treatment for chronic fatigue and various cognitive dysfunctions (brain fog) caused by long coronavirus disease 2019 (COVID-19). We aimed to clarify the effectiveness of repetitive transcranial magnetic stimulation (rTMS) for treating these symptoms. High-frequency rTMS was applied to occipital and frontal lobes in 12 patients with chronic fatigue and cognitive dysfunction 3 months after severe acute respiratory syndrome coronavirus 2 infection. Before and after ten sessions of rTMS, Brief Fatigue Inventory (BFI), Apathy Scale (AS), and Wechsler Adult Intelligence Scale-fourth edition (WAIS4) were determined and N-isopropyl-p-[123I]iodoamphetamine single photon emission computed tomography (SPECT) was performed. Twelve subjects completed ten sessions of rTMS without adverse events. The mean age of the subjects was 44.3 ± 10.7 years, and the mean duration of illness was 202.4 ± 114.5 days. BFI, which was 5.7 ± 2.3 before the intervention, decreased significantly to 1.9 ± 1.8 after the intervention. The AS was significantly decreased after the intervention from 19.2 ± 8.7 to 10.3 ± 7.2. All WAIS4 sub-items were significantly improved after rTMS intervention, and the full-scale intelligence quotient increased from 94.6 ± 10.9 to 104.4 ± 13.0. Hypoperfusion in the bilateral occipital and frontal lobes observed on SPECT improved in extent and severity after ten sessions of rTMS. Although we are still in the early stages of exploring the effects of rTMS, the procedure has the potential for use as a new non-invasive treatment for the symptoms of long COVID.

Are neuropsychiatric symptoms a marker of small vessel disease progression in older adults? Evidence from the Lothian Birth Cohort 1936.

Neuropsychiatric symptoms could form part of an early cerebral small vessel disease prodrome that is detectable before stroke or dementia onset. We aimed to identify whether apathy, depression, anxiety, and subjective memory complaints associate with longitudinal white matter hyperintensity (WMH) progression. Community-dwelling older adults from the observational Lothian Birth Cohort 1936 attended three visits at mean ages 73, 76, and 79years, repeating MRI, Mini-Mental State Examination, neuropsychiatric (Dimensional Apathy Scale, Hospital Anxiety and Depression Scale), and subjective memory symptoms. We ran regression and mixed-effects models for symptoms and normalised WMH volumes (cube root of WMH:ICV×10). At age 73, 76, and 79, m=672, n=476, and n=382 participants attended MRI respectively. Worse apathy at age 79 was associated with WMH volume increase (β=0.27, p=0.04) in the preceding 6years. A 1SD increase in apathy score at age 79 associated with a 0.17 increase in WMH (β=0.17 normalised WMH percent ICV, p=0.009). In apathy subscales, executive (β=0.13, p=0.05) and emotional (β=0.13, p=0.04) scores associated with increasing WMH more than initiation scores (β=0.11, p=0.08). Increasing WMH also associated with age (β=0.40, p=0.002) but not higher depression (β=-0.01, p=0.78), anxiety (β=0.05, p=0.13) scores, or subjective memory complaints (β=1.12, p=0.75). Apathy independently associates with preceding longitudinal WMH progression, while depression, anxiety, and subjective memory complaints do not. Patients with apathy should be considered for enrolment to small vessel disease trials.

Two pathways differentially linking tau depositions, oxidative stress, and neuronal loss to apathetic phenotypes in progressive supranuclear palsy

Patients with progressive supranuclear palsy (PSP) frequently exhibit apathy but the neuropathological processes leading to this phenotype remain elusive. We aimed to examine the involvement of tau protein depositions, oxidative stress (OS), and neuronal loss in the apathetic manifestation of PSP. Twenty patients with PSP and twenty-three healthy controls were enrolled. Tau depositions and brain volumes were evaluated via positron-emission tomography (PET) using a specific probe, 18F-PM-PBB3, and magnetic resonance imaging, respectively. Glutathione (GSH) levels in the anterior and posterior cingulate cortices were quantified by magnetic resonance spectroscopy. Tau pathologies were observed in the subcortical and cortical structures of the patient brains. The angular gyrus exhibited a positive correlation between tau accumulations and apathy scale (AS). Although PSP cases did not show GSH level alterations compared with healthy controls, GSH levels in posterior cingulate cortex were correlated with AS and tau depositions in the angular gyrus. Marked atrophy was observed in subcortical areas, and gray matter volumes in the inferior frontal gyrus and anterior cingulate cortex were positively correlated with AS but showed no correlation with tau depositions and GSH levels. Path analysis highlighted synergistic contributions of tau pathologies and GSH reductions in the posterior cortex to AS, in parallel with associations of gray matter atrophy in the anterior cortex with AS. Apathetic phenotypes may arise from PET-visible tau aggregation and OS compromising the neural circuit resilience in the posterior cortex, along with neuronal loss, with neither PET-detectable tau pathologies nor OS in the anterior cortex.

Cross‐Validation of a Novel Apathy Measurement Model in a Diverse Ambulatory Cohort of Older Adults with Memory Complaints

AbstractBackgroundApathy is a psychological syndrome characterized by a loss of motivation, goal‐directed activity, and diminished emotion (Marin, 1990), which may mediate the relationship between depression and cognitive impairment (Funes et al., 2018) and be an early risk factor for dementia that precedes predementia syndromes including non‐amnestic mild cognitive impairment (NA‐MCI) and motoric cognitive risk syndrome (MCR) (Ceïde et al., 2020). While there is no gold standard measure of apathy, assessment tools vary from subscales of depression instruments to apathy specific questionnaires. Our group conducted a confirmatory factor analysis (CFA) of the Geriatric Depression Scale (GDS) in a pooled cohort of community and memory clinic older adults which identified a novel 2‐factor model that distinguishes apathy from depression. The goal of this study was to cross‐validate this novel apathy measurement model in a bilingual urban primary care clinical cohort.MethodWe conducted a CFA in the primary care cohort that was composed of participants from the 5‐Cog Battery for Detecting Cognitive Impairment and Dementia clinical trial. We compared the reliability measures and model fit indices of both the previous 2‐factor model and this novel model. Cohort characteristics were compared as well.ResultThe primary care clinical cohort was significantly different from the community and memory clinic cohorts in all baseline characteristics. The CFA of the primary care cohort yielded depression and apathy factors with good reliability (α = .78 and .63, respectively). Despite the fact that the primary care cohort included Spanish speakers, it performed similarly to the reliability of the depression and apathy factors in the community dwelling and memory clinic pooled cohort (α = .75 and .63, respectively). Both the primary care and memory clinic cohorts had higher depression and apathy scale scores compared to the community dwelling cohort, with the primary care cohort scoring in between the community and memory clinic cohorts in both depression and apathy scale measurements.ConclusionOur 2‐factor measurement model demonstrated similar reliability and fit across 3 distinct cohorts (community dwelling, memory clinic and primary care clinic) and 2 languages (English and Spanish), indicating its appropriateness as an apathy measurement model in further clinical trials.

Unpacking the NIH Toolbox Emotion Battery in Persons With Parkinson's disease.

Examine the relationship between the National Institutes of Health Toolbox Emotion Battery (Emotion Toolbox) and traditional measures in Parkinson's disease (PD). Persons with PD (n = 30) and cognitively healthy older adults (OA; n = 40) completed the Emotion Toolbox consisting of Well-Being, Negative Affect, and Social Satisfaction scores along with traditional measures of depression (Beck Depression Inventory-II [BDI-II]), anxiety (State-Trait Anxiety Inventory [STAI]), and apathy (Apathy Scale [AS]); total raw scores). Separate bootstrapped analyses of covariance indicated that the PD group scored higher on BDI-II and STAI-State compared to OA (ps < .01); groups did not differ on Emotion Toolbox. In the PD group, bootstrapped partial correlations indicated that Negative Affect was positively related to BDI-II and STAI (ps ≤ .001). Social Satisfaction was negatively related to BDI-II and STAI-Trait (.05 < ps < .004). Psychological Well-Being was negatively related to BDI-II, AS, and STAI (p < .004). No relationships emerged in OA. In the PD group, separate binary logistic regressions showed that traditional measures (BDI-II, AS, and STAI-Trait) correctly classified 79.6% those with formal psychiatric diagnoses (presence vs. absence; p < .011), whereas Emotion Toolbox measures correctly classified 73.3% (p < .019). The Emotion Toolbox showed moderate-strong correlations with traditional measures in persons with PD. Even so, it did not capture the group differences between PD and OA and had a somewhat lower classification accuracy rate for persons with PD who had a formal psychiatric diagnosis than traditional measures. Together, findings question the utility of the Emotion Toolbox as a stand-alone emotion screener in PD.

Altered reward processing underpins emotional apathy in dementia

IntroductionWhile apathy is broadly defined as a loss of motivation, it is increasingly recognised as a multidimensional syndrome spanning executive, emotional, and initiation domains. Emotional apathy is purportedly driven by deficits in using socioemotional rewards to guide behaviour, yet the link between these symptoms and reward processing, and their common neural correlates, has not been directly examined.MethodsSixty-four patients (33 behavioural-variant frontotemporal dementia, 14 Alzheimer’s disease, 8 semantic dementia, 6 progressive nonfluent aphasia, 3 logopenic progressive aphasia) were classified into high (HEA; n = 36) and low (LEA; n = 28) emotional apathy groups based on emotional apathy subscale scores on the Dimensional Apathy Scale. Patients and age-matched healthy controls (n = 27) performed an instrumental reward learning task where they learned to associate cues with either social or monetary outcomes.ResultsHEA patients showed impaired learning on both the social and monetary reward conditions, relative to LEA patients (p = 0.016) and controls (p = 0.005). Conversely, the LEA group did not differ from controls (p = 0.925). Importantly, multiple regression analyses indicated that social reward learning significantly predicted emotional apathy. Voxel-based morphometry analyses revealed that emotional apathy and social reward learning were both associated with orbitofrontal cortex, ventral striatum, and insula atrophy.DiscussionOur results demonstrate a unique link between impaired social reward learning and emotional apathy in dementia and reveal a shared neurobiological basis. Greater understanding of these neurocognitive mechanisms of reward processing will help improve the identification of emotional apathy in dementia and inform the development of novel interventions to address these symptoms.

Disentangling Clinical Profiles of Apathy in Behavioral Variant Frontotemporal Dementia.

Apathy is highly frequent in behavioral variant frontotemporal dementia (bvFTD). It is presumed to involve different pathophysiological mechanisms and neuroanatomical regions. We explored the hypothesis that subgroups showing distinct profiles of apathy and distinct patterns of atrophy within frontal lobes could be disentangled in bvFTD. Using data-driven clustering applied to 20 bvFTD patients, we isolated subgroups according to their profiles on the three subscales of the Dimensional Apathy Scale (DAS). We explored their apathy profiles and atrophy patterns. Apathy profiles were characterized through both subjective measures of apathy by questionnaires and measures including objective behavioral metrics. Atrophy patterns were obtained by voxel-based morphometry, contrasting each bvFTD subgroup with healthy controls (N = 16). By clustering based on DAS dimensions, we disentangled three subgroups of bvFTD patients, with distinct apathy profiles and atrophy patterns. One subgroup, which presented the smallest pattern of atrophy (including orbitofrontal cortex) with a right asymmetry, was characterized by high self-reported emotional and initiation apathy and by a self-initiation deficit reversible by external guidance. In other subgroups showing more diffuse bilateral atrophies extending to lateral prefrontal cortex, apathy was not reversible by external guidance and more difficulty to focus on goal-management was observed, especially in the subgroup with the largest atrophy and highest levels of executive apathy. Distinct clinical profiles of apathy, corresponding to distinct anatomical subtypes of bvFTD, were identified. These findings have implications for clinicians in a perspective of precision medicine as they could contribute to personalize treatments of apathy.

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.

Validity and diagnostics of the Reading the Mind in the Eyes Test (RMET) in non-demented amyotrophic lateral sclerosis (ALS) patients.

The aim of this study was to explore the construct validity and diagnostic properties of the Reading the Mind in the Eyes Test (RMET) in non-demented patients with amyotrophic lateral sclerosis (ALS). A total of 61 consecutive patients and 50 healthy controls (HCs) were administered the 36-item RMET. Additionally, patients underwent a comprehensive assessment of social cognition via the Story-Based Empathy Task (SET), which encompasses three subtests targeting Causal Inference, Emotion Attribution (SET-EA), and Intention Attribution (SET-IA), as well as global cognitive [the Edinburgh Cognitive and Behavioral ALS Screen (ECAS)] and behavioral screening [the Frontal Behavioral Inventory (FBI); the Dimensional Apathy Scale (DAS); the Beck Depression Inventory (BDI); and the State and Trait Anxiety Inventory-Y]. The construct validity of the RMET was tested by regressing it within a stepwise model that encompassed as predictors the abovementioned cognitive and behavioral measures, covarying for demographic and motor confounders. Receiver-operating characteristics (ROC) analyses allowed exploring intrinsic and post-test properties of the RMET both in discriminating patients from HCs and in identifying patients with a defective SET-EA performance. The RMET was solely predicted by the SET-EA (p = 0.003) and SET-IA (p = 0.005). RMET scores showed high accuracy both in discriminating patients from HCs (AUC = 0.81) and in identifying patients with a defective SET-EA score (AUC = 0.82), with adequate-to-optimal both intrinsic and post-test properties. The RMET is a convergently and divergently valid measure of affective social cognition in non-demented ALS patients, also featuring optimal intrinsic and post-test diagnostic properties in both case-control and case-finding scenarios.

Vortioxetine Improves Depressive Symptoms and Cognition in Parkinson's Disease Patients with Major Depression: An Open-Label Prospective Study.

Depression is frequent in Parkinson's disease (PD) patients, but the evidence for many antidepressant agents to treat it in PD is insufficient. The aim of the present prospective open-label single-arm study (VOPARK, an open-label study of the effectiveness and safety of VOrtioxetine in PARKinson's disease patients with depression) was to analyze the effectiveness of vortioxetine on depressive symptoms in PD patients with major depression. The primary efficacy outcome was the change from baseline (VB) at the end of the observational period (12 weeks ± 14 days; V12w) in the 17-item Hamilton Depression Rating Scale (HAM-D17) total score. At VB, all patients had a HAM-D17 total score ≥16. A total of 30 patients (age 66.23 ± 10.27; 73.3% males) were included between February 2021 (first patient, 12/FEB/21) and March 2022 (last patient, 14/MAR/22). At 12 weeks, 27 patients completed the follow-up (90%). The total HAM-D17 total score was reduced by 52.7% (from 21.5 ± 4.75 at VB to 10.44 ± 7.54 at V12w; Cohen's effect size = -2.5; p &lt; 0.0001) and the response and remission rates were 50% and 43.3%, respectively. Apathy (Apathy Scale; p &lt; 0.0001), cognition (PD-Cognitive Rating Scale; p = 0.007), fatigue (Fatigue Severity Scale; p = 0.014), and quality of life (PDQ-39 (p = 0.001) and EUROHIS-QOL8 (p &lt; 0.0001)) improved at 3 weeks as well. A total of 11 adverse events in 10 patients (33.3%) were reported, one of which was severe (vomiting related to vortioxetine with full recovery after drug withdrawal). Vortioxetine was safe and well tolerated and improved depressive symptoms and other non-motor symptoms in PD patients.