Apathy Evaluation Scale Research Articles

The Role of Apathy in Spontaneous Verbal and Nonverbal Behaviors: A Transdiagnostic Pilot Study in Neurodegeneration.

Apathy, characterized by a quantifiable reduction in motivation or goal-directed behavior, is a multidimensional syndrome that has been observed across many neurodegenerative diseases. To develop a novel task measuring spontaneous action initiation (ie, a nonverbal equivalent to spontaneous speech tasks) and to investigate the association between apathy and executive functions such as the voluntary initiation of speech and actions and energization (ie, ability to initiate and sustain a response). We compared the energization and executive functioning performance of 10 individuals with neurodegenerative disease and clinically significant apathy with that of age-matched healthy controls (HC). We also investigated the association between self-reported scores on the Apathy Evaluation Scale (AES) and performance on energization tasks. The individuals with apathy made significantly fewer task-related actions than the HC on the novel spontaneous action task, and their scores on the AES were negatively correlated with spontaneous task-related actions, providing preliminary evidence for the task's construct validity. In addition, the individuals with apathy performed more poorly than the HC on all of the energization tasks, regardless of task type or stimulus modality, suggesting difficulty in sustaining voluntary responding over time. Most of the tasks also correlated negatively with the AES score. However, the individuals with apathy also performed more poorly on some of the executive function tasks, particularly those involving self-monitoring. Our work presents a novel experimental task for measuring spontaneous action initiation-a key symptom of apathy-and suggests a possible contribution of apathy to neuropsychological deficits such as poor energization.

Social cognition and apathy between two cognitive subtypes of schizophrenia: Are there the same or different profiles?

ObjectiveCognitive impairment is an essential feature of schizophrenia, and it involves a broad array of nonsocial and social cognitive domains. This study aimed to examine whether there are the same or different social cognition profiles between two cognitive subtypes of schizophrenia. MethodThere were one hundred and two chronic and institutionalized patients with schizophrenia from two referral tracks. One group is “Cognitively Normal Range” (CNR) (N = 52), and another group is “Below Normal Range” (BNR) (N = 50). We assessed or collected their apathy, emotional perception judgment, facial expression judgment, and empathy by the Apathy Evaluation Scale, the International Affective Picture System, the Japanese and Caucasian Facial Expression of Emotion, and the Interpersonal Reactivity Index, respectively. ResultsWe found different impairment profiles depending on the cognitive subtypes of the patient with schizophrenia. Surprisingly, the CNR presented impairments in apathy, emotional perception judgment, facial expression judgment, and empathy and feature impairment in empathy and affective apathy. In contrast, even though the BNR had significant neurocognition impairments, they had almost intact empathy with significantly impaired cognitive apathy. Both groups' global deficit scores (GDSs) were comparable, and all reached at least a mild impairment level. ConclusionsThe CNR and the BNR had similar abilities in emotional perception judgment and facial emotion recognition. They also had differentiable deficits in apathy and empathy. Our findings provide important clinical implications for neuropsychological pathology and treatment in schizophrenia.

Discrepancy Between Patient and Caregiver Estimate of Apathy Predicts Dementia in Patients with Amnestic Mild Cognitive Impairment.

Apathy is a frequent behavioral symptom of Alzheimer's disease (AD). The Apathy Evaluation Scale (AES) is a tool exploring the perception of apathy by both caregivers (CG-AES) and patients (PT-AES), and the discrepancy in their ratings is a proxy of patients' disease unawareness. To assess in a cohort study of patients with amnesic mild cognitive impairment (aMCI) whether apathy and awareness of apathy predict progression to dementia and timing. From the global AES scores of 110 patients with aMCI and their caregivers, we obtained two principal indices for analysis: 1) 'Apathy', the mean of PT-AES and CG-AES, and 2) 'Discrepancy', obtained by subtracting CG-AES from PT-AES. Patients were followed with visits every six months for three years or until dementia. AES indices and the principal demographical/neuropsychological variables were filtered from multicollinearity. The most robust variables entered a logistic regression model and survival analyses (Cox regression, log-rank test of Kaplan-Meier curves) to estimate which predicted the risk and timing of progression, respectively. Sixty patients (54.5%) developed dementia (57 AD) after 6.0-36.0 months, 22 (20%) remained in an MCI stage, and 28 (25.5%) dropped out. 'Discrepancy' was a robust and accurate predictor of the risk of progression (AUC = 0.73) and, after binarization according to a computed cutoff, of timing to dementia. A structured evaluation of apathy, both self-assessed and estimated by caregivers, can provide useful information on the risk and timing of progression from aMCI to dementia. The discrepancy between the two estimates is a fairly reliable index for prediction purposes as a proxy of disease unawareness.

Effects of Token Economy Intervention on Hospitalized Patients With Schizophrenia

Objectives: The purpose of this study was to investigate the effect of token economy intervention on the clinical characteristics and global function of patients with schizophrenia.Methods: From June 1, 2022 to September 1, 2022, token economy intervention was conducted for hospitalized patients with schizophrenia in a mental hospital. Assessments were conducted before and after the intervention. Clinical Global Impression-Schizophrenia scale (CGI-SCH), Schizophrenia Quality of Life Scale (SQLS), Insight Scale for Psychosis (ISP), and Apathy Evaluation Scale (AES) were used to evaluate clinical characteristics. World Health Organization Disability Assessment Schedule (WHODAS) was used for global functional assessment.Results: A total of 51 patients were included in the study. Through token economy intervention, depressive (p=0.001), cognitive symptom domain scores (p<0.001) in CGI-SCH, and SQLS score were significantly decreased (p=0.044). In the WHODAS evaluated by the clinician, the scores of self-care (p=0.012), life activities (p=0.006), and participation in society (p=0.040) decreased significantly.Conclusion: It was confirmed that token economy intervention had a positive effect on depressive symptoms, cognitive symptoms, quality of life, self-care function, daily living function, and social participation function in hospitalized patients with schizophrenia.

Altered Resting-State Brain Activity and Functional Connectivity in Post-Stroke Apathy: An fMRI Study.

Apathy is a common neuropsychiatric disease after stroke and is linked to a lower quality of life while undergoing rehabilitation. However, it is still unknown what are the underlying neural mechanisms of apathy. This research aimed to explore differences in the cerebral activity and functional connectivity (FC) of subjects with post-stroke apathy and those without it. A total of 59 individuals with acute ischemic stroke and 29 healthy subjects with similar age, sex, and education were recruited. The Apathy Evaluation Scale (AES) was used to evaluate apathy at 3 months after stroke. Patients were split into two groups-PSA (n = 21) and nPSA (n = 38)-based on their diagnosis. The fractional amplitude of low-frequency fluctuation (fALFF) was used to measure cerebral activity, as well as region-of-interest to region-of-interest analysis to examine functional connectivity among apathy-related regions. Pearson correlation analysis between fALFF values and apathy severity was performed in this research. The values of fALFF in the left middle temporal regions, right anterior and middle cingulate regions, middle frontal region, and cuneus region differed significantly among groups. Pearson correlation analysis showed that the fALFF values in the left middle temporal region (p < 0.001, r = 0.66) and right cuneus (p < 0.001, r = 0.48) were positively correlated with AES scores in stroke patients, while fALFF values in the right anterior cingulate (p < 0.001, r = -0.61), right middle frontal gyrus (p < 0.001, r = -0.49), and middle cingulate gyrus (p = 0.04, r = -0.27) were negatively correlated with AES scores in stroke patients. These regions formed an apathy-related subnetwork, and functional connectivity analysis unveiled that altered connectivity was linked to PSA (p < 0.05). This research found that abnormalities in brain activity and FC in the left middle temporal region, right middle frontal region, right cuneate region, and right anterior and middle cingulate regions in stroke patients were associated with PSA, revealing a possible neural mechanism and providing new clues for the diagnosis and treatment of PSA.

Patient-Reported Outcomes in Myotonic Dystrophy Type 2: Correlations with Motor and Cognitive Endpoints (S7.007)

<h3>Objective:</h3> To characterize patient-reported outcomes (PROs) and evaluate relationships between PROs and clinical endpoints in patients with myotonic dystrophy type 2 (DM2). <h3>Background:</h3> Although muscle weakness is the key feature in DM2, two-thirds of patients report that impaired cognition is among the most disabling symptoms and affects their quality of life. PROs of physical and mental status are extremely limited in DM2 but could serve as measures for clinical trial development. <h3>Design/Methods:</h3> Ten individuals with DM2 and ten age and gender-matched controls were enrolled. All participants underwent brain MRIs and a comprehensive battery of cognitive and motor measures. Additionally, they completed PROs, including the 36-Item Short Form (SF-36), PRO Measurement Information System (PROMIS-10), Beck Depression and Anxiety Inventory (BDI and BAI), and Apathy Evaluation Scale (AES). Paired t-test and Spearman’s correlation were used to determine group differences and correlations between PROs and clinical endpoints. <h3>Results:</h3> Of 20 participants (60% female), mean age and education were similar between groups. Compared to controls, the DM2 group showed a significant difference in BAI, AES, and SF-36 physical functioning (PF) subscale (<i>p</i>=0.004–0.024) and impaired PROMIS-Global Physical (GPH) and Mental Health (GMH). We found a strong correlation between SF-36 (PF) and PROMIS-GPH with a 6-minute walk test and gait speed (<i>rho</i>=0.68–0.75, <i>p</i>=0.02–0.04). Moderate correlations were observed between 1) BDI and verbal fluency test; 2) BAI and processing speed; 3) AES and a test of executive function and cerebral white matter integrity. <h3>Conclusions:</h3> Our pilot study demonstrates that changes in mental and physical health status are of significance for DM2 patient’s quality of life. The relationships between PROs (BAI, BDI, and AES) and cognitive endpoints suggest brain involvement. PROs, as measured by SF-36 and PROMIS-10, are associated with motor endpoints. These results support the use of PROs as a tool to measure disease burden in DM2. <b>Disclosure:</b> Dr. Jain has nothing to disclose. Dr. Olszewski has nothing to disclose. Dr. Flashman has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Archives of Clinical Neuropsychology. The institution of Dr. Flashman has received research support from NIH/NINDS. The institution of Dr. Flashman has received research support from Michael J Fox Foundation. Mrs. Burgos-Aguilar has nothing to disclose. Dr. Duncan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BrainQ Technologies. Dr. Duncan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for University of Pittsburg Pepper Center. Dr. Duncan has stock in CareDirections. The institution of Dr. Duncan has received research support from PCORI. The institution of Dr. Duncan has received research support from NIA and NINDS. The institution of Dr. Duncan has received research support from AHRQ. Dr. Duncan has received intellectual property interests from a discovery or technology relating to health care. The institution of Dr. Nopoulos has received personal compensation in the range of $500-$4,999 for serving as a Consultant for norvartis. The institution of Dr. Puwanant has received research support from Muscular Dystrophy Association. The institution of Dr. Puwanant has received research support from NIH/NINDS. The institution of Dr. Puwanant has received research support from NIH/NINDS.

Association between apathy in patients with maintenance dialysis and hospitalization or mortality: a prospective cohort study.

Patients receiving maintenance dialysis experience increased rates of hospitalization and mortality. Apathy is associated with reduced quality of life and increased hospitalization, institutionalization, and death. Whether apathy contributes to poor outcomes in population undergoing maintenance dialysis remain unknown. We conducted a prospective cohort study of maintenance dialysis population who were consecutively recruited at the Dialysis Center of Shanghai General Hospital between July 2017 and August 2018 and were followed up for 3 year. Apathy status was measured by the Apathy Evaluation Scale. The study outcomes were the occurrence of death and first hospitalization. A total of 647 participants included in this study, 274 (42.3%) had a current apathy and 373 (57.7%) were not. During the follow-up period, 394 (60.9%) were hospitalized, and 169 (26.1%) died. Kaplan-Meier analysis showed that the risks of hospitalization and mortality were significantly higher in individuals with apathy than in those without apathy (both p < 0.001). Apathy at baseline was associated with hospitalization and death both in univariate analysis and in all multivariable models (all p < 0.001). Apathy was highly prevalent and independently correlated with an increased risk of poor outcomes in patients with maintenance dialysis.

Apathy in melancholic depression and abnormal neural activity within the reward-related circuit

Major depressive disorder is a heterogeneous syndrome, of which the most common subtype is melancholic depression (MEL). Previous studies have indicated that anhedonia is frequently a cardinal feature in MEL. As a common syndrome of motivational deficit, anhedonia is closely associated with dysfunction in reward-related networks. However, little is currently known about apathy, another syndrome of motivational deficits, and the underlying neural mechanisms in MEL and non-melancholic depression (NMEL). Herein, the Apathy Evaluation Scale (AES) was used to compare apathy between MEL and NMEL. On the basis of resting-state functional magnetic resonance imaging, functional connectivity strength (FCS) and seed-based functional connectivity (FC) were calculated within reward-related networks and compared among 43 patients with MEL, 30 patients with NMEL, and 35 healthy controls. Patients with MEL had higher AES scores than those with NMEL (t = −2.20, P = 0.03). Relative to NMEL, MEL was associated with greater FCS (t = 4.27, P < 0.001) in the left ventral striatum (VS), and greater FC of the VS with the ventral medial prefrontal cortex (t = 5.03, P < 0.001) and dorsolateral prefrontal cortex (t = 3.18, P = 0.005). Taken together the results indicate that reward-related networks may play diverse pathophysiological roles in MEL and NMEL, thus providing potential directions for future interventions in the treatment of various depression subtypes.

Distinct Neuropsychological Correlates of Apathy Sub-Domains in Multiple Sclerosis

Apathy is relatively frequent and significantly associated with clinical and cognitive outcomes in Multiple Sclerosis (MS), even if previous research has produced mixed results. This varied picture could be due to most studies treating apathy as a unitary construct, despite the evidence showing that apathy is a multifaceted syndrome including three different sub-domains (i.e., cognitive, affective, and behavioral). This study aims to investigate the neuropsychological correlates of apathy fractionated into its three sub-domains in participants with MS. Eighty-five participants with MS underwent a comprehensive neuropsychological battery. The severity of apathy symptoms was assessed by the self-report version of the Apathy Evaluation Scale. Correlational analysis showed that cognitive apathy sub-domain scores had a high correlation with the performances obtained at cognitive tests tapping into inhibitory control (i.e., IML and Strop test-interference task), whereas the affective apathy sub-domain scores had a high correlation with the performances obtained at cognitive test tapping into the use of executive functions in visuospatial abilities (i.e., Clock Drawing Test). Moreover, linear regression analysis results showed that the cognitive apathy sub-domain scores predicted executive functioning domain scores and that the cognitive and affective apathy sub-domains scores predicted visuospatial abilities domain scores. These results confirm that apathy is a multidimensional concept with important neuropsychological correlates, visible only when it is fractionated into its sub-domains.

Long-Term Neuromodulatory Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Plasmatic Matrix Metalloproteinases (MMPs) Levels and Visuospatial Abilities in Mild Cognitive Impairment (MCI)

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique that is used against cognitive impairment in mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, the neurobiological mechanisms underlying the rTMS therapeutic effects are still only partially investigated. Maladaptive plasticity, glial activation, and neuroinflammation, including metalloproteases (MMPs) activation, might represent new potential targets of the neurodegenerative process and progression from MCI to AD. In this study, we aimed to evaluate the effects of bilateral rTMS over the dorsolateral prefrontal cortex (DLPFC) on plasmatic levels of MMP1, -2, -9, and -10; MMPs-related tissue inhibitors TIMP1 and TIMP2; and cognitive performances in MCI patients. Patients received high-frequency (10 Hz) rTMS (MCI-TMS, n = 9) or sham stimulation (MCI-C, n = 9) daily for four weeks, and they were monitored for six months after TMS. The plasmatic levels of MMPs and TIMPs and the cognitive and behavioral scores, based on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Beck Depression Inventory II, Beck Anxiety Inventory, and Apathy Evaluation Scale, were assessed at baseline (T0) and after 1 month (T1) and 6 months (T2) since rTMS. In the MCI-TMS group, at T2, plasmatic levels of MMP1, -9, and -10 were reduced and paralleled by increased plasmatic levels of TIMP1 and TIMP2 and improvement of visuospatial performances. In conclusion, our findings suggest that targeting DLPFC by rTMS might result in the long-term modulation of the MMPs/TIMPs system in MCI patients and the neurobiological mechanisms associated with MCI progression to dementia.

Interdialytic weight gain is not associated with symptoms of depression or apathy in patients on chronic hemodialysis.

Little is known about the relationships between apathy, depressive symptoms and interdialytic weight gain (IDWG) in patients on chronic hemodialysis. Aim of the present study is to investigate the association between IDWG and symptoms of depression and apathy in hemodialysis patients. A total of 139 chronic patients of the HD units between January 2020 and December 2021 were included in the present cross-sectional study. IDWG was calculated as the difference between the pre-HD weight and the weight registered after the previous session; the average of the sessions in a month was registered. Apathy Evaluation Scale (AES) was adopted to evaluate apathy. Depression was assessed by Beck Depression Inventory (BDI). Ninety-three patients had IDWG% ≤ 4 and 46 had an IDWG% > 4. Correlation between IDWG% and BDI as well that between IDWG% and AES were not statistically significant. Median BDI and mean AES did not differ significantly between the groups. In addition, 104 patients had a BDI < 16 and 35 had a BDI ≥ 6. Seventy-five patients had an AES score ≤ 35 and 63 had a AES score > 35. The IDWG (kg) and the IDWG% did not differ significantly between the two groups. IDWG is not associated with symptoms of depression or apathy in hemodialysis patients. Thus, these results may question if the use of behavioral intervention aimed at improving motivation is warranted in the hemodialysis population to reduce the IDWG.

Clinical determinants of apathy and its impact on health-related quality of life in early Parkinson disease.

Apathy is a common non-motor symptom of Parkinson disease (PD) that can affect the health-related quality of life (HRQoL) of patients and caregivers. This study aimed to investigate the clinical determinants of apathy and its impact on HRQoL in patients with early PD. We enrolled 324 patients with early PD with modified Hoehn-Yahr stages 1 to 3 and a disease duration ≤5 years. Demographic information was obtained, and motor and non-motor symptoms were evaluated with relevant scales. Apathy was present in 110 of 324 (33.9%) patients. Compared with patients with non-apathetic PD, those with apathetic PD had significantly higher modified Hoehn-Yahr stage, Unified Parkinson's Disease Rating Scale-II (UPDRS-II) score, Non-Motor Symptoms Scale (NMSS) total score, Beck Depression Inventory (BDI) score, and Parkinson's Disease Questionnaire-8 (PDQ-8) score. Clinical variables independently associated with the Apathy Evaluation Scale (AES) score were NMSS domain 3 score and BDI score. The univariate regression analysis revealed that the PDQ-8 score was significantly associated with age; disease duration; formal education duration; and UPDRS-III, UPDRS-II, NMSS total, Mini-Mental Status Examination, BDI, Beck Anxiety Inventory, and AES scores. Independent predictors of the PDQ-8 score in the multivariate regression analysis were UPDRS-III, UPDRS-II, NMSS total, NMSS domain 3, Beck Anxiety Inventory, and AES scores. In the present study, apathy was an independent predictor of HRQoL in patients with early PD. Therefore, identifying and managing apathy could help improve HRQoL in patients with early PD.

Motor and non-motor features in Parkinson's Disease patients carrying GBA gene mutations.

Mutations of the Glucocerebrosidase (GBA) gene are the most common genetic risk factor yet discovered for Parkinson's Disease (PD), being found in about 5-14% of Caucasian patients. We aimed to assess motor and non-motor symptoms (NMS) in patients with GBA-related PD (GBA-PD) in comparison with idiopathic PD (iPD) subjects using standardized and validated scales. Eleven (4M, 7 F) patients with GBA-PD and 22 iPD patients, selected from the same cohort and matched for gender, age, and disease duration, were enrolled. The disease severity was assessed by Unified Parkinson's Disease Rating Scale-section III, gait disorder and falls by Freezing of Gait Questionnaire, and motor fluctuations by Wearing off questionnaire. NMS were evaluated using the following scales: Mini-Mental State Examination and extended neuropsychological battery, if required, Non-Motor Symptoms Scale, SCOPA-AUT Questionnaire, Apathy Evaluation Scale, Beck Depression Inventory, Epworth Sleepiness Scale, Restless Legs Syndrome Rating Scale, REM Sleep Behavior Disorder Screening Questionnaire, and Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease. GBA-PD patients showed a more severe and rapidly progressive disease, and more frequent positive family history for PD, akinetic-rigid phenotype, postural instability, dementia, and psychosis in comparison to iPD. Two of three subjects carrying L444P mutation presented with early dementia. We also found a higher occurrence of fatigue, diurnal sleepiness, and intolerance to heat/cold in the carriers group. Our results confirm that NMS and a more severe and faster disease course more frequently occur among GBA-PD patients in comparison to iPD.

Empathic Accuracy Task: Indian Adaptation and Validation.

The Empathic Accuracy Task (EAT) is an objective measure to assess empathic accuracy. Due to the variability in the number and linked emotions of the narrated events, we adapted EAT for the Indian sociocultural setting as Indian EAT (I-EAT). Eight videos were adapted in three languages (English, Hindi, and Kannada), narrating emotional events with a uniform representation of age groups, different emotions, and sex. The adapted I-EAT was then validated by cross-sectional comparison with different tests similar to EAT and those that assessed concepts different from or similar to empathy, in 29 healthy young adults, 23 healthy older adults (aged ≥60 years) along with clinical groups of 15 young people with depression, 15 older people with depression, and 15 young people with schizophrenia. We selected eight videos with good content validity and internal consistency (Cronbach's alpha = 0.73. We obtained satisfactory concurrent validity of the EAT scores with the self-reported empathic assessments using the Questionnaire of Cognitive and Affective Empathy (Cognitive empathy score = 0.29, p = .034; Total score = 0.29, p = .035) and Interpersonal Reactivity Index (Empathic concern score = 0.45, p = .001). Good divergent validity was revealed in the high inverse correlation recorded with the Apathy Evaluation Scale ( = -0.67, p < .001). I-EAT did not correlate significantly with measures of social cognition. Known-groups validity was adequate in young adults with the significantly lower EAT scores (Cohen's d: 0.77 to 1.15) in the Schizophrenia group and higher EAT-N scores (Cohen's d: 0.51) in the Depression group, compared to the Healthy group. The Healthy group of the geriatric population also achieved significantly higher EAT scores (Cohen's d: 0.71 to 0.85) than the Depression group. With a good validity and internal consistency, I-EAT can be used in the Indian population to assess empathic accuracy without compromising performance of the original EAT.

Clinical characteristics and metabolic therapy of fatigue in the acute and early recovery periods of ischemic stroke

To reveal clinical characteristics of asthenic syndrome with subsequent estimation of Meldonium therapy efficacy in patients in acute and early recovery periods of ischemic stroke. The study included 94 patients diagnosed with ischemic stroke, mean age being 65.6±9.5 years. Psychoemotional status was assessed on the 10th day of hospitalization with the use of the Asthenic Disorders Inventory (MFI-20), Hospital Anxiety and Depression Scale (HADS), Apathy Evaluation Scale (AES). Patients with verified asthenic syndrome were added Mildronate in a daily dose of 1000 mg (500 mg 2 times a day) for one month to baseline therapy in a real outpatient setting, followed by an assessment of treatment efficacy. The presence of asthenic syndrome in patients in the acute period of ischemic stroke was detected on all subscales of MFI-20. A high level of general and physical asthenia was found in patients with subcortical localization stroke, with decreased motivation corresponding to lesions in the frontotemporal and decreased activity in the parieto-occipital lobes. Close correlations between the MFI-20 parameters and the level of depression, anxiety, apathy, and the degree of neurological deficit were found. The dynamic evaluation of the severity of main manifestations of psychoemotional dysfunction during treatment with Mildronate showed a decrease in the level of depression, general and mental asthenia, and decreased activity during the period of observation. The high prevalence and multifactorial character of asthenia in early ischemic stroke make it urgent to optimize the early treatment of asthenic syndrome. The results of assessment of Mildronate application in a daily dose of 1000mg for a month have shown therapy efficacy concerning affective and asthenic disorders, which allows recommending its inclusion in the complex therapy of ischemic stroke.

Hypothalamic Functional Connectivity and Apathy in People with Alzheimer's Disease and Cognitively Normal Healthy Controls.

Earlier studies have described the neural markers of apathy in Alzheimer's disease (AD) and mild cognitive impairment (MCI), but few focused on the motivation circuits. Here, we targeted hypothalamus, a hub of the motivation circuit. To examine hypothalamic resting state functional connectivity (rsFC) in relation to apathy. We performed whole-brain regression of hypothalamic rsFC against Apathy Evaluation Scale (AES) total score and behavioral, cognitive, and emotional subscores in 29 patients with AD/MCI and 28 healthy controls (HC), controlling for age, sex, education, cognitive status, and depression. We evaluated the results at a corrected threshold and employed path analyses to assess possible interaction between hypothalamic rsFCs, apathy and depression/memory. Finally, we re-examined the findings in a subsample of amyloid-β-verified AD. AES total score correlated negatively with hypothalamic precuneus (PCu)/posterior cingulate cortex (PCC) and positively with left middle temporal gyrus (MTG) and supramarginal gyrus rsFCs. Behavioral subscore correlated negatively with hypothalamic PCu/PCC and positively with middle frontal gyrus rsFC. Cognitive subscore correlated positively with hypothalamic MTG rsFC. Emotional subscore correlated negatively with hypothalamic calcarine cortex rsFC. In path analyses, hypothalamic-PCu/PCC rsFC negatively modulated apathy and, in turn, depression. The model where hypothalamic MTG rsFC and memory independently modulated apathy also showed a good fit. The findings of diminished hypothalamic-PCu/PCC rsFC in relation to apathy and, in turn, depression were confirmed in amyloid-verified AD. The findings together support a role of altered hypothalamic connectivity in relation to apathy and depression, and modulation of apathy by memory dysfunction.

Mental Health Symptoms Mediate the Association of Subjective Cognitive Function with Participation after Stroke

<h3>Research Objectives</h3> To investigate if mental health (MH) symptoms - depression, apathy, and anxiety - mediate the association of subjective (SCF) and objective (OCF) measures of cognitive function with participation after stroke. <h3>Design</h3> A prospective cross-sectional study. We performed a regression-based mediation analysis using Hayes's PROCESS macro. 12 Models were built for three MH mediators in the association of SCF and OCF measures with two participation measures, respectively. <h3>Setting</h3> Community. <h3>Participants</h3> 74 persons with stroke. <h3>Interventions</h3> Not applicable. <h3>Main Outcome Measures</h3> We used Patient Health Questionnaire-9 for depression, Apathy Evaluation Scale, and State-Trait Anxiety Inventory-Trait Anxiety Scale as MH mediators. The dependent variables were participation measured using Reintegration to Normal Living (RNL) and Activity Card Sort (ACS). Independent variables were SCF, measured using Stroke Impact Scale Memory and Thinking, and OCF, measured using Delis-Kaplan Executive Function System Trail-Making Test (Number-letter switching). <h3>Results</h3> In the model of RNL, depression (b=0.093, 95% CI=0.038∼0.157), apathy (b=0.134, 95% CI=0.071∼0.202), and anxiety (b=0.116, 95% CI=0.049∼0.194), were full mediators of the association between the SCF measure and RNL total score. For the ACS, apathy was the only mediator between the SCF measure and ACS total activity retention (b=0.144, 95% CI=0.032∼0.293). In both models, none of the MH measures were significant mediators of the association between the OCF measure and RNL or ACS after stroke (p>0.05). <h3>Conclusions</h3> These findings indicate that depression, apathy, and anxiety may be stronger mediators of the association between SCF with participation than for OCF with participation after stroke. Rehabilitation professionals should pay attention to measures of both SCF and OCF as they have different dynamics with MH symptoms and participation after stroke. <h3>Author(s) Disclosures</h3> None.

Lipid oxidation as a marker of apathy and executive dysfunction in patients at risk of vascular cognitive impairment

AbstractBackgroundApathy and executive function decline are hallmarks of vascular dysfunction in neurodegeneration and cognitive impairment. People with mild vascular cognitive impairment (mVCI) display a combined etiology of both cognitive impairment and vascular comorbidities; hence, patients with vascular risk factors are at risk for mVCI. The co‐occurrence of apathy and executive dysfunction is prevalent; however, the physiological pathway underlying these manifestations is yet to be investigated. Oxidative stress is often present in vascular dysfunction. This study investigated the relationship between oxidative stress, specifically markers of lipid oxidation, apathy, and executive dysfunction in patients at risk of mVCI.MethodPatients at risk of mVCI were recruited from a population of patients with coronary artery disease in a Cardiac Rehabilitation Program. Apathy was assessed using the Apathy Evaluation Scale and executive function with Trial Making Test B, phonemic fluency test and animal naming test. Fasting blood was collected and serum concentrations of early and late lipid oxidation markers, lipid hydroperoxides (LPH) and 8‐isoprostane (8‐ISO) respectively, were measured.ResultParticipants (n=206, Age= 63.0±7.5, 80% men, total years of education= 15.9±3.4, AES score= 28.3±8.8, composite z score for EF= 0±1) demonstrated significantly different ratios of late to early lipid oxidation markers (8‐ISO/LPH) between groups (F(3, 202) = 10.915, p &lt;0.001) with increasing levels in the following order: no apathy or executive dysfunction, only executive dysfunction, only apathy, and both apathy and executive dysfunction. A multivariate linear regression model adjusting for demographics found that lipid oxidation was significantly associated with apathy (B= 4.63, p &lt; 0.001) and executive function (B= ‐0.19, p= 0.018); however, when controlling for both demographics and vascular risk factors, lipid oxidation was significantly associated with apathy alone (B= 3.11, p= 0.002).ConclusionThe results highlight an important involvement of lipid oxidation in the co‐occurrence of apathy and executive dysfunction in patients at risk of mVCI. Our results show that increased oxidative stress may contribute to the development of apathy, which may relate to why apathy is a strong risk factor for progression to dementia in at‐risk populations.

Apathy in depression: An arterial spin labeling perfusion MRI study

IntroductionApathy, as defined as a deficit in goal-directed behaviors, is a critical clinical dimension in depression associated with chronic impairment. Little is known about its cerebral perfusion specificities in depression. To explore neurovascular mechanisms underpinning apathy in depression by pseudo-continuous arterial spin labeling (pCASL) magnetic resonance imaging (MRI). MethodsPerfusion imaging analysis was performed on 90 depressed patients included in a prospective study between November 2014 and February 2017. Imaging data included anatomical 3D T1-weighted and perfusion pCASL sequences. A multiple regression analysis relating the quantified cerebral blood flow (CBF) in different regions of interest defined from the FreeSurfer atlas, to the Apathy Evaluation Scale (AES) total score was conducted. ResultsAfter confound adjustment (demographics, disease and clinical characteristics) and correction for multiple comparisons, we observed a strong negative relationship between the CBF in the left anterior cingulate cortex (ACC) and the AES score (standardized beta = −0.74, corrected p value = 0.0008). ConclusionOur results emphasized the left ACC as a key region involved in apathy severity in a population of depressed participants. Perfusion correlates of apathy in depression evidenced in this study may contribute to characterize different phenotypes of depression.

Understanding the relationship between apathy, cognition and functional outcome in schizophrenia: The significance of an ecological assessment.

In recent years there has been an increasing interest in understanding the role apathy plays in mediating the relationship between cognitive impairment and functional outcome. In general, most studies measure cognition with traditional cognitive tests that give explicit instructions and guide the participants toward generating a response. However, given that apathy is defined by a decrease in self-initiated behavior, it is crucial to evaluate cognition with ecological tasks that do not explicitly direct the patient´s motivation to generate behaviors to assess the actual effect. This study investigated whether an ecological cognitive assessment (the Jansari Executive Function Assessment, JEF©) would uniquely contribute to the relationship between cognition, apathy, and functional outcome in schizophrenia. The Apathy Evaluation Scale (AES), neuropsychological tests and the JEF© were administered to 20 patients with schizophrenia. Hierarchical multiple regression and mediation analysis were performed to test the associations between the variables of interest. Results showed that JEF© explained a significant portion of the variance in AES (25%). In addition, apathy explained 36% of the variance in functional outcome. However, AES did not mediate between cognition and functional outcome. Our results highlight the importance of assessing cognition with tasks that require integration of cognitive functions needed for real life demands.