Apathy Scores Research Articles

Intranasal oxytocin for apathy in people with frontotemporal dementia (FOXY): a multicentre, randomised, double-blind, placebo-controlled, adaptive, crossover, phase 2a/2b superiority trial.

No treatments exist for apathy in people with frontotemporal dementia. Previously, in a randomised double-blind, placebo-controlled, dose-finding study, intranasal oxytocin administration in people with frontotemporal dementia improved apathy ratings on the Neuropsychiatric Inventory over 1 week and, in a randomised, double-blind, placebo-controlled, crossover study, a single dose of 72 IU oxytocin increased blood-oxygen-level-dependent signal in limbic brain regions. We aimed to determine whether longer treatment with oxytocin improves apathy in people with frontotemporal dementia. We conducted a multicentre, randomised, double-blind, placebo-controlled, adaptive, crossover, phase 2a/2b trial, enrolling participants from 11 expert frontotemporal dementia outpatient clinics across Canada and the USA. People aged 30-80 years with a diagnosis of probable frontotemporal dementia, a Neuropsychiatric Inventory apathy score of 2 or higher, a study partner who interacted with them for at least 3 h per day, and stable cognitive and behavioural medications for 30 days were eligible for inclusion. In stage 1, participants were randomly assigned (1:1:1:1:1:1) to one of three dose schedules (every day, every other day, and every third day) of 72 IU intranasal oxytocin or placebo and to the order they would received the intervention in the crossover; intranasal oxytocin or placebo were administered twice daily for 6 weeks, with a 6-week washout and then crossover to the other intervention. In stage 2, new participants were randomised (1:1) to the dose that had been determined as optimal in stage 1 or to placebo, with crossover as in stage 1. Randomisation used variable block sizes and was stratified by participant sex and Clinical Dementia Rating severity score. All kits of investigational product were identical and produced centrally, and all local teams, study staff, and participants were masked to treatment allocation and order. The primary outcome was difference in the change in Neuropsychiatric Inventory apathy scores for oxytocin versus placebo periods in the per-protocol population after 6 weeks of treatment. Safety was assessed at each visit via electrocardiogram, blood work, and collection of data on adverse events. This trial is registered at ClinicalTrials.gov (NCT03260920). Between Jan 31, 2018, and Dec 11, 2020, 70 patients were screened for stage 1 and 60 (86%) were enrolled. 45 (75%) completed both treatment periods of stage 1. 72 IU oxytocin every third day was the optimal dose schedule from stage 1 based on its Bayesian posterior probability (Pr(Best)=0·478). Between June 28, 2021, and Jan 31, 2023, 42 patients were screened for stage 2, and 34 (81%) were enrolled. 28 (82%) completed both treatment periods in stage 2. 38 (40%) of 94 participants were female and 56 (60%) were male (mean age 65·9 years, SD 8·2) Treatment with oxytocin every third day resulted in an improved Neuropsychiatric Inventory apathy score, with an estimated -1·32 points (95% CI -2·43 to -0·21) relative to placebo (one sided p=0·010). Two adverse events were reported in at least 5% of participants: upper respiratory tract infection (five [6%] of 78 participants on placebo and three [5%] on every third day at all doses of oxytocin) and headache (two [3%] participants on placebo, one [7%] of 15 participants on oxytocin every day, and two [4%] of 55 participants on oxytocin every third day). No adverse events were attributed to oxytocin treatment. Intranasal oxytocin given every third day was well tolerated and was associated with a small reduction in apathy in patients with frontotemporal dementia. Future trials might investigate intermittent dosing of more potent formulations than in this study, to establish whether larger effects are possible. Canadian Institutes of Health Research and Weston Foundation.

Apathy in Alzheimer's disease: Eye movements characteristics and neurostructural basis.

We sought to evaluate the characteristics of eye movements in Alzheimer's disease (AD) patients with apathy (AD-A) and their ability to identify AD-A and explore the shared neurostructure of eye movements and apathy. Total 32 normal controls, 36 AD-A and 72 AD with no apathy (AD-NA) patients were recruited. Parameters of smooth pursuit, fixation, prosaccade and antisaccade were compared among the three groups. Correlation analyses were conducted on apathy score, eye movement parameters and gray matter volume (GMV) in AD patients. Receiver operating characteristic curves were used to determine the power of eye movement parameters to identify AD-A patients. AD-A group exhibited a longer start-up duration of smooth pursuit, latency of gap and overlap prosaccades than AD-NA and normal control groups. In AD patients, apathy score was positively correlated with latency of overlap prosaccade. The GMVs of right pregenual anterior cingulate cortex (ACC) and left supracallosal ACC were negatively correlated with apathy score. Regions shared by apathy and latency of overlap prosaccade included right pregenual ACC and left supracallosal ACC. The area under curve discriminated AD-A from AD-NA patients by combining start-up duration, latency of gap and overlap prosaccade, and demographic information was 0.812. AD-A patients exhibit delayed initiation in eye movements, and the more prominent apathy indicates prolonged latency of overlap prosaccade in AD patients. Apathy and latency of overlap prosaccade share a neurostructural basis in AD patients. Our results contribute to providing a new method for early identification and severity assessment for AD-A.

BEDROOM ENVIRONMENTAL QUALITY PARAMETERS ASSOCIATED WITH OLDER ADULTS’ BEHAVIORAL AND PSYCHOLOGICAL SYMPTOMS

Abstract Behavioral and psychological symptoms are common among older adults with apathy, depression and anxiety being the most prevalent. Identifying factors associated with such symptoms may help mitigate them. The study, Monitoring Apathy, Depression and Anxiety Using Technology Evaluations, aimed to identify indoor environmental quality factors that may trigger these symptoms. The study was a 9-month observational study in 12 participants’ personal residences. Participant mean age was 79.0 (6.4) years, 7 were males (58.3%), 7 had normal cognition, 4 had MCI and 1 had early-stage AD. The participants self-reported the severity of their apathy, depression and anxiety weekly online by answering standard surveys sent via email, which consisted of the 6-item Withdrawal-Apathy-Vigor subscale from the Geriatric Depression Scale for assessing apathy, and depression, and anxiety subscales from Patient-Reported Outcomes Measurement Information System for assessing depression and anxiety respectively. Bedroom environments were assessed with environmental sensors (Awair Omni, San Francisco) which measured light level, noise level, temperature, humidity and air quality every 5 minutes. Individual mixed-effect models were built with each symptom severity being the outcome, and each weekly mean bedroom environmental quality factor being the predictor, while controlling for age, sex and the week the data was collected. Lower light level in the bedroom was significantly associated with more severe depression scores (p< 0.01) and higher temperature was associated with more severe apathy scores (p< 0.05). Optimizing specific aspects of indoor environmental quality in older adults’ personal homes can potentially assist in improving management of behavioral and psychological symptoms.

Correlation between blood biomarkers and neuropsychiatric symptoms: Siriraj cohort, Thailand

AbstractBackgroundWe explored the relationship of neuropsychiatric symptoms (assesses by NPI) and Alzheimer disease pathophysiology from blood AB42/40, GFAB, NFL, and pTau181. We also investigated if age and cognition were related to these neuropsychiatric symptoms.Method222 subjects included 96 dementia, 66 MCI, and 60 normal controls (NC). Spearman correlation was used to calculation the correlation coefficient. Mann‐Whitney U test is used to compare biomarkers of those with and without subitem symptoms of NPI.ResultMean ages were 71.26±9.82 years old in dementia group, 68.83±8.01 years old in MCI group, and 59.28±9.22 years old in NC group. Sum of 12 NPI subscale scores showed significant low correlation (r=0.20‐0.29) were correlated with blood AB42/AB40, Ptau 181, NFL, and GFAB. Sum of 12 NPI subscale scores showed significant moderate correlation with age and global cognition (assessed by Thai mental state examination, TMSE). Blood pTau181 displayed low correlation with hallucination, depression, anxiety, apathy, and irritability subscale scores. There was a significant low correlation between blood AB42/AB40 and delusion and irritability subscale scores. Blood NFL showed low correlation with euphoria, a, apathy, disinhibition, irritability, and aberrant motor activity. Inflammation process appeared to be significantly related with psychosis, apathy, disinhibition, and irritability. After controlled by age and TMSE; only apathy and AMA NPI subscale scores were correlated to NFL and GFAB accordingly.ConclusionWe discovered that psychosis and mood factors of NP symptoms were related to blood pTau. While most frontal factors of NP symptoms showed significant relationship with axonal destruction and microglia activation/inflammation.This study was supported by grants from Health Systems Research Institute (HSRI), Thailand.

Psychological predictors of incident subjective cognitive complaints in community dwelling older adults

Background Subjective cognitive complaint (SCC) is associated with future cognitive decline and may be a marker for clinical intervention in the progression to dementia. Among the viable predictors of SCC, psychological factors are clinically relevant, non-invasive early indicators of older adults at elevated risk. This aim of this study is to determine whether psychological symptoms: dysphoria and apathy precede incident SCC in the dementia pathway. Methods Participants (n = 592) enrolled in the Central Control of Mobility in Aging Study were includes in the analyses, with prevalent cases excluded. Apathy and dysphoria scale scores were derived using confirmatory factor analysis of the Geriatric Depressive Scale. Cox regression analyses was used to determine the association between apathy and dysphoria scores and incident SCC. Results Over a mean follow up of 1.90 years, 44 individuals (9.26%) developed incident SCC. Baseline apathy scale score was significantly associated with 4-fold increased risk of SCC (HR 4.39, 95%CI: 1.32–14.67), adjusted for cognition but not age and dysphoria scale score. Baseline dysphoria scale score was not associated with increased risk of SCC in adjusted analyses. Conclusion In this longitudinal analysis of community dwelling older adults, apathy was associated with an increased risk of SCC, when adjusting for cognition but not dysphoria. Finally, this study highlights apathy as an early risk factor, which may precede SCC in the progression to dementia and consequently, may identify a high risk group for clinical screening and intervention.

Examining Leisure Re-Engagement and Its Relationship With Self-Regulation After Traumatic Brain Injury: A Cross-Sectional Study.

Engagement in leisure activities is a significant contributor to health. Individuals with traumatic brain injury (TBI) report not returning to pre-injury levels of leisure participation. Self-regulation (SR) is a possible factor of limited re-engagement. This study aimed to examine leisure re-engagement patterns and the impact of SR on these patterns. Fifty-five adults with TBI were included in a cross-sectional study. Participants completed a leisure activity survey, rating engagement before and after injury. Participants and an informant completed the Frontal Systems Behavior Scale (FrSBe) to assess SR. Leisure was significantly lower after injury than before injury, t(54) = 3.83, p < .001. The FrSBe apathy score was significantly associated with lower re-engagement (eta = 0.42) and may predict engagement after injury (ΔR2 = .09, p < .05). Apathy may contribute to difficulty re-engaging in leisure activities. Re-engagement in leisure activities should be a focus of occupational therapy intervention after TBI.

Apathy and effort-based decision-making in Alzheimer's disease and subjective cognitive impairment.

Apathy is a significant feature in Alzheimer's disease (AD) and subjective cognitive impairment (SCI), though its mechanisms are not well established. An effort-based decision-making (EBDM) framework was applied to investigate apathy in 30 AD patients, 41 SCI participants, and 55 healthy controls (HC). Data were analyzed using a drift-diffusion model (DDM) to uncover latent psychological processes. SCI participants reported higher apathy than AD patients and HC. However, informant reports of apathy in AD patients were higher than self-reports and indicated significant apathy compared to HC. Both the AD and SCI groups showed reduced sensitivity to effort changes, linked to executive dysfunction in AD and apathy in SCI. Increased resting functional cortical connectivity with the nucleus accumbens (NA) was associated with higher apathy in SCI. These results highlight a similar disruption of EBDM in AD and SCI, differentially related to executive functioning in AD and apathy in SCI. This is the first study investigating apathy using an effort-based decision-making (EBDM) framework in Alzheimer's disease (AD) and subjective cognitive impairment (SCI).Self-reports underestimate apathy in AD patients when compared to informant reports and healthy controls (HC). SCI participants, in whom self and informant reports were more concordant, also showed higher degrees of apathy.Both AD and SCI groups showed reduced sensitivity to effort.Reduced sensitivity to effort correlates with executive dysfunction in AD and apathy, but not depression, in SCI.Increased nucleus accumbens (ventral striatum) connectivity with the frontoparietal network was associated with higher apathy scores in SCI.The results thus suggest that while AD and SCI can have similar deficits in EBDM, these deficits correlate with distinct clinical manifestations: executive dysfunction in AD and apathy in SCI.

Psychiatric predictors of quality of life in Parkinson's disease: A three-year longitudinal study

IntroductionParkinson's disease (PD) is associated with worsened quality of life (QOL) over time. Few longitudinal studies exist investigating the relationship of psychiatric comorbidities with QOL in people with PD (PwP). We sought to determine specific psychiatric symptoms associated with decreasing QOL in PwP over time. MethodsWe recruited PwP without dementia from a movement disorders clinic at an academic medical center. Participants were evaluated annually with motor and neuropsychological assessments at each visit. QOL was measured using the Parkinson's Disease Questionnaire-39 (PDQ-39). We assessed psychiatric symptoms, including depression (Beck Depression Inventory II, BDI-II), anxiety (Beck Anxiety Index, BAI), and apathy (Apathy Scale). Psychosis and impulse control disorders (ICDs) were recorded as present or absent. Using random coefficient regression, we analyzed psychiatric features associated with worsened QOL in PwP over three years. ResultsFrom the 105 participants enrolled at baseline, 67 completed three years of follow up. Mean PDQ-39 scores increased from 16.0 at baseline to 19.8 at year three. In multivariate analysis, higher BDI-II scores, BAI scores, and apathy scores were uniquely associated with worsened QOL over time (p < 0.001 for all measures), while presence of ICDs (p = 0.18) or psychosis (p = 0.10) were not. Changes in the BAI score and the BDI-II score exerted similar effects on the overall PDQ-39 score. ConclusionDepression, anxiety, and apathy are all associated with worsening quality of life over time in PwP, while presence of ICDs and psychosis are not. Treatment of these symptoms may lead to improved QOL in PwP.

Validation of a Malayalam Version of the Apathy Evaluation Scale.

The apathy evaluation scale (AES) measures apathy, but its usefulness as a screening tool in diverse populations is limited without translation into more languages. To date, there is no reported translation of the AES into Malayalam, a language spoken by over 32 million people in the southern Indian state of Kerala. In the present study, we aimed to validate the Malayalam version of the AES. Six hundred sixty-one community-dwelling older adults without dementia participating in the Kerala Einstein study completed the Malayalam AES. We assessed the internal consistency and the validity of the Malayalam AES, using another measure of apathy, as well as measures of depression and anxiety. We also used principal component analysis (PCA) to determine the dimensionality of the Malayalam AES. Finally, we assessed possible sex differences in apathy. The Malayalam AES demonstrated high internal consistency and good validity, and the results of our PCA indicate that it has a three-component structure, as in the original English version and other translated versions. We found that while overall apathy scores were similar, the relationship with other neuropsychiatric symptoms differed by sex, with stronger relationships found in male participants compared to female participants. Our study provides another tool to screen for apathy in non-English-speaking populations, an important early risk factor for cognitive and functional decline, and enables future research across diverse cultures.

Mixed effects models but not t-tests or linear regression detect progression of apathy in Parkinson’s disease over seven years in a cohort: a comparative analysis

IntroductionWhile there is an interest in defining longitudinal change in people with chronic illness like Parkinson’s disease (PD), statistical analysis of longitudinal data is not straightforward for clinical researchers. Here, we aim to demonstrate how the choice of statistical method may influence research outcomes, (e.g., progression in apathy), specifically the size of longitudinal effect estimates, in a cohort.MethodsIn this retrospective longitudinal analysis of 802 people with typical Parkinson’s disease in the Luxembourg Parkinson's study, we compared the mean apathy scores at visit 1 and visit 8 by means of the paired two-sided t-test. Additionally, we analysed the relationship between the visit numbers and the apathy score using linear regression and longitudinal two-level mixed effects models.ResultsMixed effects models were the only method able to detect progression of apathy over time. While the effects estimated for the group comparison and the linear regression were smaller with high p-values (+ 1.016/ 7 years, p = 0.107, -0.056/ 7 years, p = 0.897, respectively), effect estimates for the mixed effects models were positive with a very small p-value, indicating a significant increase in apathy symptoms by + 2.345/ 7 years (p < 0.001).ConclusionThe inappropriate use of paired t-tests and linear regression to analyse longitudinal data can lead to underpowered analyses and an underestimation of longitudinal change. While mixed effects models are not without limitations and need to be altered to model the time sequence between the exposure and the outcome, they are worth considering for longitudinal data analyses. In case this is not possible, limitations of the analytical approach need to be discussed and taken into account in the interpretation.

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.

#1353 Apathy and fatigue in patients treated with haemodialysis and peritoneal dialysis

Abstract Background and Aims Apathy is a distinct syndrome manifesting with a loss of interest in social or emotional situations, lack of sense of purpose, low energy levels and detachment from life and personal events. Previous studies showed that apathy is associated with vascular impairment and consequent cognitive dysfunction, reduced quality of life and increased hospitalization, institutionalization, healthcare costs and death. So far there has been little research on the prevalence of apathy among dialysis patients although this population could be considered at risk for this condition due to increasing age, and disease and treatment burden. Fatigue is also common in dialyzed patients and impacts daily living, impairs the quality of life, increases the risk of cardiovascular events and negatively influences survival. This study aimed to explore the link between apathy and fatigue among hemodialysis (HD) and peritoneal dialysis (PD) patients. Method We conducted a cross-sectional cohort study which included 75 HD (57.3% male, median age 64 years) and 62 PD patients (48.4% male, median age 61 years) from two dialysis centres. Apathy status was assessed by the Apathy Evaluation Scale (AES) by Starkstein. Fatigue was evaluated with the Functional Assessment of Chronic Illness Therapy (FACIT) scale. AES score of 14 and higher denotes the presence of apathy, while a FACIT score of less than 30 indicates severe fatigue. Demographic, clinical and laboratory data were obtained by a focused questionnaire and from electronic medical records. Data were analyzed with T-test, Hi-square, ANOVA and Pearson correlation as applicable. Results HD patients were significantly longer on dialysis than PD patients (p=0.046). Apathy was more frequent among PD patients compared to the HD group (64.5% vs 48%), but the difference was not statistically significant (p = 0.053). Severe fatigue was more frequent in the HD group (33.8% vs 27.4%), but the difference was not statistically significant (p = 0.424). Elderly patients had a higher prevalence of apathy in both HD (70.3% vs 29.7%, p&amp;lt;0.001) and PD groups (84.2% vs 16.3%, p = 0.008), and a significantly higher prevalence of severe fatigue in the HD group (68% vs 32%, p = 0.017). Among HD patients higher education level was significantly associated with higher FACIT and lower apathy scores (p = 0.002 and p = 0.001 respectively). HD patients taking psychotropic medication had significantly lower FACIT (27.2±13.5 vs 35.0 ± 11.9, p = 0.03). Also, the presence of apathy was significantly associated with lower hemoglobin levels (101.7±9.7 vs 110.3±11.2, p = 0.001), red blood cells count (3.2±0.2 vs 3.5±0.6, p = 0.004), lower serum creatinine (900.0±149.1 vs 1001.5±266.4, p = 0.047) and lower Kt/V (1.35±0.22 vs 1.49±0.24, p = 0.008) in the HD group, while PD patients with severe fatigue had significantly higher creatinine levels (796.7±176.9 vs 646.4±200.0, p = 0.009). Gender, dialysis vintage, primary renal disease, and comorbidities were not significantly associated with either apathy or fatigue in either group of patients. Apathy and fatigue were significantly correlated in both the HD (p = 0.04) and the PD (p = 0.001) groups. Conclusion Apathy is a highly prevalent and often overlooked condition among dialyzed patients regardless of dialysis modality. Longitudinal studies should explore whether apathy is a causative factor for fatigue in these populations.

Effect of Noise in the Emergency Department on Occupational Burnout and Resignation Intention of Medical Staff.

This study aims to explore the effect of noise in the emergency department on the occupational burnout and the resignation intentions of medical staff. This retrospective study selected 42 medical staff (group A) in the emergency department of our hospital from March 2020 to March 2021 and 39 medical staff (group B) in the rehabilitation department during the same period as research subjects. Noise levels in the daily working environment of medical staff were collected. The Maslach Burnout Inventory General Survey and Intent to Leave Scale was used to evaluate occupational burnout and resignation intention. A multivariate linear regression analysis was adopted to explore the effects of noise exposure level in the emergency department on occupational burnout and resignation intention. The scores of emotional fatigue, work apathy and sense of achievement in group A were higher than those in group B (P < 0.05), among which reverse scoring was adopted for sense of accomplishment. Group A had significantly higher scores of resignation intention I, resignation intention II and resignation intention III than group B (P < 0.001). The department of group A had significantly higher noise level than that of group B (P < 0.001). The Multivariate linear regression analysis showed that noise level in the emergency department was correlated with the occupational burnout and resignation intention of medical staff (all P < 0.05). The emergency department is exposed to a high noise level, which is correlated with the occupational burnout and resignation intentions of medical staff. Therefore, hospitals should give importance to noise exposure in the emergency departments and adopt positive coping strategies to reduce the effect of noise on medical staff and the resignation rate.

Neuropsychiatric symptoms and brain morphology in patients with mild cognitive impairment, cerebrovascular disease and Parkinson disease: A cross sectional and longitudinal study.

Neuropsychiatric symptoms (NPS) increase risk of developing dementia and are linked to various neurodegenerative conditions, including mild cognitive impairment (MCI due to Alzheimer's disease [AD]), cerebrovascular disease (CVD), and Parkinson's disease (PD). We explored the structural neural correlates of NPS cross-sectionally and longitudinally across various neurodegenerative diagnoses. The study included individuals with MCI due to AD, (n=74), CVD (n=143), and PD (n=137) at baseline, and at 2-years follow-up (MCI due to AD, n=37, CVD n=103, and PD n=84). We assessed the severity of NPS using the Neuropsychiatric Inventory Questionnaire. For brain structure we included cortical thickness and subcortical volume of predefined regions of interest associated with corticolimbic and frontal-executive circuits. Cross-sectional analysis revealed significant negative correlations between appetite with both circuits in the MCI and CVD groups, while apathy was associated with these circuits in both the MCI and PD groups. Longitudinally, changes in apathy scores in the MCI group were negatively linked to the changes of the frontal-executive circuit. In the CVD group, changes in agitation and nighttime behavior were negatively associated with the corticolimbic and frontal-executive circuits, respectively. In the PD group, changes in disinhibition and apathy were positively associated with the corticolimbic and frontal-executive circuits, respectively. The observed correlations suggest that underlying pathological changes in the brain may contribute to alterations in neural activity associated with MBI. Notably, the difference between cross-sectional and longitudinal results indicates the necessity of conducting longitudinal studies for reproducible findings and drawing robust inferences.

Apathy After Stroke: Incidence, Symptom Trajectory, and Impact on Quality of Life and Disability

Apathy is one of the most common symptoms following stroke and is often associated with worse functional outcome and poor quality of life (QoL). The trajectory of apathy symptoms has been previously described, and different trajectories have been identified. We determined group and individual changes in apathy symptomatology from the acute phase until 1 year after stroke. We also examined the association of apathy and depression with disability and QoL 1 year after stroke. We measured apathy in a cohort of ischemic stroke survivors at 4 time points from 0 to 12 months after stroke. The Apathy Evaluation Scale (AES) and Dimensional Apathy Scale (DAS) were administered at each time point. Where possible we obtained apathy measured from carers. Depression was assessed with the Geriatric Depression Scale (GDS). Disability and QoL were assessed with the modified Rankin Scale (mRS) and 36-Item Short Form Survey (SF-36). We examined the cross-sectional and individual trajectory of apathy symptoms in each dimension and looked at associations of apathy and depression soon after stroke with mRS and SF-36 at 1 year. Of 200 participants enrolled, 165 completed apathy measures at 12 months. Patient-rated apathy scores increased in both tests at the group level (AES: χ2(3) = 9.86, p = 0.019; DAS: χ2(3) = 8.49, p = 0.037) and individual level (AES: β = 0.13, p = 0.002; DAS β = 0.13, p = 0.005; DAS: executive β = 0.08, p < 0.001). By contrast, carer-rated apathy did not significantly increase (AES: χ2(3) = 0.75, p = 0.862; DAS: χ2(3) = 2.45, p = 0.484). Apathy scores were associated with worse mRS and SF-36, although most associations were no longer significant when controlling for depression. GDS was associated with worse mRS and SF-36 after controlling for covariates and apathy (mRS: β = 0.08, p = 0.006; SF-36 Mental Component Summary: β = -1.53, p < 0.001; SF-36 Physical Component Summary: β = -0.57, p = 0.016). Self-reported apathy progressively increases after stroke, especially in the executive dimension. Apathy is associated with worse QoL and greater disability, although some of these associations might be mediated by depression.

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.

Prodromal Cognitive Changes as a Prognostic Indicator of Forthcoming Huntington's Disease Severity: A Retrospective Longitudinal Study.

Cognitive changes in Huntington's disease (HD) precede motor manifestations. ENROLL-HD platform includes four cognitive measures of information processing speed (IPS). Our group is eager to seek clinical markers in the life stage that is as close as possible to the age of onset (ie, the so called prodromal HD phase) because this is the best time for therapeutic interventions. Our study aimed to test whether cognitive scores in prodromal ENROLL-HD mutation carriers show the potential to predict the severity of motor and behavioral changes once HD became fully manifested. From the global ENROLL-HD cohort of 21,343 participants, we first selected a premanifest Cohort#1 (ie, subjects with Total Motor Score (TMS) <10 and Diagnostic Confidence Level (DCL) <4, N = 1.222). From this cohort, we then focused on a prodromal Cohort#2 of subjects who were ascertained to phenoconvert into manifest HD at follow-up visits (ie, subjects from 6 ≤ TMS≤9 and DCL <4 to TMS≥10 and DCL = 4, n = 206). The main results of our study showed that low IPS before phenoconversion in Cohort#2 predicted the severity of motor and behavioral manifestations. By combining the four IPS cognitive measures (eg, the Categorical Verbal Fluency Test; Stroop Color Naming Test; Stroop Word Reading; Symbol Digit Modalities Test), we generated a Composite Cognition Score (CCS). The lower the CCS score the higher the TMS and the apathy scores in the same longitudinally followed-up patients after phenoconversion. CCS might represent a clinical instrument to predict the prognosis of mutation carriers who are close to manifesting HD.

Longitudinal associations of apathy and regional tau in mild cognitive impairment and dementia: Findings from the Alzheimer's Disease Neuroimaging Initiative.

It is important to study apathy in Alzheimer's disease (AD) to better understand its underlying neurobiology and develop effective interventions. In the current study, we sought to examine the relationships between longitudinal apathy and regional tau burden in cognitively impaired older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Three hundred and nineteen ADNI participants with mild cognitive impairment (MCI) or AD dementia underwent flortaucipir (FTP) tau positron emission tomography (PET) imaging and clinical assessment with the Neuropsychiatric Inventory (NPI) annually. Longitudinal NPI Apathy (NPI-A) scores were examined in relation to baseline tau PET signal in three a priori selected regions implicated in AD and AD-related apathy (supramarginal gyrus, entorhinal cortex [EC] and rostral anterior cingulate cortex [rACC]). Secondary models were adjusted for global cognition (Mini-Mental State Examination score) and cortical amyloid (florbetapir PET). Higher baseline supramarginal gyrus and EC tau burden were each significantly associated with greater NPI-A over time, while rACC tau was associated with higher NPI-A but did not predict its trajectory over time. These results were retained for supramarginal and EC tau after adjusting models for global cognition and cortical amyloid. Our findings suggest that baseline in vivo tau burden in parietal and temporal brain regions affected in AD, and less so in a medial frontal region involved in motivational control, is associated with increasing apathy over time in older adults with MCI and AD dementia. Future work studying emergent apathy in relation to not only core AD pathology but also circuit level dysfunction may provide additional insight into the neurobiology of apathy in AD and opportunities for intervention. Tau (Flortaucipir PET) in regions implicated in AD was associated with increasing apathy over timeCortical amyloid was also found to be a robust predictor of the trajectory of apathyEvidence of synergy between regional tau and amyloid in overall higher levels of apathy.

Apathy scores in Parkinson's disease relate to EEG components in an incentivized motor task.

Apathy is one of the most prevalent non-motor symptoms of Parkinson's disease and is characterized by decreased goal-directed behaviour due to a lack of motivation and/or impaired emotional reactivity. Despite its high prevalence, the neurophysiological mechanisms underlying apathy in Parkinson's disease, which may guide neuromodulation interventions, are poorly understood. Here, we investigated the neural oscillatory characteristics of apathy in Parkinson's disease using EEG data recorded during an incentivized motor task. Thirteen Parkinson's disease patients with apathy and 13 Parkinson's disease patients without apathy as well as 12 healthy controls were instructed to squeeze a hand grip device to earn a monetary reward proportional to the grip force they used. Event-related spectral perturbations during the presentation of a reward cue and squeezing were analysed using multiset canonical correlation analysis to detect different orthogonal components of temporally consistent event-related spectral perturbations across trials and participants. The first component, predominantly located over parietal regions, demonstrated suppression of low-beta (12-20 Hz) power (i.e. beta desynchronization) during reward cue presentation that was significantly smaller in Parkinson's disease patients with apathy compared with healthy controls. Unlike traditional event-related spectral perturbation analysis, the beta desynchronization in this component was significantly correlated with clinical apathy scores. Higher monetary rewards resulted in larger beta desynchronization in healthy controls but not Parkinson's disease patients. The second component contained gamma and theta frequencies and demonstrated exaggerated theta (4-8 Hz) power in Parkinson's disease patients with apathy during the reward cue and squeezing compared with healthy controls (HCs), and this was positively correlated with Montreal Cognitive Assessment scores. The third component, over central regions, demonstrated significantly different beta power across groups, with apathetic groups having the lowest beta power. Our results emphasize that altered low-beta and low-theta oscillations are critical for reward processing and motor planning in Parkinson's disease patients with apathy and these may provide a target for non-invasive neuromodulation.