UNASSIGNED: Discrepancy between caregiver and patient assessments of apathy in mild cognitive impairment (MCI) is considered an index of apathy unawareness, independently predicting progression to AD dementia. However, its neural underpinning are uninvestigated.
UNASSIGNED: To explore the [18F]FDG PET-based metabolic correlates of apathy unawareness measured through the discrepancy between caregiver and patient self-report, in patients diagnosed with MCI.
UNASSIGNED: We retrospectively studied 28 patients with an intermediate or high likelihood of MCI-AD, progressed to dementia over an average of two years, whose degree of apathy was evaluated by means of the Apathy Evaluation Scale (AES) for both patients (PT-AES) and caregivers (CG-AES). Voxel-based analysis at baseline was used to obtain distinct volumes of interest (VOIs) correlated with PT-AES, CG-AES, or their absolute difference (DISCR-AES). The resulting DISCR-AES VOI count densities were used as covariates in an inter-regional correlation analysis (IRCA) in MCI-AD patients and a group of matched healthy controls (HC).
UNASSIGNED: DISCR-AES negatively correlated with metabolism in bilateral parahippocampal gyrus, posterior cingulate cortex, and thalamus, PT-AES score with frontal and anterior cingulate areas, while there was no significant correlation between CG-AES and brain metabolism. IRCA revealed that MCI-AD patients exhibited reduced metabolic/functional correlations of the DISCR-AES VOI with the right cingulate gyrus and its anterior projections compared to HC.
UNASSIGNED: Apathy unawareness entails early disruption of the limbic circuitry rather than the classical frontal-subcortical pathways typically associated with apathy. This reaffirms apathy unawareness as an early and independent measure in MCI-AD, marked by distinct pathophysiological alterations.

OBJECTIVE: To investigate the relationship among patients\' apathy, cognitive impairment, depression, anxiety, and caregiver burden in amyotrophic lateral sclerosis (ALS).
METHODS: A cross-sectional study design was used.
METHODS: The study was conducted at a tertiary hospital in Wuhan, Hubei, China.
METHODS: A total of 109 patients with ALS and their caregivers were included.
METHODS: Patients with ALS were screened using the Edinburgh Cognitive and Behavioural Screen, Beck Depression Inventory-II, Generalised Anxiety Disorder-7 and Apathy Scale to assess their cognition, depression, anxiety and apathy, respectively. The primary caregivers completed the Zarit Burden Interview. The association between apathy, cognitive impairment, depression, anxiety and caregiver burden was analysed using logistic regression. Mediation models were employed to investigate the mediating effect of patients\' apathy on the relationship between depression/anxiety and caregiver burden.
RESULTS: Patients in the high caregiver burden group exhibited significantly higher levels of depression, anxiety and apathy compared with those in the low caregiver burden group (p<0.05). There was a positive association observed between caregiver burden and disease course (rs=0.198, p<0.05), depression (rs=0.189, p<0.05), anxiety (rs=0.257, p<0.05) and apathy (rs=0.388, p<0.05). There was a negative association between caregiver burden and the Revised ALS Functional Rating Scale (rs=-0.275, p<0.05). Apathy was an independent risk factor for higher caregiver burden (OR 1.121, 95% CI 1.041 to 1.206, p<0.05). Apathy fully mediated the relationship between depression and caregiver burden (β=0.35, 95% CI 0.16 to 0.54, p<0.05) while partially mediating the relationship between anxiety and caregiver burden (β=0.34, 95% CI 0.16 to 0.52, p<0.05).
CONCLUSIONS: Apathy, depression and anxiety exerted a detrimental impact on caregiver burden in individuals with ALS. Apathy played a mediating role in the relationship between depression and caregiver burden and between anxiety and caregiver burden. These findings underscore the importance of identifying apathy and developing interventions for its management within the context of ALS.

Neuropsychiatric symptoms (including anxiety, depression, apathy, impulse-compulsive behaviors and hallucinations) are among the most common non-motor features of Parkinson\'s disease. Whether these symptoms should be considered as a direct consequence of the pathophysiologic mechanisms of Parkinson\'s disease is controversial. Morphometric similarity network analysis and epicenter mapping approach were performed on T1-weighted images of 505 patients with Parkinson\'s disease and 167 age- and sex-matched healthy participants from Parkinson\'s Progression Markers Initiative database to reveal the commonalities and specificities of distinct neuropsychiatric symptoms. Abnormal cortical co-alteration pattern in patients with neuropsychiatric symptoms was in somatomotor, vision and frontoparietal regions, with epicenters in somatomotor regions. Apathy, impulse-compulsive behaviors and hallucinations shares structural abnormalities in somatomotor and vision regions, with epicenters in somatomotor regions. In contrast, the cortical abnormalities and epicenters of anxiety and depression were prominent in the default mode network regions. By embedding each symptom within their co-alteration space, we observed a cluster composed of apathy, impulse-compulsive behaviors and hallucinations, while anxiety and depression remained separate. Our findings indicate different structural mechanisms underlie the occurrence and progression of different neuropsychiatric symptoms. Based upon these results, we propose that apathy, impulse-compulsive behaviors and hallucinations are directly related to damage of motor circuit, while anxiety and depression may be the combination effects of primary pathophysiology of Parkinson\'s disease and psychosocial causes.

BACKGROUND: In long-term care facilities (LTCF), apathy is a prevalent issue, leading to cognitive decline, functional impairment, and increased mortality risk. Despite its significance, apathy often remains underrecognized and undermanaged in these settings. Recognizing and addressing the predictors of apathy is critical for early intervention and improved care outcomes.
OBJECTIVE: This study aims to assess the prevalence of apathy and identify its associated risk factors among newly admitted residents in the Canadian LTCF, using the InterRAI Minimum Data Set (MDS 2.0).
METHODS: We conducted a cross-sectional analysis of MDS 2.0 admission assessment data between 2015 and 2019, covering 157,596 residents across six Canadian provinces and one territory. Apathy was measured using the Apathy Index of the MDS 2.0, with the biopsychosocial model guiding the analysis.
RESULTS: The prevalence of apathy was 12.5% (19,758 individuals). The most significant predictors include cognitive impairments, specific age groups, hearing impairments, vision impairments, facility size and location.
CONCLUSIONS: The findings of this study underscore the need for tailored strategies in LTCF to address apathy, considering individual, institutional, and regional variations. Emphasis on environmental and personal factors is crucial in the management and prevention of apathy in these settings.

BACKGROUND: While 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.
METHODS: In 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.
RESULTS: Mixed 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).
CONCLUSIONS: The 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.

UNASSIGNED: Parkinson\'s disease (PD) is associated with both sleep disturbances and apathy, and within PD, apathy has been associated with REM behavior disorder and excessive daytime sleepiness. Whether other forms of sleep disturbance are similarly associated with apathy in PD remains unclear. This study explored associations between a broad array of sleep disturbances and apathy in 50 individuals with idiopathic PD (PD) and 48 matched controls (MC).
UNASSIGNED: Participants were adults aged 53-80 (Mdn = 67), 23 % female, and 96 % white. Sleep disturbances were measured with various questionnaires (ISI, PSQI, PROMIS-SD, ESS, PROMIS-SRI, RBDSQ). Mood was measured with the STAI and BDI-II. Apathy was evaluated using the Apathy Scale (AS). Spearman correlations and regression analyses were performed between measures of sleep disturbance and AS in the total sample and each group. Group correlations were compared using 2-sample Fisher\'s z test.
UNASSIGNED: The AS total score significantly correlated with PROMIS-SRI in the total sample and multiple measures of sleep disturbance in the PD group. The apathy subscales were each significantly correlated with sleep disturbance measures in the total sample, MC, and PD groups. The correlations between several sleep and apathy values were significantly stronger in the PD group than MC. When accounting for anxiety and depression most differences were no longer significant, only the PROMIS-SRI was significantly predictive of the behavioral apathy sub score.
UNASSIGNED: Evidence supports an association between sleep disturbances and apathy in individuals with PD. Specifically, insomnia severity, poor sleep quality, and daytime sleepiness were uniquely associated with apathy in this group. We did not find these associations in the matched control group. Anxiety and depression are likely involved in the association between sleep and apathy in PD. Experimental studies that manipulate or improve sleep may further elucidate the mechanisms underlying the association between sleep disturbance and apathy in PD.

UNASSIGNED: This study aimed to evaluate the effects of a multicomponent psychotherapy programme for people with mild Alzheimer\'s dementia (AD) and their caregivers on depression and related neuropsychiatric symptoms.
UNASSIGNED: The cognitive behavioural therapy (CBT)-based treatment consisted of 25 weekly sessions, including behavioural activation, behaviour management, interventions for the caregiver, reminiscence, couples counselling, and cognitive restructuring. 41 participants and their caregivers were randomised to either the CBT or the control group, which received treatment-as-usual (TAU). Follow-ups took place at 6 and 12 months posttreatment. The primary outcome was depression in the patient with AD. The secondary outcomes were apathy, other neuropsychiatric symptoms, functional abilities, quality of life, and quality of the relationship with the caregiver.
UNASSIGNED: Linear mixed models revealed a statistically significant superiority of CBT regarding clinician-rated depression at the 12-month follow-up with large effect sizes (within-subject d = 1.22, between-subject d = 1.00). Effect sizes were only moderate for self-rated depression and small for informant-rated depression. There was also a significant advantage for CBT regarding clinician-rated apathy, relationship quality, and informant-rated quality of life (QoL) but not for the other neuropsychiatric symptoms or self-rated QoL.
UNASSIGNED: The results are very encouraging and support an adequately powered multicentre study.
Trial registration: ClinicalTrials.gov NCT01273272. Date of registration: 3 Jan 2011.

UNASSIGNED: Apathy is a frequent and debilitating condition among subarachnoid hemorrhage (SAH) survivors. Few studies have evaluated apathy in SAH, and none have examined the course of the condition, predictors of persistent apathy, or its impact on functional outcomes. The proposed study will examine, for the first time, the 12-month course of apathy and its impact on functional outcomes in the largest cohort of SAH survivors to date.
UNASSIGNED: The current study is designed as a prospective cohort study with a duration of 36 months. We will recruit 240 participants. A trained research assistant will assess apathy using the Apathy Evaluation Scale 3 months after SAH. Patients\' level of functioning, comorbidity, global cognitive functioning, and depressive symptoms will be assessed. All SAH patients will participate in follow-up assessments of apathy and functioning at 9 (T2) and 15 months (T3) post-SAH or at 6 and 12 months after the first assessment. Predictors of persistent apathy and the impact of apathy on functional outcomes will be examined.
UNASSIGNED: This will be the first large-scale 1-year follow-up study of apathy in SAH survivors. The findings will provide valuable data to advance our understanding of the clinical course of apathy in this population. Moreover, the results will have clinical relevance by providing essential information to patients, caregivers, and clinicians; promoting the evaluation of apathy; and facilitating the development of prevention strategies, rehabilitation programs, and therapeutic options.
UNASSIGNED: Ethical approval for this study was obtained from the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (CREC Ref. No.: 2023.339) on 3 October 2023. The findings of this study will be shared through publication in a peer-reviewed journal, presentations at relevant conferences, and dissemination through social media platforms.

OBJECTIVE: Alzheimer\'s disease is a progressive neurodegenerative disorder characterized by cognitive decline, behavioral changes, and functional impairments. Apathy, a common symptom in Alzheimer\'s disease, refers to a lack of motivation, interest, and emotional responsiveness. It can significantly impact patients\' quality of life and increase caregiver burden. This study aimed to determine the effects of a diversified rehabilitation program combined with donepezil on apathy, cognitive function, and family caregiver burden of Alzheimer\'s disease patients.
METHODS: A total of 105 Alzheimer\'s disease patients treated at our hospital between January 2020 and January 2023 were selected and analyzed retrospectively. They were assigned to the control group (n = 50) or the observation group (n = 55). The two groups did not differ in terms of general data such as age and sex. All patients were treated with donepezil orally. The control group was given routine nursing, whereas the observation group was given a diversified rehabilitation program intervention, including cognitive training and emotional support. The Hasegawa\'s dementia scale, mini-mental state examination, and Montreal cognitive assessment scale were adopted to evaluate the cognitive function of the two groups before and after treatment. A caregiver burden scale, the Zarit Burden Interview (ZBI) and the Apathy Evaluation Scale Informant version (AES-I) were used to evaluate the caregiver burden and apathy of the two groups.
RESULTS: A significantly higher overall response rate to treatment was found in the observation group (94.55%) than in the control group (80.00%) (p = 0.024). After treatment, scores on the Hasegawa\'s dementia scale, mini-mental state examination, and Montreal cognitive assessment scale of the two groups increased to varying degrees, with greater increases in the observation group than in the control group (p < 0.05). The ZBI and AES-I scores of the two groups decreased to different degrees after treatment, with greater decreases in the observation group than in the control group (p < 0.05).
CONCLUSIONS: A diversified rehabilitation program combined with donepezil can substantially alleviate the apathy of Alzheimer\'s disease patients, improve their cognitive function, and reduce the burden on their families.

BACKGROUND: Apathy, defined as a lack of motivation towards goal-directed behavior, is a common neuropsychiatric symptom in Alzheimer\'s (AD) and Parkinson\'s (PD) disease. However, the mechanism underlying apathy is still unclear. Studies have postulated that the degeneration of frontal cortical and subcortical structures may play a major role in the mechanism of apathy. This study investigates whether associations between degeneration in structural and functional connectivity between frontal and subcortical regions contributes to the development of apathetic behavior and whether these associations differ by diseases.
METHODS: Forty-four patients, 8 with AD, 14 amnestic mild cognitive impairment (aMCI), and 22 PD, received MRI brain scans, a decision-making behavioral task, cognitive and psychosocial assessments including the dimensional apathy scale (DAS). We quantified functional connectivity and white matter tract integrity for a set of frontal and subcortical regions of interest, and examined the associations among fronto-subcortical connectivity, behavioral measures, and the DAS. These associations were tested for patient group interactions.
RESULTS: Combining AD and aMCI into one patient group, the AD/aMCI group showed worse apathy than PD in terms of the total, the executive, and the behavioral/cognitive subscores (see Table 1), while the DAS emotional subscore was not different between the two groups. For the decision-making task, the proportion of trial acceptance was similar between the groups, but AD/aMCI had slower decision latency than PD. Group interaction with brain measures was observed in the association between DAS total score and the functional connectivity between the right pars triangularis in the inferior frontal gyrus and the caudate (See Figure 1; interaction effect: beta = -.367, p = .0422 FDR corrected). The white matter tract connecting the right pars triangularis to subcortical regions also showed a group interaction with DAS total score but at an uncorrected statistical level (Figure 2; beta = 3.61, p = .0454, uncorrected).
CONCLUSIONS: Our preliminary analyses exposed phenotypic differences in apathy profiles and decision-making behavior between AD and PD. Furthermore, the observed functional and structural neurodegenerative changes associated with higher apathy severity may also differ between the two diseases. Future analyses in a larger cohort will examine distinct neurodegeneration patterns between the two diseases.