Apathy In Patients Research Articles

Relationship between psychiatric symptoms and activities of daily living in patients undergoing hemodialysis

BackgroundAccurately identifying the factors contributing to decline in activities of daily living (ADL) is important for preventing such decline in patients undergoing hemodialysis (HD). We studied the prevalence and number of overlapping psychiatric symptoms (depressive symptoms, apathy, and sleep disturbance) in patients undergoing HD and examined the relationship between psychiatric symptoms and ADL.MethodsThe study utilized a cross-sectional research design. The sample included 203 outpatients (median age: 69 years) undergoing stable HD treatment three times a week. Patient characteristics, including age, sex, body composition, dialysis vintage, primary kidney disease, comorbidity, and nutritional status, were collected from patients’ medical records. Functional status was assessed based on the self-reported questionnaire that combined five basic and eight instrumental ADL items. Usual walking speed was used as an index of physical function. Additionally, the short version of the Center for Epidemiologic Studies Depression Scale was used to assess depressive symptoms. Further, apathy and sleep disturbance were assessed using the Motivation Score and the Athens Insomnia Scale, respectively.ResultsOverall, 59 (29.1%) patients demonstrated depressive symptoms, 100 (49.3%) reported apathy, 83 (40.9%) had sleep disturbance, 31 (15.3%) had three overlapping psychiatric symptoms, 43 (21.2%) had two overlapping psychiatric symptoms, 63 (31.0%) had only one symptom, and 66 (32.5%) had no psychiatric symptoms. Multiple logistic regression analysis showed that having two or three overlapping psychiatric symptoms was independently and significantly associated with ADL (functional status of 13 points for the ADL maintenance group, and of < 13 points for the ADL decline group, respectively), even after adjusting for patient characteristics and walking speed (odds ratio: 2.74, 95% confidence interval: 1.12–6.69, reference; no psychiatric symptoms).ConclusionThe present study clarified that the overlapping symptoms, including depressive symptoms, apathy, and sleep disturbance, were independently associated with ADL decline in patients undergoing HD. It is useful to examine not only depressive symptoms but also other symptoms such as apathy and sleep disturbance to elucidate factors associated with deteriorated ADL in chronic patients. Our findings provide a strong basis for targeted interventions to prevent functional dependence in the HD population.

Detecting apathy in patients with cerebral small vessel disease.

BackgroundApathy is attracting more and more attention in clinical practice. As one of the most common features of cerebral small vessel disease (CSVD), the assessment of apathy still mainly relies on observers. With the development of Information and Communication Technologies (ICTs), new objective tools take part in the early detection of apathy.ObjectivesTo detect apathy in patients with CSVD and find out the relationship between apathy and actigraphic data sampled from the diurnal and nocturnal periods.MethodsA total of 56 patients with CSVD were recruited for a cross-sectional observational study. Apathy was diagnosed by the diagnostic criteria for apathy in neurocognitive disorders. The presence of lacunes, white matter hyperintensities, cerebral microbleeds (CMBs), and perivascular spaces (PVS) in magnetic resonance imaging (MRI) images were rated independently. Actigraph devices were worn in the non-dominant hands of each subject for 7 consecutive days to collect samples of raw data, and diurnal vector magnitude (VM) and a series of sleep quality variables were obtained.ResultsWe found that the frequency of apathy in Chinese patients with CSVD reached 37.50%. Patients in the Apathy+ group showed more lacunes and CMBs, and higher Fazekas scores in comparison to apathy-group individuals. Diurnal VM, instead of other sleep quality variables, was lower in CSVD patients with apathy relative to those without apathy. Lastly, we discovered that diurnal VM and total time in bed (TTB) correlated negatively with apathy severity in patients with CSVD.ConclusionActigraphy is a promising choice to evaluate apathy in patients with CSVD.

Olfaction and apathy in early idiopathic Parkinson's disease

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

A longitudinal study on the effects of COVID-19 pandemic on non-motor symptoms in Parkinson’s disease

IntroductionThe COVID-19 pandemic led to psychological consequences on people’s mental health, representing a condition of increased vulnerability for the weakest sections of population, including elderly patients with Parkinson’s disease (PD).This longitudinal study aimed at exploring the impact of the most frequent non-motor symptoms and their contribute on health-related quality of life of PD patients after the COVID-19 outbreak, in comparison with the pre-pandemic status.MethodsForty-two non-demented PD patients underwent a first assessment between December 2018 and January 2020 (T0). Then, between March and May 2021 (T1), they were contacted again and asked to complete the second assessment. Levels of global functioning, several non-motor symptoms (i.e. depression, apathy, anxiety, anhedonia) and health-related quality of life were investigated.ResultsResults of the the paired Wilcoxon signed-rank test showed that at T1, PD patients scored lower on the emotional subscale of the DAS, Z = − 2.49; p = 0.013; Cohen dz = 0.691. Higher scores of the TEPS total score, Z = − 2.38; p = 0.025; Cohen dz = 0.621, and LEDD, Z = − 2.63; p = 0.008; Cohen dz = 0.731, were also reported at T1.ConclusionThe present study suggested that self-isolation at home might lead to a reduction of apathy and anhedonia in PD patients due to the increase in social support provided by families during COVID-19 restrictions. This evidence brings out the need of a consistent and persistent social support which might be represented by caregivers or/and social assistive robotics.

Post-stroke apathy: A case series investigation of neuropsychological and lesion characteristics

Apathy is a multi-dimensional syndrome associated with reduced initiation, executive function and emotion toward goal-directed behaviour. Affecting ∼30% of stroke patients, apathy can negatively impact rehabilitation outcomes and increase caregiver burden. However, relatively little is known about the multi-dimensional nature of post-stroke apathy and whether these dimensions map onto neuropsychological and neuroanatomical correlates. The present study aimed to address this question in a case series of stroke patients with apathy. 65 patients with acute stroke were assessed on a comprehensive battery of neuropsychological tasks and 12 patients were identified as having clinically significant apathy on one or more domains on the Dimensional Apathy Scale. Individual scores were compared to a group of healthy controls and normative data where available. Lesion mapping was completed from clinical CT and MRI scans to characterise the extent and locations of each patient's lesion. All participants performed significantly poorer than controls on one or more tasks. Difficulties with inhibition were observed across all dimensions. Prospective memory deficits were also common, while speed and social cognition were only reduced in initiation and emotional apathy, respectively. Verbal fluency was not impaired in any of the patients, despite previously established relationships with apathy. Lesions were predominantly located in right subcortical regions, with some additional frontal, temporal and cerebellar/brainstem involvement. There was substantial overlap in lesion locations within and between dimensions, such that similar apathy symptoms occurred in patients with very different lesion sites. Overall, our results suggest that neuropsychological and lesion profiles of apathy in stroke patients may be more complex and heterogenous than in neurodegenerative disease, possibly due to functional changes occurring beyond the lesion site.

Multi-site rTMS with cognitive training improves apathy in the long term in Alzheimer’s disease: A 4-year chart review

ObjectiveTo assess the long-term effects of multi-site repetitive transcranial magnetic stimulation combined with cognitive training (NeuroAD procedure) on cognitive symptoms and apathy in patients with Alzheimer's disease (AD) as part of a 4-year chart review. MethodsThe study included the 30 AD patients who underwent NeuroAD treatment between 2015 and 2019 at our center. The clinical evaluation was based on the Mini Mental State Examination (MMSE), Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and Apathy Inventory (AI). Assessment was performed before treatment (baseline), after an initial 6-week protocol of 30 sessions (M1.5), then 3 months (M3), 1 year (M12), and between 1.5 and 4 years (mean 28 months, M28) after treatment initiation. ResultsDuring the first year of follow-up, the AI score improved at all time points (M1.5, M3, M12, p < 0.0001), the ADAS-Cog score improved at the end of the initial procedure (M1.5, p = 0.003) then deteriorated (M12, p = 0.01), while the MMSE score did not change. At final assessment (M28), the AI score was still improved from baseline (p < 0.0001), while the MMSE and ADAS-Cog scores worsened (p < 0.0001). Regarding the ADAS-Cog score, the prolonged improvement at M12 or M28 was correlated with the initial improvement at M1.5. ConclusionThe NeuroAD procedure produced long-term improvement in apathy and more general cognitive improvement only in patients who responded well to the initial 6-week protocol. SignificanceOur results suggest long-term beneficial effects of the NeuroAD procedure on apathy, which need to be confirmed in controlled studies. The criteria for predicting a good outcome before starting the procedure remain to be defined.

Improving Mood and Cognitive Symptoms in Huntington's Disease With Cariprazine Treatment.

In Huntington's disease (HD), the main clinical symptoms include depression, apathy, cognitive deficits, motor deficiencies and involuntary movements. Cognitive, mood and behavioral changes may precede motor symptoms by up to 15 years. The treatment of these diverse symptoms is challenging. Tetrabenazine and deutetrabenazine are the only medications specifically approved for Huntington's chorea, but they do not affect the non-motor symptoms. For these, antidepressants, antipsychotics, and benzodiazepines have demonstrated benefit in some cases and can be used off-label. These drugs, due to sedative side effects, may negatively influence cognition. Sixteen patients having HD received a 12-week off-label cariprazine (CAR) treatment (1.5–3 mg/day). Cognitive performance and behavioral changes were measured by the Addenbrooke Cognitive Examination (ACE) test, the Cognitive and Behavioral part of the Unified Huntington's Disease Rating Scale (UHDRS), and the Beck Depression Inventory (BDI). Mixed model for repeated measures was fitted to the data, with terms of visit, baseline (BL) and their interaction. Cariprazine treatment resulted in the following changes from BL to week 12, respectively: the mean score of BDI decreased from 17.7 ± 10.7 to 10.0 ± 10.7 (p <0.0097), while the Behavioral Assessment score of the UHDRS decreased from 54.9 ± 11.3 to 32.5 ± 15.4 (p < 0.0001); ACE score increased from 75.1 ± 11.0 to 89.0 ± 9.3 (p < 0.0001); Cognitive Verbal Fluency score from 6.2 ± 2.5 to 7.7 ± 2.7 (p < 0.0103); Symbol Digit Test from 9.2 ± 6.9 to 12.3 ± 8.9 (p < 0.0009). Mild akathisia was the most frequent side effect, presenting in 2 out of 16 patients (12.5%). We conclude that CAR had a positive effect on depressive mood, apathy and cognitive functions in patients with early stage of HD. Based on the neurobiological basis of these symptoms, CAR can improve the dopamine imbalance of the prefrontal cortex. This draws attention to the transdiagnostic approach which supports the further understanding of the similar symptomatology of different neuropsychiatric disorders and helps to identify new indications of pharmaceutical compounds.

The Effects of Safinamide Adjunct Therapy on Depression and Apathy in Patients With Parkinson's Disease: Post-hoc Analysis of a Japanese Phase 2/3 Study.

Background and PurposeNeuropsychiatric symptoms in Parkinson's disease (PD) have been shown to significantly affect quality of life (QOL). We investigated the impact of safinamide on depression and apathy when administered as an adjunct to levodopa in Japanese patients with PD.MethodsThis was a post-hoc analysis of data from a phase 2/3 clinical study of safinamide in Japanese patients with PD experiencing wearing-off (JapicCTI-153056; https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?japicId=JapicCTI-153056). Patients received placebo, safinamide 50 mg, or safinamide 100 mg as an adjunct therapy. The endpoints for this analysis were changes from baseline to Week 24 in the Unified Parkinson's Disease Rating Scale (UPDRS) Part I item 3 (depression) and item 4 (apathy) scores and the Parkinson's Disease Questionnaire (PDQ-39) “emotional well-being” domain score. Subgroup analyses investigated the relationship between neuropsychologic symptoms and improvements in motor fluctuation and assessed which patient populations might be expected to obtain neuropsychologic benefit from safinamide.ResultsCompared with placebo, safinamide (both doses) significantly improved UPDRS Part I item 3 scores in the overall analysis population, and the 100-mg dose improved UPDRS Part I item 4 scores in the population with apathy at baseline. Changes in the PDQ-39 “emotional well-being” score showed numerical, but not significant, dose-related improvements. Notable reductions in depression were associated with a change in daily ON-time ≥1 h, pain during OFF-time at baseline, and female sex.ConclusionsThe results from this post-hoc analysis of the Japanese phase 2/3 study suggest that safinamide could bring benefits to patients with PD who have mild depression, pain during the OFF phase. In addition, safinamide might provide particular benefits for patients with PD who have mild apathy and female.

Methylphenidate and Other Pharmacologic Treatments for Apathy in Alzheimer's Disease.

Apathy is a common and important yet often ignored neuropsychiatric symptom of Alzheimer's disease (AD). Cholinesterase inhibitors and memantine, used to treat AD, appear ineffective against apathy. A meta-analysis of 4 randomized, placebo-controlled trials (RCTs) found that psychostimulants significantly attenuated apathy ratings in AD. However, the pooled sample size in this meta-analysis was just 156, and one of the trials was a 2-week crossover study with a large effect. A large RCT (n = 200) has now been published. This study found that methylphenidate (MPH; 20 mg/d) was superior to placebo in the attenuation of apathy scores in patients with possible or probable, mild to moderate AD; the advantage was evident by the end of the second month of treatment and remained evident to the end of 6 months. The effect size at 6 months was small (Cohen d = 0.37). In this RCT, disappointingly, MPH was not superior to placebo on secondary outcomes, including informant-rated apathy, dependence, activities of daily living, quality of life, and neurocognitive performance; caregiver burden was not formally studied. Speculatively, the psychosocial intervention provided to all participants in this RCT may have boosted response in the placebo group, thereby attenuating differences in outcomes between the MPH and placebo groups. A reasonable conclusion is that whereas MPH may attenuate the severity of apathy in patients with AD across as long as 6 months, the absence of improvements in measures of dependence, activities of daily living, and quality of life suggest that this effect of MPH on apathy may not be clinically significant. An unanswered question is whether the benefits of MPH may be clinically significant in real world practice settings in which the delivery of behavioral interventions is not feasible.

Fatigue and apathy in patients on chronic hemodialysis.

This study explores the link between fatigue and apathy in patients on chronic hemodialysis (HD). One hundred thirty-nine chronic HD patients underwent the assessment of fatigue, apathy, depression, and their functional status, with the fatigue severity scale (FSS), the Apathy Evaluation Scale (AES), the beck depression inventory (BDI), the activity of daily living (ADL), and instrumental activity of daily living (IADL). Patients with high FSS had a significantly lower ADL and IADL score, higher BDI, Charlson Comorbidity Index, and AES score, and lower serum levels of creatinine, compared to low FSS patients. FSS was highly correlated with the AES, as well as with the BDI and the AES correlates with the BDI. At multiple regression analyses, only apathy and IADL were independent predictor variables of fatigue in HD population. Future longitudinal studies could determine if apathy is a causative factor for fatigue manifestation and development in HD patients.

Validation of a European Spanish adaptation of the Apathy Evaluation Scale-self-rated version (AES-S) in patients with schizophrenia

IntroductionApathy is a negative symptom of schizophrenia and is associated with poor real world functioning. Therefore, it is important to have validated psychometric instruments to assess this symptom. This is the first study to validate the Spanish adaptation of the self-rated version of the Apathy Assessment Scale (AES-S) in patients with schizophrenia. Materials and methodsNaturalistic, cross-sectional, validation study in 104 patients with schizophrenia evaluated using the following scales: Clinical Global Impression-Severity (CGI-S), Personal and Social Performance (PSP), Clinical Assessment Interview for Negative Symptoms (CAINS), Self-report of Negative Symptoms (SNS), Motivation and Pleasure Scale-Self-Report (MAP-SR), Calgary Depression Scale for Schizophrenia (CDSS), and Apathy Evaluation Scale-self-rated version (AES-S). ResultsReliability: Internal consistency (Cronbach's alpha) was 0.908. Convergent validity: The Pearson correlation coefficient between AES-S and CAINS-MAP total scores was −0.483 (p<0.001). For SNS, total and avolition subscale scores were −0.803 and −0.639 (p<0.001), respectively. With the MAP-SR, the correlation coefficient was −0.727 (p<0.001). Divergent validity: The Pearson correlation coefficient between AES-S and PSP total scores was 0.504 (p<0.001). Furthermore, with the CDSS, the correlation coefficient was −0.431 (p<0.001). Discriminant validity: The AES-S discriminated between different levels of illness severity according to CGI-S scores. Factor analysis: A three-component solution explained 57.32% of the variance. Pearson correlations between coefficients were 1–2=0.265, 1–3=0.464, and 2–3=0.060. ConclusionThe Spanish AES-S is a reliable and valid instrument for assessing apathy in Spanish patients with schizophrenia. It seems to be appropriate for use in everyday clinical practice as a means of monitoring apathy in these patients.

Methylphenidate improves severity of apathy in patients with Alzheimer's disease

Methylphenidate at a dose of 20 mg/day reduced symptoms of apathy compared with placebo in a 6‐month Phase 3 trial of patients with Alzheimer's disease. The largest change in apathy scores occurred in the first 2 months of treatment.

7T locus coeruleus imaging correlates of apathy and cognition in patients with Parkinson’s disease and progressive supranuclear palsy

AbstractBackgroundApathy is a common neuropsychiatric feature of both Parkinson’s disease and progressive supranuclear palsy (PSP) (Aarsland, et al., 2001). Early neuropathology in the locus coeruleus (LC) and consequent noradrenergic deficiency are proposed to be key contributors to the pathogenesis of apathy (Passamonti et al., 2018). Here we test the hypothesis that in vivo LC integrity measured by ultra‐high field 7T‐MRI is predictive of apathy in Parkinson’s disease and PSP.MethodSixty‐three participants aged 50‐80 years were recruited: 25 people with idiopathic Parkinson’s disease, 14 patients with PSP Richardson’s syndrome and 24 age‐ and sex‐matched healthy controls (HC). Patients underwent clinical assessments for apathy, impulsivity, global cognition, motor severity, mood and sleep (Figure 2A&amp;B). The LC was measured in vivo using a sensitive magnetisation transfer (MT) weighted sequence with ultra‐high 7T‐MRI (0.1mm3 voxels). The contrast‐to‐noise ratio of an atlas‐based signal was used to estimate the LC structural integrity (Ye et al., 2021). The LC integrity was correlated with clinical assessments. To estimate the spatial extent of the correlation within LC, voxelwise analyses used FSL randomise for localising the group differences and the clinical correlations.ResultReduced LC integrity was observed along the rostrocaudal axis for both PD and PSP patients, most prominently in the caudal subregion (Figure 1A‐D). This was confirmed by significant voxelwise comparisons between the patient groups and controls (HC&gt;PD, right caudal LC, 37 voxels; HC&gt;PSP, bilateral caudal LC, 206 voxels; FWE‐corrected p&lt;0.05), Figures 1E&amp;F. Patients with PSP and PD showed similar levels of LC degeneration relative to controls, but this was more spatially widespread in PSP. The variability of LC integrity in both disease groups was associated with ACER, MoCA and apathy (Figure 2C&amp;D). Distinctive spatial patterns were identified for the correlations, with the caudal LC consistently associated with cognitive impairment and apathy.ConclusionReduced LC integrity was confirmed in both PD and PSP using in vivo 7T‐MRI. LC degeneration, particularly in the caudal subregion, was associated with apathy and cognitive impairment. Our results suggest, noradrenergic therapies may be beneficial in targeting cognitive and behavioural features of Parkinson’s disease and PSP.

Associations between apathy and fatigue in patients with neurocognitive disorders

AbstractBackgroundApathy and fatigue are two disabling symptoms of neurocognitive disorders causing a reduction of activity in daily functioning, including in motor activity, and contributing to loss of autonomy. Fatigability is characterized by a reduction in the ability to produce a motor work during a physical task and is a central element in the circle of deconditioning because many activities of daily living require the ability to exert effort over an extended period of time. This study aims to explore the fatigability of apathetic and non‐apathetic patients with neurocognitive disorders (ND).Method20 subjects (out of 40 still to include) with mild to major ND (age= 78,0 ± 6,3y, MMSE= 26,0±2,3) were classified as apathetic (n=10, BMI= 25 ± 2,5) vs non‐apathetic (n=10, BMI= 25 ± 4,5) based on the apathy diagnostic criteria[1]. Subjects performed a 6 minutes walk test, a handgrip test with a sustained maximal isometric contraction for 15 seconds, and a sit to stand task until exhaustion surrounded by a maximal voluntary contraction of extensors knee.ResultPreliminary results showed a significant greater decrease of performance in apathetic patients during the handgrip sustained maximal isometric test (p=0,028). On the 6 minutes walk test and the sit to stand task, no significant differences of fatigability index were found between two groups.ConclusionThe greater decrease of performance during the handgrip test suggests a higher fatigability in apathetic ND patients. This is not yet confirmed by the two other tasks, probably due to the small sample size. As data collection for the study will finish in June 2021, I will present at the conference more reliable results. Reference: [1] Robert P, Lanctôt KL, Agüera‐Ortiz L, et al. Is it time to revise the diagnostic criteria for apathy in brain disorders? The 2018 international consensus group. Eur Psychiatry. 2018;54:71‐76.

The Relation between Behavioral, Emotional and Cognitive Apathy and Everyday Executive Dysfunction in Alcoholic Korsakoff’s Syndrome

ABSTRACT Background: Apathy is an important neuropsychiatric symptom in alcohol-related cognitive impairment in general, and Korsakoff’s syndrome in specific. However, research in patients with Korsakoff’s syndrome on the multifaceted nature of apathy is lacking. Objectives: Aim of the current study was to examine behavioral, cognitive and emotional apathy in alcoholic Korsakoff patients, also investigating the association with overall cognitive and executive dysfunction. Methods: We studied 43 patients with Korsakoff’s syndrome (mean age 60.9, SD=6.5, range 38-70) using the Apathy Evaluation Scale - Informant Version (AES-I) and also administered the Montreal Cognitive Assessment and the Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) as a measure of daily executive problems. Results: In our sample, 76% of the Korsakoff patients were classified as being apathetic. AES-I scores correlated with overall cognitive function and were related to observer-rated daily executive problems. Discussion: Apathy is highly prevalent in Korsakoff patients and related to overall cognitive dysfunction and everyday executive problems. Our results stress the need to further examine underlying mechanisms of apathy in Korsakoff patients and the need for interventions aimed at reducing apathy.

Effect of Methylphenidate on Apathy in Patients With Alzheimer Disease

Apathy, characterized by diminished will or initiative and one of the most prevalent neuropsychiatric symptoms in individuals with Alzheimer disease, is associated with significant caregiver burden, excess disability, increased medical costs, and mortality. To measure whether methylphenidate compared with placebo decreases the severity of apathy in individuals with Alzheimer disease. This multicenter randomized placebo-controlled clinical trial was conducted from August 2016 to July 2020 in 9 US clinics and 1 Canadian clinic specializing in dementia care. A total of 307 potential participants were screened. Of those, 52 did not pass screening and 55 were not eligible. Participants with Alzheimer disease, mild to moderate cognitive impairment, and frequent and/or severe apathy as measured by the Neuropsychiatric Inventory (NPI) were included. Ten milligrams of methylphenidate, twice daily, vs matching placebo. The coprimary outcomes included (1) change from baseline to 6 months in the NPI apathy subscale or (2) improved rating on the Alzheimer's Disease Cooperative Study Clinical Global Impression of Change. Other outcomes include safety, change in cognition, and quality of life. Of 200 participants, 99 were assigned to methylphenidate and 101 to placebo. The median (interquartile range) age of study participants was 76 (71-81) years; 68 (34%) were female and 131 (66%) were male. A larger decrease was found from baseline to 6 months in the NPI apathy score in those receiving methylphenidate compared with placebo (mean difference, -1.25; 95% CI, -2.03 to -0.47; P = .002). The largest decrease in the NPI apathy score was observed in the first 100 days, with a significant hazard ratio for the proportion of participants with no apathy symptoms receiving methylphenidate compared with placebo (hazard ratio, 2.16; 95% CI, 1.19-3.91; P = .01). At 6 months, the odds ratio of having an improved rating on the Alzheimer's Disease Cooperative Study Clinical Global Impression of Change for methylphenidate compared with placebo was 1.90 (95% CI, 0.95-3.84; P = .07). The difference in mean change from baseline to 6 months estimated using a longitudinal model was 1.43 (95% CI, 1.00-2.04; P = .048). Cognitive measures and quality of life were not significantly different between groups. Of the 17 serious adverse events that occurred during the study, none were related to the study drug. No significant differences in the safety profile were noted between treatment groups. This study found methylphenidate to be a safe and efficacious medication to use in the treatment of apathy in Alzheimer disease. ClinicalTrials.gov Identifier: NCT02346201.

Relationship between emotional apathy and motor symptoms, sleep and cognitive function in patients with early Parkinson's disease

Objective: To study the relationship between emotional apathy and motor symptoms, sleep, and cognitive function in patients with early Parkinson's disease (PD). Methods: One hundred and twenty-nine early PD patients who were treated in the Second Affiliated Hospital of Soochow University from June to October 2020 were included, including 82 male and 47 female patients. The emotional apathy was assessed by modified apathy rating scale (MAES). The above 129 patients were divided into 67 patients in the PD with emotional apathy group (MAES>14 points) and 62 patients in the PD without emotional apathy group (MAES≤ 14 points). Age, gender, course of disease and levodopa equivalent dose were also collected. Hoehn-Yahr stage and unified Parkinson's disease rating scale PartⅢ(UPDRS-Ⅲ), Pittsburgh Sleep Quality Index (PSQI), polysomnography, and Montreal Cognitive Assessment Scale (MoCA) were used to evaluate the motor symptoms, sleep and cognitive functions of patients with early PD, and the clinical characteristics of patients with early PD with apathywere determined. Results: Compared with PD patients without apathy, those with apathy had longer disease duration [M(Q1,Q3)][5.0 (3.0, 7.0) years vs 3.0 (2.0, 5.0) years, P=0.006] and severer motor symptoms [20.0 (10.0, 28.0) vs 14.0 (8.5, 23.0), P=0.047]. There was no significant difference in PSQI score between the two groups. Among the 33 patients who completed polysomnography, compared with PD patients without apathy (n=16), those with apathy (n=17) had a longer rapid eye movement (REM) sleep latency [150 (124, 184) min vs 87 (57, 133) min, P=0.035)] and more frequent periodic limb movements in the REM phase(P=0.042).The REM sleep ratio (r=0.373, P=0.042), apnea-hypopena index (AHI)(r=0.374, P=0.046) and oxygen deficit index (r=0.409, P=0.025) were positively correlated with the degree of apathy in PD patients. PD patients with apathy had relatively poorer performance in cognition assessment than those without apathy and total MoCA score was inversely correlated with the degree of apathy (r=-0.231, P=0.017). Conclusion: Early PD patients with apathy have objective sleep disorders dominated by REM sleep disorders, which can have a negative impact on cognitive function.

Assessment of apathy in neurological patients using the Apathy Motivation Index caregiver version

Apathy is a common, disabling neuropsychiatric syndrome that occurs across many brain disorders and may be associated with diminished motivation in behavioural, cognitive, emotional and social domains. Assessment is complicated by the variability of symptoms across apathy domains and self‐report from patients, which can be misleading due to their lack of insight. Independent evaluation by clinicians also has limitations though if it has to be performed with limited time. Caregiver reports are a viable alternative, but current assessments for them either do not distinguish between different apathy domains or are interview‐based and take long to administer. In this study, we developed a brief caregiver questionnaire version of the recently developed Apathy Motivation Index (AMI), which is a self‐report tool. We confirmed three apathy factors in this new caregiver measure (AMI‐CG) that were also present in the AMI: Behavioural Activation, Emotional Sensitivity and Social Motivation. Furthermore, we validated the scores against more extensive caregiver interviews using the established Lillle apathy rating scale as well as patient self‐reports of apathy, measures of depression, anhedonia, cognition, activities of daily living and caregiver burden across four different neurological conditions: Parkinson's disease, Alzheimer's disease, subjective cognitive impairment and limbic encephalitis. The AMI‐CG showed good internal reliability, external validity and diagnostic accuracy. It also uncovered cases of social apathy overlooked by traditional instruments. Crucially, patients who under‐rated their apathy compared to informants were more likely to have difficulties performing everyday activities and to be a greater burden to caregivers. The findings provide evidence for a multidimensional conceptualization of apathy and an instrument for efficient detection of apathy based on caregiver reports for use in clinical practice.

Diagnosis and Assessment of Apathy in Elderly Chinese Patients With Cerebral Small Vessel Disease.

Objective: The study aimed to estimate the frequency of apathy in Chinese patients with cerebral small vessel disease (CSVD) and investigate the relationship between apathy and neuroimaging markers of CSVD.Methods: A total of 150 CSVD aged patients were recruited for a cross-sectional observational study. Following the new revised version of diagnostic criteria for apathy (DCA), each patient was evaluated successively by the neuropsychiatric inventory (NPI-apathy), geriatric depression scale (GDS), and caregiver burden scale (CBS). The MRI presence of lacunes, white matter hyperintensities, cerebral microbleeds, and perivascular spaces were rated independently. Furthermore, presence of all these MRI markers were summed in a score of 0–4 representing all CSVD features combined.Results: According to the DCA, we found that the frequency of apathy in Chinese Alzheimer's disease patients reached 37.33%, with lack of and diminished goal-directed activities in the dimension of behavior/cognition. We did not find a close relationship between apathy and depression. Caregiver burden was positively correlated with apathy severity. Apathy, but not depression, was positively associated with total CSVD burden, rather than a separate MRI marker of CSVD.Conclusion: As a key component of neuropsychiatric symptoms, apathy was common in Chinese elderly with CSVD, more attention should be paid to apathy in clinical practice of CSVD.

White matter microstructural associates of apathy-avolition in schizophrenia

Apathy is present at the onset in nearly half the patients with schizophrenia. Current therapies lack the efficiency to improve apathy in patients. The presence of apathy is also associated with poorer outcomes. Despite its clinical importance, the underlying mechanism of apathy in schizophrenia is unclear, but it seems frontostriatal connections play a role. In this study, we investigated whole-brain white matter microstructural properties associated with the severity of apathy-avolition in schizophrenia. We included 80 schizophrenia patients (60 Male, 20 Female) from the Mind Clinical Imaging Consortium database and associated Apathy-Avolition score of “Scale for Assessment of Negative Symptoms” with fiber integrity measures derived from diffusion-weighted imaging using Tract-Based Spatial Statistics (TBSS). We also did tractography on eight tracts, including bilateral superior longitudinal fasciculus, uncinate fasciculus, cingulum, genu and splenium of the corpus callosum. Age, gender, years of education, chlorpromazine equivalent cumulative dose, and acquisition site were inserted as covariates. We showed a widespread association between lower fiber integrity (by measures of increased mean diffusivity and decreased fractional anisotropy) and increased apathy-avolition in TBSS, which we also validated in tractography. Moreover, mean diffusivity, and not fractional anisotropy, was associated with apathy independent of disease severity. In conclusion, we propose diffuse white-matter pathology, within the corpus callosum, limbic system, and the frontostriatal circuit is involved in apathy-avolition in schizophrenia. Also, we suggest that diffuse neuroinflammatory processes may play a part in apathy-avolition, independent of disease severity.