Apathy Scale Research Articles

Mood Disorders After COVID-19

Introduction. The COVID-19 pandemic has led to a high prevalence of post-COVID-19 syndrome (PCS), with mood disorders being the most common manifestations.
 Objective: To study the prevalence of PCS-associated mood disorders and their features.
 Materials and methods. We examined patients after COVID-19 (n = 91; age: 24-84 years; median time to recovery: 7 months) using the following tools: the BDI and HADS (screening for anxiety and depression); the Starkstein Apathy Scale; FIS and FSS (fatigue assessment); the MoCA, MMSE, and FAB (cognitive assessment); the FIRST, ESS, PSQI, and ISI (sleep disorders evaluation); the EQ5D (quality of life measurement). We designed a special questionnaire to collect data related to a history of COVID-19 and patients' condition after discharge. In addition, we analyzed electronic medical records and discharge summaries and performed neurological examination.
 Results. Of all the examined patients, 65 (71.4%) participants had signs and symptoms of PCS. Mood disorders were observed in 33 (50.8%) cases, with apathy (78.7%), anxiety (66.7%), and fatigue (60.6%) being the most common. Depressive disorders were found in 12 (36.3%) patients. Cognitive functions were impaired in 7 (21.2%) patients; sleep disorders were observed in 16 (48.5%) cases. We found a positive correlation between depressive disorders and fatigue based on the BDI, FIS, and FSS scores (rS = 0.711; rS = 0.453), depressive disorders and anxiety (rS = 0.366), fatigue and apathy (rS = 0.350). Anxiety increased the risk of sleep disorders (rS = 0.683). Quality of life has been shown to decrease in patients with mood disorders due to the negative effect of long-term fatigue and depressive disorders.
 Conclusions. There is a close connection between different types of mood disorders that develop after COVID-19 and exacerbate symptoms of each other. Early diagnosis and treatment of these disorders can improve patients' quality of life and preserve their ability to work.

The association of single-nucleotide polymorphism rs6265 of the brain-derived neurotrophic factor gene with clinical features in Parkinson's disease

To evaluate the frequency and severity of various clinical symptoms of Parkinson's disease (PD) depending on the BDNF rs6265 polymorphism. The study included 533 patients with PD. The stage of PD was assessed using the Hoehn and Yahr scale (1967), motor symptoms were evaluated with MDS-UPDRS. Assessment of non-motor symptoms (NMS) in PD was conducted using the Beck Depression Inventory II (BDI-II); the Hospital Anxiety and Depression Scale (HADS); the Apathy Scale; the Montreal Cognitive Assessment (MoCA test); the Questionnaire for Impulsive-Compulsive Disorders in PD -Rating Scale (QUIP-RS). Genotyping of the BDNF variant (rs6265) was performed using real-time PCR with TaqMan probes. Most PD patients have a combination of NMS increasing as the disease progresses and is determined by molecular-genetic individual characteristics. There are significant differences in the severity of motor symptoms and NMS: individuals with the AA genotype showed significantly pronounced motor symptoms (p<0.0001); emotional-affective symptoms (p<0.0001); cognitive and impulsive behavioral disorders (p<0.0001). The rs6265 BDNF allele A is associated with a wide range of NMS, increasing the risk of their development in patients with PD, thus playing the important role in the etiopathogenesis of this pathology.

Obrasci neuropsihijatrijskih simptoma u primarnim i sekundarnim tauopatijama iz ugla negovatelja i pacijenata

Introduction/Aims: Understanding the differences in neuropsychiatric symptoms (NPSs) across tauopathies, particularly in the early stages of the disease, may aid in differential diagnosis. The aims of the research are as follows: a) to examine the patterns of NPSs in primary (frontotemporal dementia - FTD and progressive supranuclear palsy - PSP) and secondary (Alzheimer's disease - AD) tauopathies; b) to examine the differences in NPSs reported by patients and caregivers. Methods: The study included 312 patients, 176 of whom had a disease duration of ≤3 years. The presence of NPSs based on caregiver's report was assessed by neuropsychiatric questionnaire (NPI). Patient's assessment of NPSs was examined by Hamilton's Depression and Anxiety Scales and the Apathy Scale. Results: In AD, the most common and severe neuropsychiatric symptoms are mood disorders and apathy. In contrast, agitation-related symptoms are also prominent in FTD and PSP. The profile of NPSs in FTD and PSP is similar, but irritability and aberrant motor behavior are more pronounced in FTD, while sleep disturbances are dominant in PSP. The prevalence of NPSs reported by caregivers on NPI was higher than that reported by patients. Conclusions: FTD and PSP are characterized by more frequent and more severe NPSs and have distinct psychiatric patterns compared to AD, even in the early disease course. Caregiver's observations of the patient's behavior could be of key importance in distinguishing these tauopathies, particularly in the absence of hard motor and cognitive symptoms in early disease course. Assessments of depression, anxiety, and apathy by patients themselves and their caregivers differ significantly, and data from these two sources cannot be considered interchangeable and comparable.

Impacts of depression, apathy, and anxiety on cognitive function in older adults with subjective cognitive decline

AbstractBackgroundAlthough previous studies showed that neuropsychiatric symptoms are associated with cognitive decline, the results are controversial. We investigated the impacts of depression, apathy, and anxiety on cognitive function in older adults with subjective cognitive decline (SCD).MethodAltogether, 464 subjects aged 65‐85 years who had SCD were enrolled in this study. All participants were evaluated with the short version of Geriatric Depression Scale (GDS15), Starkstein’s Apathy Scale (AS), the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS), and 9 cognitive tasks assessed using the Mini‐Mental State Examination, Logical Memory and Visual Reproduction subtests of the Wechsler Memory Scale‐Revised, Verbal Fluency Test, Digit Span, Visual Memory Span and Digit‐Symbol subtests of the Wechsler Adult Intelligence Scale‐III, Stroop Test, and Trail Making Test. We performed a Pearson correlation analysis to examine the associations between depression, apathy, and anxiety, and a multiple linear regression analysis, adjusted for age, sex, educational level, and global cognitive state to determine the impacts of depression, apathy, and anxiety on cognitive function.ResultPearson correlation analysis revealed a low‐ to moderate‐grade relationship among depression, apathy, and anxiety, as shown by the correlation between GDS15 and AS (r = 0.49, p &lt; 0.01), GDS15 and HADS (r = 0.36, p &lt; 0.01), and AS and HADS (r = 0.18, p &lt; 0.01). The multiple linear regression analysis, with each cognitive task score as dependent variable, indicated a significant association of the HADS with lower scores on Logical Memory I (beta = −0.18, p &lt; 0.001) and II (beta = −0.14, p = 0.002), after adjusting for the subjects’ age, sex, educational level, and global cognitive state.ConclusionOur results suggest that anxiety may be associated with immediate and delayed memory functions in older adults with SCD.

P105: Measuring clinically relevant change in apathy symptoms in ADMET 2

Objective:Treatments trials for apathy in Alzheimer’s disease assess change scores on widely used assessment scales. Here, we aimed to determine whether such change scores on the Neuropsychiatric Inventory - Apathy (NPI-A) scale indicate clinically meaningful change.Methods:Participants completing the Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) were included. Participants in this randomized trial received methylphenidate or placebo for 6- months along with a psychosocial intervention. Assessments included Clinical Global Impression of Change in apathy (CGIC-A) and the NPI-A. Participants in both groups with complete data at the six-month visit were included. CGIC-A was assessed as improved (minimal, moderate or marked), no change, or worsened (minimal, moderate or marked). For CGIC-A levels, mean and standard deviation (SD) of the change in NPI-A from baseline was calculated. Spearman correlation determined the association between change in NPI-A and CGIC-A, and Mann-Whitney U tests determined differences between the ‘no change’ group and the ‘improved’ and ‘worsened’ groups. Effect size (mean NPI-A difference between either ‘improved’ and ‘no change’/ SD of overall change) were calculated. Differences were also assessed at 3 months as a sensitivity analysis.Results:Overall, 177 participants were included (median age: 77years, Mini Mental State Examination score: 19.3 (4.8), baseline NPI-A [mean, SD]: 7.9, 2.3), change in NPI-A: -3.7 (3.9). On the CGIC-A, 69 were improved, 82 showed no change, and 26 worsened. The Spearman correlation between NPI-A change and CGIC-A was 0.41 (p= 1x 10-8). The change in NPI-A among participants who improved was -5.3 (4.1) [W=1873, p= 3x10-4], among those who worsened was -1.2 (3.1) (W= 1426.5, p= 0.009) compared to those with no change (-3.2 [3.4]),. The NPI-A score for minimal clinical improvement was -4.5 (4.6) with a small effect size of -0.32, which was consistent at 3-months (-0.31).Conclusion:A minimal clinically significant improvement over 3 and 6-months corresponded to a mean decline of 4.5 points on the NPI-A; however, there is considerable overlap in the NPI-A between levels of clinical impression of change.

Apathy, empathy and depression in Alzheimer’s disease and frontotemporal dementia: Examining the constructs and white matter correlates

AbstractBackgroundApathy and reduced empathy are commonly observed in Alzheimer’s disease (AD) and the core features of behavioural‐variant frontotemporal dementia (bvFTD). Depression is also prevalent in these syndromes. Recent work has proposed a multidimensional framework of apathy which includes three aspects of apathy: executive apathy (reduction of planning and organisation), emotional apathy (emotional indifference and decreased social engagement) and initiation apathy (reduced behaviour execution). These aspects can manifest as symptoms resembling empathy loss and/or depression. The extent to which these symptoms represent similar/divergent clinical dimensions, and their underpinning neural networks, remains unclear. This study investigated the interrelations between apathy, empathy loss and depression, and its white matter correlates, in AD and bvFTD.MethodThirty‐four AD and 51 bvFTD patients participated in the study. Items of the Dimensional Apathy Scale, Interpersonal Reactivity Index and Depression Anxiety Stress‐Depression Subscale were examined using Principal Component Analysis (PCA). White matter integrity and its associations with clinical components were measured via changes in fibre density and cross‐section using fixel‐based analysis.ResultThree components were identified through the PCA (Fig 1). Component 1 consisted of items assessing emotional apathy and empathy, while Component 2 included executive apathy items. Finally, all depression items loaded into Component 3. Regarding white matter correlates, Component 2 were strongly related to reduced white matter bundle density and cross‐section in fibres connecting the bilateral frontal lobe and subcortical structures (Fig 2), whereas Components 1 and 3 were associated with distributed white matter reductions.ConclusionThis study demonstrates that while emotional apathy and empathy loss share the underlying construct, executive apathy and depression are rather independent. White matter changes have strong implications for executive apathy, but not for emotional apathy, empathy and depression. Improved conceptualisation of these symptoms will be important for the development of personalised symptom‐specific therapies.

Developing Topics.

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. 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. 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). 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.

Cognitive symptoms associated with COVID‐19: neuropsychological and biochemical characterization

AbstractBackgroundDespite previous studies establishing cognitive impairment as a major complaint in post‐acute COVID‐19 syndrome (PACS), a deeper understanding of the neuropsychological features and underlying causes is needed. We aimed to characterize the cognitive profile of patients affected with cognitive PACS and the influence of biological and psychological factors.MethodWe performed a prospective single‐center study. We included participants with confirmed SARS‐CoV‐2 infection and long‐term symptoms ≥ 8 weeks after onset who were referred to our unit because of cognitive complaints. All participants completed a comprehensive neuropsychological battery (NPS) and questionnaires assessing depression (Beck Depression Inventory), anxiety (Beck Anxiety Inventory), apathy (Starkstein Apathy Scale) and fatigue (Multidimensional Fatigue Inventory) at baseline and +1, +3 and +6 months. We collected blood samples and cerebrospinal fluid (CSF) to obtain biochemical and immunological profiles. Group comparisons, correlations and Principal component analysis (PCA) were performed. Longitudinal analyses are ongoing.ResultForty‐nine participants were included (79.6% female, mean age 50.1 (SD 7.9). At the time of assessment, they presented multiple symptoms other than cognitive complaints (88% fatigue, 61% headache, 63% dyspnea, and 10% fever). The NPS showed that executive functions were the most affected (up to 29% of the sample had at least one test altered), followed by memory (at least one test altered in 25%) (Figure 1). On the contrary, language and praxis were preserved. Participants presented with anxiety symptoms (minimal 8.7%, mild in 34.8%, moderate 26.1%, severe 30.4%), depressive symptoms (none 34.8%, mild 26.1%, borderline clinical depression 23.9%, moderate 8.7%, severe 6.5%), and clinically relevant apathy in 64.4%.The sample presented a mean score of total fatigue of 58 (min 48, max 68), (scores 20‐100). Fever and or moderate/severe anxiety were associated with lower scores in some memory and executive functions subtests (Figure 2). Most of the variability in the sample was explained by executive functions subtests (PCA, Figure 3). Patients presented increased levels of interleukins (IL) IL‐1b, IL‐17a and IL‐18 in CSF compared to controls.ConclusionCognitive PACS predominantly affected executive functions and memory. Fever and moderate/severe anxiety were associated with worse cognitive outcomes. Several inflammatory markers were altered in cognitive PACS.

Parkinson’s Disease Non-Motor Subtypes Classification in a Group of Slovenian Patients: Actuarial vs. Data-Driven Approach

Background and purpose: The aim of this study was to examine the risk factors, prodromal symptoms, non-motor symptoms (NMS), and motor symptoms (MS) in different Parkinson’s disease (PD) non-motor subtypes, classified using newly established criteria and a data-driven approach. Methods: A total of 168 patients with idiopathic PD underwent comprehensive NMS and MS examinations. NMS were assessed by the Non-Motor Symptom Scale (NMSS), Montreal Cognitive Assessment (MoCA), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ), Epworth Sleepiness Scale (ESS), Starkstein Apathy Scale (SAS) and Fatigue Severity Scale (FSS). Motor subtypes were classified based on Stebbins’ method. Patients were classified into groups of three NMS subtypes (cortical, limbic, and brainstem) based on the newly designed inclusion criteria. Further, data-driven clustering was performed as an alternative, statistical learning-based classification approach. The two classification approaches were compared for consistency. Results: We identified 38 (22.6%) patients with the cortical subtype, 48 (28.6%) with the limbic, and 82 (48.8%) patients with the brainstem NMS PD subtype. Using a data-driven approach, we identified five different clusters. Three corresponded to the cortical, limbic, and brainstem subtypes, while the two additional clusters may have represented patients with early and advanced PD. Pearson chi-square test of independence revealed that a priori classification and cluster membership were significantly related to one another with a large effect size (χ2(8) = 175.001, p &lt; 0.001, Cramer’s V = 0.722). The demographic and clinical profiles differed between NMS subtypes and clusters. Conclusion: Using the actuarial and clustering approach, marked differences between individual NMS subtypes were found. The newly established criteria have potential as a simplified tool for future clinical research of NMS subtypes of Parkinson’s disease.

Establishing the link between motivational disturbances and behavioural rigidity in frontotemporal dementia.

Rigid and inflexible behaviours are common in frontotemporal dementia (FTD), manifesting in compulsive pursuit of specific interests, routines, and rituals. Paradoxically, these changes occur alongside profound motivational disturbances including apathy and anhedonia. While posited to be related, no study to date has explored the link between motivational changes and behavioural rigidity in FTD. Carer ratings for 71 FTD participants (26 semantic dementia [SD], 45 behavioural variant [bvFTD]) were obtained on the Dimensional Apathy Scale (apathy), the Snaith-Hamilton Pleasure Scale (hedonic tone) and the Cambridge Behavioural Inventory-Revised (CBI-R; behavioural changes). A rigidity index was created from existing items on the CBI-R. Whole-brain voxel-based morphometry was used to explore associations between rigidity and grey matter intensity in the combined FTD group. Behavioural rigidity was significantly related to apathy severity (r = 0.57) and decreased hedonic tone (r = -0.36) in the combined FTD group. Multiple linear regression revealed a significant diagnosis × hedonic tone interaction (β = -1.40), whereby lower hedonic tone predicted rigidity in SD (r = -0.65) but not in bvFTD (r = -0.18). In contrast, the relationship between rigidity and apathy did not differ between the groups (β = -0.42). At the neural level, rigidity correlated with degeneration of predominantly right-sided frontostriatal structures including, notably, the nucleus accumbens. As the first study to demonstrate a link between motivational changes and behavioural rigidity in FTD, our findings have important clinical implications. By identifying candidate mechanisms of behavioural rigidity, our findings can inform targeted interventions to manage inflexible patterns of thought and behaviour in daily life.

4 An Update: Greater Apathy Associated with Selective Serotonin Reuptake Inhibitor Use in Parkinson’s Disease

Objective:Apathy is a primary lack of motivation that is frequently reported in Parkinson’s disease (PD) and often misdiagnosed as depression. In PD, apathy worsens over time with motor symptom progression. Evidence over the past 15 years has documented that use of selective serotonin reuptake inhibitors (SSRIs) is associated with increased apathy in patients with depression, including individuals with PD. In PD, this appears to be related to downregulation of dopaminergic systems by serotonin. Despite increasing evidence, SSRIs continue to be heavily prescribed in individuals with PD— potentially worsening apathy and decreasing quality of life for these individuals. This study is an update, re-examining the relationship between apathy and the use of SSRIs and other antidepressants in a large cohort of individuals with PD.Participants and Methods:Participants included a convenience sample of 387 nondemented individuals with idiopathic PD who were in their mid-60's (mean age=64.9+8.72 years), well-educated (mean=14.95+2.78 years), predominantly male (72.4%), non-Hispanic white (94.5%), and in mid-stage of disease severity (on medication Unified Parkinson Disease Rating Scale motor score=25.3+10.1). All scored above clinical cutoff for dementia on a cognitive screener (Dementia Rating Scale-2 (DRS) &gt; 125). Medications, cognitive, mood, and clinical data were extracted from chart review. Depression and apathy were measured using the Beck Depression Inventory-II (BDI-Il) and the Apathy Scale (AS). Antidepressant medications were grouped into SSRIs, serotonin and norepinephrine reuptake inhibitors (SNRIs) and other. Analyses included bootstrapped Pearson’s correlations, Pearson’s chi-square, and linear regressionsResults:Among 387 individuals with PD, 41.3% (N=160) were taking antidepressant medications. Of these 160, 61.3% were on SSRIs, 24.4% on SNRIs, and the remainder on other antidepressants. Approximately 36.9% of the 387 PD patients exceeded recommended clinical cutoffs for apathy (AS &gt;14) and 23.5% for depression (BDI-II &gt;14) (Starkstein et al., 1992; Beck et al., 1996). Individuals taking SSRIs (N=98, x2=5.14, p=0.023) or SNRIs (N=39; x2=5.43, p=0.020) were more likely to be clinically apathetic than those taking other depression medications (N=23; x2=1.28, p=0.26). Results of a multiple regression with age, education, disease duration, motor severity, DRS-2, BDI-II, and all psychotropic medications (anti-depressants, anti-anxiety, anti-psychotics) as independent variables explained 42.8% of the variance in total apathy scores (F[17,285]=12.550, p&lt;0.001). SSRIs were the only medication to significantly predict greater AS scores (ß=0.110, p=0.020) in this model. Less education (ß=-0.119, p=0.017) worse cognition (ß=-0.128, p=0.009), and greater depressive symptoms (ß=0.561, p&lt;0.001) were also significant predictors of apathy.Conclusions: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 as a potential adverse effect when determining which anti-depressants to prescribe to individuals with PD. Similarly, switching a SSRI for an alternative anti-depressant in individuals with PD who are apathetic may be a potential treatment for apathy that needs further study. Longitudinal studies are also needed to elucidate the relationship of apathy and anti-depressant use over time, specifically to determine potential causality of this observed association. Funding: T32-NS082168

21 Exploratory Factor Analysis of the Cognitive Change Index-20 in Individuals with Parkinson disease or Essential Tremor

Objective:Subjective cognitive complaints are common in individuals with Parkinson’s disease and Essential Tremor. One scale often used to capture the type and severity of subjective cognitive concerns is the Cognitive Change Index-20 (CCI-20). Created by Saykin et al (2006), the CCI-20 is a questionnaire that assesses perception of cognitive changes in memory, executive function, and language domains. Despite its multidomain structure, previous research has not empirically examined whether the CCI-20's underlying factor structure aligns with the cognitive domains proposed during its original development. Thus, the goal of the current study was to investigate the factor structure of the CCI-20 in individuals with movement disorders (Parkinson’s disease, Essential Tremor) who are known to experience varying degrees of cognitive sequelae as part of their disease progression.Participants and Methods:Participants included a convenience sample of 216 non-demented individuals with Parkinson disease (n=149) or Essential Tremor (n=67) who were seen at the University of Florida Fixel Institute Movement Disorders Center. All received the CCI-20 as part of a neuropsychological evaluation. The CCI-20 consists of 20 items, rated on a 5-point Likert scale, that ask questions about change in memory (12 items), executive function (5 items), and language (3 items) over the past 5 years. An exploratory factor analysis was conducted on CCI-20 scores using Promax rotation with factor extraction based on scree plot visual inspection and Kaiser’s rule (eigenvalues &gt;1.0). Cronbach’s alpha was used to assess internal consistency reliability. Finally, Spearman correlations determined associations between factors and mood measures of depression (Beck Depression Inventory-II, BDI-II), apathy (Apathy Scale, AS), and anxiety (State-Trait Anxiety Inventory, STAI).Results:Because the Parkinson’s disease and Essential Tremor groups did not statistically differ in their CCI-20 total scores, they were combined into a single group for analyses. This resulted in 216 participants who were well-educated (m=15.01±2.92), in their mid-60's (m=67.72±9.33), predominantly male (63%), and non-Hispanic White (93.6%). The factor analysis resulted in 3 factors: factor 1 included 8 memory items (items 1-4, 6, 10-12; loadings from .524 to .920); factor 2 included all executive and language (items 13-20; loadings from .605 to .824), and factor 3 included four remaining memory items (items 5, 7-9; loadings from .628 to .810). Reliability of the 20 CCI items was good (a = .94), and reliability within each factor ranged from adequate (Factor 3, a = .78) to good (Factors 1 and 2, a = .90). All factors showed significant weak to moderate associations with BDI-II, AS, and STAI (state and trait) scores.Conclusions:The CCI-20 revealed three distinct dimensions of subjective cognitive complaints that did not correspond to the memory, executive function, and language domains. Rather, the CCI-20 was decomposed into two different dimensions of memory complaints and one dimension of non-memory complaints. Mood symptoms played a significant role in driving all dimensions of subjective cognitive complaints. Future studies should confirm this triadic structure in a healthy older adult sample and explore the relationship between factors and objective cognitive performance beyond the contribution of mood. T32-AG061892; T32-NS082168

20 Laterality of Motor Symptom Onset is Not Associated with Cognitive Performance or Mood Symptoms in a Sample of 600 Individuals with Idiopathic Parkinson’s Disease”

Objective:Parkinson’s disease (PD) is typically characterized by unilateral onset of motor symptoms (i.e., tremors, rigidity) which is caused by dopaminergic degeneration of the substantia nigra that influences basal ganglia-prefrontal circuitry. Over time, motor symptoms become more bilateral, though continue to remain asymmetric. Many neuropsychological studies suggest that laterality of motor onset may be linked to hemispheric specific cognitive or mood changes. Namely, worse verbal/language performance may be present in individuals with right body (left hemisphere) onset and conversely for visuospatial performance, with depression symptoms relating more so to individuals with right body (left hemisphere) onset. To date, findings are often inconsistent, with some studies showing evidence for laterality effects and others not. The basis for this inconsistency is unclear, though one possibility relates to small sample sizes and varying methodologies. Thus, the goal of this study was to examine potential cognitive and mood laterality effects in a large clinical sample of individuals with PD.Participants and Methods:Participants included a convenience sample of 600 nondemented individuals with idiopathic PD from the University of Florida Fixel Institute Movement Disorders Center. As a group, participants were around 60 years of age (Mean Age=63.9+9.4), well educated (Mean years=14.9+2.7), predominantly male (70%), and white non-Hispanic (93%). Side of initial motor symptom onset was based on self-report: Right (N=337) and Left (N=263). Approximately 79% were tremor predominant. All received mood and neurocognitive measures as part of standard clinical care, including indices of executive function (Stroop Color-Word, Trails B, Letter Fluency), recent verbal memory (delayed recall: Hopkin’s Verbal Learning Test, WMS-III Logical Memory), language (Boston Naming Test, Animal fluency), visuospatial skills (Judgment of Line Orientation, Facial Recognition Test). Evaluation of emotion symptoms included: depression (Beck Depression Inventory-II), apathy (Apathy Scale), and anxiety (State-Trait Anxiety Inventory). Analyses used raw scores from these measures. Due to non-normality of most measures’ distributions, laterality effects were examined using bootstrapped multivariate methods (multivariate analysis of variance [MANOVA]). Separate MANOVA’s were run for each cognitive domain (i.e., EF, language, etc.) and mood measures.Results:The right and left sided onset groups did not significantly differ in demographic (age, education, sex) or disease characteristics (duration, PD subtype). Results of the MANOVA’s with cognitive variables were all nonsignificant broadly (all with F’s ranging from .33 to .94) and at the single test level. Similarly, the left and right onset groups did not significantly differ (a=0.05) across standard scales of depression (F=0.031), anxiety (Trait F=0.463; State F=3.29), and apathy (F=0.74).Conclusions:We found no evidence that laterality of initial motor symptoms influenced cognitive or mood symptoms in a large cohort of 600 individuals with PD. These findings raise questions about importance of motor onset laterality for cognitive and emotion related changes in PD. Future studies should move beyond self-report and behavioral motor scales for determining hemispheric contributions. In PD, use of refined metrics for determining the extent of asymmetric dopaminergic degeneration (e.g., DAT scan) at the hemispheric level coupled with sensitive neuropsychological measures may provide clearer understanding of potential neural circuitry relationships.

Validation study of the apathy motivation index in French adults.

Apathy is present in many brain disorders, but it is also prevalent to varying degrees in healthy people. While many tools have been developed to assess levels of apathy in pathology, no standardized measure of apathy in healthy people exists. Therefore, this study aimed to validate the French version of the Apathy Motivation Index (f-AMI). The results of 729 participants were analyzed using an exploratory factorial analysis. Preliminary analyses suggested that the three domains of apathy extracted in the original AMI scale-behavioral activation (BA), social motivation (SM), and emotional sensitivity (ES)-could be found also in the f-AMI. A further exploratory analysis showed that a higher number of factors could be extracted, particularly for women. Specifically, both social and emotional factors could be divided into two sub-factors: (1) social motivation toward strangers or toward an acquaintance and (2) self-directed emotional sensitivity directed toward others. Regarding construct validity, the scores of f-AMI were correlated with the French Dimensional Apathy Scale results. Concerning the divergent validity, emotional sensitivity in apathy is different from depression, anhedonia, and fatigue levels. These results suggest that the f-AMI can be used to assess levels of apathy in healthy adults.

H - 68 Effects of Depression, Apathy and Anxiety in Hispanic Parkinson Disease Individuals' Cognition.

Previous research in individuals with Parkinson's disease (PD) found that heightened apathy is associated with worse executive function. Most studies to-date have involved primarily White, non-Hispanic individuals. Indeed, recent research suggests that mood/motivation's relationship to cognitive decline differs between Hispanic and non-Hispanic individuals (Thakur et al., 2021). In this study, we examined relationships between depression, apathy, anxiety, and cognition in Hispanic PD participants who were seen in a specialized movement disorders center. Participants included 31 non-demented Hispanic individuals with PD (age mean = 59.94, SD = 8.49years; education mean = 14.39, SD = 2.79; 83.9% male) who completed neuropsychological and mood measures (Beck Depression Inventory-II, Apathy Scale, STAI-Trait Anxiety Scale). Prevalence estimates were calculated using established cut-offs (BDI-II:14, AS:14, STAI-Trait:40). Cognitive raw scores were z-scored and averaged into the composites: attention (WAIS-III Digit Span Forward, Backward), processing speed (Stroop Word, Trails A), executive function (Trails B, Stroop Color-Word), and memory (Hopkin's Verbal Learning Test, WMS-III Logical Memory delayed recalls). Non-parametric partial correlations (correcting for age/education) assessed mood and cognitive composite relationships. 17% had clinically significant depressive symptoms, 12% had apathy, and 35% had anxiety. More depressive symptoms were significantly associated with worse memory (r = -0.54, p = 0.007). Greater anxiety symptoms trended with worse processing speed (r = -0.41, p = 0.065) and memory (r = -0.38, p = 0.094). Apathy did not relate to cognition (p's > 0.05). This pattern of associations differs from existing studies with predominantly White, non-Hispanic samples (Butterfield et al., 2010; Ratajska, et al.,2022), highlighting the importance of further investigating ethnic differences in PD.

Frontotemporal-spectrum disorders and functional independence in non-demented ALS patients

BackgroundThe present study aimed at determining whether, net of motor confounders, neuropsychological features affect functional independence (FI) in activities of daily living (ADLs) in non-demented amyotrophic lateral sclerosis (ALS) patients.MethodsN = 88 ALS patients without frontotemporal dementia were assessed for FI—Katz’s Basic ADL Scale (BADL) and Lawton-Brody’s Instrumental ADL Scale (IADL)—, cognition—Edinburgh Cognitive and Behavioural ALS Screen (ECAS)—and behaviour—Beaumont Behavioural Inventory and Dimensional Apathy Scale. The association between cognitive and behavioural measures and BADL/IADL scores was assessed by covarying for demographics, anxiety and depression levels, disease duration and motor confounders—i.e. ALS Functional Rating Scale-Revised (ALSFRS-R) scores, progression rate and both King’s and Milano-Torino stages.ResultsHigher scores on the ECAS-Language were associated with higher IADL scores (p = 0.005), whilst higher apathetic features—as measured by the Dimensional Apathy Scale (DAS)—were inversely related to the BADL (p = 0.003). Whilst IADL scores were related to all ECAS-Language tasks, the DAS-Initiation was the only subscale associated with BADL scores. Patients with abnormal ECAS-Language (p = 0.023) and DAS (p = 0.008) scores were more functionally dependent than those without.DiscussionAmong non-motor features, language changes and apathetic features detrimentally affect FI in non-demented ALS patients.

Association of Parental Support with Reduced Stereotypy in Children with Autism Spectrum Disorder: A Cross-Sectional Study.

Background and Objectives: To analyze the influence of parental presence and use of risperidone on social interaction and apathy among patients with Autism Spectrum Disorder (ASD). Materials and Methods: Cross-sectional study in a reference center for patients with ASD in a city in northeastern Brazil. The research was carried out using a sociodemographic questionnaire, the Dimensional Apathy Scale, and the Social Communication Questionnaire (SCQ) with the domains of social interaction, language, stereotypy, and communication. The referred questionnaire was answered by the parents or guardians of the children with ASD according to the DSM V criteria. Data were analyzed via independent t-test using the SPSS software version 20. Results: Interviews were conducted with 51 parents/guardians of autistic children with a mean age of 8.8 years (±2.95) and a predominance of males, 34 (66.7%). Of this total, 49 (96.1%) of the children attended school; 40 (78.4%) children were on medication, of which 38 (74.5%) were on risperidone. Those children on risperidone had a higher score on the SCQ scale (p = 0.049) and on the domain of stereotyped behaviors (p = 0.033), which indicated greater impairment. Another statistically relevant variable was the presence of married parents, whereby children who did not have the presence of married parents had a higher average of stereotyped behaviors compared to those who had married parents. Conclusions: The results showed differences in the means of social interactions for children on risperidone, especially regarding stereotyped behaviors. However, it is not possible to state whether this difference was due to the use of risperidone or whether they used risperidone precisely because of these behaviors. Also important was that children who had the presence of married parents showed fewer stereotyped behaviors. There was no difference in apathetic behavior between children.

Fluctuations in Parkinson's disease and personalized medicine: bridging the gap with the neuropsychiatric fluctuation scale.

Neuropsychiatric fluctuations (NpsyF) are frequent and disabling in people with Parkinson's disease (PD). In OFF-medication, NpsyF entail minus neuropsychiatric symptoms (NPS) like anxiety, apathy, sadness, and fatigue. In ON-medication, NpsyF consist in plus NPS, such as high mood, hypomania, and hyperactivity. Accurate identification of these NpsyF is essential to optimize the overall PD management. Due to lack of punctual scales, the neuropsychiatric fluctuation scale (NFS) has been recently designed to assess NpsyF in real time. The NFS comprises 20 items with two subscores for plus and minus NPS, and a total score. To evaluate the psychometric properties of the NFS in PD. PD patients with motor fluctuations and healthy controls (HC) were assessed. In PD patients, the NFS was administrated in both the ON-and OFF-medication conditions, together with the movement disorders society-unified Parkinson disease rating scale parts I-IV. Depression (Beck depression scale II), apathy (Starkstein apathy scale) and non-motor fluctuations items of the Ardouin scale of behaviour in PD (ASBPD OFF and ON items) were also assessed. NFS internal structure was evaluated with principal component analysis consistency (PCA) in both medication conditions in PD patients and before emotional induction in HC. NFS internal consistency was assessed using Cronbach's alpha coefficient. NFS convergent and divergent validity was measured through correlations with BDI-II, Starktein, and ASBPD OFF and ON non motor items. Specificity was assessed comparing NFS global score between the HC and PD populations. Sensitivity was evaluated with t-student test comparing the ON-and the OFF-medication conditions for NFS global score and for minus and plus subscores. In total, 101 consecutive PD patients and 181 HC were included. In PD patients and HC, PCA highlighted one component that explained 32-35 and 42% of the variance, respectively. Internal consistency was good for both the NFS-plus (alpha =0.88) and NFS-minus items (alpha =0.8). The NFS showed a good specifity for PD (p < 0.0001) and a good sensitivity to the medication condition (p < 0.0001). The satisfactory properties of the NFS support its use to assess acute neuropsychiatric fluctuations in PD patients, adding to available tools.

Clinimetrics of the Italian version of the Montreal Cognitive Assessment (MoCA) in adult-onset idiopathic focal dystonia

This study aimed at assessing the clinimetrics of the Montreal Cognitive Assessment (MoCA) in an Italian cohort of patients with adult-onset idiopathic focal dystonia (AOIFD). N = 86 AOIFD patients and N = 92 healthy controls (HCs) were administered the MoCA. Patients further underwent the Trail-Making Test (TMT) and Babcock Memory Test (BMT), being also screened via the Beck Depression Inventory-II (BDI-II) and the Dimensional Apathy Scale (DAS). Factorial structure and internal consistency were assessed. Construct validity was tested against TMT, BMT, BDI-II and DAS scores, whilst diagnostics against the co-occurrence of a defective performance on at least one TMT measure and on the BMT. Case–control discrimination was examined. The association between MoCA scores and motor-functional measures was explored. The MoCA was underpinned by a mono-component structure and acceptably reliable at an internal level. It converged towards TMT and BMT scores, as well as with the DAS, whilst diverging from the BDI-II. Its adjusted scores accurately detected cognitive impairment (AUC = .86) at a cut-off of < 17.212. The MoCA discriminated patients from HCs (p < .001). Finally, it was unrelated to disease duration and severity, as well as to motor phenotypes. The Italian MoCA is a valid, diagnostically sound and feasible cognitive screener in AOIFD patients.

Clinical correlates of Fear of Falling in Progressive Supranuclear Palsy and Multiple System Atrophy.

Clinical correlates of fear of falling (FoF) are scarcely studied in patients with Progressive Supranuclear Palsy (PSP) and Multiple System Atrophy (MSA). To evaluate the clinical correlates of FoF in PSP and MSA. A cross-sectional study with motor , cognitive and psychiatric assessment and longitudinal evaluation of falls and FoF at 6-month follow-up. Twenty-one patients with PSP-P, 22 with MSA (13 MSA-P and 9 MSA-C) and 22 healthy controls were evaluated. 76.2% of patients with PSP and 86.4%of patients with MSA had FoF regardless of falls. Berg Balance Scale (p<0.001), Tinetti Mobility Test (p<0.01), Beck Anxiety Inventory (p=0.001) and Beck Depression Inventory-II (p=0.01) correlated with FoF in patients with PSP and MSA, whereas Timed up and Go test (p=0.01) and Starkstein's Apathy Scale only in MSA (p=0.04). Mobility, balance and gait performance as well as anxiety and depression in PSP and MSA, and apathy in MSA were determinants of FoF. These findings underline the importance of a multidisciplinary approach to FoF in neurodegenerative atypical parkinsonism.