Among participants with Alzheimer's disease (AD) we estimated the minimal clinically important difference (MCID) in apathy symptom severity on three scales.

Retrospective anchor- and distribution-based analyses of change in apathy symptom scores.

Apathy in Dementia Methylphenidate Trial (ADMET) and ADMET 2 randomized controlled trials conducted at three and ten clinics specialized in dementia care in United States and Canada, respectively.

Two hundred and sixty participants (60 ADMET, 200 ADMET 2) with clinically significant apathy in Alzheimer’s disease.

The Clinical Global Impression of Change in Apathy scale was used as the anchor measure and the MCID on the Neuropsychiatric Inventory – Apathy (NPI-A), Dementia Apathy Interview and Rating (DAIR), and Apathy Evaluation Scale-Informant (AES-I) were estimated with linear mixed models across all study visits. The estimated thresholds were evaluated with performance metrics.

Among the MCID was a decrease of four points (95% CI: −4.0 to −4.8) on the NPI-A, 0.56 points (95% CI: −0.47 to −0.65) on the DAIR, and three points on the AES-I (95% CI: −0.9 to −5.4). Distribution-based analyses were largely consistent with the anchor-based analyses. The MCID across the three measures showed ∼60% accuracy. Sensitivity analyses found that MMSE scores and apathy severity at baseline influenced the estimated MCID.

MCIDs for apathy on three scales will help evaluate treatment efficacy at the individual level. However, the modest correspondence between MCID and clinical impression of change suggests the need to consider other scales.

Apathy, or loss of motivation and interest, is a common sequela of moderate to severe traumatic brain injury (msTBI) and has been associated with frontal lesions and with executive dysfunction in a sample an average of one year post injury (Andersson & Bergdalen, 2002). In older adults sustaining msTBI in particular, the appearance of apathy is more likely to be comorbid with depression when compared to injury in younger adults (Kant et al., 1998). However, studies have consistently shown an important dissociation between apathy and depression, despite overlapping symptoms, with apathy in particular associated with frontal lobe damage (Worthington & Wood, 2018). The present study holds two primary goals. First, to examine the relationship between current apathy ratings and cognition after controlling for ratings of depression and perceived changes in apathy, to account for the unique relationship of injury-related apathy on cognition. Second, to examine the potential variable role of APOE4 carrier status on depression and apathy ratings.

110 older adults with a lifetime history of msTBI (M=9.5 years post-injury) were included as part of a cross-sectional study. Apathy was measured using the Frontal Systems and Behaviors Scale (FrSBe) for both current apathy ratings and perceived change in apathy from pre- to post-injury. Depression was measured using the depression subscale of the Brief Symptom Inventory (BSI). Outcome measures included normed scores for learning (HVLT-R total recall), retention (HVLT-R percent retention), processing speed (Trails A), set-shifting and working memory (Trails B, Digit Span Backwards), and phonemic and category fluency (D-KEFS letter and category fluency). The main independent variable of interest was current apathy ratings. Depression and perceived apathy change were included as control variables for all analyses. Vif scores were calculated for all analyses to ensure that variables were not multicollinear. Finally, we ran an ANOVA to examine the relationship between apathy, depression, and APOE4 carrier status.

When controlling for depression and perceived changes in apathy, current apathy ratings were associated with poorer performance on learning (p=.04, n2=.04), processing speed (p=.001, n2=.10), set-shifting (p=.02, n2=.05), attention (p=.04, n2=.04), phonemic fluency (p=.001, n2=.09), category fluency (p=.001, n2=.10). Current apathy ratings were not associated with retention or working memory. Apathy was significantly associated with depression (p <.001), but was not associated with APOE4 carrier status or the interaction between depression and carrier status.

Despite overlap between depressive symptoms and apathy questionnaires (i.e., loss of interest/pleasure), by controlling for depressive symptoms and perceived changes following injury, we demonstrate the significant independent association of apathy and cognition in an older sample with chronic msTBI. Further, although previous work has shown strong associations between depression and APOE4 carrier status in chronic msTBI samples (Vervoordt et al., 2021), there was no significant relation with apathy directly in our sample, providing further evidence that these are neurobiologically distinct syndromes.

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 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) > 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 regressions

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 >14) and 23.5% for depression (BDI-II >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<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<0.001) were also significant predictors of apathy.

These findings suggest that use of SSRIs, but not other antidepressants, is associated with greater apathy in PD. Given the interactive relationship between serotonin and dopamine, the current findings highlight the importance of considering apathy 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

Severe OCD is often nonresponsive to pharmacological and behavioral therapies and thus surgical interventions are emerging. Surgical interventions have proven to be efficacious for treating refractory OCD, however limited publications suggest 22–40% of patients experience transient apathy and disinhibition post-surgery (McLaughlin et al., 2021). Apathy is highly associated with the same brain regions, the prefrontal cortex, striatum, and thalamus, which have also been implicated in OCD symptoms (Le Heron et al., 2018). Prior research noting post-surgical changes in apathy in OCD either used physician observations or less precise surgical methods (i.e., gamma knife or radiofrequency ablation). Apathy has also been highly associated with depression and executive dysfunction (Raffard et al, 2020) and often not co-assessed in prior studies. The newest intervention, cutting-edge MR-guided laser interstitial thermal therapy (LITT), limits damage outside the region of interest by precise control of thermal application in real-time. Thus, the current case series aims to investigate objective patient-reported change in apathy, disinhibition, depression, and executive dysfunction following anterior capsulotomy via this newest surgical approach for OCD.

In this retrospective study, the responses of ten consecutive patients pre- and post-LITT on the following measures were examined: Frontal Systems Behavior Scale (FrSBe), Beck Depression Inventory-II (BDI-II), and Yale Brown Obsessive-Compulsive Scale (Y-BOCS). Reliable Change Index (RCI) was used to evaluate meaningful change in pre- and post-LITT self-reported levels of apathy, disinhibition, executive dysfunction, along with depressive symptoms. Per prior published guidelines, patient-reported Y-BOCS (range 0–40) scores were used to measure OCD symptoms with 24–34 % score reduction representing partial and 35% or greater score reduction representing full response (Pepper et al., 2019).

Seven patients (70%) were male, with a sample mean age of 38.4 (SD=13.6) and a mean of 14.6 (SD =2.27) years of education. Mean Y-BOCS score decreased from 32 (SD=5.3) before surgery to 18.8 (SD=11.1) after. Over 65% had partial or full response in OCD symptoms post-surgery. Six patients endorsed increased apathy, with others endorsing no change. Half of the non-responders reported this increase in apathy. The cohort remained relatively stable in disinhibition and executive dysfunction. Over half the cohort demonstrated a significant decrease in depressive symptoms. Interestingly, two of the non-responders and one responder endorsed increased apathy despite stable or improving depressive symptoms, disinhibition, and executive dysfunction.

Surgical interventions for psychiatric disorders are emerging quickly and being refined daily. In this cohort, anterior capsulotomy via LITT provided full or partial OCD recovery for most patients. However, most patients reported significant increases in apathy, despite experiencing a decrease in depressive symptoms, with stable disinhibition and executive dysfunction. Despite these promising improvements in OCD symptomatology via LITT, impact of surgery on apathy levels is clearly warranted using objective, quantifiable methods. As apathy has consistently been related to functional impairment and poorer quality of life, understanding this outcome is imperative in larger trials. Better understanding of this finding and underlying circuity will allow patients to be fully informed regarding this promising surgical intervention.

Evaluate measures used to operationalize apathy in relation to cognitive impairment among Hispanic/Latin Americans and synthesize associations of apathy with cognitive impairment.

A systematic review of the available literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. This review covered studies on the relationship between apathy and cognitive impairment among Hispanic/Latin Americans across normal aging and neurocognitive disorders. The first stage of the review consisted of collecting all publications that contained (1) English or Spanish-speaking participants, (2) with measures for reported apathy, (3) assessment of cognitive functioning or diagnosis of neurocognitive disorder, (4) with Hispanic/Latin Americans represented in the sample. There was no limit regarding publication date. The required minimum of H/L participants in selected studies was determined based on a standard of representation in the United States general population, which is around 18.5%. In the second stage of the review, studies were screened excluding all studies that did not meet the criteria.

Thirteen, 37, and 17 studies were identified by APA PsychInfo, EMBASE, and PubMed, respectively. After removing 19 duplicate records, 48 reports were then assessed for eligibility. Thirty-five of those reports were missing apathy and cognition associations, were under-reported in information such as conference abstracts, or were missing adequate representation of H/L participants. This resulted in a total of 13 papers included in this review. Of the eleven cross-sectional studies, nine demonstrated significant differences or associations between apathy and cognitive status, one demonstrated a descriptive difference between apathy and cognitive status (i.e., no hypothesis test conducted), while one demonstrated null effects. All effects suggested that as apathy increased, cognitive impairment increased. These cross-sectional studies spanned across Säo Paulo, Brazil, Los Angeles, California, West Texas, Cuba, the Dominican Republic, Peru, Venezuela, Mexico, Puerto Rico, and Southwestern United States. This included community and clinic samples of participants. Of the two longitudinal studies, they both demonstrated non-significant associations of apathy and cognitive status. One study in Mexico suggested a risk ratio over 1 where apathy was non-significantly associated with dementia risk, while the other study in Texas, United States had hazard ratios below 1 where apathy was non-significantly associated with mild cognitive impairment risk.

The Neuropsychiatric Inventory (NPI) apathy subscale was the most used measure for apathy in this review (81.8% of included studies). However, a recent systematic review on apathy measurement in older adults and people with dementia specifically stated that the apathy dimension commonly used in the NPI should not be employed outside of screening for apathy. This suggests potential bias and poor evidence in the current literature consisting of apathy research with H/Ls. Longitudinal studies evaluating the utility of examining apathy in relation to cognitive impairment with diverse ethnoracial groups, in addition to Hispanic/Latin Americans, are warranted. Assessing construct equivalence of apathy across demographic characteristics such as language, education, and informant characteristics should be conducted to elucidate potential biases in measurement.

Multiple sclerosis (MS) is a chronic neurodegenerative autoimmune disease of the central nervous system. Apathy is significantly higher in adults with MS compared to healthy populations. Apathy is a lack of motivation that can cause dysfunctions in each step of goal-directed behaviors. Apathy is associated with diminished ability to perform activities of daily living, tasks requiring normal executive function, and quality of life. Across various neurodegenerative disorders, apathy has been regarded as a predictor of poor cognition and functional outcomes. However, the severity of apathy and its association with cognitive function in older adults with MS have not been reported. This study's objective was to address this gap of knowledge. Hence, we evaluated: 1) the severity of apathy symptoms in older adults with MS compared to healthy older adults and, 2) the association of apathy symptoms and global cognitive functioning in older adults with MS compared to controls.

Participants were community-residing older adults (age >60ys) enrolled in a cohort study, “Brain Predictors of Mobility and Falls in Older Adults with Multiple Sclerosis.” Healthy controls (n=59; mean age=66.25± 3.37; %female=47.5) and persons with MS (n=69; mean age=64.58± 3.88; %female=62.3) were included in the analysis. Using McDonald criteria, MS diagnosis was physician-confirmed by medical record review, apathy symptoms were assessed through 4 apathy symptom questions on the 30-item Geriatric Depression Scale (GDS), and global cognitive functioning was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Covariates included age, gender, years of education, global health score (GHS), and depression (GDS w/out apathy questions). For the first objective, a linear regression model was used with a bi-level group status variable (MS vs controls) serving as a predictor of apathy symptoms. For the second objective, two linear regression models stratified by group status were run with apathy symptoms as a predictor of global cognitive functioning.

The presence of MS was significantly associated with worse apathy (β=.34, p < .001) and it remained significant after adjusting for covariates (β=.19, p=.03). Additionally, apathy was negatively associated with global cognition in persons with MS (β=-.32, p =.01) and this association remained significant after adjusting for covariates (β=-.33, p =.01) except depression (β=-.27, p =.08). The association of apathy and global cognitive functioning was not significant in healthy controls (β=.01, p=.95).

This study is the first to report worse apathy symptoms in older persons with MS compared to healthy controls. Additionally, worse apathy symptoms were associated lower global cognitive functioning in older adults with MS but not in healthy controls.

People with Korsakoff syndrome (KS) experience severe neuropsychological and neuropsychiatric complications following vitamin B1 deficiency predominantly due to alcoholism. KS often presents itself with neuropsychological symptoms such as problems in episodic memory, executive functioning, and social cognition. Common neuropsychiatric symptoms in KS are disorders of affect, confabulations, anosognosia, and apathy. Apathy can be defined by a pathological lack of goal-directed behaviors, goal-directed cognitions, and goal-directed emotions. Patients with KS have an increased risk of cerebrovascular comorbidity. Cerebrovascular accidents are known to increase the risk for developing apathy. Apathy in KS patients can negatively influence the ability to live an autonomous life, often making 24-hour care a necessity. Limited research on apathy in KS patients has been published to this day. Our aim was to assess apathy in Korsakoff patients with and without neurovascular comorbidity.

General apathy and related subconstructs, such as judgment and decision-making skills, emotional blunting, and the intentions to perform pleasurable activities, were studied in fifteen KS patients, fifteen KS patients with additional cerebrovascular comorbidity, and fifteen healthy controls. The first responsible caregiver of each patient filled in the Apathy Evaluation Scale and Scale for Emotional Blunting. An examiner administered the interview-based Judgement scale of the Neuropsychology Assessment Battery with the KS patients and each KS patient filled in the self-report section of the Pleasurable Activities List. Both KS patient groups receive 24-hour care in a specialized facility for Korsakoff Syndrome.

Our study found higher levels of general apathy in both KS patient groups, when rated by their caregiver compared to healthy controls. No difference was found between the KS patient groups and the healthy control group on the self-reported section of the Pleasurable Activities List, which might suggest the presence of intrinsic motivation in KS patients. However, a discrepancy was found between the self-reported activity levels and proxy reported levels of apathy. KS patients with cerebrovascular comorbidity showed increased levels of emotional blunting compared to KS patients without cerebrovascular comorbidity and healthy controls. Decreased judgment and decision-making skills were found in both patient groups compared to healthy controls, with no difference found between KS patients with cerebrovascular comorbidity and KS patients without.

Our findings suggest that people with Korsakoff syndrome experience more general apathy compared to healthy controls. Both patient groups showed decreased judgement and decision-making skills and increased emotional blunting. Intrinsic motivation was found to be intact in KS patients. Experiencing cerebrovascular comorbidity in KS carries a risk for developing emotional blunting. Our findings show that apathy greatly affects people with KS. Future scientific research is warranted to further benefit the care for this complex patient population.

Post-stroke depression (PSD) and anxiety disorders are the most common psychiatric issues that occur after cerebrovascular accident (CVA), with prevalence rates of up to 50%. Less studied, post-stroke apathy and pseudobulbar affect (PBA) also occur in a subset of individuals after CVA leading to reduced quality of life. Cognitive impairments also persist, especially memory, language, and executive difficulties. Residual cognitive and emotional sequelae after CVA limit return-to-work with between 20-60% becoming disabled or retiring early. This study examined the frequency and relative contribution of cognitive, behavioral and emotional factors for not returning-to-work after CVA.

Participants included 242 stroke survivors (54% women, average age of 59.2 years) who underwent an outpatient neuropsychological evaluation approximately 13 months after unilateral focal CVA. Exclusion criteria were a diagnosis of dementia, comprehension issues identified during assessment, multifocal or bilateral CVA, and inpatients. Predictors of return-to-work included in logistic regression analyses were psychological (depressive and anxiety disorders, apathy, PBA, history of psychiatric treatment before stroke) and neuropsychological (memory, executive functioning) variables. Depression and anxiety were diagnosed using DSM-IV-TR or -5 criteria. Apathy was operationalized as diminished goal-directed behavior, reduced initiation and decreased interest that impacted daily life more than expected from physical issues after stroke (including self- and family-report using the Frontal Systems Behavior Scale [FrSBe]). PBA was defined by the Center for Neurologic Study-Lability Scale and clinical judgment based on chart review.

Post-stroke apathy persisted in 27.3% of patients 13 months after stroke, PBA persisted in 28.2% of patients (i.e., uncontrollable crying spellings not simply attributable to depression alone, uncontrollable laughing spells), anxiety disorders persisted in 18.6% of patients (mainly panic attacks), and PSD persisted in 29.8% of patients. Memory loss persisted in 67.4% of patients and executive difficulties persisted in 74.4% of patients. Thirteen months after stroke, 34.7% of individuals had returned-to-work and 47.1% had not returned-to-work. The other 18.2% were not working either at the time of their stroke or after the stroke. Logistic regression indicated that post-stroke apathy, PBA, and memory loss were significant predictors of not returning-to-work (odds ratio p < 0.001). Patients who experienced post-stroke apathy were 7.1 times more likely to not return-to-work after stroke (p=0.008), those who suffered from PBA were 4.8 times more likely to not return-to-work (p=0.028), and those with memory loss were 6.6 times more likely to not return-to-work (p=0.005). PSD, history of treatment for psychiatric issues before the stroke, presence of an anxiety disorder after stroke, and executive difficulties were not significant predictors (p’s>0.05).

Results replicate the finding that return-to-work is hindered by residual cognitive deficits after stroke and extends previous research by clarifying the multifactorial emotional and behavioral barriers to not returning-to-work. Results highlight the importance of quantifying post-stroke apathy and pseudobulbar affect in a standard neuropsychological work-up after stroke to identify candidates for services to facilitate efforts in returning to work (e.g., vocational rehabilitation services, psychotherapy, interventions for decreased initiation).

The Cognitive Change Index (CCI-20) is a validated questionnaire that assesses subjective cognitive complaints (SCCs) across memory, language, and executive domains. We aimed to: (a) examine the internal consistency and construct validity of the CCI-20 in patients with movement disorders and (b) learn how the CCI-20 corresponds to objective neuropsychological and mood performance in individuals with Parkinson’s disease (PD) or essential tremor (ET) seeking deep brain stimulation (DBS).

216 participants (N = 149 PD; N = 67 ET) underwent neuropsychological evaluation and received the CCI-20. The proposed domains of the CCI-20 were examined via confirmatory (CFA) and exploratory (EFA) factor analyses. Hierarchical regressions were used to assess the relationship among subjective cognitive complaints, neuropsychological performance and mood symptoms.

PD and ET groups were similar across neuropsychological, mood, and CCI-20 scores and were combined into one group who was 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%). Previously proposed 3-domain CCI-20 model failed to achieve adequate fit. Subsequent EFA revealed two CCI-20 factors: memory and non-memory (p < 0.001; CFI = 0.924). Regressions indicated apathy and depressive symptoms were associated with greater memory and total cognitive complaints, while poor executive function and anxiety were associated with more non-memory complaints.

Two distinct dimensions were identified in the CCI-20: memory and non-memory complaints. Non-memory complaints were indicative of worse executive function, consistent with PD and ET cognitive profiles. Mood significantly contributed to all CCI-20 dimensions. Future studies should explore the utility of SCCs in predicting cognitive decline in these populations.

Geriatric depression (GD) is associated with significant medical comorbidity, cognitive impairment, brain atrophy, premature mortality, and suboptimal treatment response. While apathy and anxiety are common comorbidities, resilience is a protective factor. Understanding the relationships between brain morphometry, depression, and resilience in GD could inform clinical treatment. Only few studies have addressed gray matter volume (GMV) associations with mood and resilience.

Forty-nine adults aged >60 years (38 women) with major depressive disorder undergoing concurrent antidepressant treatment participated in the study.

Anatomical T1-weighted scans, apathy, anxiety, and resilience data were collected. Freesurfer 6.0 was used to preprocess T1-weighted images and qdec to perform voxel-wise whole-brain analyses. Partial Spearman correlations controlling for age and sex tested the associations between clinical scores, and general linear models identified clusters of associations between GMV and clinical scores, with age and sex as covariates. Cluster correction and Monte-Carlo simulations were applied (corrected alpha = 0.05).

Greater depression severity was associated with greater anxiety (r = 0.53, p = 0.0001), lower resilience (r = −0.33, p = 0.03), and greater apathy (r = 0.39, p = 0.01). Greater GMV in widespread, partially overlapping clusters across the brain was associated with reduced anxiety and apathy, as well as increased resilience.

Our results suggest that greater GMV in extended brain regions is a potential marker for resilience in GD, while GMV in more focal and overlapping regions may be markers for depression and anxiety. Interventions focused on improving symptoms in GD may seek to examine their effects on these brain regions.

This paper used data from the Apathy in Dementia Methylphenidate Trial 2 (NCT02346201) to conduct a planned cost consequence analysis to investigate whether treatment of apathy with methylphenidate is economically attractive.

A total of 167 patients with clinically significant apathy randomized to either methylphenidate or placebo were included. The Resource Utilization in Dementia Lite instrument assessed resource utilization for the past 30 days and the EuroQol five dimension five level questionnaire assessed health utility at baseline, 3 months, and 6 months. Resources were converted to costs using standard sources and reported in 2021 USD. A repeated measures analysis of variance compared change in costs and utility over time between the treatment and placebo groups. A binary logistic regression was used to assess cost predictors.

Costs were not significantly different between groups whether the cost of methylphenidate was excluded (F(2,330) = 0.626, ηp2 = 0.004, p = 0.535) or included (F(2,330) = 0.629, ηp2 = 0.004, p = 0.534). Utility improved with methylphenidate treatment as there was a group by time interaction (F(2,330) = 7.525, ηp2 = 0.044, p < 0.001).

Results from this study indicated that there was no evidence for a difference in resource utilization costs between methylphenidate and placebo treatment. However, utility improved significantly over the 6-month follow-up period. These results can aid in decision-making to improve quality of life in patients with Alzheimer’s disease while considering the burden on the healthcare system.

Apathy is a common symptom in mild cognitive impairment (MCI) and may predict progression to dementia. Little research, however, has investigated the longitudinal trajectory of apathy in patients with MCI or controlled for depression, which can mimic apathy, when examining its clinical correlates. The current study sought to address these issues.

A prospective longitudinal study was conducted over 3 years.

Nine memory clinics around Australia

One hundred and eighty-five patients with MCI at baseline.

Measures of cognition, function, neuropsychiatric symptoms, caregiver burden, and medication use were completed annually with additional assessments at 3 and 6 months. Patients were also assessed for dementia by expert clinicians at these time points.

Of 164 patients who completed measures of neuropsychiatric symptoms, 59 (36.0%) had apathy and 61 (37.2%) had depression. The proportion affected by apathy and overall apathy scores increased over time, in contrast to measures of depression, which remained relatively stable. Apathy was associated with incident dementia and worse cognition, function, neuropsychiatric symptoms, and caregiver burden independent of both depression and incident dementia. Depression was associated with worse function, albeit to lesser degree than apathy, and neuropsychiatric symptoms.

Apathy increases in MCI and is associated with worse clinical outcomes. These findings provide further evidence for apathy as a marker of clinical decline in older people and poorer outcomes across neurocognitive disorders.

To investigate if executive and social cognitive dysfunction was associated with apathy in a large cohort of Huntington’s disease gene expansion carriers.

Eighty premanifest and motor-manifest Huntington’s disease gene expansion carriers (Mini-Mental State Examination score ≥ 24 and Montreal Cognitive Assessment score ≥ 19) and thirty-two controls were examined with the Lille Apathy Rating Scale (LARS), a tailored and quantitative measure of apathy, and a comprehensive cognitive battery on executive functions and social cognition (emotion recognition, theory of mind and sarcasm detection), as well as general correlates like demographic variables, and neuropsychiatric and cognitive screening tests.

The motor-manifest Huntington’s disease gene expansion carriers had significantly different scores on most measures of social cognition and executive functions, compared to premanifest and control participants. Apathy was significantly correlated with most executive test scores, but the Emotion Hexagon was the only social cognitive test score significantly correlated with apathy. We found that the motor score and the depression score were the only significant predictors of the apathy score, when the social cognitive and executive tests with the strongest association with the global LARS score were entered into a multiple stepwise regression model. No cognitive test score could significantly predict apathy. The model explained 21 % of the total variance.

Despite being significantly correlated with apathy neuropsychological variables did not have a significant impact on apathy when variables as depression and motor symptoms were taken into account. Apathy should be considered an independent symptom of Huntington’s disease that requires specific examination.