Apathy In Dementia Research Articles

A Systematic Review on the Pharmacologic Treatment of Apathy in Dementia

Introduction: Dementia is a neurocognitive disorder that causes functional impairment usually accompanied by neuropsychiatric symptoms. Majority of individuals with dementia suffer from behavioral dysfunction. Apathy, defined as presence of diminished initiative, interest and emotional expression, is a common neuropsychiatric symptom of dementia which currently has no established pharmacologic treatment.

Medications for apathy in dementia.

Medications for apathy in dementia.

Neuromodulation in Behavioral and Psychological Symptoms of Dementia (BPSD)

Behavioral and psychological symptoms of dementia (BPSD) affect up to 90% of people living with dementia and include agitation, hallucinations, delusions, sleep or mood changes. BPSD are challenging to treat and there are limited safe and effective pharmacologic treatments. Electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), Deep Brain Stimulation (DBS), Vagal nerve stimulation (VNS), ketamine, and cannabinoids are interventions that have proven effectiveness for other psychiatric conditions including depression and psychosis. More recently, many of these have also been investigated for the treatment of BPSD.This presentation will review the current evidence for using ECT, TMS, ketamine, DBS, VNS, and cannabinoids for the treatment of BPSD. Out of these techniques, ECT has been the most studied and shows some benefit for the treatment of BPSD. TMS has also been studied in over 10 trials and most of these studies show an improvement in BPSD. The effect of TMS on apathy in dementia has been examined in multiple studies, the majority of which have shown benefit. DBS has shown some benefit for improving hallucinations in Parkinson disease dementia in one small RCT of six patients, and the procedure was well tolerated. VNS for BPSD has not been studied. Ketamine, in evidence from heterogeneous case reports, has shown to target three distinct behavioral disturbances, agitation, catatonia and depression, in dementia.Cannabinoids, particularly dronabinol and nabilone, have also been investigated in a number of RCTs and show mixed results for treating agitation in dementia. Sedation was the most common side effect reported but often did not result in discontinuation of therapy.In conclusion, neuromodulation has increasing evidence for the treatment of BPSD and most studies show good safety profiles. Larger and more rigorous trials are needed to further investigate the effectiveness, safety, and practicality of these interventions in this population. This presentation will summarize the effects of these various interventions, their side effects, doses used, and durations of treatment.

Virtual Group Music Therapy for Apathy in Parkinson's Disease: A Pilot Study.

To evaluate the effect of virtual group music therapy on apathy in people with Parkinson's disease (PD). Apathy affects 40% of people with PD, lacks effective therapies, and independently predicts poorer quality of life and greater caregiver burden. Music therapy is the clinical application of music to address a person's physical or emotional needs and is effective in treating apathy in dementia. People with idiopathic PD and apathy (Movement Disorders Society-Unified Parkinson's Disease Rating Scale, apathy item ≥ 2) and their caregivers participated in twelve, weekly virtual group music therapy sessions, with session attendance signifying adherence. Participants completed pre- and post-intervention assessments of apathy (Apathy Scale (AS)), quality of life (Parkinson's Disease Questionnaire-short form), functional ability (Schwab & England Activities of Daily Living Scale), depression (Beck Depression Inventory (BDI-II)), and cognition (Montreal Cognitive Assessment-Blind). Among secondary outcomes, we assessed caregiver burden (Zarit Burden Interview-short form) and strain (Multidimensional Caregiver Strain Index). Sixteen PD participants (93.8% men, mean age 68.3 ± 8.4years, median 6 years PD duration) and their caregivers (93.8% women, mean age 62.6 ± 11years) completed the study. All PD participants and 88% of caregivers were >70% adherent to the intervention. Apathy (AS, effect size = 0.767, P = 0.002) and depression (BDI-II, effect size = 0.542, P = 0.03) improved, with no change in caregiver measures. Group music therapy is an effective treatment for apathy in PD and may improve mood. The virtual format is a feasible alternative to in-person sessions with high adherence and satisfaction.

Alleviating the social, health, and economic costs of apathy in dementia.

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Altered reward processing underpins emotional apathy in dementia

IntroductionWhile apathy is broadly defined as a loss of motivation, it is increasingly recognised as a multidimensional syndrome spanning executive, emotional, and initiation domains. Emotional apathy is purportedly driven by deficits in using socioemotional rewards to guide behaviour, yet the link between these symptoms and reward processing, and their common neural correlates, has not been directly examined.MethodsSixty-four patients (33 behavioural-variant frontotemporal dementia, 14 Alzheimer’s disease, 8 semantic dementia, 6 progressive nonfluent aphasia, 3 logopenic progressive aphasia) were classified into high (HEA; n = 36) and low (LEA; n = 28) emotional apathy groups based on emotional apathy subscale scores on the Dimensional Apathy Scale. Patients and age-matched healthy controls (n = 27) performed an instrumental reward learning task where they learned to associate cues with either social or monetary outcomes.ResultsHEA patients showed impaired learning on both the social and monetary reward conditions, relative to LEA patients (p = 0.016) and controls (p = 0.005). Conversely, the LEA group did not differ from controls (p = 0.925). Importantly, multiple regression analyses indicated that social reward learning significantly predicted emotional apathy. Voxel-based morphometry analyses revealed that emotional apathy and social reward learning were both associated with orbitofrontal cortex, ventral striatum, and insula atrophy.DiscussionOur results demonstrate a unique link between impaired social reward learning and emotional apathy in dementia and reveal a shared neurobiological basis. Greater understanding of these neurocognitive mechanisms of reward processing will help improve the identification of emotional apathy in dementia and inform the development of novel interventions to address these symptoms.

Apathy in UK Care Home Residents with Dementia: Longitudinal Course and Determinants.

Apathy in dementia is common and associated with worse disease outcomes. To describe the longitudinal course of apathy in dementia and identify associated sociodemographic and disease-related factors. Prospective cohort study of UK care home residents with dementia. At baseline, 4, 8, 12, and 16 months, care home staff rated apathy using the Neuropsychiatric Inventory (clinically-significant apathy if≥4), dementia severity, and provided other sociodemographic information about each participant. We examined the prevalence and persistence of apathy and, in mixed linear models, its association with time, age, sex, dementia severity, antipsychotic use, and baseline apathy and other neuropsychiatric symptoms. Of 1,419 included participants (mean age 85 years (SD 8.5)), 30% had mild dementia, 33% moderate, and 37% severe. The point prevalence of clinically-significant apathy was 21.4% (n = 304) and the 16-month period prevalence was 47.3% (n = 671). Of participants with follow-up data, 45 (3.8%) were always clinically-significantly apathetic, 3 (0.3%) were always sub-clinically apathetic, and 420 (36.2%) were never apathetic until death or end of follow-up. In adjusted models, apathy increased over time and was associated with having more severe dementia, worse baseline apathy and other neuropsychiatric symptoms. It is important for clinicians to know that most people with dementia are not apathetic, though it is common. Most of those with significant symptoms of apathy improve without specific treatments, although some also relapse, meaning that intervention may not be needed. Future research should seek to target those people with persistent severe apathy and test treatments in this group.

Pharmacological Management of Apathy in Dementia

Apathy is a highly prevalent symptom of dementia. Despite its association with faster cognitive and functional decline, decreased quality of life and increased mortality, no therapies are currently approved to treat apathy. The objective of this review was to summarize the drugs that have been studied for apathy treatment in patients with dementia (specifically Alzheimer's disease [AD], Huntington's disease [HD] and Parkinson's disease [PD] dementia; dementia with Lewy bodies [DLB]; vascular dementia [VaD]; and frontotemporal dementia [FTD]) based on their putative mechanisms of action. A search for relevant studies was performed using ClinicalTrials.gov and PubMed. Eligible studies were randomized controlled trials that were available in English and included at least one drug intervention and an apathy measure scale. A total of 52 studies that included patients with AD (n = 33 studies), PD (n = 5), HD (n = 1), DLB (n = 1), FTD (n = 3), VaD (n = 1), VaD and AD (n = 4), VaD and mixed dementia (n = 1), and AD, VaD and mixed dementia (n = 3) were eligible for inclusion. These studies showed that methylphenidate, olanzapine, cholinesterase inhibitors, choline alphoscerate, citalopram, memantine, and mibampator are the only beneficial drugs in AD-related apathy. For PD-related apathy, only methylphenidate, rotigotine and rivastigmine showed benefits. Regarding FTD- and DLB-related apathy, initial studies with agomelatine and rivastigmine showed benefits, respectively. As for HD- and only-VaD-related apathy, no drugs demonstrated benefits. With regards to mixed populations, memantine, galantamine and gingko biloba showed effects on apathy in the AD plus VaD populations and nimodipine in the VaD plus mixed dementia populations. Of the drugs with positive results, some are already prescribed to patients with dementia to target other symptoms, some have characteristics-such as medical contraindications (e.g., cardiovascular) and adverse effects (e.g., gastrointestinal disturbances)-that limit their clinical use and some require further study. Future studies should investigate apathy as a primary outcome, making use of appropriate sample sizes and study durations to ensure durability of results. There should also be a consensus on using scales with high test/retest and interrater reliabilities to limit the inconsistencies between clinical trials. In conclusion, there are currently no US FDA-approved drugs that target apathy in dementia, so there is an ongoing need for the development of such drugs.

Examining Caregiver-Resident Communication and Apathy in Dementia in Nursing Homes During the COVID-19 Pandemic

This presentation shares lessons learned from conducting a study examining the impact of staff caregivers’ communication approach on apathy in residents with dementia in nursing homes. Due to COVID-19 restrictions, this study had to be paused and required major revisions to continue, which resulted in significant delays and increased expenses. Additionally, this study required in-person data collection and video recordings to capture staff caregivers’ communication with residents with dementia during caregiving activities. However, due to the pandemic, nursing home residents’ daily routines have been significantly changed, making it challenging to capture the nature of caregiver-resident interactions. Furthermore, using masks created unforeseen barriers for capturing communication between staff caregivers and residents including difficulties in identifying residents’ facial expressions, which are a vital component of assessing apathy. The presentation describes approaches to communication with founders, collaborators, and clinical sites and discusses strategies to recruit participants and conduct data collection.

The experience of apathy in dementia: A qualitative study

AbstractBackgroundThe presence of apathy is associated with less favourable outcomes in dementia, including more rapid functional and cognitive decline, greater disease severity and increased mortality. We aimed to explore and gain an understanding into how people with dementia experience apathy, and consequently suggest effective interventions to help them and their carers.Method12 participants (6 dyads of 6 people with dementia and their family carers) were recruited from memory cafés, social groups, seminars and Patient and Public Involvement (PPI) meetings. People with dementia and their carers were interviewed separately and simultaneously. Quantitative data was collected using the following validated scales: Apathy Evaluation Scale (AES), short Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Montreal Cognitive Assessment (MOCA), Cornell Scale for Depression in Dementia (CSSD) and Hospital Anxiety and Depression (HAD). The interviews were semi‐structured, focusing on the subjective interpretation of apathy and impact on behaviour, habits, hobbies, relationships, mood and activities of daily living. Interviews were recorded and transcribed and analysed using interpretative phenomenological analysis (IPA) which generated codes and patterns, which were collated into themes.ResultThe participants with dementia had mild to moderate degrees of cognitive impairment, with a range between 9‐22 (out of 30) on the MOCA. They reported moderate levels of apathy on the AES.Four superordinate themes were identified, three of which highlighted the challenging aspects of apathy: “Losing one’s sense of self”; “Feeling like a burden” and “Hindered by invisible obstacles”. One theme: ''What keeps me going’’, described the positive aspects of the individuals’ efforts to overcome apathy and remain connected with the world and people around them.ConclusionThis study is the first to illustrate and conceptualise the subjective experience of apathy in dementia, portraying it as a more complex and active phenomenon than the traditional view of apathy being simply negative and hopeless. Our study reveals a struggle against cognitive difficulties, fear of failure and invisible obstacles, with individuals desperate to remain connected, and appreciative of their carers’ efforts to help them. Apathy and its effects warrant more attention from clinicians, researchers and others involved in dementia care.

"He Just Doesn't Want to Get Out of the Chair and Do It": The Impact of Apathy in People with Dementia on Their Carers.

Apathy, defined as a lack of motivation, is a prevalent and persistent behavioural and psychological symptom of dementia. Limited research suggests that apathy is associated with increased carer burden, but there are no studies investigating carers’ subjective experiences of apathy. This study aimed to fill this gap and explore the lived experience of apathy in dementia from the perspectives of the people with dementia and their carers. This article reports on the carers’ perspectives. Six dyads of people with dementia and carers participated in semi-structured interviews, which were analysed using interpretative phenomenological analysis. Three superordinate themes were identified: (1) achieving a balance of conflicting emotions—the challenges of apathy led to feelings of guilt, acceptance, and frustration; (2) new roles imposed by caring, which involved taking on new responsibilities and promoting remaining interests of person with dementia; and (3) having a life of one’s own—coping with apathy by talking to others, and spending time away from the caring role. This study highlighted that carers are caught in a struggle between wanting to involve the person with dementia in decisions and finding that they cannot if they want to overcome the hurdle of apathy. Implications of this study suggest that a wider understanding of apathy at a societal level could lead to the provision of a helpful forum for carers to share their experiences.

Apathy in patients with schizophrenia: Treatment perspectives

Apathy occurs in many neuropsychiatric disorders and is a central negative symptom of schizophrenia. Apathy has severe functional consequences for patients with schizophrenia and the development of evidence-based treatments is a major challenge. There is now increasing evidence that dysfunctions in reward processing underly apathy, in particular regarding reward anticipation, cost-benefit computation and reward learning. In addition, metacognitive processes such as defeatist performance beliefs modulate reward processing. Psychological interventions for negative symptoms target these processes. While the evidence for cognitive-behavioral therapy for negative symptoms remains limited, recent findings suggest that specifically targeting reward-related dysfunctions may improve efficacy of these interventions. On the neurobiological level, there is now considerable evidence that a dysregulation of the dopaminergic reward system is related to reward processing dysfunctions. Regarding pharmacological treatment approaches, psychostimulants have successfully been used for apathy in dementia to target the reward system. Pro-dopaminergic drugs to target apathy in schizophrenia seem to be safer than anticipated, but their efficacy remains to be established. At the current state of knowledge, there is no evidence-based treatment that specifically targets apathy in patients with schizophrenia today. However, there are encouraging results from research inspired by basic research in neuroscience and clinical research in patients with other neuropsychiatric disorders.DisclosureSK has received royalties from Schuhfried (Austria) for cognitive test and training software.

The Experience of Apathy in Dementia: A Qualitative Study.

We aimed to explore and gain an understanding into how people with dementia experience apathy, and consequently suggest effective interventions to help them and their carers. Twelve participants (6 dyads of 6 people with dementia and their family carers) were recruited from “memory cafes” (meeting groups for people with dementia and their families), social groups, seminars, and patient and public involvement (PPI) meetings. People with dementia and their carers were interviewed separately and simultaneously. Quantitative data were collected using validated scales for apathy, cognition, anxiety, and depression. The interviews were semi-structured, focusing on the subjective interpretation of apathy and impacts on behaviour, habits, hobbies, relationships, mood, and activities of daily living. Interviews were recorded and transcribed. Transcripts were analysed using interpretative phenomenological analysis (IPA), which generated codes and patterns that were collated into themes. Four major themes were identified, three of which highlighted the challenging aspects of apathy. One described the positive aspects of the individuals’ efforts to overcome apathy and remain connected with the world and people around them. This study is the first to illustrate the subjective experience of apathy in dementia, portraying it as a more complex and active phenomenon than previously assumed. Apathy and its effects warrant more attention from clinicians, researchers, and others involved in dementia care.

Function-Focused Person-Environment Fit for Long-Term Care Residents With Dementia: Impact on Apathy.

Apathy is a common symptom in dementia and is associated with rapid cognitive decline, poor quality of life, and higher mortality. Lawton's Competence and Environmental Press model suggests that an individual's behavior and affect are influenced by the fit of their functional abilities with the environmental demands. Yet, empirical evidence on the association between person-environment (P-E) fit and apathy is lacking. Thus, this study examined the relationship between P-E fit and apathy in dementia. Specifically, this study focused on the extent the physical environment fits individual functional limitations. This is a cross-sectional study using the baseline data from long-term care residents with dementia. The sample included 199 residents with moderate-to-severe cognitive impairment from 4 assisted living and 4 nursing homes. Function-focused P-E fit was measured using the Housing Enabler scale. Apathy was measured using the Apathy Evaluation Scale. Multilevel linear models were used to analyze the relationship between P-E fit and apathy. Findings revealed that greater P-E fit, specifically indoor environment, was significantly associated with lower apathy after controlling for age, gender, and years living in the facility. Yet, the association became not significant after controlling for individual physical function. Findings support the association between function-focused P-E fit and apathy, but the association is no longer significant after physical function is adjusted. Future research may explore other aspects of P-E fit and the impact of social and organizational environment on apathy in dementia.

Four Potentially Practice-Changing Articles From 2018

Four key articles published in 2018 have been selected to represent clinical situations where recent evidence may prompt changes in practice relevant to the nursing home population. There is no evidence of benefit for levothyroxine replacement in mild subclinical hypothyroidism. Duloxetine may be considered as an option for the treatment of pain and stiffness in osteoarthritis of the knees. Supplemental oxygen in the absence of hypoxemia is unnecessary and potentially harmful. Methylphenidate has modest benefit in treating apathy in dementia. For each subject, a brief review of the pertinent article is followed by a “bottom line” recommendation.

Apathy is associated with faster global cognitive decline and early nursing home admission in dementia with Lewy bodies

BackgroundLittle is known about the consequences of apathy in dementia with Lewy bodies (DLB), because previous research on apathy in dementia focused mainly on Alzheimer’s disease (AD).MethodsIn this longitudinal study, we included patients with AD (n = 128) and patients with DLB (n = 81). At baseline, we analyzed the associations between apathy and cognition in the total sample and in AD and DLB separately. Generalized linear mixed models were used to investigate the association between apathy and Mini Mental State Examination (MMSE) over 4 years, and the Kaplan-Meier method was used to assess the association between apathy and survival or nursing home admission.ResultsIn patients with DLB, apathy was associated with a faster global cognitive decline (MMSE) over 4 years. Patients with DLB and apathy had shorter time until nursing home admission than DLB patients without apathy and patients with AD, regardless of apathy. At baseline, patients with apathy had decreased performance on the Stroop color test and a composite executive function score. Neurocognition was unaffected by apathy in AD, but DLB patients with apathy had more verbal learning difficulties.ConclusionsApathy seems to be associated with more serious symptomatology in DLB than in AD. It is important to focus on apathy in dementia because it is one of the most prevalent and disturbing behavioral and psychological symptoms.

Diagnosing and Treating Apathy in Dementia

Diagnosing and Treating Apathy in Dementia

A systematic review of non‐pharmacological treatments for apathy in dementia

Apathy is one of the most frequent neuropsychiatric symptoms encountered in dementia. Early diagnosis and timely treatment of apathy in dementia are crucial because apathy has been associated with poor disease outcome, reduced daily functioning, and caregiver distress. Extensive electronic search from the databases included in the National Library of Medicine as well as PsychInfo and Google Scholar for studies which have investigated the effect of non-pharmacological treatments of apathy in dementia. Quality of the studies was appraised. A total of 1303 records were identified and 120 full-texts assessed. Forty-three unique studies were reviewed. A variety of interventions were found to be effective in reducing apathy in demented patients, particularly when provided in a multidisciplinary manner. However, quantification of the effect was limited by the marked methodological heterogeneity of the studies and the small number of studies where apathy was the primary outcome measure. Treatment of apathy in dementia is a complex and underexplored field. Certain studies suggest promise for a variety of non-pharmacological interventions. Standardized and systematic efforts primarily focusing on apathy may establish a benefit from individualized treatments for specific disease groups.

Different apathy clinical profile and neural correlates in behavioral variant frontotemporal dementia and Alzheimer's disease

Apathy is one of the most common and disabling syndromes of dementia. Clinical apathy expression and neuroanatomical basis of apathy seem to differ between behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD), although evidence is scarce and poorly understood. Our main purposes were to compare the clinical apathy profile from patients with bvFTD and AD and analyze the relationship between apathy and brain metabolism measured using positron emission tomography imaging with 18 F fluorodeoxyglucose (FDG-PET). Forty-two bvFTD, 42 AD, and 30 healthy volunteers without cognitive or behavioral complaints were included. Apathy was defined using Robert's 2009 diagnostic criteria, and specific apathy characteristics were assessed with the Lille Apathy Rating Scale. All participants underwent FDG-PET brain scan to provide data for voxel-based morphometric analysis. Multivariate analysis showed that subjects affected by bvFTD displayed greater impairment of emotional apathy and self-awareness in comparison with AD sample. Additionally, FDG-PET imaging analyses revealed that apathy was associated with different neuroanatomical substrates in each dementia group: left lateral prefrontal, medial frontal/anterior cingulate, lateral orbitofrontal and anterior insular cortices in bvFTD, and right anterior cingulate in AD. These results support that apathy is a complex syndrome, with different clinical expressions across different pathological conditions. Those differences in qualitative aspects of apathy seem to be associated with differences in the damage sites, as shown by our FDG-PET imaging analysis. Our findings provide a better knowledge about pathophysiology of apathy in dementia, which could have practical implications for therapeutic management. Copyright © 2017 John Wiley & Sons, Ltd.

Apathy in Dementia: Systematic Review of Recent Evidence on Pharmacological Treatments.

Increasing recognition that apathy is one of the most prevalent behavioral and psychological symptoms of dementia and causes substantial caregiver distress has led to trials evaluating psychosocial and pharmacological treatments of apathy in dementia. We evaluated evidence of the efficacy of pharmacotherapies for apathy in dementia from studies since 2013. Previously reported benefits of acetylcholinesterase inhibitors and memantine were not replicated in recent studies. Antidepressants had mixed results with positive effects for apathy shown only for agomelatine, while stimulants, analgesics, and oxytocin study results were inconclusive. For some approaches, such as antipsychotic review, positive effects were found only in combination with nonpharmacological approaches. Relatively few studies assessed apathy outcomes specifically, complicating interpretation of potentially positive treatment effects; none dissected outcomes for emotional, motivational and behavioral components of apathy. Better trial design and more detailed analysis are needed in order to evaluate outcomes of pharmacological treatments for apathy.