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Alzheimer's & Dementia : the Journal of... Sep 2011Neuropsychiatric symptoms (NPS) are core features of Alzheimer's disease and related dementias. Once thought to emerge primarily in people with late-stage disease, these...
Neuropsychiatric symptoms (NPS) are core features of Alzheimer's disease and related dementias. Once thought to emerge primarily in people with late-stage disease, these symptoms are currently known to manifest commonly in very early disease and in prodromal phases, such as mild cognitive impairment. Despite decades of research, reliable treatments for dementia-associated NPS have not been found, and those that are in widespread use present notable risks for people using these medications. An Alzheimer's Association Research Roundtable was convened in the spring of 2010 to review what is known about NPS in Alzheimer's disease, to discuss classification and underlying neuropathogenesis and vulnerabilities, and to formulate recommendations for new approaches to tailored therapeutics.
Topics: Aged; Aggression; Alzheimer Disease; Apathy; Cognitive Dysfunction; Depressive Disorder; Humans; Neurocognitive Disorders
PubMed: 21889116
DOI: 10.1016/j.jalz.2011.05.2410 -
BMJ Open Sep 2020To conduct a scoping review of the literature on apathy in Parkinson's disease (PD), to better understand how apathy in Parkinson's disease is diagnosed, treated and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To conduct a scoping review of the literature on apathy in Parkinson's disease (PD), to better understand how apathy in Parkinson's disease is diagnosed, treated and managed.
METHODS
MEDLINE, Embase, PsycINFO, CINAHL, Cochrane Central Register of Control Trials and Cochrane Database of Systematic Reviews were searched to 17 May 2017. An updated review was run from 17 May 2017 to 28 January 2019. The grey literature was searched using the CADTH Grey Matters tool. Original peer-reviewed research was included if it included individuals with PD and apathy. Non-original data was only included if it was in the form of meta-analysis. All information regarding diagnosis, treatment and management of PD was extracted. Citation screening and extraction were performed in duplicate.
RESULTS
From 11 375 citations, 362 articles were included in the final review. The majority of included studies focussed on prevalence, with few studies examining treatment. Twenty screening tools for apathy were identified. Fifty per cent of treatment studies were randomised control trials (RCTs). RCTs applied treatment methods including: exercise, mindfulness, rotigotine (Neupro) transdermal patch and rivastigmine (Exelon).
CONCLUSIONS
This review identified a large body of literature describing current knowledge on diagnosing, treating and managing apathy in PD. Future research should aim to detect an ideal screening tool for apathy in PD, to identify the best treatment options for apathy and the variety of comorbidities it may present with and finally aim to better understand postoperative apathy in those with deep brain stimulation.
Topics: Apathy; Humans; Parkinson Disease; Systematic Reviews as Topic; Transdermal Patch
PubMed: 32907903
DOI: 10.1136/bmjopen-2020-037632 -
International Journal of Stroke :... Jul 2021Apathy is a reduction in goal-directed activity in the cognitive, behavioral, emotional, or social domains of a patient's life and occurs in one out of three patients... (Review)
Review
Apathy is a reduction in goal-directed activity in the cognitive, behavioral, emotional, or social domains of a patient's life and occurs in one out of three patients after stroke. Despite this, apathy is clinically under-recognized and poorly understood. This overview provides a contemporary introduction to apathy in stroke for researchers and practitioners, covering topics including diagnosis, neurobiological mechanisms, associated consequences, and potential treatments for apathy. Apathy is often misdiagnosed as other post-stroke conditions such as depression. Accurate differential diagnosis of apathy, which manifests as reductions in initiative, and depression, which manifests as negative emotionality, is important as it informs prognosis. Research on the neurobiology of apathy suggests that there are few consistent associations between stroke lesion location and the development of apathy. These may be resolved by adopting a network neuroscience approach, which models apathy as a pathology arising from structural or functional damage to brain networks underlying motivated behavior. Importantly, networks can be affected by physiological changes related to stroke, including the acute infarct but also diaschisis and neurodegeneration. Aside from neurobiological changes, apathy is also associated with other negative outcome measures such as functional disability, cognitive impairment, and emotional distress, suggesting that apathy is indicative of a worse prognosis following stroke. Unfortunately, high-quality trials aimed at treating apathy are scarce. Antidepressants may have limited effects on apathy. Acetylcholine and dopamine pharmacotherapy, behavioral interventions, and transcranial magnetic stimulation may be more promising avenues for treatment.
Topics: Apathy; Brain; Cognitive Dysfunction; Emotions; Humans; Stroke
PubMed: 33527880
DOI: 10.1177/1747493021990906 -
Psychotherapy and Psychosomatics 2019Negative symptoms are frequent in patients with schizophrenia and are associated with marked impairments in social functioning. The efficacy of drug-based treatments and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Negative symptoms are frequent in patients with schizophrenia and are associated with marked impairments in social functioning. The efficacy of drug-based treatments and psychological interventions on primary negative symptoms remains limited. The Positive Emotions Programme for Schizophrenia (PEPS) is designed to improve pleasure and motivation in schizophrenia patients by targeting emotion regulation and cognitive skills relevant to apathy and anhedonia. The main hypothesis of this study is that patients who attend 8 one-hour sessions of PEPS and treatment as usual (TAU) will have lower total apathy-avolition and anhedonia-asociality composite scores on the Scale for the Assessment of Negative Symptoms (SANS) than patients who attend only TAU.
METHODS
Eighty participants diagnosed with schizophrenia or schizoaffective disorder were randomized to receive either TAU or PEPS + TAU. The participants were assessed by independent evaluators before randomization (T0), in a post-test after 8 weeks of treatment (T1) and at a 6-month follow-up (T2).
RESULTS
The post-test results and 6-month follow-up assessments according to an intention-to-treat analysis showed that the apathy and anhedonia composite scores on the SANS indicated statistically greater clinical improvements in PEPS participants than in non-PEPS participants. In the post-test, anhedonia but not apathy was significantly improved, thus favouring the PEPS condition. These results were sustained at the 6-month follow-up.
CONCLUSIONS
PEPS is an effective intervention to reduce anhedonia in schizophrenia. PEPS is a short, easy-to-use, group-based, freely available intervention that is easy to implement in a variety of environments (ClinicalTrials.gov ID: NCT02593058).
Topics: Adult; Anhedonia; Apathy; Cognitive Behavioral Therapy; Female; Humans; Male; Motivation; Pleasure; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Treatment Outcome
PubMed: 30783071
DOI: 10.1159/000496479 -
JAMA Neurology Nov 2021Apathy, characterized by diminished will or initiative and one of the most prevalent neuropsychiatric symptoms in individuals with Alzheimer disease, is associated with... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Apathy, characterized by diminished will or initiative and one of the most prevalent neuropsychiatric symptoms in individuals with Alzheimer disease, is associated with significant caregiver burden, excess disability, increased medical costs, and mortality.
OBJECTIVE
To measure whether methylphenidate compared with placebo decreases the severity of apathy in individuals with Alzheimer disease.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter randomized placebo-controlled clinical trial was conducted from August 2016 to July 2020 in 9 US clinics and 1 Canadian clinic specializing in dementia care. A total of 307 potential participants were screened. Of those, 52 did not pass screening and 55 were not eligible. Participants with Alzheimer disease, mild to moderate cognitive impairment, and frequent and/or severe apathy as measured by the Neuropsychiatric Inventory (NPI) were included.
INTERVENTIONS
Ten milligrams of methylphenidate, twice daily, vs matching placebo.
MAIN OUTCOMES AND MEASURES
The coprimary outcomes included (1) change from baseline to 6 months in the NPI apathy subscale or (2) improved rating on the Alzheimer's Disease Cooperative Study Clinical Global Impression of Change. Other outcomes include safety, change in cognition, and quality of life.
RESULTS
Of 200 participants, 99 were assigned to methylphenidate and 101 to placebo. The median (interquartile range) age of study participants was 76 (71-81) years; 68 (34%) were female and 131 (66%) were male. A larger decrease was found from baseline to 6 months in the NPI apathy score in those receiving methylphenidate compared with placebo (mean difference, -1.25; 95% CI, -2.03 to -0.47; P = .002). The largest decrease in the NPI apathy score was observed in the first 100 days, with a significant hazard ratio for the proportion of participants with no apathy symptoms receiving methylphenidate compared with placebo (hazard ratio, 2.16; 95% CI, 1.19-3.91; P = .01). At 6 months, the odds ratio of having an improved rating on the Alzheimer's Disease Cooperative Study Clinical Global Impression of Change for methylphenidate compared with placebo was 1.90 (95% CI, 0.95-3.84; P = .07). The difference in mean change from baseline to 6 months estimated using a longitudinal model was 1.43 (95% CI, 1.00-2.04; P = .048). Cognitive measures and quality of life were not significantly different between groups. Of the 17 serious adverse events that occurred during the study, none were related to the study drug. No significant differences in the safety profile were noted between treatment groups.
CONCLUSIONS AND RELEVANCE
This study found methylphenidate to be a safe and efficacious medication to use in the treatment of apathy in Alzheimer disease.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02346201.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Apathy; Central Nervous System Stimulants; Female; Humans; Male; Methylphenidate
PubMed: 34570180
DOI: 10.1001/jamaneurol.2021.3356 -
Drugs & Aging Jun 2022Depression is one of the most frequent and burdensome non-motor symptoms in Parkinson's disease (PD), across all stages. Even when its severity is mild, PD depression... (Review)
Review
Depression is one of the most frequent and burdensome non-motor symptoms in Parkinson's disease (PD), across all stages. Even when its severity is mild, PD depression has a great impact on quality of life for these patients and their caregivers. Accordingly, accurate diagnosis, supported by validated scales, identification of risk factors, and recognition of motor and non-motor symptoms comorbid to depression are critical to understanding the neurobiology of depression, which in turn determines the effectiveness of dopaminergic drugs, antidepressants and non-pharmacological interventions. Recent advances using in vivo functional and structural imaging demonstrate that PD depression is underpinned by dysfunction of limbic networks and monoaminergic systems, depending on the stage of PD and its associated symptoms, including apathy, anxiety, rapid eye movement sleep behavior disorder (RBD), cognitive impairment and dementia. In particular, the evolution of serotonergic, noradrenergic, and dopaminergic dysfunction and abnormalities of limbic circuits across time, involving the anterior cingulate and orbitofrontal cortices, amygdala, thalamus and ventral striatum, help to delineate the variable expression of depression in patients with prodromal, early and advanced PD. Evidence is accumulating to support the use of dual serotonin and noradrenaline reuptake inhibitors (desipramine, nortriptyline, venlafaxine) in patients with PD and moderate to severe depression, while selective serotonin reuptake inhibitors, repetitive transcranial magnetic stimulation and cognitive behavioral therapy may also be considered. In all patients, recent findings advocate that optimization of dopamine replacement therapy and evaluation of deep brain stimulation of the subthalamic nucleus to improve motor symptoms represents an important first step, in addition to physical activity. Overall, this review indicates that increasing understanding of neurobiological changes help to implement a roadmap of tailored interventions for patients with PD and depression, depending on the stage and comorbid symptoms underlying PD subtypes and their prognosis.
Topics: Antidepressive Agents; Apathy; Depression; Humans; Parkinson Disease; Quality of Life
PubMed: 35705848
DOI: 10.1007/s40266-022-00942-1 -
Hong Kong Medical Journal = Xianggang... Jun 2018
Topics: Apathy; Breast Neoplasms; Colorectal Neoplasms; Humans; Mutation; Stroke
PubMed: 29937435
DOI: No ID Found -
Psychological Medicine Apr 2023Apathy, a disabling and poorly understood neuropsychiatric symptom, is characterised by impaired self-initiated behaviour. It has been hypothesised that the (OCT) may...
BACKGROUND
Apathy, a disabling and poorly understood neuropsychiatric symptom, is characterised by impaired self-initiated behaviour. It has been hypothesised that the (OCT) may be a key computational variable linking self-initiated behaviour with motivational status. OCT represents the amount of reward which is foregone per second if no action is taken. Using a novel behavioural task and computational modelling, we investigated the relationship between OCT, self-initiation and apathy. We predicted that higher OCT would engender shorter action latencies, and that individuals with greater sensitivity to OCT would have higher behavioural apathy.
METHODS
We modulated the OCT in a novel task called the 'Fisherman Game', Participants freely chose when to self-initiate actions to either collect rewards, or on occasion, to complete non-rewarding actions. We measured the relationship between action latencies, OCT and apathy for each participant across two independent non-clinical studies, one under laboratory conditions ( = 21) and one online ( = 90). 'Average-reward' reinforcement learning was used to model our data. We replicated our findings across both studies.
RESULTS
We show that the latency of self-initiation is driven by changes in the OCT. Furthermore, we demonstrate, for the first time, that participants with higher apathy showed greater sensitivity to changes in OCT in younger adults. Our model shows that apathetic individuals experienced greatest change in subjective OCT during our task as a consequence of being more sensitive to rewards.
CONCLUSIONS
Our results suggest that OCT is an important variable for determining free-operant action initiation and understanding apathy.
Topics: Adult; Humans; Apathy; Cognition; Computer Simulation; Motivation; Reinforcement, Psychology
PubMed: 37310334
DOI: 10.1017/S0033291721003469 -
Journal of Neurology, Neurosurgery, and... Mar 2019The past few decades have seen growing interest in the neuropsychiatric syndrome of apathy, conceptualised as a loss of motivation manifesting as a reduction of... (Review)
Review
The past few decades have seen growing interest in the neuropsychiatric syndrome of apathy, conceptualised as a loss of motivation manifesting as a reduction of goal-directed behaviour. Apathy occurs frequently, and with substantial impact on quality of life, in a broad range of neurological and psychiatric conditions. Apathy is also consistently associated with neuroimaging changes in specific medial frontal cortex and subcortical structures, suggesting that disruption of a common systems-level mechanism may underlie its development, irrespective of the condition that causes it. In parallel with this growing recognition of the clinical importance of apathy, significant advances have been made in understanding normal motivated behaviour in humans and animals. These developments have occurred at several different conceptual levels, from work linking neural structures and neuromodulatory systems to specific aspects of motivated behaviour, to higher order computational models that aim to unite these findings within frameworks for normal goal-directed behaviour. In this review we develop a conceptual framework for understanding pathological apathy based on this current understanding of normal motivated behaviour. We first introduce prominent theories of motivated behaviour-which often involves sequences of actions towards a goal that needs to be maintained across time. Next, we outline the behavioural effects of disrupting these processes in animal models, highlighting the specific effects of these manipulations on different components of motivated behaviour. Finally, we relate these findings to clinical apathy, demonstrating the homologies between this basic neuroscience work and emerging behavioural and physiological evidence from patient studies of this syndrome.
Topics: Apathy; Brain Diseases; Humans; Motivation
PubMed: 30366958
DOI: 10.1136/jnnp-2018-318265 -
Scientific Reports May 2022Apathy and fatigue have a high prevalence in many pathological populations, but they are also present in healthy adults. The relationship between apathy and fatigue,...
Apathy and fatigue have a high prevalence in many pathological populations, but they are also present in healthy adults. The relationship between apathy and fatigue, which are both multidimensional, is still poorly understood. This study aims to describe the associations between the subdimensions of both apathy and fatigue and to investigate their overlaps and dissociations in healthy people. 729 participants (mean age = 30.8 ± 10.7 years) completed online self-assessment questionnaires. The Apathy Motivation Index and Dimensional Apathy Scale were used to assess apathy. The Multidimensional Fatigue Inventory was used to assess fatigue. The executive dimension of apathy showed the strongest correlations with mental fatigue and the two appeared to be underpinned by the same latent factor, according to exploratory factor analysis (EFA). The factor structure of EFA showed overlaps between behavioral apathy and both reduced motivation and activity in fatigue. Emotional and social dimensions of apathy were separately underpinned by a latent factor that comprised no items of fatigue. Apathy and fatigue have reduced activity and mental difficulties in common, whereas emotional and social disorders distinguish apathy from fatigue. This has important implications for assessing apathy and fatigue in the general population, and may be relevant for clinical practice.
Topics: Adult; Apathy; Emotions; Factor Analysis, Statistical; Humans; Motivation; Surveys and Questionnaires; Young Adult
PubMed: 35513461
DOI: 10.1038/s41598-022-11071-5