Relationship between apathy and cognitive dysfunctions in de novo untreated Parkinson's disease: a prospective longitudinal study (original) (raw)
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Cognitive correlates of “pure apathy” in Parkinson's disease
Parkinsonism & Related Disorders, 2018
Introduction: Previous studies exploring the association between apathy and cognitive deficits in Parkinson's disease (PD) employed scales and questionnaires for apathy, which did not control for the possible confounding effect of motor symptoms. Here we investigated the cognitive correlates of "pure apathy" by the Dimensional Apathy Scale, which allows us to assess apathy minimizing the influence of motor symptoms. Methods: Consecutive PD outpatients referred to our centre were screened. All participants underwent a neuropsychological battery to assess verbal memory, executive functions and visuospatial abilities, apathy and depressive symptoms. Results: We enrolled 56 non-depressed and non-demented PD patients, of whom 28 were apathetic and 28 were not. The two groups did not differ on demographic and clinical aspects; apathetic PD patients performed worse than non-apathetic PD patients on the part A, B and B-A of Trail Making Test and the interference task of Stroop test. No significant differences were found on memory and perceptual visuospatial tasks. Conclusions: Our results demonstrated that "pure apathy" is associated with more severe executive dysfunctions such as alteration of set-shifting and inhibitory control, which are mediated by prefrontal cortex and subcortical regions (i.e. basal ganglia). Our findings also supported the hypothesis that co-occurrence of apathy and executive deficits may be the epiphenomenon of damage in prefrontal-striatal cortical circuitries connecting dorsolateral prefrontal cortex, anterior cingulate cortex and basal ganglia.
The syndromal validity and nosological position of apathy in Parkinson's disease
Movement Disorders, 2009
Although apathy is among the most frequent behavioral changes in Parkinson's disease (PD), its diagnosis is still problematic, and the overlap with depression and dementia poorly studied. Aim of the study was validate specific criteria to diagnose apathy in PD, and to examine its association with subsyndromes of depression and dementia. A series of 164 patients with PD, 44 patients with ''primary'' depression and no PD, 23 patients with Alzheimer's disease, and 26 age-comparable healthy controls underwent a comprehensive psychiatric assessment that included a structured psychiatric interview and the Apathy Scale. A set of seven diagnostic criteria showed high sensitivity and specificity for clinically diagnosed apathy. Fifty-two of the 164 patients with PD (32%) met diagnostic criteria for apathy. Eighty-three percent of patients with apathy had comorbid depression and 56% had dementia. Only 5 of the 40 PD patients (13%) with neither depression nor dementia had apathy. We validated a set of standardized criteria for the diagnosis of apathy in PD. About one third of a series of patients attending a Movement Disorders Clinic showed apathy. Both depression and dementia were the most frequent comorbid conditions of apathy in PD.
Apathy may herald cognitive decline and dementia in Parkinson's disease
Movement Disorders, 2009
Apathy is usually defined as a lack of motivation. It may occur as part of another disorder (notably depression and dementia) or as an isolated syndrome. In Parkinson's disease (PD), apathy is common and several studies have reported an association between this condition and more severe cognitive symptoms, such as executive dysfunction. However, this association has not been thoroughly investigated. The aim of this study (in nondepressed, nondemented PD patients) was to examine whether or not cognitive decline and/or dementia occurred more frequently in apathetic subjects than in nonapathetic subjects. Forty consecutive PD patients participated in the study (20 with apathy and 20 without). None of the subjects were either demented or depressed at the time of study entry. The patients' cognitive functions were extensively assessed twice: at study entry and after an 18-month follow-up period. At study entry, the apathetic PD patients had significantly lower global cognitive status and executive function scores than the nonapathetic subjects. After a median period of 18 months, the rate of conversion to dementia was found to be significantly higher in the apathetic group than in the nonapathetic group (8 of 20 and 1 of 20, respectively). Even in nondemented patients, the decrease over time in cognitive performance (mainly executive function but also memory impairment) was significantly greater in apathetic subjects than in nonapathetic subjects. These findings suggest that in nondemented, nondepressed PD patients, apathy may be a predictive factor for dementia and cognitive decline over time.
Behavioural neurology, 2013
Apathy has been defined as lack of motivation. It has been traditionally considered as a symptom of psychiatric disorders, such as major depression and schizophrenia, but more recently it has been recognized as a specific neuropsychiatric syndrome associated with neurodegenerative such as Parkinson's disease (PD). As a consequence the reported prevalence of apathy in PD ranges from 13.9% to 70%; the mean prevalence is 35%. Prevalence of "pure apathy" (i.e., of apathy without comorbid depression and dementia) seems to be substantially lower, from 3 to 47.9%. High levels of apathy in PD are associated with decreased daily function, specific cognitive deficits and increased stress for families. Although neuroimaging studies do not provide a unique anatomic pattern, several data suggest that the ventromedial prefrontal cortex and the basal ganglia connected through frontal-subcortical circuits, are particularly involved in the genesis of apathy. At present, there are no approved medications for the treatment of apathy in and no proof of efficacy exists for any drug in current use. Further studies and innovative pharmacologic approaches are thus needed to ameliorate our understanding and treatment of apathy in PD.
Characteristics of apathy in Parkinson's disease
Movement Disorders, 2007
The objective of this study was to use the Lille Apathy Rating Scale to assess apathy in a large population of Parkinson's disease (PD) patients and identify several different apathy profiles. One hundred fifty-nine patients with probable PD and 58 healthy controls participated in the study. Apathy was assessed using the Lille Apathy Rating Scale. Motor, cognitive, and depressive symptoms were rated on standardized scales. Data were analyzed using linear regression and multivariate analyses of variance. Thirty-two percent of the PD patients were classified as apathetic. Apathy was more frequent in patients with dementia. The four apathy dimensions contributed differently to the overall severity of the apathetic condition. Action initiation and intellectual curiosity had a marked influence. Linear regression analysis revealed that the apathy level was mainly determined by cognitive impairment, not associated with the severity of motor symptoms, and only associated with the apathy subcomponent of the Montgomery and Asberg Depression Rating Scale. Apathy is highly prevalent in PD patients. Apathy profiles vary according to the clinical presentation of PD. The high prevalence of apathy in PD suggests the involvement of frontal-subcortical circuits. Although the neurochemical substrate of apathy remains poorly characterized, the strong link between apathy and cognitive impairment observed in several studies suggests the participation of nondopaminergic circuits.
Neuropsychologia, 2018
Apathy is frequently reported in individuals with Parkinson's disease (PD) and is hypothesized to be associated with frontal-striatal related cognitive functions. Available data, however, do not provide univocal results. Moreover, this relationship has been poorly investigated in PD patients with mild cognitive impairment (MCI). This study was aimed at investigating the association between severity of apathy of PD patients and their performance on neuropsychological tests investigating executive abilities. Individuals with PD (i.e., with and without MCI) and healthy controls (HCs) were administered a neuropsychological test battery that investigated episodic memory, language, short-term memory and attention, visual-spatial abilities and executive functions. Subjects were also administered additional neuropsychological tests to evaluate the different executive subcomponents (i.e., planning/abstract reasoning, self-monitoring/response inhibition, working memory, shifting and fluen...
The Negative Impact of Apathy in Parkinson’s Disease
Symptoms of Parkinson's Disease, 2011
Aside from diagnostic criteria, apathy can also be rated using a number of different validated apathy rating scales. These scales were reviewed by the Movement Disorder Society (MDS) and the recommendation for PD was that the Apathy Scale (AS) (Starkstein et al., 1992) or the Apathy Evaluation Scale (AES; clinician version, AES-C) (Marin, 1991) were the most robust scales for use in PD (Leentjens et al., 2008). PD-specific apathy rating scales which have recently been developed include the Apathy Inventory (AI) (Robert al., 2002), which can be either patient-or informant-rated, as well as the Lille Apathy Scale (LARS) (Sockeel et al., 2006). The LARS is a 33-item scale comprised of nine domains underscoring the apathy syndrome. Scores can range from an optimal score (no apathy) of +36 to the most severe score of-36, and the cutoff score for moderate apathy is-16. Principal component analysis of data derived from a study of 159 PD participants (51 with apathy as per the LARS cutoff) revealed a four-factor solution describing apathy dimensions. These were: intellectual curiosity, action initiation, emotion and self-awareness (Dujardin et al., 2007). Gallagher et al. (2008) used the LARS to determine how useful the Unified Parkinson's Disease Rating Scale, Part I (UPDRS) (Fahn & Elton, 1987) is as an apathy screening and diagnostic instrument by rating both scales in 74 PD sufferers. Using the LARS cutoff , 20% of the sample had apathy and they found that the UPDRS apathy item was sensitive (73%) in detecting apathy in PD but did not have sufficient diagnostic quality. Finally, the apathy domain of the informant-based Neuropsychiatric Inventory (NPI) (Cummings et al., 1994), has also been validated for identifying apathy, as either a "present/absent", or in terms of magnitude (frequency x severity). On this scale, a domain score for magnitude of symptoms of ≥ 4 indicates "clinically significant" pathology although no clear cutoff score for apathy per se has been established. A clinician-rated version of the NPI (NPI-C) is currently being developed and may be useful in the assessment and diagnosis of apathy (de Medeiros et al., 2010). The underlying pathophysiology of apathy is related to specific disease-related degenerative brain changes that impact on motivation, and possibly, reward pathways. In particular, deficits in the frontal-subcortical circuit involving the anterior cingulated cortex (ACC) are likely to result in an apathy syndrome, or in specific dimensions of the syndrome (Robert et al., 2009; Devinsky et al., 1995). Neurotransmitter deficits which may play a role in apathy include: dopamine, which is important in reward and motivation; serotonin (5-HT), which may also have a role in PD-related depression in PD; and acetylcholine, a key neurotransmitter whose loss is related to dementia in PD (Czernecki et al., 2002; Leentjens et al., 2006). The syndrome of apathy may occur as a sole behavioural complication of PD, or, as is frequently the case, may be co-morbid with other psychiatric complications such as depression or anxiety (Pluck and Brown, 2002; Aarsland et al, 1999). In our own cross-sectional study of a sample of 99 PD participants without dementia, the proportion of the 26 participants with apathy (on AES-C) who also experienced moderate to severe depression (Hospital Anxiety and Depression Rating Scale (HADS), depression sub-score ≥ 11) was 45%, which was significantly higher than in the PD participants with no apathy. Furthermore, HADS anxiety ratings were also significantly higher in those with apathy compared to those with no apathy (Leroi et al., 2009). The co-occurrence of apathy and depression in PD may be a diagnostic challenge, however, it is important to distinguish these syndromes in order to ensure that management strategies for depression, which are commonly prescribed, do not worsen or leave apathy symptoms untreated. If properly validated scales for apathy and depression are used in the diagnosis, it is possible to parse out the diagnostic entities with a degree of accuracy (Marin et al., 1993; Dujardin et al., 2007).
Clinical, neuropsychological, and morphometric correlates of apathy in Parkinson's disease
Movement Disorders, 2002
Apathy is a salient feature of various neuropsychiatric disorders, from depression to Alzheimer's disease. We formally assess its prevalence in idiopathic Parkinson's disease (PD) together with its clinical, neuropsychological, and morphometric correlates. Thirty patients with PD and 25 normal controls were assessed using an extensive neuropsychological battery and Marin's Apathy Scale; parkinsonian patients also underwent MRI scan, followed by linear measurement of various frontotemporal structures. Approximately 45% of the PD sample showed apathy. For comparison analysis, given the unimodal distribution of the apathy scores, the PD sample was divided into three groups on the basis of the apathy tertiles. All three PD groups had worse cognitive and depression scores than controls, whereas they did not differ in terms of demographic, neurological, general cognitive, or affective features. By contrast, a significant positive association was found between apathy scores and performance on tests of executive function. As regards the morphometric data, we failed to find any specific measure of frontotemporal atrophy correlating with the presence or severity of apathy. Thus, apathy seems to be a frequent and important companion of PD, in many cases probably due to a primary motivational impairment, possibly related to a frontosubcortical dysfunction.
Apathy in Parkinson's disease: Diagnostic and etiological dilemmas
Movement Disorders, 2012
About one-third of patients with Parkinson's disease (PD) are diagnosed with apathy in cross-sectional studies. However, once patients with concomitant depression and dementia are excluded, the frequency of apathy drops to 5% to 10%. Several scales have been recommended to rate apathy in PD, but specific psychiatric interviews have not been developed, and recently proposed standardized diagnostic criteria are still in the validation process. Most studies assessing the association between subthalamic deep brain stimulation (STN-DBS) and apathy have reported a relative increase in the frequency and severity of apathy, although discrepant findings have also been reported. Several mechanisms to explain apathy in PD have been proposed, from dopaminergic imbalances in frontal-basal ganglia circuits to dysfunction of nondopaminergic circuits and the cingulate gyrus. Future studies should provide reliable and valid instruments to diagnose apathy in PD, and should examine the mechanism of apathy accounting for relevant confounders, such as depression and cognitive deficits, and important contextual factors. Finally, treatment for apathy in PD should not be restricted to psychoactive drugs, but should also include nonpharmacological techniques such as psychotherapy and occupational therapy.