Apathy was first formally described by Marin in 1990
1 as a primary “lack of motivation,” resulting in defects within cognitive, affective, and behavioral domains. It is characterized by decreased initiative, flattened affect, and reduced interest in new experiences, which cannot be attributed to “diminished level of consciousness, cognitive impairment, or emotional distress.”
1 Since Marin’s initial formulation a growing body of research has examined apathy across various neurological disorders, resulting in several major findings. Although associated with reduced cognitive status, apathy also occurs in cognitively intact individuals and is dissociable from depression. The underlying neural mechanisms appear to involve mesial-frontal motivational systems and alterations in dopamine.
2–6The main purpose of the present study was to examine apathy in Parkinson’s disease (PD) and its relationship to experimental indices of behavioral initiation. As is well known, PD is a common neurodegenerative disorder, involving dopamine depletion, that affects 2% of adults over the age of 65. Primarily typified by motor symptoms (rigidity, tremor, akinesia, and postural instability), the disorder also includes neuropsychiatric symptoms, with apathy and depression being particularly prominent.
7 Apathy occurs in a large proportion of patients, ranging from 16.5% to 60% across studies.
3–5 Recent studies support the view that apathy is a unique syndrome in PD, rather than being a symptom of depression or secondary to physical disability per se.
6,8 Although concomitant dementia and depression can be present,
9 a recent publication supports the dissociation of apathy and depression in PD.
10 Longitudinal studies suggest that apathy symptoms in PD progressively worsen in parallel with nondopaminergic motor symptoms, whereas depression symptoms do not.
11,12 Further support for the distinction between apathy and depression in PD includes the differential effects on depression and apathy symptoms after deep brain stimulation (DBS)
11,13 and failure of antidepressant medications in treating apathy symptoms.
14 In fact, serotonergic reuptake inhibitors (SSRIs) are well known to increase symptoms of apathy in non-PD samples.
15–17Currently, the most widely used tool for assessing apathy in PD is the Apathy Scale (AS), a modification of Marin’s original 18-item measure, the Apathy Evaluation Scale (AES).
18 A more recent measure is the Lille Apathy Rating Scale (LARS),
19 a semistructured interview providing an overall apathy score as well as four domain-specific scores, overlapping with Marin’s original conceptualization of apathy. These four domains include intellectual curiosity (cognitive), action-initiation (behavioral), emotional response (affect), and concern.
Although the AS and LARS have reasonable psychometric properties and have been endorsed by a taskforce of the Movement Disorders Society, their criterion validity has been sparsely assessed.
20 This type of assessment is essential, as clinicians base their evaluations on current apathy measures. Marin initially examined the criterion validity of his scale (AES) in patients with unilateral stroke and dementia.
18 One way this was done was by examining scores on the AES in relation to an “incidental” laboratory-based measure that quantified the extent to which patients spontaneously spent time playing with toys and gadgets.
18 Unfortunately, a similar approach has not been taken with PD patients using the modified Apathy Scale. Because growing evidence suggests that apathy may be a key neuropsychiatric signature of PD, independent of depression, it becomes increasingly important to use indices of apathy that are meaningful in a real-world context. Thus, we aimed to examine the construct validity of two well-recognized measures, the AS and the LARS, by utilizing a measure of initiation modeled after that of Marin.
18 Our first hypothesis was that high levels of apathy, as defined by two frequently-used measures, the AS and the LARS, would be associated with reduced initiative and active engagement during a laboratory-based measure. Our second hypothesis was that reduced engagement during the laboratory-based measure would not be associated with depression symptom severity.
Discussion
In this study, the hypothesis that high levels of apathy would be associated with reduced initiative and engaged behaviors during a laboratory-based task, was tested in PD patients. We used a convenience sample of PD patients who were well-educated, predominantly male, and in the middle stages of the disorder. Fifty percent were candidates for DBS, and none met criteria for clinical dementia. The prevalence of apathy (46%–50%) and depression (25%) were in line with previous reports in the literature.
6,24 Our sample might not reflect the true prevalence of apathy in the population because of the large proportion of DBS candidates. Nonetheless, this study is the first to evaluate the construct validity of apathy by use of the AS and the LARS in a sample of PD patients.
The hypothesis—that higher levels of apathy would result in reduced initiative and engaged behaviors during the laboratory-based measure—was supported by our data. Using apathetic and non-apathetic grouping, we found that both the AS and the LARS demonstrated convergent validity with our laboratory-based measure of apathy, the NTT. These findings indicate that participants displaying higher levels of apathy spent less time examining gadgets/toys that were available during a relatively unstructured, laboratory-based task. Furthermore, the lack of discrepancy between PD and control groups on NTT variables signifies that reduced time on tasks was not related to having PD, per se, but, rather, to the presence of apathy in the context of PD. We demonstrated a marked difference between groups in overall time spent engaged in activity, with significantly less time spent on the IQ-Wood puzzle, Etch-A-Sketch, and Metal Puzzles. This broadly confirms the view that apathy involves decreased curiosity, interest, and motivation to engage in the environment.
Looking closer at the LARS and its composite subscales, we observed that, irrespective of apathy status, participants with lower time engaged during the task displayed reduced levels of initiative, interest, novelty-seeking, motivation, and everyday productivity. Indexed by the composite subscale Intellectual Curiosity and Action-Initiation of the LARS, this finding affirms the convergent validity of the cognitive and behavioral domains of the scale.
19 The reduced levels of LARS domains also coincide with the cognitive and behavioral domains of recent diagnostic criteria for apathy put forth by a worldwide task force.
29In the current study, the AS seemed slightly less sensitive than the LARS in detecting differences in the initiation and of use of novel gadgets and toys. AS Apathy classification yielded differences between apathetic/non-apathetic groups at a trend level (p=0.056; effect size: 0.37) on the NTT. In contrast, group differences were stronger using the LARS (p=0.01; effect size: 0.43). Future studies with larger sample sizes are important to determine whether true differences in sensitivity exist between these two measures. Although each measure has well-described psychometric properties,
20 there are a variety of differences in the structure of the two scales that could potentially contribute to these findings. The version of the AS used in our study was self-administered (paper-and-pencil version), whereas the LARS is a semistructured interview. It is unclear whether a clinician-administered version of the AS would be more sensitive. The two scales also differ in number of items and range of scores, which is well known to contribute to increased reliability of a measure. Also, the LARS includes more items that specifically query “activities.” Despite differences between the AS and LARS, previous studies have found good reliability between the AS (self-administered) and the LARS in both U.S.
26 and European samples.
19Our second hypothesis regarding depression was supported. In contrast to apathy, we found no relationship between severity of depression symptoms as indexed by the BDI–II and any of the NTT variables, despite higher depression scores in the apathetic PD groups. Furthermore, this implies that time spent engaged during the NTT was primarily influenced by apathy scores and not depression per se. Although no psychiatric interviews were conducted, our findings add to the literature finding that apathy and depression symptoms are distinct constructs, at a symptomatic level of depression. Recent neuroimaging findings also support this view in older adults and patients with PD.
30–32One prevailing view regarding apathy is that it relates to dopaminergic depletion and the effects of this depletion on reward circuitry. The relationship between apathy and dopamine availability remains complex; however, we found no association between levodopa-equivalent dosage (LED)
33 and NTT variables. A key issue, of course, is that the amount of dopamine replacement is limited in PD because of its clinical side-effect profile (i.e., disabling dyskinesias, hallucinations). Thus, it is not possible to discount dopaminergic influences on apathy in general; these just were not apparent in our study with a measure of dopamine medication usage.
There are several confounding factors that might contribute to reduced engagement during the NTT by the “apathetic” PD groups. One relates to motor symptom severity. Indeed, motor symptoms, as indexed by the UPDRS total motor score (on medication) were greater in the apathetic than the non-apathetic groups. This raises the possibility that poor motor skills may have reduced the propensity for PD patients to engage in the NTT task. However, we found no relationship between motor symptom severity and performance variables of the NTT task (i.e., nonsignificant correlations).
Another issue relates to the validity of the NTT task as a true index of behavioral initiation and engagement. Although directly modeled after the one originally used to validate Marin’s initial apathy measure (i.e., the Apathy Evaluation Scale),
18 it is possible that the specific toys (Rubik’s cube, Etch-A-Sketch, Slinky) did not engender sufficient interest and curiosity. However, this appears to be a moot argument, in that task differences were found when apathy was defined by the LARS and were at trend level when the AS was used. Future studies could extend this work by examining true “ecological validity” by evaluating home-base behaviors, using techniques such as experience-based sampling or actigraphy.
34 Moreover, future studies should consider utilizing factor scores of current apathy scales when evaluating their ecological validity.
35Our study has several limitations, including generalizability of our sample, as the majority of our Parkinson patients were men, and approximately half were candidates for DBS. Our sample size was relatively small, as well. A broader limitation is that there are no formal DSM-IV diagnostic clinical criteria for apathy. Although Marin
1 originally, and more recent work-groups
36,37 have attempted to develop and validate criteria, current decisions about “apathy” classification continue to be psychometrically-based. Furthermore, the exclusion of participants on the basis of MMSE (≤24) instead of current diagnostic criteria
38 may have led to the inclusion of individuals with dementia or exclusion of those without. Nevertheless, the high mean MMSE score of the PD sample speaks against this being a major limitation of the current study.