The perception of apathy by caregivers of patients with dementia in Parkinson's disease

Background Apathy is one of the main neuropsychiatric symptoms in patients with Parkinson's disease (PD) and is associated with Parkinson's disease dementia (PDD). Objective To identify the characteristics of apathy in individuals with PDD according to caregiver perception. Methods Thirty-nine patients with PD according to MDS criteria for PDD were included. The following scales were used: the Hoehn and Yahr, the Unified Parkinson's Disease Rating Scale III, Scales for Outcomes in Parkinson's Disease-Cognition (SCOPA Cog), the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Apathy Evaluation Scale (AES). Results A total of 97.4% of the patients showed results consistent with apathy. Analysis of question 14 of the AES revealed no correlation with the total result of all the questions [r=–1293, r2=0.0167, 95%CI (–0.4274 to 0.1940), P=0.2162], however, there was a correlation of responses to the same question with depression data on the MADRS scale [r=–0.5213, r2=0.2718, 95%CI (–0.7186 to –0.2464), P=0.00033]. Conclusion Apathy is a disorder associated with PDD. However, the scoring scheme of the AES questions can lead to different interpretations of caregiver responses, highlighting limitations of the tool for use in studies of PDD.


INTRODUCTION
N umbering among the most common neuropsychiatric features in Parkinson's disease (PD) are dementia, apathy and depression, 1-4 sometimes confounded because they are closely related. 5 Parkinson's disease dementia (PDD) has a prevalence of 30-40% in PD patients and a cumulative prevalence of 48-75% after 15 years of follow-up. 6 Apathy is a frequent disorder in PD 7,8

with a prevalence
This study was conducted at the Universidade Estadual de Ponta Grossa -Hospital Universitário Regional dos Campos Gerais, Ponta Grossa, PR, Brazil. of 16-60% in PD and 50% in PDD. 5,6,9,10 It can precede the onset of symptoms, tends to regress after the initiation of treatment with dopamine, and returns as PD progresses, with greater frequency in the presence of PDD. 5 Apathy has been associated with greater executive motor dysfunction and higher risk of developing dementia relative to PD patients without apathy. 11 Although depression is often confused with apathy, clinical evidence helps differentiate the latter from depression, a relatively common symptom in PD. 2,3,12 The main differentiating feature is that apathy typically presents with predominantly "neutral" mood, while in depression, mood is clearly negative, causing emotional suffering. 8 Further evidence is that the occurrence of apathy can be present in the absence of depression and vice-versa. 8,13 In addition, predominantly apathetic signs and symptoms are evident, such as reduced initiative, decreased participation in external activities, loss of interest in activities of daily living, less interest in starting new activities, emotional indifference, decreased emotional reactivity, lower level of affection than usual, and a lack of concern with the feelings or interests of others. 11 The objective of the current study was to identify the characteristics of apathy in individuals with PDD according to caregiver perception of patient behavior.

METHODS
A total of 39 patients with PD were selected according to the diagnostic criteria of the Brain Bank of London for Parkinson's disease 14 and with PDD according the criteria of the Movement Disorder Society (MDS) for PDD, 15 seen at the Neurology Service of the Hospital Universitário Regional dos Campos Gerais (HURCG) and at INOVARE Serviços de Saúde Ltda., who agreed to participate in the study. Patients that exhibited clinical conditions which precluded an adequate cognitive assessment and/or application of the proposed tests were excluded: (a) advanced clinical conditions of the disease; (b) the presence of psychotic symptoms; (c) the presence of another dementia other than that associated with PD. The study was approved by the Research Ethics Committee (COEP) of the Universidade Estadual de Ponta Grossa (reference n # 631.285 FA).
All patients were evaluated in the ON phase of therapy with L-DOPA, preferably at two hours after use of the medication. The clinical evaluation was performed by trained staff in movement disorders. Patients were classified for abnormalities using the Hoehn and Yahr scale 16 and the Unified Parkinson's Disease Rating Scale III (UPDRS-III). 17 Cognition was assessed by the test from the Scales for Outcomes in Parkinson's Disease-Cognition (SCOPA-Cog). Out of the maximum 43 points, test scores <22 points indicated cognitive impairment. 18 Depression was measured using the Montgomery-Åsberg Depression Rating Scale (MADRS). The values considered for analysis were 0-7 for the absence of symptoms and above 8 for presence of depression. 19 Apathy was quantified using the Brazilian version of the modified Apathy Evaluation Scale (AES) (14 questions -1992) for caregivers. 20 Values above 14 (possible score 0-72) indicated apathy. 12,13 The 14 questions can be found in Table 1.
Pearson's correlation coefficients were used to determine correlations. Fisher's exact test was employed for differences between found and expected values . The results are expressed as mean±standard deviation or as value followed by the 95% confidence interval (CI) [r (95%)]. Differences were considered significant for P<0.05. The statistical analysis was performed with the Statistics for Windows software release 99.

RESULTS
Among the 39 patients, the male-female ratio was 1.78:1. The average age of the patients was 70.7±10.93 years, with high disease duration and time in use of L-DOPA. The motor abnormalities detected by the UPDRS and H&Y scales also showed advanced stages of the disease (Table 2).
Only one patient with PDD did not exhibit apathy. This patient also had no depressive symptoms. Of the 38 patients with apathy, 27 (71.05%) had some degree of depression and 11 (28.95%) had no symptoms sufficient to characterize depression. There was a weak inverse correlation between the values of the MADRS and AES in patients with PDD [r=-0.2722; r 2 =0.0741; 95%CI (-0.0473 to 0.5412), P=0.0468].
During the implementation of the instrument chosen to measure apathy, a difference in scoring scheme between Questions 1-8 and Questions 9-14 was noted. While in the first group of questions the higher the score achieved, the greater the incapacity of the patient, in the second group, the higher the score, the lower the incapacity evaluated. Question 9, on mood, planning capacity and execution and interest, had the highest Hence, for the question "Is there anything that interests him/her?" positive answers also indicate a low degree of apathy. For question 14, which directly addresses perceived apathy, scores were highest (1.692±1.089), pointing to a lower perception of apathy in patients with PDD. The values of the responses to question 14 differed from values observed in the first questions ( Figure 1). There was no correlation between the data from the question 14 (Do you consider him/her apathetic?) and the overall results of the scale [r=-0.1293, r²=0.0167, 95%CI (-0.4274 to 0.1940), P=0.2162], i.e., the impression of the caregivers about the state of apathy of patients was not consistent with the overall results of the scale for apathy identification. However, there was an inverse correlation between the scores on question 14 and the data for depression as measured by the

DISCUSSION
Of the 39 patients evaluated, 97.4% had high scores on the AES, confirming apathy as a relevant disorder associated with PDD. 6,7 The rate found was above those found in the literature of 23-50% in patients with PDD. 6 This high prevalence of apathy in the study might be explained by the more advanced stages of PD in the patients assessed. At advanced stages, cerebral cortex deficits occur through depletion of cortical dopamine and not by dysfunction of the frontal lobe due to incomplete afferents through depletion of dopamine in the striatum. 6,21 Apathy, in general, is associated with these changes and with more severe cases of the disease, as observed in patients of the present study, with a high average of duration of disease and abnormalities. 1,5 An inverse correlation between depression and apathy, and independence between the presence of apathy and depression was found in the PDD patients, corroborating findings of other studies. 12,22 However, the perception of the state of apathy of patients by caregivers was unreliable with confounding of apathy and depression symptoms. These data draw attention to a possible difficulty of transfer of information from the caregiver to the physician, where this may lead to an erroneous diagnosis and wrong treatment. The distinction of these syndromes is of extreme importance in the therapeutic setting, averting a situation where apathy in patients with PDD may be precipitated or worsened by the inadvertent use of serotonin reuptake inhibitors 5,6,11 The scale was applied to caregivers with different socioeconomic levels, where the definition of "interests" may have been misinterpreted, leading to an erroneous conclusion about the patient's diagnosis. However, the fact that higher scores for some questions in the scale indicated the presence of apathy yet for others indicated lack of apathy may represent an important bias altering and possibility invalidating the results. This is perhaps the main limitation of studies of apathy in PD patients. 12,13,22 The present study corroborated the high prevalence of apathy in patients with PDD. However, the limitations of the instrument used for measuring apathy were highlighted, including the lack of uniformity among its items, although the tool has been previously validated for this use. Therefore, although the caregiver responses in this study pointed to the existence of apathy in patients with PDD, these results require further validation in larger groups and using other research tools.