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Apathy in multiple sclerosis: A validation study of the apathy evaluation scale

Journal of the Neurological Sciences, 1-2, 347, pages 295 - 300



Apathy is defined as lack of motivation affecting cognitive, emotional, and behavioral domains and is usually assessed by standardized scales, such as the Apathy Evaluation Scale (AES). Recently, apathy has been recognized as a frequent behavioral symptom in multiple sclerosis (MS).


To evaluate applicability and clinical-metric properties of AES in MS and the agreement between patients' and caregivers' evaluation of apathy.

Materials and methods

Seventy non-demented MS patients underwent a thorough clinical and neuropsychological assessment, including evaluation of apathy according to established clinical criteria. All patients also completed the self-report version of AES (AES-S).


AES-S was easy to administer and acceptable, and showed fair internal consistency (Cronbach's alpha,α = 0.87). The factorial analysis identified three factors, representing the cognitive dimension (α = 0.87), a general aspect of apathy (α = 0.84), and the behavioral–emotional aspects (α = 0.74), respectively. The factors were significantly correlated with the total AES score (allrrho ≥ 0.73,p < 0.001). The total AES score showed fair convergent validity (rrho = 0.38) and discriminant validity when compared to Expanded Disability Status Scale (rrho = 0.38), Mini Mental State Examination (rrho = − 0.17), and Hamilton Depression Rating Scale (rrho = 0.37). Receiver-operating characteristic curve analysis demonstrated that a cutoff > 35.5 can identify clinically significant apathy with good sensitivity (88%) and specificity (72%); such a cutoff identified apathy in 35.7% of our sample of non-demented MS patients. Total AES score was significantly correlated with reduced global cognitive efficiency and more severe frontal executive dysfunctions.


AES-S can be considered as an easy and reliable tool to assess apathy in non-demented MS. The use of AES-S in non-demented MS patients is clinically important since apathy is relatively frequent and is correlated to more severe cognitive dysfunction.



  • Apathy is a relatively frequent behavioral symptom in multiple sclerosis (MS).
  • Apathy is particularly correlated with frontal executive dysfunctions.
  • Apathy Evaluation Scale–Self-Report version is reliable in non-demented MS patients.

Keywords: Multiple sclerosis, Apathy, Cognitive dysfunction, Behavioral disorders, Depression, Validation study.

1. Introduction

Apathy is a complex neurobehavioral syndrome characterized by lack of motivation not attributable to emotional distress, intellectual impairment, or diminished level of consciousness [1] . Apathy is associated with poor treatment compliance, cognitive deficits (in particular frontal/executive dysfunctions), low level of functioning, and high caregiver distress in several psychiatric and neurological diseases such as major depression, Alzheimer's disease, and Parkinson's disease[2], [3], [4], [5], [6], and [7].

In recent years, apathy is receiving growing attention in multiple sclerosis (MS) too. A first indication that apathy is a symptom independent from disability, and disease duration has been reported by Figved et al. [8] in a study on neuropsychiatric manifestations in MS patients. Subsequently, apathy has been found to be significantly associated with cognitive dysfunctions [9] , and particularly with executive dysfunctions [10] , and with increased caregivers' distress [11] . However, data about prevalence of apathy in MS are rather mixed, with some authors reporting prevalence rates as high as 35% [12] .

Uncertainty about prevalence estimates of apathy in MS can be partially ascribed to the fact that in most studies apathy has been evaluated by means of assessment tools not specifically developed to detect apathy, such as the Neuropsychiatric Inventory and the Frontal Systems Behavior Scale[8], [12], and [13].

Availability of a standardized and validated scale to evaluate apathy would allow to increase comprehension of clinical impact of apathy in MS and to improve management strategies. The Apathy Evaluation Scale (AES,[1], [14], [15], [16], and [17]) appears to be a good candidate for clinical evaluation of apathy in MS patients. The AES has been validated in several neurological diseases, such as Alzheimer's disease and other dementias, stroke, traumatic brain injury, major depression, and Parkinson's disease, in which it can reliably discriminate apathetic from non-apathetic individuals[15], [18], [19], [20], [21], [22], and [23]. The AES has been validated in three versions: self-report version, devised for use in non-demented patients without severe cognitive impairment, with relatively preserved insight; a clinical-rated version and an informant-rated version (AES-I), suitable to evaluate patients with severe cognitive impairment or dementia, who likely have poor awareness of their emotional blunting and lack of initiative [15] .

All versions of AES are brief and easy to complete, provide a quantitative assessment of general loss of motivation, and also include three specific subscores relative to cognitive, behavioral, and emotional aspects of apathy. These characteristics make AES particularly suitable for assessing changes in the manifestation of apathy over time and in response to specific treatment[24] and [25]. However, applicability of AES in MS has not been tested yet.

The present study aimed at evaluating applicability and clinical-metric properties of the self-rated version of AES (AES-S) in a large cohort of patients affected by MS. In particular, we assessed internal consistency, convergent and divergent validity, factorial structure, and the agreement between patients' and caregivers' evaluations of apathy. We also aimed at identifying a cutoff score to detect presence of clinically significant apathetic symptoms and at evaluating cognitive correlates of apathy in non-demented MS patients.

2. Subjects and methods

2.1. Subjects

We screened 103 consecutive outpatients with diagnosis of MS according to established diagnostic criteria [26] referred to the Multiple Sclerosis Center of Moscati Hospital, Avellino (Italy). Patients were excluded from the present study on the basis of the following criteria: diagnosis of clinically evident dementia according to Diagnostic and Statistical Manual of Mental Disorders (DSM) IV-Text Revised [27] ; general intellectual decline, as defined by an age- and education-adjusted score lower than 23.8 on the Mini Mental State Examination (MMSE; [28] ), according to Italian norms [29] ; severe disability as indicated by a score higher than 7 on the Expanded Disability Status Scale (EDSS; [30] ); history of alcohol or drug abuse; history of previous psychiatric illness; history of head trauma or other neurologic diseases; illiteracy; non-native Italian-speaking subjects.

2.2. Assessment

In all patients, we collected information about demographic aspects (age, sex, level of education), medical history, and current pharmacological treatment. An interview based on Robert et al.'s [31] criteria was used for clinical diagnosis of apathy. Severity of motor symptoms and disability was assessed by EDSS [30] . Global cognitive status was assessed by MMSE [28] , whereas the presence of clinically relevant depressive symptoms was assessed by Hamilton Depression Rating Scale (HDRS; [32] ). Moreover, visuospatial and executive functions were assessed by Clock Drawing Test (CDT; [33] ) and Frontal Assessment Battery (FAB; [34] ), respectively.

After completing the above tests, all patients fulfilled the Italian version of AES-S[15] and [35], a questionnaire including 18 items concerning behavioral (items 2, 6, 10, 11, 12), cognitive (items 1, 3, 4, 5, 7, 9, 13, 16), emotional (items 8, 14), and other (items 15, 17, 18) aspects of apathy. All items are scored on 4-point Likert scale (to mean “not at all true”, “slightly true”, “somewhat true” or “very true”; scoring is reversed for items 6, 7, 11 because of the way they are written). The total score ranges from 18 to 72 points (higher scores indicate more severe apathy).

Finally, available patients' caregivers were required to complete the Neuropsychiatric Inventory (NPI; [36] ) for evaluation of several psychological and behavioral symptoms. According to standard instructions, the frequency of each symptom is rated on a 4-point scale, and its severity on a 3-point scale; then the score for each symptom is obtained by multiplying severity by frequency. For the purpose of the present study, we considered apathy to be present according to caregivers' evaluation if the apathy score was ≥ 1[37] and [38].

2.3. Statistical analysis

The following psychometric attributes were explored: acceptability, internal consistency, and construct validity.

Acceptability was considered appropriate if there was < 5% of missing values and < 15% of the respondents with the lowest and highest possible scores (floor and ceiling effect, [39] ). Moreover, skewness of the total AES score (limits: − 1 to + 1) was determined [40] .

Internal consistency was evaluated by means of Cronbach's alpha [41] . A value ≥ 0.70 was considered as acceptable [42] . Scaling assumptions referring to the correct grouping of items and the appropriateness of their summed score were checked using corrected item-total correlation (standard ≥ 0.40; [43] ).

The principal component analysis was used to extract the factors followed by Promax rotation. Non-parametric correlation analysis (Spearman'srfor non-parametric data) was performed to investigate the association of AES-S total score with Factor Scores.

Convergent validity was assessed by correlation analysis between AES-S total score and NPI apathy score. Discriminant validity was assessed by correlation analysis between AES and MMSE, HDRS, and EDSS. The correlation between severity of apathy and cognitive functions was assessed by correlation analysis between AES and two neuropsychological tests: FAB and CDT. Bonferroni's adjustment to the p-value was performed for multiple correlations (p < 0.008). Effect size for the correlation coefficient was defined by the following criteria:rrho < 0.3 weak;rrho = 0.3–0.5 moderate;rrho > 0.05 strong [44] .

For the purpose of standardization, we employed receiver-operating characteristic (ROC) curve analysis, using diagnostic criteria for apathy [31] as the gold standard to determine the optimal cutoff score for screening of clinically relevant apathy. Finally, we tested diagnostic agreement between patients' self-report evaluation on AES and caregivers' impression on NPI by kappa statistic [45] .

All analyses were performed using SPSS version 20, with p value < 0.05 considered statistically significant.

3. Results

On the bases of exclusion criteria, 3 patients were not enrolled in the study because of clinically evident dementia, 8 for a global cognitive decline, 16 because of severe disability, 1 because of illiteracy, 2 for presence of relevant traumatic brain injury, and 3 because they were not native Italian-speakers.

The final sample consisted of 70 patients affected by MS (56 females and 14 males); 62 patients were affected by remitting relapsing MS, 5 by secondary progressive MS, and 3 by primary progressive MS. Forty-five patients were treated with interferon beta 1a, 4 patients with interferon beta 1b, 6 patients with glatiramer, 2 patients with natalizumab, 1 patient with fingolimod and 12 patients received no treatment. The demographic and clinical characteristics of the whole sample are shown in Table 1 .

Table 1 Demographic and clinical characteristics of the MS sample (n = 70).

  Mean ± SD Range (max–min)
Age (years) 42.2 ± 9.5 22–63
Education (years) 12.84 ± 3.3 5–19
Disease duration (months) 102.85 ± 84.4 9–432
Age at onset of MS (years) 33.64 ± 8.9 17–54
MMSE 28.8 ± 1.2 26–30
HDRS 11.16 ± 7.1 0–28
EDSS 3.3 ± 1.4 1–7

MS: multiple sclerosis; MMSE: Mini Mental State Examination; HDRS: Hamilton Depression Rating Scale; EDSS: Expanded Disability Status Scale.

3.1. Validation

AES-S showed very good acceptability as shown by the lack of missing data, and by low floor or ceiling effects (1.42% and 0%, respectively). The difference between the mean and the median in the AES was 0.6 point (skewness = 0.336, kurtosis = − 0.270).

AES-S had high internal validity (Cronbach's alpha = 0.87). Analysis of the AES items (corrected Pearson's item-total correlation) showed good and acceptable item characteristics (all correlations are > 0.30) for all items except that for item 7 (he or she is less concerned about his/her problems than him/her should be; correlation = 0.13; Table 2 ). After removing item 7 from the scale, the Cronbach's alpha was 0.89.

Table 2 AES-S item characteristics.

Item Mean ± SD Correlation with total AES score a Item—total correlation b
1. S/he is interested in things. 1.67 ± 0.6 0.67 0.586
2. S/he gets things done during the day. 1.83 ± 0.6 0.68 0.594
3. Getting things started on his/her own is important to her/him. 1.66 ± 0.7 0.73 0.705
4. S/he is interested in having new experiences. 1.86 ± 0.8 0.72 0.624
5. S/he is interested in learning new things. 1.83 ± 0.7 0.75 0.708
6. Someone has to tell her/him what to do each day. 1.44 ± 0.6 0.39 0.379
7. S/he is less concerned about his/her problems than her/him should be. 2 ± 1.1 0.30 0.138
8. S/he approaches life with intensity. 2.09 ± 0.8 0.56 0.445
9. Seeing a job through to the end is important to her/him. 1.70 ± 0.7 0.60 0.533
10. He/she spends time doing things that interest her/him. 1.99 ± 0.8 0.65 0.586
11. S/he puts little effort into anything. 1.57 ± 0.7 0.61 0.516
12. S/he has friends. 1.64 ± 0.7 0.67 0.641
13. Getting together with friends is important to her/him. 1.64 ± 0.8 0.58 0.512
14. When something good happens, he/she gets excited. 1.90 ± 0.8 0.39 0.348
15. S/he has an accurate understanding of her/him problems. 1.77 ± 0.7 0.45 0.352
16. Getting things done during the day is important to her/him. 1.71 ± 0.6 0.51 0.480
17. S/he has initiative. 1.89 ± 0.7 0.61 0.517
18. S/he has motivation. 1.90 ± 0.7 0.63 0.571

a Spearman correlation coefficient (non-parametric), all items are p < 0.001, except 7 with p = 0.009.

b Pearson correlation coefficient.

AES-S: self-report of Apathy Evaluation Scale.

The principal component analysis followed by Promax rotation revealed six eigenvalues, which exceeded 1 and accounted 74.8% of the variance. The first three factors ( Table 3 ) were considered, in analogy with the three-factorial scale proposed by Marin [1] . The first factor explained 35.7% of the variance and included items representing cognitive aspects of apathy (items 3–5, 9, 11–13; Cronbach's alpha = 0.87). The second factor explained 10.9% of the variance and included items representing a general apathy dimension (items 8, 10, 17, 18; Cronbach's alpha = 0.84). The third factor explained 8.6% of the variance and included items representing behavioral–emotional aspect of apathy (items 1, 2, 6, 14–16; Cronbach's alpha = 0.74). The three factors correlated among them (rrho≥ 0.41,p < 0.001). Item 7 did not belong to any factor.

Table 3 Factor analysis of AES-S.

Item Factor 1 (cognitive apathy) Factor 2 (general apathy) Factor 3 (behavioral–emotional apathy)
13. Getting together with friends is important to her/him 0.877 − 0.204
12. S/he has friends 0.834
5. S/he is interested in learning new things 0.728 0.311
4. S/he interested in having new experiences 0.646 0.376 − 0.128
9. Seeing a job through to the end is important to her/him 0.631 0.161
3. Getting things started on his/her own is important to her/him 0.590 0.382
11. S/he puts little effort into anything 0.470 0.248
7. S/he is less concerned about his/her problems than her/him should be 0.178 − 0.126 0.151
17. S/he has initiative − 0.175 0.950
18. S/he has motivation − 0.180 0.927 0.137
8. S/he approaches life with intensity 0.721
10. S/he spends time doing things that interest her/him 0.247 0.706 − 0.106
15. S/he has an accurate understanding of her/his problem − 0.300 0.105 0.809
16. Getting things done during the day is important to her/him 0.689
2. S/he gets things done during the day 0.140 0.669
1. S/he interested in things 0.201 0.644
14. When something good happens, he/she get excited 0.132 − 0.107 0.528
6. Someone has to tell her/him what to do each day 0.179 0.381
Eigenvalue 6.43 1.97 1.55
Variance explained 35.74 10.99 8.65

AES: self-report of Apathy Evaluation Scale.

Major loadings > 0.40 for each items are in bold.

–, coefficient value lower than 0.10.

The correlation between total AES-S score and scores of each factor was strong (rrho = 0.84,p < 0.001 for factor 1;rrho = 0.73,p < 0.001 for factor 2;rrho = 0.74,p < 0.001 for factor 3).

Convergent validity was moderate since the apathy score of NPI significantly correlated with AES-S total score and cognitive apathy factor ( Table 4 ). After Bonferroni correction, divergent validity was also moderate, since the total AES-S score and the three factors showed poor correlation with MMSE score, and only moderate correlation with EDSS and HDRS ( Table 4 ).

Table 4 Convergent and discriminant validity of the AES-S and three-factor model.

Variables Total AES score Cognitive apathy factor General apathy factor Behavioral–emotional factor
NPI-apathy 0.38* 0.31* 0.28* 0.29*
EDSS 0.38* 0.28* 0.34* 0.27*
MMSE − 0.17 − 0.03 − 0.28* − 0.13
HDRS 0.37* 0.16 0.47* 0.27*

NPI-apathy, neuropsychiatric inventory–apathy (frequency × severity); EDSS, Expanded Disability Status Scale; MMSE, Mini Mental State Examination; HDRS, Hamilton Depression Rating Scale. *Bonferroni correction (p < 0.008).

3.2. Standardization

ROC analysis was used to identify the cutoff score that produced the highest rates of sensitivity (ability to diagnose true positive) and specificity (ability to diagnose true negative) with respect to the clinical diagnosis of apathy ( Table 5 ). The score of 35.5 provided the best trade-off between sensibility (88%) and specificity (72%; Youden's index = 0.61). The area under the curve was 0.84 indicating a good discriminant power of the test (see Fig. 1 ).

Table 5 Abbreviated rates of sensitivity and specificity for the AES-S cutoff scores.

AES value Sensitivity Specificity
31.50 1.000 0.574
32.50 0.889 0.59
33.50 0.889 0.623
34.50 0.889 0.656
35.50 lowast 0.889 0.721
36.50 0.778 0.754
37.50 0.667 0.82
38.50 0.556 0.852
39.50 0.444 0.902
40.50 0.444 0.934
42.50 0.444 0.967
46.00 0.333 0.984

lowast Cutoff for clinically relevant apathetic symptoms


Fig. 1 Receiver operating curve (ROC) analysis of the self-evaluation of apathy evaluation scale (AES-S).

The above cutoff identified 25 patients (35.7%) as affected by clinically relevant apathy, whereas presence of apathy was detected in 12.8% of patients according to recent clinical diagnostic criteria [31] . The agreement between patients' self-evaluation and examiner's diagnosis on the basis of clinical criteria ( Table 6 ) was fair (k = 0.347, SE of Kappa = 0.106, 95% CI: 0.140–0.555).

Table 6 Agreement (comparison) between identification of clinically relevant apathy according to AES-S cutoff score versus examiner's evaluation based on diagnostic clinical criteria [31] , and caregivers' evaluation based on the Apathy subdomain of NPI.

  AES-S cutoff
Patients with apathy Patients without apathy
Clinical criteria (n = 70)
Patients with apathy 8 1
Patients without apathy 17 44
Apathy subdomain of NPI (n = 50)
Patients with apathy 6 1
Patients without apathy 13 30

Note: AES-S, self-evaluation of Apathy Evaluation Scale; NPI, Neuropsychiatric Inventory; caregivers' evaluation was available for 50 patients.

Caregivers' evaluation of apathy by the apathy subdomain-NPI was available for 50 patients; in this subsample, apathy was identified in 14% patients. The agreement between patients' self-evaluation and caregivers' impression ( Table 6 ) was fair (k = 0.323, SE of Kappa = 0.122, 95% CI: 0.083–0.563). In particular, 6 patients were considered as apathetic by both AES-S and caregivers' NPI evaluation, 13 patients were considered as apathetic by AES-S only, 30 patients were judged as nonapathetic by both AES-S and NPI, and 1 patient was identified as nonapathetic by AES-S but judged as apathetic by caregiver's NPI evaluation.

3.3. Correlation between apathy and neuropsychological tests

After Bonferroni correction (0.05/6 = 0.008), the AES-S total score correlated moderately and significantly with FAB score (r = − 0.36,p = 0.002), but not with CDT score (r = − 0.07,p = 0.51). The pattern of correlations of the three factors of AES-S identified by factorial analysis (general, cognitive, and behavioral–emotional) with the neuropsychological scores showed that the cognitive and the behavioral–emotional factors were moderately and significantly correlated with FAB score (r = − 0.32,p = 0.007;r = − 0.30,p = 0.009, respectively), whereas the general apathy factor was poorly correlated with the FAB score (r = − 0.26,p = 0.025). The three factors were not correlated with the CDT score (cognitive factor:r = − 0.9,p = 0.443; general apathy factor:r = 0.03,p = 0.769; behavioral–emotional factor:r = 0.06,p = 0.582).

4. Discussion

The present study explored the psychometric properties of the AES-S. Our results demonstrated that AES-S in MS patients has good acceptability and an internal consistency close to that reported in the original study of Marin et al. [15] in healthy elderly patients.

The results from the exploratory factor analysis of the AES-S indicated that the scale seems to measure more than one aspect of apathy. In the present study, three factors were identified: factor 1 included items evaluating cognitive aspects of apathy and accounted for a large part of total variance, whereas factors 2 and 3 included items evaluating general and behavioral–emotional aspects of apathy, and together accounted for 19% of total variance. In their original study, Marin et al. [15] found that the factor explaining most total variance of AES-S accounted for “general” aspects of apathy, whereas the second and the third factors investigated aspects related to curiosity, novelty seeking and insight. However, according to the authors the AES-S is a substantially unidimensional scale because the first “general” factor included most of items. This stands in contrast with the present results in which factor 1, evaluating cognitive aspects of apathy, seemed to best characterize apathy in patients with MS, whereas factor 2 “general apathy,” evaluating overall lack of motivation, explained a lower percentage of total variance and showed higher correlation with scales evaluating depressive symptoms (HDRS) and motor and functional disability (EDSS).

Reliability analysis revealed that the majority of AES-S items showed good discriminative power, with the exception of item 7 (concerns about one's problem), that was not included in any of the three factors; removal of the item 7 increased internal consistency of the total score. Therefore, the item might be removed from the scale for use in MS patients, in analogy with what reported by Pedersen et al. [46] ) in a study evaluating clinical properties of an abbreviated version of AES in patients with PD.

The correlation between AES-S score and score of apathy subdomain-NPI indicated a fair convergent validity of AES-S. This finding suggests that the low correlation between the two instruments (r = 0.2,p < 0.05) reported in patients affected by dementia [18] can be likely ascribed to the specific characteristics of the sample: demented patients often show impaired insight, and their self-report evaluations are not always reliable. Instead, nondemented MS patients as those enrolled in the present study are likely aware of their psychological status, and their self-report evaluation is significantly correlated with that provided by their caregivers.

The total AES-S score showed high correlations with the three component factors we identified here. Moreover, the total AES-S score correlated moderately with the total score on the scale for depression (HDRS), as also found in the original study (r = 0.35; [15] ), and with severity of neurological disability, as assessed by EDSS. However, as recalled above, these correlations may be ascribed to the moderate correlation between the factor 2 and scores on both scales (HDRS and EDSS), whereas the factors 1 and 3 showed poor correlation with both scales.

The AES total score was highly correlated with FAB score but had a low and non-significant correlation with MMSE and CDT. Altogether, these results indicated a fair discriminant validity of the AES-S in MS and would suggest that severity of apathy is significantly associated with frontal lobe dysfunctions but is not correlated with tests assessing other cognitive domains. This observation is supported by the significant association of the cognitive and the behavioral–emotional factors of AES (factors 1 and 3) with frontal dysfunctions. Therefore, the present results are in line with previous studies on degenerative brain diseases suggesting an important role of frontal lobe dysfunction (i.e., dorsolateral–prefrontal and dorsomedial–prefrontal circuits) in the genesis of apathy[4], [47], [48], [49], [50], and [51].

In the present study, ROC analysis revealed that 35.5 is the AES-S total score best suited to identify MS patients with clinically relevant apathy. This value is higher than that reported in a study on healthy subjects (34; [52] ). However, it is important to stress that Kant et al. [52] computed their cutoff value on the basis of the mean score of their normal sample, whereas in the present study we used ROC analysis to obtain a cutoff value with reference to a diagnostic gold standard. On the other hand, the cutoff value reported here is lower than that reported in a previous study on demented patients (36.5; [18] ). This discrepancy can be likely ascribed to the specific features of patients with MS. As in the present sample, MS patients are usually assessed in young and middle adult age and often show variable motor disability, selective cognitive defects, and frequent depressive symptoms (e.g., [53] ), with at least relatively preserved self-awareness of neurobehavioral symptoms (e.g. [54] ). These characteristics make this population very different from the others in which apathy has been evaluated, and therefore a specific cutoff score is strongly needed and can help clinicians to improve patients' management.

It is important to underline that the AES-S cutoff score proposed here identified clinically relevant apathy more often than clinical diagnostic criteria [31] applied by the examiner than the NPI apathy subscale completed by caregivers, although overall agreement of AES-S score with the clinical evaluation and with caregivers' impression was fair. The apparent overestimation of apathy by AES-S could be related to the finding that in the present sample of nondemented MS patients the largest part of total variance was explained by the cognitive factor. Taken together, these findings might suggest that the cognitive aspects of apathy, predominant in the present sample, are more easily detectable by means of self-report scales than on the basis of examiners' or caregivers' evaluation. This speculation receives some support by previous studies on prevalence of apathy in MS. For instance, Diaz-Olavarrieta et al. [55] and Fishman et al. [13] assessed presence of apathy by administration of NPI, and reported prevalence rates (20.5% and 19%, respectively) lower than reported here. Chiaravalloti et al. [12] , instead, use of a non-specific self-report scale (the Frontal System Behavioral Scale; [56] ) and reported a prevalence of 34.6%, very similar to that reported in the present study. These observations suggest that use of specific and validated self-report tools can help in identifying apathy in nondemented MS patients, and that it might be more frequent than previously reported.

We acknowledge some limitations of our study. First, we selected for the present study predominantly middle-aged patients, with a low or moderate level of disability and without global cognitive decline, in view of the administration of a self-report questionnaire. Therefore, our sample might not be representative of the entire population of MS patients. However, we underline that the present results demonstrate applicability and reliability of the AES-S in MS, when the lack of global cognitive impairment permits application of a self-report scale. Further studies on MS patients affected by severe clinical and cognitive defects might consider to evaluate apathy by means of the clinical-rated or the informant-rated versions of the AES.

Second, further clinic–metric properties of the AES-S might be explored, such as test–retest reliability. However, since we adopted a well-established diagnostic tool, and only evaluated its applicability and reliability in a specific pathology, we took for granted psychometric properties (such as test–retest reliability) largely proved in previous studies[15], [19], and [20]. It also important to underline that we assessed convergent validity of AES-S by correlating results with those obtained on NPI, that is widely used in MS[8] and [55], and has been validated in Italy [57] ; in future studies, clinic–metric properties of AES-S might be assessed by a comparison with the informant based version of AES, when it will be validated in MS patients.

In conclusion, our results demonstrated that AES-S is reliable and valid for assessing apathy in MS patients, independently from depressive symptoms, and seems to be particularly suited to identify cognitive aspects of apathy that can be underestimated by clinicians and caregivers. Future longitudinal studies will clarify whether AES-S can predict the impact of apathy on cognitive profile and motor disability in patients with MS.


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a Department of Psychology, Second University of Naples, Caserta, Italy

b Salvatore Maugeri Foundation, Scientific Institute of Telese Terme, Italy

c Institute of Neurology San G. Moscati Hospital, Avellino, Italy

d IDC Hermitage Capodimonte, Naples, Italy

lowast Corresponding author at: Department of Psychology, Second University of Naples, Viale Ellittico, 31, Caserta, Italy. Tel.: + 39 0823 274784.