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The association between fatigue and apathy in patients with either Parkinson's disease or multiple sclerosis
Parkinsonism & Related Disorders, Volume 21, Issue 9, September 2015, Pages 1093 - 1095
Fatigue and apathy are common symptoms in both multiple sclerosis (MS) and Parkinson's disease (PD). Both symptoms are considered “amotivational”—fatigue is a lack of energy to start or complete an action and apathy is a loss of interest in activities. Whether the two symptoms are related to each other is not known. The present study sought to investigate the prevalence and severity of fatigue and apathy in MS and PD, and the relationship between the two.
The Fatigue Severity Scale (FSS) and the Apathy Scale (AS) were administered to 89 consecutive PD and 73 consecutive MS subjects.
The mean FSS score for PD subjects was 4.46 and 5.01 for MS; the average total AS score for PD was 12.4 and 12.5 for MS. Using a cutoff of >4.0 on the FSS to assess fatigue, 64% of PD subjects and 74% of MS subjects suffered from severe fatigue. Using an AS cutoff score of >14.0 to determine apathy, 57% of PD subjects and 52% of MS subjects were apathetic. There was a significant correlation between FSS score and AS score in both disorders. FSS average scores and AS total scores were significantly correlated with motor severity in PD but not in MS. Duration of disease was not correlated with either scale scores in either disorder.
Results confirm that AS and FSS are correlated with each other in both disorders and that MS subjects rate their fatigue significantly higher.
- 64% of PD patients and 74% of MS patients suffered from fatigue.
- 57% of PD and 52% of MS patients suffered from apathy.
- Apathy correlated with the presence of fatigue.
- Fatigue was mildly worse in MS than PD.
- Apathy was equally severe in the disorders.
Keywords: Parkinson's disease, Multiple sclerosis, Fatigue, Apathy.
Fatigue and apathy are two problematic symptoms commonly present in both Parkinson's Disease (PD) and Multiple Sclerosis (MS) , , , and . We are unaware of studies that compared the prevalence and severity of these symptoms in different neurological disorders.
Fatigue may be defined as an overwhelming sense of tiredness, lack of energy, and a feeling of total exhaustion. The present study investigated fatigue as measured by the Fatigue Severity Scale (FSS). Fatigue is highly prevalent in PD, with estimates as high as 40% of patients experiencing significant fatigue , , and . The etiology of fatigue in PD is not understood. Approximately one-third of patients with PD report fatigue as their most debilitating symptom  . Fatigue affects 53%–92% of MS patients and is often considered their most debilitating symptom , , and .
Apathy has been reported in 16.5%–45% of patients with PD and from 10% to 20% in MS , , , and . Apathy is defined as a lack of motivation that is reflected by a physical, mental, or emotional loss of interest in goal-oriented behavior  . This lack of motivation is very common in neurodegenerative disorders, usually associated with dementia-causing disorders  .
While the rates of fatigue and apathy are high in patients with either PD or MS, the extent to which fatigue and apathy are correlated and whether this association is different in these disorders is unknown. The present study seeks to investigate the prevalence and severity of fatigue and apathy in patients with PD or MS, and to examine the strength of association between these two symptoms.
Subjects were recruited consecutively from one Movement Disorder clinic and one M.S. clinic. PD subjects had to meet UK brain bank criteria for the diagnosis of PD and M.S. subjects had to meet the McDonald criteria for the diagnosis of MS. Subjects had to be fluent in English, able to provide written, informed consent, and able to reliably answer all questions. Patients exhibiting dementia or psychiatric disorders that were severe enough to make their responses to questions unreliable were not invited. Dementia was assessed using DSM-V criteria for dementia assessed at the office visit. No formal dementia screening was completed; only patients who passed the physician's assessment for dementia were invited to participate. Patients who did not pass this assessment were not recorded.
90 consecutive PD patients and 73 MS patients were asked to participate in this study immediately following their checkups in a PD clinic and an MS clinic, respectively. Some MS patients participated during their Natalizumab infusions without having been seen by a physician that day. EDSS scores for these patients were obtained from their most recent appointment with their MS physician. One PD and three MS patients refused to participate. IRB approved written consent was obtained from 89 PD patients and 70 MS patients. Following informed consent, the research assistant (GC) administered the FSS and AS verbally to all participants. Data obtained from clinic records included: age, duration of disease, and UPDRS score/EDSS score for PD and MS subjects respectively. No participant had both PD and MS.
The Fatigue Severity Scale (FSS) is a 9-item measure that assesses the level of daily fatigue of the individual with responses to each question being a 1–7 Likert scale rated from strongly disagree (1) to strongly agree (7)  . A tenth question, “Exercise alleviates my fatigue”, was also asked and rated on a 1–7 scale. The FSS has been utilized in both patients with PD and MS and has been recommended in both groups  and . For analysis the average response for these nine items was used; the tenth question was analyzed separately. Subjects with an average score of greater than 4 were considered to have significant fatigue, per Krupp et al. who suggested a cutoff total score of greater than 36  .
The Apathy Scale (AS) is a 14-item measure that uses a 0–3 Likert scale with a 0 being “No” and a 3 being “Yes”  . This scale has been utilized with patients with PD and MS and is a recommended scale  and . Answering positively to the first seven items indicates a lack of apathy, whereas answering positively to the second half indicates apathy. Because of this, when calculating the total score to assess the level of apathy in the subjects, the responses for the first seven questions were reverse coded. Therefore, a higher total apathy score indicated more apathy as measured by the AS. Subjects with a total score ≥ 14 were considered to have significant apathy, consistent with Marin et al.'s recommendations  .
Participants were asked to rate their general level of daily anxiety over the preceding week (barring any specific anxiety-inducing events) on a 0–10 scale, where 0 was “no anxiety” and 10 was “extremely anxious all the time”.
2.4. PD severity
The Unified Parkinson's Disease Rating Scale (UPDRS) motor subscale was scored by movement disorder specialist investigator (JHF) at the routine clinic visit immediately prior to the study visit for patients with PD to determine their overall level of PD severity.
2.5. MS severity
The Expanded Disability Status Scale (EDSS) was completed by the multiple sclerosis specialist investigators (SR,JC) immediately prior to the study visit for patients with MS to determine overall MS severity.
All analyses were done using SPSS 20.0. Pearson correlation coefficients are used in the results section for correlation data.
3.1. Participant characteristics (see Table 1 )
EDSS score significantly correlated with age and duration of MS (r = 0.213, p = 0.030; r = .470, p < 0.001). The mean UPDRS motor score was 31.26 (+/− 14.8) and was significantly correlated with age (r = 0.213, p = 0.046) but not duration of disease.
|PD (N = 89)||MS (N = 70)||Significance|
|Gender||53M/36F||13M/57F||p = < 0.001**|
|Age (60.2)||71.8||45.4||p = < 0.001**|
|Duration of Disease (7.5 years)||6.2 years||8.9 years||p = 0.014*|
|UPDRS Score||31.3 ± 14.8||N/A|
|EDSS Score||3.4 ± 2.0||N/A|
|FSS (4.7 ± 1.6)||4.5 ± 1.6||5.0 ± 1.5||p = 0.047*|
|AS (12.4 ± 6.9)||12.4 ± 6.8||12.5 ± 7.2||p = 0.46|
|Anxiety Rating (4.5 ± 2.4)||4.7 ± 2.2||4.3 ± 2.6||p = 0.14|
3.2. Associations between fatigue and apathy
64% of participants with PD and 74% of those with MS experienced significant fatigue; 39% of the PD and 41% of the MS participants experienced significant apathy. There was a significant difference in fatigue scores between the diseases (χ = 2.00, p = 0.047). The mean fatigue and apathy scores for the PD and MS subjects who suffered from significant fatigue (average score of >4 on the FSS) were 5.5 (SD = 0.82) and 15.11 (SD = 6.5), and 5.74 (SD = 0.91) and 14.10 (SD = 7.00) respectively.
FSS and AS scores significantly correlated with each other within each disease group (MS: r = 0.442, p < 0.001; PD: r = 0.546, p < 0.001). Self-reported anxiety scores were significantly correlated with both FSS score and AS score in the MS population (r = 0.528, p < 0.001; r = .447, p < 0.001, respectively). In patients with PD, FSS was correlated with anxiety (r = 0.221, p = 0.05) but not apathy (p = 0.237).
Among subjects with PD, both fatigue (r = 0.317, p < 0.01) and apathy (r = 0.378, p < 0.001) were significantly correlated with UPDRS motor score. However, EDSS scores were not correlated with fatigue or apathy in patients with MS.
Responses to the question on exercise's effect on fatigue indicated that PD subjects believe that their fatigue is alleviated by exercise significantly more than MS subjects. PD subjects responded with an average of a 4.1 (SD: 2.2) compared with the MS subjects' average response of 3.1 (SD: 2.13) which was significant (F-value = 6.471, df = 2, p-value = 0.012). In addition, the responses for FSS item 2 (“Exercise brings on my fatigue) were significantly different between the PD and MS subjects (p-value = 003). PD patients responded with an average 3.72 (indicating they did not agree with the statement), while MS patients responded with an average 4.9 (indicating that they did somewhat agree).
Thirty-two out of the 56 (57.2%) fatigued PD subjects and 27 of 52 (51.9%) fatigued MS subjects were apathetic as measured by the AS. Only two of the 34 (6%) PD subjects and 2 of the 29 (7%) MS subjects who were apathetic were not severely fatigued.
This study compared two subjective neuropsychiatric symptoms in patients with PD or MS. Our goal was to determine what commonalities and what differences there were in attempting to better understand the extremely common, often disabling and poorly understood problem of fatigue, which is increased in almost all somatic and psychiatric disorders. We were specifically focused on determining whether there was a relationship between fatigue and apathy as both may be considered “amotivational” symptoms and thus share a common etiology.
This study confirms reports that fatigue in PD is comparable to that experienced by patients with MS in prevalence and severity  . Etiology of fatigue and apathy could very well be different between the two groups. For instance, our results showed a significant difference between the two groups regarding whether or not they believed exercise improved or led to fatigue, with PD subjects believing it alleviated fatigue and MS patients believing it led to fatigue. Although the causes of fatigue and apathy may be different between the two diseases, our results indicate that the two symptoms can be correlated with each other in both groups, supported also by the observation that only 6% of PD subjects and 7% of MS patients who were apathetic were not also severely fatigued. This strong association between apathy and fatigue is, we believe, a new finding in MS although it has been recently suggested in PD, and the similar association between the two symptoms in two very different neurological disorders suggests that fatigue and apathy may be overlapping symptoms with a common substrate  .
We found that anxiety was associated with fatigue in both disorders but that it correlated with apathy only in MS. While the subjective measure of anxiety utilized in this study (participants self-reported their level of daily anxiety on a scale from 0 to 10) is not a powerful measure of each participant's anxiety levels, a proper measure of anxiety was not taken as to limit the time the participants were asked to commit to the interview. Therefore, it is hard to draw hard conclusions from this data but we hope that this preliminary suggestion will be expanded upon with more objective measurements of anxiety in the future.
The link between apathy and fatigue is undoubtedly complex. Fatigue and apathy are both common symptoms of both depression and anxiety. Anxiety and depression are closely linked to each other, as well as to dementia in PD patients.
There were a few weaknesses in the present study. First, the population was not large, and depression and cognition were not assessed beyond the exclusion of clinically demented individuals. Multiple medication regimens were too complex and varied to be analyzed, and other medical problems were not considered, which undoubtedly contributed to both apathy and fatigue. The scoring system for fatigue and apathy is very subjective for each subject, and in many cases the subject was asked questions in the presence of family or friends which may have altered their answers. Family was asked not to help the subject respond, but their presence in the room may have made the subject uncomfortable.
Despite these weaknesses, there were many advantages to how we collected our data. The subjects were consecutive and therefore were relatively random representatives of the populations at the two specialty clinics, and we used rating instruments for fatigue and apathy that had been used in both MS and PD studies.
Longitudinal studies would be extremely helpful in helping to better understand the relationship between apathy and fatigue. Although fatigue remains a common problem throughout the course of both disorders, many patients' fatigue level varies, so that it would be of interest to determine if apathy varies with it. Studies of this sort cannot determine whether one symptom “causes” the other or whether they both represent a common precursor or etiology, but the relationship between the two may suggest treatment approaches. For example, drugs are being developed to treat apathy, a common problem in schizophrenia as well as dementia disorders and these may be relevant to treating fatigue, as well as apathy in both MS and PD.
-  L.B. Krupp, L.A. Alvarez, N.G. LaRocca, L.C. Scheinberg. Fatigue in multiple sclerosis. Neurology. 2007;45(4):435-437
-  N. Figved, G. Kievan, K.M. Myhr, et al. Neuropsychiatric symptoms in patients with multiple sclerosis. Acta Psychiatr. Scand.. 2005;112(6):463-468 Crossref
-  J.H. Friedman, H. Friedman. Fatigue in Parkinson's disease: a nine-year follow-up. Mov. Disord.. 2001;16(6):1120-1122 Crossref
-  G.C. Pluck, R.G. Brown. Apathy in Parkinson's disease. J. Neurol. Neurosurg. Psychiatry. 2002;73(6):636-642 Crossref
-  J.J. van Hilten, M. Weggeman, E.A. van der Velde, G.A. Kerkhof, J.G. van Dijk, R.A. Roos. Sleep, excessive daytime sleepiness and fatigue in Parkinson's disease. J. Neural Transm.. 1993;5(3):235-244
-  K. Karlsen, J.P. Larsen, E. Tandberg, K. Jørgensen. Fatigue in patients with Parkinson's disease. Mov. Disord.. 1999;14(2):237-241 Crossref
-  L.M. Shulman, R.L. Taback, A.A. Rabinstein, W.J. Weiner. Non-recognition of depression and other non-motor symptoms in Parkinson's disease. Parkinsonism Relat. Disord.. 2002;8(3):193-197 Crossref
-  J.E. Freal, G.H. Kraft, J.K. Coryell. Symptomatic fatigue in multiple sclerosis. Arch. Phys. Med. Rehabil.. 1984;65(3):135-138
-  P. Brañas, R. Jordan, A. Fry-Smith, A. Burls, C. Hyde. Treatments for fatigue in multiple sclerosis: a rapid and systematic review. Health Technol. Assess.. 2000;4(27)
-  K.J. Aronson. Quality of life among persons with multiple sclerosis and their caregivers. Neurology. 1997;48(1):74-80 Crossref
-  S.E. Starkstein, H.S. Mayberg, T.J. Preziosi, et al. Reliability, validity, and clinical correlates of apathy in Parkinson's disease. J. Neuropsychiatry Clin. Neurosci.. 1992;4:134-139
-  V. Isella, P. Melzi, M. Grimaldi, et al. Clinical, neuropsychological, and morphometric correlates of apathy in Parkinson's disease. Mov. Disord.. 2000;17(2):366-371
-  D. Surridge. An investigation into some psychiatric aspects of multiple sclerosis. Br. J. Psychiatry. 1969;115:749-764 Crossref
-  C. Diaz-Olavarrieta, J.L. Cummings, J. Velazquez, C. Garcia de la Cadena. Neuropsychiatric manifestations of multiple sclerosis. J. Neuropsychiatry Clin. Neurosci.. 1999;11(1):51-57 Crossref
-  R.S. Marin, R.C. Biedrzycki, S. Firinciogullari. Reliability and validity of the apathy evaluation scale. Psychiatry Res.. 1991;38(2):143-162 Crossref
-  M.L. Levy, J.L. Cummings, L.A. Fairbanks, et al. Apathy is not depression. J. Neuropsychiatry Clin. Neurosci.. 1998;10:314-319 Crossref
-  L.B. Krupp, N.G. LaRocca, J. Muir-Nash, A.D. Steinberg. The fatigue severity scale. application to patients with multiple sclerosis and systemic lupus erythematosus. Neurology. 1989;46:1121-1123 Crossref
-  K. Herlofsen, J.P. Larsen. Measuring fatigue in patients with Parkinson's disease – the fatigue severity scale. Eur. J. Neurol.. 2002;9(6):595-600
-  P.O. Valko, C.L. Bassetti, C.R. Baumann. Validation of the fatigue severity scale in a Swiss cohort. Sleep. 2008;31(11):1601-1607
-  A.F. Leentjens, K. Dujardin, L. Marsh, et al. Apathy and ahedonia rating scales in Parkinson's disease: critique and recommendations. Mov. Disord.. 2008;23(14):2004-2014 Crossref
-  M. Niino, N. Mifune, T. Kohriyama, et al. Apathy/depression, but not subjective fatigue, is related with cognitive dysfunction in patients with multiple sclerosis. BMC Neurol.. 2014;14(3)
-  J.H. Friedman, R.G. Brown, C. Cornella, et al. Fatigue in Parkinson's disease: a review. Mov. Disord.. 2007;22(3):297-308 Crossref
-  N. Saez-Francas, J. Hernandez-Vara, M. Roso, J. Martin, M. Brugue. The association of apathy with central fatigue perception in patients with Parkinson's disease. Behav. Neurosci.. 2013;127(2):237-244 Crossref
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