Journal of Neurology

, Volume 265, Issue 1, pp 187–193 | Cite as

Apathy and its impact on patient outcome in amyotrophic lateral sclerosis

  • J. CagaEmail author
  • S. Hsieh
  • E. Highton-Williamson
  • M. C. Zoing
  • E. Ramsey
  • E. Devenney
  • R. M. Ahmed
  • M. C. Kiernan
Original Communication


Apathy is one of the most common behavioural symptoms of amyotrophic lateral sclerosis (ALS), yet there are few studies that have investigated the relationship between apathy and quality of life (QOL) as they are experienced by the patient. A cohort of 60 ALS patients were evaluated using the Apathy Evaluation Scale which measured cognitive, behavioural, emotional and non-specific symptoms of apathy combined with the Personal Wellbeing Index, a multidimensional measure of QOL. The relationship between patient-rated apathy and QOL scores, controlling for potential clinical and psychological confounders were analysed using univariate and multivariate methods. Apathy was identified in 30% of ALS patients. Patients with apathy reported higher levels of depression (p = 0.0001). Compared to non-apathetic patients, patients with apathy had lower overall QOL (p = 0.001), most pronounced in the domains related to achievements in life (p = 0.001) and community-connectedness (p = 0.0001). Of the cognitive, behavioural, emotional and non-specific manifestations of apathy, only the emotional symptoms explained a significant amount of variance in achievements in life (p = 0.003) and community-connectedness (p = 0.001). As such, emotional manifestations of apathy may underlie worse QOL in ALS patients presenting with behavioural impairment. Patient-reported outcomes, particularly those assessing psychosocial functioning may be important for demonstrating the efficacy of interventions designed to improve QOL in ALS patients with behavioural impairment.


Amyotrophic lateral sclerosis Motor neuron disease Quality of life Patient-reported outcome measures Apathy Depression 


Compliance with ethical standards

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.


This work was supported by a National Health and Medical Research Council of Australia Postgraduate Research Scholarship (APP1092891) (J. Caga) and a National Health and Medical Research Council of Australia Program Grant (1037746) (M.C. Kiernan).

Ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.


  1. 1.
    Mega MS et al (1996) The spectrum of behavioral changes in Alzheimer’s disease. Neurology 46:130–135CrossRefPubMedGoogle Scholar
  2. 2.
    Kirsch-Darrow L et al (2006) Dissociating apathy and depression in Parkinson disease. Neurology 67:33–38CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Dujardin K et al (2009) Apathy may herald cognitive decline and dementia in Parkinson’s disease. Mov Disord 24:2391–2397CrossRefPubMedGoogle Scholar
  4. 4.
    Rascovsky K et al (2011) Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 134:2456–2477CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Turner MR et al (2013) Controversies and priorities in amyotrophic lateral sclerosis. Lancet Neurol 12:310–322CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Strong MJ et al (2017) Amyotrophic lateral sclerosis—frontotemporal spectrum disorder (ALS-FTSD): Revised diagnostic criteria. Amyotroph Lateral Scler Frontotemporal Degener 18:153–174CrossRefPubMedGoogle Scholar
  7. 7.
    Caga J et al (2016) Apathy is associated with poor prognosis in amyotrophic lateral sclerosis. Eur J Neurol 23:891–897CrossRefPubMedGoogle Scholar
  8. 8.
    Chio A et al (2010) Neurobehavioral symptoms in ALS are negatively related to caregivers’ burden and quality of life. Eur J Neurol 17:1298–1303CrossRefPubMedGoogle Scholar
  9. 9.
    Andrews SC et al (2017) Which behaviours? Identifying the most common and burdensome behaviour changes in amyotrophic lateral sclerosis Psychol Health Med 22:483–492PubMedGoogle Scholar
  10. 10.
    Cui B et al (2015) Behavioral symptoms in motor neuron disease and their negative impact on caregiver burden. Chin Med J (Engl) 128:2295–2300CrossRefGoogle Scholar
  11. 11.
    Burke T et al (2015) Caregiver burden in amyotrophic lateral sclerosis: a cross-sectional investigation of predictors. J Neurol 262:1526–1532CrossRefPubMedGoogle Scholar
  12. 12.
    Watermeyer TJ et al (2015) Impact of disease, cognitive and behavioural factors on caregiver outcome in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 16:316–323CrossRefPubMedGoogle Scholar
  13. 13.
    Rabkin J et al (2016) Cognitive impairment, behavioral impairment, depression, and wish to die in an ALS cohort. Neurology 87:1320–1328CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Bock M et al (2016) Cognitive-behavioral changes in amyotrophic lateral sclerosis: screening prevalence and impact on patients and caregivers. Amyotroph Lateral Scler Frontotemporal Degener 17:366–373CrossRefPubMedGoogle Scholar
  15. 15.
    Marin RS (1991) Apathy: a neuropsychiatric syndrome. J Neuropsychiatry Clin Neurosci 3:243–254CrossRefPubMedGoogle Scholar
  16. 16.
    Starkstein SE (2000) Apathy and withdrawal International Psychogeriatrics 12:135–137CrossRefGoogle Scholar
  17. 17.
    Radakovic R et al (2016) Multidimensional apathy in ALS: validation of the Dimensional Apathy Scale. J Neurol Neurosurg Psychiatry 87:663–669CrossRefPubMedGoogle Scholar
  18. 18.
    Santangelo G et al (2017) Apathy in amyotrophic lateral sclerosis: insights from Dimensional Apathy Scale Amyotroph Lateral Scler Frontotemporal Degener 18:434–442PubMedGoogle Scholar
  19. 19.
    Radakovic R et al (2017) Multidimensional apathy and executive dysfunction in amyotrophic lateral sclerosis. Cortex 94:142–151CrossRefPubMedGoogle Scholar
  20. 20.
    Kiernan MC et al (2011) Amyotrophic lateral sclerosis Lancet 377:942–955PubMedGoogle Scholar
  21. 21.
    Swash M (1997) Health outcome and quality-of-life measurements in amyotrophic lateral sclerosis. J Neurol 244(Suppl 2):S26–S29CrossRefPubMedGoogle Scholar
  22. 22.
    Miller RG et al (2009) Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: multidisciplinary care, symptom management, and cognitive/behavioral impairment (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 73:1227–1233CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Brooks BR et al (2000) El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 1:293–299CrossRefPubMedGoogle Scholar
  24. 24.
    Strong MJ et al (2009) Consensus criteria for the diagnosis of frontotemporal cognitive and behavioural syndromes in amyotrophic lateral sclerosis. Amyotroph Lateral Scler 10:131–146CrossRefPubMedGoogle Scholar
  25. 25.
    Cedarbaum JM et al (1999) The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III). J Neurol Sci 169:13–21CrossRefPubMedGoogle Scholar
  26. 26.
    Moore SR et al (1997) A self report measure of affective lability. J Neurol Neurosurg Psychiatry 63:89–93CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Hsieh S et al (2015) The Mini-Addenbrooke’s Cognitive Examination: a new assessment tool for dementia. Dement Geriatr Cogn Disord 39:1–11CrossRefPubMedGoogle Scholar
  28. 28.
    Hsieh S et al (2013) Validation of the Addenbrooke’s Cognitive Examination III in frontotemporal dementia and Alzheimer’s disease. Dement Geriatr Cogn Disord 36:242–250CrossRefPubMedGoogle Scholar
  29. 29.
    Hsieh S et al (2016) Cognitive and behavioral symptoms in ALSFTD: detection, differentiation, and progression. J Geriatr Psychiatry Neurol 29:3–10CrossRefPubMedGoogle Scholar
  30. 30.
    Abrahams S et al (2000) Verbal fluency and executive dysfunction in amyotrophic lateral sclerosis (ALS). Neuropsychologia 38:734–747CrossRefPubMedGoogle Scholar
  31. 31.
    Mioshi E et al (2014) A novel tool to detect behavioural symptoms in ALS. Amyotroph Lateral Scler Frontotemporal Degener 15:298–304CrossRefPubMedGoogle Scholar
  32. 32.
    Zigmond AS, Snaith RP (1983) The hospital anxiety and depression scale. Acta Psychiatr Scand 67:361–370CrossRefPubMedGoogle Scholar
  33. 33.
    Wicks P et al (2007) Prevalence of depression in a 12-month consecutive sample of patients with ALS. Eur J Neurol 14:993–1001CrossRefPubMedGoogle Scholar
  34. 34.
    Marin RS, Biedrzycki RC, Firinciogullari S (1991) Reliability and validity of the Apathy Evaluation Scale. Psychiatry Res 38:143–162CrossRefPubMedGoogle Scholar
  35. 35.
    Clarke DE et al (2007) Apathy in dementia: an examination of the psychometric properties of the apathy evaluation scale. J Neuropsychiatry Clin Neurosci 19:57–64CrossRefPubMedGoogle Scholar
  36. 36.
    International Wellbeing Group (2006) Personal wellbeing index. Australian centre on quality of life, Deakin University, Melbourne.
  37. 37.
    IBM Corp, IBM SPSS Statistics for Macintosh, Version 24.0. Released 2016, Armonk, NY: IBM CorpGoogle Scholar
  38. 38.
    Bromberg MB, Forshew DA (2002) Comparison of instruments addressing quality of life in patients with ALS and their caregivers. Neurology 58:320–322CrossRefPubMedGoogle Scholar
  39. 39.
    Felgoise SH et al (2009) The SEIQoL-DW for assessing quality of life in ALS: strengths and limitations. Amyotroph Lateral Scler 10:456–462CrossRefPubMedGoogle Scholar
  40. 40.
    Pagnini F (2013) Psychological wellbeing and quality of life in amyotrophic lateral sclerosis: a review. Int J Psychol 48:194–205CrossRefPubMedGoogle Scholar
  41. 41.
    Lou JS et al (2003) Fatigue and depression are associated with poor quality of life in ALS. Neurology 60:122–123CrossRefPubMedGoogle Scholar
  42. 42.
    Chio A et al (2004) A cross sectional study on determinants of quality of life in ALS. J Neurol Neurosurg Psychiatry 75:1597–1601CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Gauthier A et al (2007) A longitudinal study on quality of life and depression in ALS patient-caregiver couples. Neurology 68:923–926CrossRefPubMedGoogle Scholar
  44. 44.
    Marin RS (1990) Differential diagnosis and classification of apathy. Am J Psychiatry 147:22–30CrossRefPubMedGoogle Scholar
  45. 45.
    Pagonabarraga J et al (2015) Apathy in Parkinson’s disease: clinical features, neural substrates, diagnosis, and treatment. Lancet Neurol 14:518–531CrossRefPubMedGoogle Scholar
  46. 46.
    Landes AM et al (2001) Apathy in Alzheimer’s disease. J Am Geriatr Soc 49:1700–1707CrossRefPubMedGoogle Scholar
  47. 47.
    Levy R, Dubois B (2006) Apathy and the functional anatomy of the prefrontal cortex-basal ganglia circuits. Cereb Cortex 16:916–928CrossRefPubMedGoogle Scholar
  48. 48.
    Palmieri A et al (2010) Right hemisphere dysfunction and emotional processing in ALS: an fMRI study. J Neurol 257:1970–1978CrossRefPubMedGoogle Scholar
  49. 49.
    Woolley SC et al (2011) Neuroanatomical correlates of apathy in ALS using 4 Tesla diffusion tensor MRI. Amyotroph Lateral Scler 12:52–58CrossRefPubMedGoogle Scholar
  50. 50.
    Tsujimoto M et al (2011) Behavioral changes in early ALS correlate with voxel-based morphometry and diffusion tensor imaging. J Neurol Sci 307:34–40CrossRefPubMedGoogle Scholar
  51. 51.
    Elamin M et al (2012) Social cognition in neurodegenerative disorders: a systematic review. J Neurol Neurosurg Psychiatry 83:1071–1079CrossRefPubMedGoogle Scholar
  52. 52.
    Abrahams S et al (2014) Screening for cognition and behaviour changes in ALS Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration 15:9–14PubMedGoogle Scholar
  53. 53.
    Simmons Z et al (2010) Validation of a Shorter ALS-Specific Quality of Life Instrument: the ALSSQOL-R. Neurology 74:A177–A178CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Brain and Mind CentreUniversity of SydneyCamperdownAustralia
  2. 2.Sydney Medical SchoolUniversity of SydneyCamperdownAustralia

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