Opinion statement
Apathy is one of the most prevalent neurobehavioral symptoms in Huntington’s disease (HD), occurring in approximately 70% of the symptomatic HD population. Apathy scores in patients with HD are highly correlated with duration of illness, suggesting that apathy is an inevitable consequence of advanced disease. Although less distressing than symptoms like depression and less disruptive than irritability or aggression, apathy has a considerable adverse impact on those affected with HD because it leads to a decrease of the goal-directed behaviors that contribute much to the day-to-day quality of life. As a neuropsychiatric syndrome, apathy is also common in patients with other neuropsychiatric disorders such as Parkinson’s disease, traumatic brain injury, cerebrovascular accident, dementia, and other neurodegenerative conditions. The nosologic status of apathy and lack of a clear definition has probably contributed to the paucity of therapeutic evidence in this area. Several different scales are available to measure apathy, including the Apathy Evaluation Scale, Apathy Inventory, Lilles Apathy Rating Scale, and the apathy items from the Unified HD Rating Scale, the Problem Behaviours Assessment for HD, and the Neuropsychiatric Inventory, but all are based on slightly different definitions of apathy, so the scores obtained may not be directly comparable. Assessment may also be complicated by overlap between the manifestations of apathy and other complications of HD such as depression, so the identification and treatment of these comorbid conditions is important. No adequate evidence currently supports any specific pharmacologic or psychological intervention for apathy in HD. Evidence can only be extrapolated from interventional studies done in other basal ganglia disorders such as Parkinson’s disease or other neurodegenerative disorders such as dementia. The neurobiology of apathy points towards three areas of functional connectivity: connections between the dorsolateral prefrontal cortex (PFC) and basal ganglia, orbitomedial PFC and basal ganglia, and dorsomedial PFC and basal ganglia. Pharmacologic interventions such as cholinesterase inhibitors, the dopaminergic antidepressant bupropion, amantadine, levodopa, bromocriptine, methylphenidate, and atypical antipsychotics have all been tried in other neurodegenerative disorders, but not in HD. Psychosocial interventions such as cognitive stimulation therapy and multisensory stimulation, which have been used in patients with dementia, have not been properly studied in HD. Individualized treatment should be considered, using a combination of methods, as there is no evidence to support one particular type of treatment. Multidisciplinary input, environmental modifications, improved psychosocial support, and psychoeducation programs designed to help caregivers to understand and compensate for the deficits caused by this symptom may all have a role to play in the treatment of apathy.
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References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance, •• Of major importance
Huntington’s Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell. 1993;72:971–83.
Watt DC, Seller A: A clinico-genetic study of psychiatric disorder in Huntington’s chorea. Psychol Med Monogr Suppl 1993:23.
Cummings JL. Behavioral and psychiatric symptoms associated with Huntington’s disease. In: Weiner WJ, Lang AE, editors. Behavioral neurology of movement disorders. New York: Raven; 1995. p. 179–86.
Paulsen JS, Ready RE, Hamilton JM, et al. Neuropsychiatric aspects of Huntington’s disease. J Neurol Neurosurg Psychiatry. 2001;71:310–14.
Van Duijn E, Kingma EM, van der Mast RC. Psychopathology in verified Huntington’s disease gene carriers. J Neuropsychiatry Clin Neurosci. 2007;19:441–8.
Craufurd D, Thompson JC, Snowden JS. Behavioral changes in Huntington disease. Neuropsychiatry Neuropsychol Behav Neurol. 2001;14(4):219–26.
Naarding P, Janzing JG, Eling P, van der Werf S, Kremer B. Apathy is not depression in Huntington’s disease. J Neuropsychiatry Clin Neurosci. 2009;21(3):266–70.
Rickards H, De Souza J, van Walsem M, van Duijn E, Simpson SA, Squitieri F, et al. The European Huntington’s Disease network. Factor analysis of behavioural symptoms in Huntington’s disease. J Neurol Neurosurg Psychiatry. 2011;82(4):411–2.
Marin RS, Wilkosz PA. Disorders of diminished motivation. J Head Trauma Rehabil. 2005;20:377–88.
Starkstein SE. Apathy and withdrawal. Int Psychogeriatr. 2000;12 Suppl 1:135–8.
Isella V, Melzi P, Grimaldi M, Iurlaro S, Piolti R, Ferrarese C, et al. Clinical, neuropsychological, and morphometric correlates of apathy in Parkinson’s disease. Mov Disord. 2002;17(2):366–71.
Starkstein SE, Leentjens AF. The nosological position of apathy in clinical practice. J Neurol Neurosurg Psychiatry. 2008;79(10):1088–92.
Levy R, Dubois B. Apathy and the functional anatomy of the prefrontal cortex-basal ganglia circuits. Cereb Cortex. 2006;16(7):916–28.
Gauthier S, Feldman H, Hecker J, Vellas B, Ames D, Subbiah P, et al. Efficacy of donepezil on behavioral symptoms in patients with moderate to severe Alzheimer’s disease. Int Psychogeriatr. 2002;14(4):389–404.
Waldemar G, Gauthier S, Jones R, Wilkinson D, Cummings J, Lopez O, et al. Effect of donepezil on emergence of apathy in mild to moderate Alzheimer’s disease. Int J Geriatr Psychiatry. 2011;26(2):150–7.
Cubo E, Shannon KM, Tracy D, Jaglin JA, Bernard BA, Wuu J, et al. Effect of donepezil on motor and cognitive function in Huntington disease. Neurology. 2006;67(7):1268–71.
Gauthier S, Juby A, Dalziel W, Réhel B, Schecter R. EXPLORE investigators. Effects of rivastigmine on common symptomatology of Alzheimer’s disease (EXPLORE). Curr Med Res Opin. 2010;26(5):1149–60.
Rot U, Kobal J, Sever A, Pirtosek Z, Mesec A. Rivastigmine in the treatment of Huntington’s disease. Eur J Neurol. 2002;9(6):689–90.
de Tommaso M, Difruscolo O, Sciruicchio V, Specchio N, Livrea P. Two years’ follow-up of rivastigmine treatment in Huntington disease. Clin Neuropharmacol. 2007;30(1):43–6.
Brodaty H, Woodward M, Boundy K, Barnes N, Allen G, NATURE Investigators. A naturalistic study of galantamine for Alzheimer’s disease. CNS Drugs. 2006;20(11):935–43.
Herrmann N, Rothenburg LS, Black SE, Ryan M, Liu BA, Busto UE, et al. Methylphenidate for the treatment of apathy in Alzheimer disease: prediction of response using dextroamphetamine challenge. J Clin Psychopharmacol. 2008;28(3):296–301.
Padala PR, Burke WJ, Shostrom VK, Bhatia SC, Wengel SP, Potter JF, et al. Methylphenidate for apathy and functional status in dementia of the Alzheimer type. Am J Geriatr Psychiatry. 2010;18(4):371–4.
Spiegel DR, Kim J, Greene K, Conner C, Zamfir D. Apathy due to cerebrovascular accidents successfully treated with methylphenidate: a case series. J Neuropsychiatry Clin Neurosci. 2009;21(2):216–9.
Keenan S, Mavaddat N, Iddon J, Pickard JD, Sahakian BJ. Effects of methylphenidate on cognition and apathy in normal pressure hydrocephalus: a case study and review. Br J Neurosurg. 2005;19(1):46–50.
Jansen IH, Olde Rikkert MG, Hulsbos HA, Hoefnagels WH. Toward individualized evidence-based medicine: five ‘N of 1’ trials of methylphenidate in geriatric patients. J Am Geriatr Soc. 2001;49:474–6.
Waugh JL, Miller VS, Chudnow RS, Dowling MM. Juvenile Huntington disease exacerbated by methylphenidate: case report. J Child Neurol. 2008;23(7):807–9.
Marsh L, Biglan K, Gerstenhaber M, Williams JR. Atomoxetine for the treatment of executive dysfunction in Parkinson’s disease: a pilot open-label study. Mov Disord. 2009;24(2):277–82.
Weintraub D, Mavandadi S, Mamikonyan E, Siderowf AD, Duda JE, Hurtig HI, et al. Atomoxetine for depression and other neuropsychiatric symptoms in Parkinson disease. Neurology. 2010;75:448–55.
Beglinger LJ, Adams WH, Paulson H, Fiedorowicz JG, Langbehn DR, Duff K, et al. Randomized controlled trial of atomoxetine for cognitive dysfunction in early Huntington disease. J Clin Psychopharmacol. 2009;29(5):484–7.
Padala PR, Burke WJ, Bhatia SC. Modafinil therapy for apathy in an elderly patient. Ann Pharmacother. 2007;41(2):346–9.
Czernecki V, Pillon B, Houeto JL, Pochon JB, Levy R, Dubois B. Motivation, reward, and Parkinson’s disease: influence of dopatherapy. Neuropsychologia. 2002;40(13):2257–67.
Newburn G, Newburn D. Selegiline in the management of apathy following traumatic brain injury. Brain Inj. 2005;19(2):149–54.
Moutaouakil F, El Otmani H, Fadel H, Slassi I. Severe apathy following head injury: improvement with selegiline treatment. Neurochirurgie. 2009;55(6):551–4.
Van Reekum R, Bayley M, Garner S, Burke IM, Fawcett S, Hart A, et al. N of 1 study: amantadine for the amotivational syndrome in a patient with traumatic brain injury. Brain Inj. 1995;9(1):49–53.
Kraus MF, Smith GS, Butters M, Donnell AJ, Dixon E, Yilong C, et al. Effects of the dopaminergic agent and NMDA receptor antagonist amantadine on cognitive function, cerebral glucose metabolism and D2 receptor availability in chronic traumatic brain injury: a study using positron emission tomography (PET). Brain Inj. 2005;19(7):471–9.
O’Suilleabhain P, Dewey Jr RB. A randomized trial of amantadine in Huntington disease. Arch Neurol. 2003;60:996–8.
Verhagen Metman L, Morris MJ, Farmer C, Gillespie M, Mosby K, Wuu J, et al. Huntington’s disease: a randomized, controlled trial using the NMDA-antagonist amantadine. Neurology. 2002;59(5):694–9.
Debette S, Kozlowski O, Steinling M, Rousseaux M. Levodopa and bromocriptine in hypoxic brain injury. J Neurol. 2002;249(12):1678–82.
Frattola L, Albiazzati MG, Spano PF, Trabucchi M. Treatment of Huntington’s chorea with bromocriptine. Acta Neurol Scand. 1977;56(1):37–45.
Corcoran C, Wong ML, O’Keane V. Bupropion in the management of apathy. J Psychopharmacol. 2004;18(1):133–5.
Strassburger K, Andrich J, Saft C. Bupropion: first experience in Huntington’s disease. J Neurol Neurosurg Psychiatry. 2008;79:A29–30.
Siniscalchi A, Gallelli L, Tolotta GA, Loiacono D, De Sarro G. Open, uncontrolled, nonrandomized, 9-month, off-label use of bupropion to treat fatigue in a single patient with multiple sclerosis. Clin Ther. 2010;32(12):2030–4.
Hopman-Rock M, Staats PG, Tak EC, Dröes RM. The effects of a psychomotor activation programme for use in groups of cognitively impaired people in homes for the elderly. Int J Geriatr Psychiatry. 1999;14(8):633–42.
Ferrero-Arias J, Goñi-Imízcoz M, González-Bernal J, Lara-Ortega F, da Silva-González A, Díez-Lopez M. The efficacy of nonpharmacological treatment for dementia-related apathy. Alzheimer Dis Assoc Disord. 2011 Feb 22 (Epub ahead of print).
Staal JA, Sacks A, Matheis R, Collier L, Calia T, Hanif H, et al. The effects of Snoezelen (multi-sensory behavior therapy) and psychiatric care on agitation, apathy, and activities of daily living in dementia patients on a short term geriatric psychiatric inpatient unit. Int J Psychiatry Med. 2007;37(4):357–70.
Raglio A, Bellelli G, Traficante D, Gianotti M, Ubezio MC, Villani D, et al. Efficacy of music therapy in the treatment of behavioral and psychiatric symptoms of dementia. Alzheimer Dis Assoc Disord. 2008;22(2):158–62.
Niu YX, Tan JP, Guan JQ, Zhang ZQ, Wang LN. Cognitive stimulation therapy in the treatment of neuropsychiatric symptoms in Alzheimer’s disease: a randomized controlled trial. Clin Rehabil. 2010;24(12):1102–11.
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Conflicts of interest: A. Krishnamoorthy: honoraria for invited lectures from Pfizer, Shire, Novartis, and Eisai; D. Craufurd: payment from Amarin Neuroscience, Neurosearch, and Medivation for participation in clinical trials.
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Krishnamoorthy, A., Craufurd, D. Treatment of Apathy in Huntington’s Disease and Other Movement Disorders. Curr Treat Options Neurol 13, 508–519 (2011). https://doi.org/10.1007/s11940-011-0140-y
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DOI: https://doi.org/10.1007/s11940-011-0140-y