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Behavioural and emotional symptoms of apathy are associated with distinct patterns of brain atrophy in neurodegenerative disorders

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Abstract

Apathy is a neurocognitive syndrome of reduced goal-directed behaviour and is an important cause of disability in neurodegenerative disorders. Frontal–subcortical dysfunction is thought to be important in apathy, but the contribution of individual brain regions to different aspects of the apathy syndrome is poorly understood. We aimed to test the hypotheses that apathy in two distinct neurodegenerative disorders would be associated with frontal lobe atrophy and that reduced initiative and emotional blunting would be associated with distinct patterns of atrophy in functionally relevant brain areas. Seventeen patients with progressive supranuclear palsy (PSP) and 17 patients with Alzheimer’s disease (AD) underwent structural MRI scanning at 3 T to provide data for voxel based morphometric analysis. Apathy was defined using Robert’s 2009 diagnostic criteria and specific symptoms were assessed with the Apathy Inventory. Patients with and without apathy were matched for important demographic and clinical characteristics. Apathy was associated with atrophy of the ventromedial orbitofrontal cortex and left insula in both AD and PSP. Reduced initiative was specifically associated with atrophy of the anterior cingulate and ventrolateral orbitofrontal cortex whilst emotional blunting was specifically associated with atrophy of the left insula. These findings provide further support for the role of medial frontal regions and insular cortex in apathy and suggest that behavioural and emotional aspects of the apathy syndrome may have distinct neuroanatomical bases.

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References

  1. Brown RG, Pluck G (2000) Negative symptoms: the ‘pathology’ of motivation and goal-directed behaviour. Trends Neurosci 23:412–417

    Article  PubMed  CAS  Google Scholar 

  2. Starkstein SE, Leentjens AF (2008) The nosological position of apathy in clinical practice. J Neurol Neurosurg Psychiatry 79:1088–1092

    Google Scholar 

  3. Davis JD, Tremont G (2007) Impact of frontal systems behavioral functioning in dementia on caregiver burden. J Neuropsychiatry Clin Neurosci 19:43–49

    Article  PubMed  Google Scholar 

  4. Zawacki TM, Grace J, Paul R, Moser DJ, Ott BR, Gordon N, Cohen RA (2002) Behavioral problems as predictors of functional abilities of vascular dementia patients. J Neuropsychiatry Clin Neurosci 14:296–302

    Article  PubMed  Google Scholar 

  5. Chase TN (2011) Apathy in neuropsychiatric disease: diagnosis, pathophysiology, and treatment. Neurotox Res 19:266–278

    Article  PubMed  Google Scholar 

  6. Marin RS (1991) Apathy: a neuropsychiatric syndrome. J Neuropsychiatry Clin Neurosci 3:243–254

    PubMed  CAS  Google Scholar 

  7. Lau HC, Rogers RD, Ramnani N, Passingham RE (2004) Willed action and attention to the selection of action. Neuroimage 21:1407–1415

    Article  PubMed  CAS  Google Scholar 

  8. Murphy FC, Nimmo-Smith I, Lawrence AD (2003) Functional neuroanatomy of emotions: a meta-analysis. Cogn Affect Behav Neurosci 3:207–233

    Article  PubMed  Google Scholar 

  9. Passingham RE, Bengtsson SL, Lau HC (2010) Medial frontal cortex: from self-generated action to reflection on one’s own performance. Trends Cogn Sci 14:16–21

    Article  PubMed  Google Scholar 

  10. Fusar-Poli P, Placentino A, Carletti F, Landi P, Allen P, Surguladze S, Benedetti F, Abbamonte M, Gasparotti R, Barale F, Perez J, McGuire P, Politi P (2009) Functional atlas of emotional faces processing: a voxel-based meta-analysis of 105 functional magnetic resonance imaging studies. J Psychiatry Neurosci 34:418–432

    PubMed  Google Scholar 

  11. Cummings JL (1993) Frontal–subcortical circuits and human behavior. Arch Neurol 50:873–880

    Article  PubMed  CAS  Google Scholar 

  12. Apostolova LG, Akopyan GG, Partiali N, Steiner CA, Dutton RA, Hayashi KM, Dinov ID, Toga AW, Cummings JL, Thompson PM (2007) Structural correlates of apathy in Alzheimer’s disease. Dement Geriatr Cogn Disord 24:91–97

    Article  PubMed  Google Scholar 

  13. Lavretsky H, Ballmaier M, Pham D, Toga A, Kumar A (2007) Neuroanatomical characteristics of geriatric apathy and depression: a magnetic resonance imaging study. Am J Geriatr Psychiatry 15:386–394

    Article  PubMed  Google Scholar 

  14. Rosen HJ, Allison SC, Schauer GF, Gorno-Tempini ML, Weiner MW, Miller BL (2005) Neuroanatomical correlates of behavioural disorders in dementia. Brain 128:2612–2625

    Article  PubMed  Google Scholar 

  15. Bruen PD, McGeown WJ, Shanks MF, Venneri A (2008) Neuroanatomical correlates of neuropsychiatric symptoms in Alzheimer’s disease. Brain 131:2455–2463

    Article  PubMed  Google Scholar 

  16. Reijnders JS, Scholtissen B, Weber WE, Aalten P, Verhey FR, Leentjens AF (2010) Neuroanatomical correlates of apathy in Parkinson’s disease: a magnetic resonance imaging study using voxel-based morphometry. Mov Disord 25:2318–2325

    Article  PubMed  Google Scholar 

  17. Massimo L, Powers C, Moore P, Vesely L, Avants B, Gee J, Libon DJ, Grossman M (2009) Neuroanatomy of apathy and disinhibition in frontotemporal lobar degeneration. Dement Geriatr Cogn Disord 27:96–104

    Article  PubMed  Google Scholar 

  18. Zamboni G, Huey ED, Krueger F, Nichelli PF, Grafman J (2008) Apathy and disinhibition in frontotemporal dementia: insights into their neural correlates. Neurology 71:736–742

    Article  PubMed  CAS  Google Scholar 

  19. Tunnard C, Whitehead D, Hurt C, Wahlund LO, Mecocci P, Tsolaki M, Vellas B, Spenger C, Kloszewska I, Soininen H, Lovestone S, Simmons A (2011) Apathy and cortical atrophy in Alzheimer’s disease. Int J Geriatr Psychiatry 26:741–748

    Article  PubMed  CAS  Google Scholar 

  20. Litvan I, Bhatia KP, Burn DJ, Goetz CG, Lang AE, McKeith I, Quinn N, Sethi KD, Shults C, Wenning GK (2003) Movement Disorders Society Scientific Issues Committee report: sIC Task Force appraisal of clinical diagnostic criteria for Parkinsonian disorders. Mov Disord 18:467–486

    Article  PubMed  Google Scholar 

  21. Litvan I, Agid Y, Jankovic J, Goetz C, Brandel JP, Lai EC, Wenning G, D’Olhaberriague L, Verny M, Chaudhuri KR, McKee A, Jellinger K, Bartko JJ, Mangone CA, Pearce RK (1996) Accuracy of clinical criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome). Neurology 46:922–930

    Article  PubMed  CAS  Google Scholar 

  22. Litvan I (2001) Diagnosis and management of progressive supranuclear palsy. Semin Neurol 21:41–48

    Article  PubMed  CAS  Google Scholar 

  23. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology 34:939–944

    Article  PubMed  CAS  Google Scholar 

  24. Molloy DW, Standish TI (1997) A guide to the standardized Mini-Mental State Examination. Int Psychogeriatr 9(Suppl 1):87–94

    Article  PubMed  Google Scholar 

  25. van Marwijk HW, Wallace P, de Bock GH, Hermans J, Kaptein AA, Mulder JD (1995) Evaluation of the feasibility, reliability and diagnostic value of shortened versions of the geriatric depression scale. Br J Gen Pract 45:195–199

    PubMed  Google Scholar 

  26. Martinez-Martin P, Gil-Nagel A, Gracia LM, Gomez JB, Martinez-Sarries J, Bermejo F (1994) Unified Parkinson’s Disease Rating Scale characteristics and structure. The cooperative multicentric group. Mov Disord 9:76–83

    Article  PubMed  CAS  Google Scholar 

  27. Leentjens AF, Dujardin K, Marsh L, Martinez-Martin P, Richard IH, Starkstein SE, Weintraub D, Sampaio C, Poewe W, Rascol O, Stebbins GT, Goetz CG (2008) Apathy and anhedonia rating scales in Parkinson’s disease: critique and recommendations. Mov Disord 23:2004–2014

    Article  PubMed  Google Scholar 

  28. Schrag A (2011) Apathy and depression scales in Parkinson’s disease: are they good enough? J Neurol Sci 310:216–219

    Article  PubMed  Google Scholar 

  29. Robert P, Onyike CU, Leentjens AF, Dujardin K, Aalten P, Starkstein S, Verhey FR, Yessavage J, Clement JP, Drapier D, Bayle F, Benoit M, Boyer P, Lorca PM, Thibaut F, Gauthier S, Grossberg G, Vellas B, Byrne J (2009) Proposed diagnostic criteria for apathy in Alzheimer’s disease and other neuropsychiatric disorders. Eur Psychiatry 24:98–104

    Article  PubMed  CAS  Google Scholar 

  30. Drijgers RL, Dujardin K, Reijnders JS, Defebvre L, Leentjens AF (2010) Validation of diagnostic criteria for apathy in Parkinson’s disease. Parkinsonism Relat Disord 16:656–660

    Article  PubMed  Google Scholar 

  31. Marin RS, Biedrzycki RC, Firinciogullari S (1991) Reliability and validity of the Apathy Evaluation Scale. Psychiatry Res 38:143–162

    Article  PubMed  CAS  Google Scholar 

  32. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J (1994) The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 44:2308–2314

    Article  PubMed  CAS  Google Scholar 

  33. Robert PH, Clairet S, Benoit M, Koutaich J, Bertogliati C, Tible O, Caci H, Borg M, Brocker P, Bedoucha P (2002) The Apathy Inventory: assessment of apathy and awareness in Alzheimer’s disease, Parkinson’s disease and mild cognitive impairment. Int J Geriatr Psychiatry 17:1099–1105

    Article  PubMed  CAS  Google Scholar 

  34. Ashburner J, Friston KJ (2005) Unified segmentation. Neuroimage 26:839–851

    Article  PubMed  Google Scholar 

  35. Jones DK, Symms MR, Cercignani M, Howard RJ (2005) The effect of filter size on VBM analyses of DT-MRI data. Neuroimage 26:546–554

    Article  PubMed  Google Scholar 

  36. Bullmore ET, Suckling J, Overmeyer S, Rabe-Hesketh S, Taylor E, Brammer MJ (1999) Global, voxel, and cluster tests, by theory and permutation, for a difference between two groups of structural MR images of the brain. IEEE Trans Med Imaging 18:32–42

    Article  PubMed  CAS  Google Scholar 

  37. Lancaster JL, Woldorff MG, Parsons LM, Liotti M, Freitas CS, Rainey L, Kochunov PV, Nickerson D, Mikiten SA, Fox PT (2000) Automated Talairach atlas labels for functional brain mapping. Hum Brain Mapp 10:120–131

    Article  PubMed  CAS  Google Scholar 

  38. Jouvent E, Reyes S, Mangin JF, Roca P, Perrot M, Thyreau B, Herve D, Dichgans M, Chabriat H (2011) Apathy is related to cortex morphology in CADASIL. A sulcal-based morphometry study. Neurology 76:1472–1477

    Article  PubMed  CAS  Google Scholar 

  39. Jenkins IH, Jahanshahi M, Jueptner M, Passingham RE, Brooks DJ (2000) Self-initiated versus externally triggered movements. II. The effect of movement predictability on regional cerebral blood flow. Brain 123 (Pt 6):1216–1228

    Article  Google Scholar 

  40. Robert G, Le JF, Lozachmeur C, Drapier S, Dondaine T, Peron J, Travers D, Sauleau P, Millet B, Verin M, Drapier D (2012) Apathy in patients with Parkinson disease without dementia or depression: a PET study. Neurology 79:1155–1160

    Article  PubMed  CAS  Google Scholar 

  41. Brenneis C, Seppi K, Schocke M, Benke T, Wenning GK, Poewe W (2004) Voxel based morphometry reveals a distinct pattern of frontal atrophy in progressive supranuclear palsy. J Neurol Neurosurg Psychiatry 75:246–249

    PubMed  CAS  Google Scholar 

  42. Cordato NJ, Duggins AJ, Halliday GM, Morris JG, Pantelis C (2005) Clinical deficits correlate with regional cerebral atrophy in progressive supranuclear palsy. Brain 128:1259–1266

    Article  PubMed  CAS  Google Scholar 

  43. Schofield EC, Hodges JR, Macdonald V, Cordato NJ, Kril JJ, Halliday GM (2011) Cortical atrophy differentiates Richardson’s syndrome from the parkinsonian form of progressive supranuclear palsy. Mov Disord 26:256–263

    Article  PubMed  Google Scholar 

  44. Brooks JC, Tracey I (2007) The insula: a multidimensional integration site for pain. Pain 128:1–2

    Article  PubMed  CAS  Google Scholar 

  45. Ihme K, Dannlowski U, Lichev V, Stuhrmann A, Grotegerd D, Rosenberg N, Kugel H, Heindel W, Arolt V, Kersting A, Suslow T (2013) Alexithymia is related to differences in gray matter volume: a voxel-based morphometry study. Brain Res 1491:60–67

    Article  PubMed  CAS  Google Scholar 

  46. Craig AD (2002) How do you feel? Interoception: the sense of the physiological condition of the body. Nat Rev Neurosci 3:655–666

    PubMed  CAS  Google Scholar 

  47. Bechara A, Damasio H, Damasio AR (2000) Emotion, decision making and the orbitofrontal cortex. Cereb Cortex 10:295–307

    Article  PubMed  CAS  Google Scholar 

  48. Aalten P, Van Valen E, Clare L, Kenny G, Verhey F (2005) Awareness in dementia: a review of clinical correlates. Aging Ment Health 9:414–422

    Article  PubMed  Google Scholar 

  49. Eslinger PJ, Dennis K, Moore P, Antani S, Hauck R, Grossman M (2005) Metacognitive deficits in frontotemporal dementia. J Neurol Neurosurg Psychiatry 76:1630–1635

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The study was supported by the Medical Research Council through a Clinical Research Training Fellowship (G0500443) (BS). Author RB receives salary support from the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre and Dementia Biomedical Research Unit at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

Conflicts of interest

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

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Authors and Affiliations

  1. Department of Neurology, Royal Free London NHS Foundation Trust, London, NW3 2QG, UK

    Biba R. Stanton

  2. Brighton and Sussex Medical School, Trafford Centre for Biomedical Research, University of Sussex, East Sussex, BN1 9RY, UK

    P. Nigel Leigh

  3. Department of Old Age Psychiatry, Institute of Psychiatry, King’s College London, London, SE5 8AF, UK

    Robert J. Howard

  4. Department of Neuroimaging, Institute of Psychiatry, King’s College London, London, SE5 8AF, UK

    Gareth J. Barker

  5. Department of Psychology, Institute of Psychiatry, King’s College London, PO 77, De Crespigny Park, London, SE5 8AF, UK

    Richard G. Brown

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  1. Biba R. Stanton
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  2. P. Nigel Leigh
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Correspondence to Richard G. Brown.

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Stanton, B.R., Leigh, P.N., Howard, R.J. et al. Behavioural and emotional symptoms of apathy are associated with distinct patterns of brain atrophy in neurodegenerative disorders. J Neurol 260, 2481–2490 (2013). https://doi.org/10.1007/s00415-013-6989-9

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  • DOI: https://doi.org/10.1007/s00415-013-6989-9

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