Behavioural and emotional symptoms of apathy are associated with distinct patterns of brain atrophy in neurodegenerative disorders
Open accessAbstract
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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Apathy in Alzheimer's disease is associated with volume loss in anterior cingulate cortex, including reduced gray matter volume and cortical thinning.
“Structural imaging studies report volume loss in ACC, including reduced gray matter volume (Apostolova et al., 2007; Bruen et al., 2008; Stanton et al., 2013) and cortical thinning (Tunnard et al., 2011).”
From Neuropsychiatric symptoms in Alzheimer's disease: what might be associated brain circuits? (2015) · cites this paper as Stanton et al., 2013
Apathy in Alzheimer's disease is associated with decreased insula volume.
“Two studies report an association of apathy with decreased insula volume (Moon et al., 2014; Stanton et al., 2013) although they disagree on whether this is bilateral or unilateral.”
From Neuropsychiatric symptoms in Alzheimer's disease: what might be associated brain circuits? (2015) · cites this paper as Stanton et al., 2013
Apathy in Alzheimer's disease is associated with volume loss and/or cortical thinning in frontal cortex.
“There are also links between apathy and volume loss and/or cortical thinning in frontal cortex (Apostolova et al., 2007; Bruen et al., 2008; Stanton et al., 2013; Tunnard et al., 2011), though there is no strict concordance on the specific regions of frontal cortex which include medial, lateral, and orbital regions.”
From Neuropsychiatric symptoms in Alzheimer's disease: what might be associated brain circuits? (2015) · cites this paper as Stanton et al., 2013
Reduced initiative in Alzheimer's disease is associated with volume loss in anterior cingulate cortex.
“Two studies have endeavored to map specific subdomains of apathy (i.e., reduced initiative, emotional blunting, or lack of initiative) to neuroimaging findings in specific brain regions (Benoit et al., 2004; Stanton et al., 2013), with the only notable finding being that reduced initiative was associated with volume loss in ACC.”
From Neuropsychiatric symptoms in Alzheimer's disease: what might be associated brain circuits? (2015) · cites this paper as Stanton et al., 2013
Cites
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · see citing works
The Neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia
Cummings, J. L., Mega, M., Gray, K., Rosenberg-Thompson, S., Carusi, D. A., & Gornbein, J. (1994) · Neurology · doi:10.1212/wnl.44.12.2308 · Cited by 7,568 · see citing works
Ashburner, J., & Friston, K. J. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.02.018 · Cited by 7,507 · see citing works
How do you feel? Interoception: The sense of the physiological condition of the body
Craig, A. D. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn894 · Cited by 6,006 · see citing works
Emotion, Decision Making and the Orbitofrontal Cortex
Bechara, A. (2000) · Cerebral Cortex · doi:10.1093/cercor/10.3.295 · Cited by 3,589 · see citing works
Frontal-subcortical circuits and human behavior
Cummings, J. L. (1993) · Archives of Neurology · doi:10.1001/archneur.1993.00540080076020 · Cited by 2,262 · see citing works
Reliability and validity of the apathy evaluation scale
Marin, R. S., Biedrzycki, R. C., & Firinciogullari, S. (1991) · Psychiatry Research · doi:10.1016/0165-1781(91)90040-v · Cited by 1,805 · see citing works
Fusar‐Poli, P., Placentino, A., Carletti, F., Landi, P., Allen, P., Surguladze, S., Benedetti, F., Abbamonte, M., Gasparotti, R., Barale, F., et al. (2009) · Journal of Psychiatry and Neuroscience · doi:10.1139/jpn.0953 · Cited by 1,292 · see citing works
Functional neuroanatomy of emotions: A meta-analysis
MURPHY, F. C., NIMMO-SMITH, I., & LAWRENCE, A. D. (2003) · Cognitive, Affective, & Behavioral Neuroscience · doi:10.3758/cabn.3.3.207 · Cited by 1,135 · see citing works
Apathy: a neuropsychiatric syndrome
Marin, R. S. (1991) · Journal of Neuropsychiatry · doi:10.1176/jnp.3.3.243 · Cited by 1,088 · see citing works
Bullmore, E. T., Suckling, J., Overmeyer, S., Rabe-Hesketh, S., Taylor, E., & Brammer, M. J. (1999) · IEEE Transactions on Medical Imaging · doi:10.1109/42.750253 · Cited by 1,088 · see citing works
SIC Task Force appraisal of clinical diagnostic criteria for parkinsonian disorders
Litvan, I., Bhatia, K. P., Burn, D. J., Goetz, C. G., Lang, A. E., McKeith, I. G., Quinn, N. P., Sethi, K. D., Shults, C. W., & Wenning, G. K. (2003) · Movement Disorders · doi:10.1002/mds.10459 · Cited by 1,006 · see citing works
Unified Parkinson's disease rating scale characteristics and structure
Martínez‐Martín, P., Gil‐Nagel, A., Gracia, L. M., Gomez, J., Martínez‐Sarriés, J., Bermejo, F., & The Cooperative Multicentric Group (1994) · Movement Disorders · doi:10.1002/mds.870090112 · Cited by 794 · see citing works
Self-initiated versus externally triggered movements
Jenkins, I. H., Jahanshahi, M., Jueptner, M., Passingham, R. E., & Brooks, D. J. (2000) · Brain · doi:10.1093/brain/123.6.1216 · Cited by 746 · see citing works
Proposed diagnostic criteria for apathy in Alzheimer’s disease and other neuropsychiatric disorders
Robert, P. H., Onyike, C. U., Leentjens, A. F. G., Dujardin, K., Aalten, P., STARKSTEIN, S. E., Verhey, F. R. J., Yessavage, J., Clément, J., Drapier, D., et al. (2009) · European Psychiatry · doi:10.1016/j.eurpsy.2008.09.001 · Cited by 618 · see citing works
The effect of filter size on VBM analyses of DT-MRI data
Jones, D. K., Symms, M. R., Cercignani, M., & Howard, R. J. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.02.013 · Cited by 562 · see citing works
Self-citationA Guide to the Standardized Mini-Mental State Examination
Molloy, D. W., & Standish, T. I. M. (1997) · International Psychogeriatrics · doi:10.1017/s1041610297004754 · Cited by 505 · see citing works
Neuroanatomical correlates of behavioural disorders in dementia
Rosen, H. J., Allison, S. C., Schauer, G. F., Gorno-Tempini, M. L., Weiner, M. W., & Miller, B. L. (2005) · Brain · doi:10.1093/brain/awh628 · Cited by 497 · see citing works
Robert, P. H., Clairet, S., Benoît, M., Koutaich, J., Bertogliati, C., Tible, O., Caci, H. M., Borg, M., Brocker, P., & Bedoucha, P. (2002) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.755 · Cited by 403 · see citing works
Neuroanatomical correlates of neuropsychiatric symptoms in Alzheimer's disease
Bruen, P. D., McGeown, W. J., Shanks, M. F., & Venneri, A. (2008) · Brain · doi:10.1093/brain/awn151 · Cited by 374 · see citing works
The nosological position of apathy in clinical practice
STARKSTEIN, S. E., & Leentjens, A. F. G. (2008) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2007.136895 · Cited by 372 · see citing works
Litvan, I., Agid, Y., Jankovic, J. J., Goetz, C. G., Brandel, J., Lai, E. C., Wenning, G. K., D'Olhaberriague, L., Verny, M., Chaudhuri, К. R., et al. (1996) · Neurology · doi:10.1212/wnl.46.4.922 · Cited by 347 · see citing works
Apathy and anhedonia rating scales in Parkinson's disease: Critique and recommendations
Leentjens, A. F. G., Dujardin, K., Marsh, L., Martínez‐Martín, P., Richard, I. H., STARKSTEIN, S. E., Weintraub, D. A., Sampaio, C., Poewe, W. H., Rascol, O., et al. (2008) · Movement Disorders · doi:10.1002/mds.22229 · Cited by 346 · see citing works
Negative symptoms: the ‘pathology’ of motivation and goal-directed behaviour
Brown, R. G., & Pluck, G. C. (2000) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)01626-x · Cited by 297 · see citing works
Self-citationvan Marwijk, H., Wallace, P., de Bock, G. H., Hermans, J., Kaptein, A. A., & Mulder, J. (1995) · Europe PMC (PubMed Central) · Cited by 296 · see citing works
Apathy and disinhibition in frontotemporal dementia
Zamboni, G., Huey, E. D., Krueger, F. W., Nichelli, P., & Grafman, J. H. (2008) · Neurology · doi:10.1212/01.wnl.0000324920.96835.95 · Cited by 276 · see citing works
Medial frontal cortex: From self-generated action to reflection on one's own performance
Passingham, R. E., Bengtsson, S. L., & Lau, H. C. (2010) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2009.11.001 · Cited by 252 · see citing works
Willed action and attention to the selection of action
Lau, H. C., Rogers, R. D., Ramnani, N., & Passingham, R. E. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2003.10.034 · Cited by 220 · see citing works
Reijnders, J., Scholtissen, B., Weber, W., Aalten, P., Verhey, F., & Leentjens, A. (2010) · Movement Disorders · doi:10.1002/mds.23268 · Cited by 192 · see citing works
Structural correlates of apathy in Alzheimer's disease
Apostolova, L. G., Akopyan, G. G., Partiali, N., Steiner, C. A., Dutton, R. A., Hayashi, K. M., Dinov, I. D., Toga, A. W., Cummings, J. L., & Thompson, P. M. (2007) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000103914 · Cited by 190 · see citing works
Neuroanatomy of Apathy and Disinhibition in Frontotemporal Lobar Degeneration
Massimo, L., Powers, C., Moore, P., Vesely, L., Avants, B., Gee, J., Libon, D. J., & Grossman, M. (2009) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000194658 · Cited by 156 · see citing works
Metacognitive deficits in frontotemporal dementia
Eslinger, P. J. (2005) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2004.053157 · Cited by 151 · see citing works
Clinical deficits correlate with regional cerebral atrophy in progressive supranuclear palsy
Cordato, N. J., Duggins, A., Halliday, G. M., Morris, J. G., & Pantelis, C. (2005) · Brain · doi:10.1093/brain/awh508 · Cited by 146 · see citing works
Lavretsky, H., Ballmaier, M., Pham, D., Toga, A., & Kumar, A. (2007) · The American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e3180325a16 · Cited by 143 · see citing works
Apathy in Neuropsychiatric Disease: Diagnosis, Pathophysiology, and Treatment
Chase, T. N. (2010) · Neurotoxicity Research · doi:10.1007/s12640-010-9196-9 · Cited by 141 · see citing works
Awareness in dementia: A review of clinical correlates
Aalten, P., van Valen, E., Clare, L., Kenny, G., & Verhey, F. R. J. (2005) · Aging & Mental Health · doi:10.1080/13607860500143075 · Cited by 140 · see citing works
Brenneis, C., Seppi, K., Schocke, M. F. H., Benke, T., Wenning, G. K., & Poewe, W. H. (2004) · PubMed Central · Cited by 135 · see citing works
The insula: A multidimensional integration site for pain
Brooks, J. C. W., & Tracey, I. (2007) · Pain · doi:10.1016/j.pain.2006.12.025 · Cited by 124 · see citing works
Validation of diagnostic criteria for apathy in Parkinson’s disease
Drijgers, R. L., Dujardin, K., Reijnders, J. S. A. M., Defebvre, L., & Leentjens, A. F. G. (2010) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2010.08.015 · Cited by 112 · see citing works
Apathy in patients with Parkinson disease without dementia or depression
Robert, G., Jeune, F. L., Lozachmeur, C., Drapier, S., Dondaine, T., Péron, J., Travers, D., Sauleau, P., Millet, B., Vérin, M., et al. (2012) · Neurology · doi:10.1212/wnl.0b013e3182698c75 · Cited by 103 · see citing works
Apathy and cortical atrophy in Alzheimer's disease
Tunnard, C., Whitehead, D. L., Hurt, C. S., Wahlund, L., Mecocci, P., Tsolaki, M., Vellas, B. J., Spenger, C., Kłoszewska, I., Soininen, H. S., et al. (2010) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.2603 · Cited by 102 · see citing works
Impact of Frontal Systems Behavioral Functioning in Dementia on Caregiver Burden
Davis, J. D., & Tremont, G. N. (2007) · Journal of Neuropsychiatry · doi:10.1176/jnp.2007.19.1.43 · Cited by 99 · see citing works
Diagnosis and Management of Progressive Supranuclear Palsy
Litvan, I. (2001) · Seminars in Neurology · doi:10.1055/s-2001-13118 · Cited by 72 · see citing works
Behavioral Problems as Predictors of Functional Abilities of Vascular Dementia Patients
Zawacki, T. M., Grace, J., Paul, R. H., Moser, D. J., Ott, B. R., Gordon, N. M., & Cohen, R. A. (2002) · Journal of Neuropsychiatry · doi:10.1176/jnp.14.3.296 · Cited by 66 · see citing works
Alexithymia is related to differences in gray matter volume: A voxel-based morphometry study
Ihme, K. A., Dannlowski, U., Lichev, V., Stuhrmann, A., Grotegerd, D., Rosenberg, N., Kugel, H., Heindel, W. L., Arolt, V., Kersting, A., et al. (2012) · Brain Research · doi:10.1016/j.brainres.2012.10.044 · Cited by 63 · see citing works
Schofield, E. C., Hodges, J. R., Macdonald, V., Cordato, N. J., Kril, J. J., & Halliday, G. M. (2011) · Movement Disorders · doi:10.1002/mds.23295 · Cited by 48 · see citing works
Apathy is related to cortex morphology in CADASIL: A sulcal-based morphometry study
Jouvent, E., Reyes, S., Mangin, J.-F., Roca, P., Perrot, M., Thyreau, B., Hervé, D., Dichgans, M., & Chabriat, H. (2011) · Neurology · doi:10.1212/wnl.0b013e31821810a4 · Cited by 44 · see citing works
Apathy and depression scales in Parkinson's disease: Are they good enough?
Schrag, A. E. (2011) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2011.05.045 · Cited by 23 · see citing works
Lurito (2000) · doi:10.1002/1097-0193(200007)10:3
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Rosenberg, P. B., Nowrangi, M. A., & Lyketsos, C. G. (2015) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2015.05.005 · Cited by 302 · see citing works
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- Authors
- Stanton, B. R., Leigh, P. N., Howard, R. J., Barker, G. J., & Brown, R. G.
- Affiliations
- Royal Free London NHS Foundation Trust (GB)
- Brighton and Sussex Medical School (GB)
- King's College London (GB)
- Corresponding author
- Brown, Richard G.
- Venue
- Journal of Neurology
- Published
- 2013-06-23
- Volume
- 260
- Issue
- 10
- Pages
- 2481-2490
- ISSN
- 0012-1037 (ISSN-L)
- 0340-5354
- 1432-1459
- OpenAlex
- W2076785018
- Cited by
- 92
- References
- 49
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 12 · 2021: 8 · 2020: 6 · 2019: 9 · 2018: 6 · 2017: 11 · 2016: 10 · 2015: 9 · 2014: 5
- FWCI
- 5.66
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Licence
- Locations
- Journal of Neurology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- apathy, neurodegenerative diseases, progressive supranuclear palsy, Alzheimer's disease, brain atrophy, frontal lobe atrophy, orbitofrontal cortex, insula, anterior cingulate cortex, emotional blunting, goal-directed behavior, voxel-based morphometry
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Analysis of Variance, Atrophy, Behavioral Symptoms, Brain, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Mental Status Schedule, Middle Aged, Supranuclear Palsy, Progressive, Apathy
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