Hostname: page-component-cd9895bd7-jn8rn Total loading time: 0 Render date: 2024-12-28T12:26:18.891Z Has data issue: false hasContentIssue false
  • English
  • Français

A review of neuroimaging findings of apathy in Alzheimer's disease

Published online by Cambridge University Press:  18 October 2013

Christos Theleritis ,
Antonios Politis ,
Kostas Siarkos  and
Costantine G. Lyketsos
Christos Theleritis*
Affiliation:
First Department of Psychiatry, National and Kapodistrian University of Athens, Eginition Hospital, 74 Vas. Sofias Ave., 11528 Athens, Greece University Mental Health Research Institute, 2 Soranou Efesiou Str., Papagou 156 01, Athens, Greece Department of Psychosis Studies, Institute of Psychiatry, De Crespigny Park, King's College London, UK
Antonios Politis
Affiliation:
First Department of Psychiatry, National and Kapodistrian University of Athens, Eginition Hospital, 74 Vas. Sofias Ave., 11528 Athens, Greece The Johns Hopkins University, Baltimore, MD, USA
Kostas Siarkos
Affiliation:
First Department of Psychiatry, National and Kapodistrian University of Athens, Eginition Hospital, 74 Vas. Sofias Ave., 11528 Athens, Greece
Costantine G. Lyketsos
Affiliation:
The Johns Hopkins University, Baltimore, MD, USA
*
Correspondence should be addressed to: Christos Theleritis, MD, 1st Psychiatry Department, University of Athens Medical School, Eginition Hopsital, 72–74 Vas. Sofias Avenue, 11528 Athens, Greece. Phone: +30 210 7289324. Email: chtheler@med.uoa.gr; christos.theleritis@kcl.ac.uk.
Get access

Abstract

Background:

Apathy is one of the most frequent “behavioral and psychological signs and symptoms of dementia” (BPSD) encountered in Alzheimer's disease (AD). There is a growing interest in the early diagnosis of apathetic elderly patients in the community since apathy has been associated with reduced daily functioning, caregiver distress, and poor outcome. The generalization of neuroimaging techniques might be able to offer help in this domain.

Methods: Within this context we conducted an extensive electronic search from the databases included in the National Library of Medicine as well as PsychInfo and Google Scholar for neuroimaging findings of apathy in AD.

Results:

Neuroimaging findings lend support to the notion that frontal-subcortical networks are involved in the occurrence of apathy in AD.

Conclusions: Longitudinal studies comparing patients and normal individuals might allow us to infer on the association between apathy and neurodegenerative diseases and what can brain imaging markers tell us about the characterization of this association, thus revealing disease patterns, helping to distinguish clinically distinct cognitive syndromes, and allowing predictions.

Keywords

neuroimaging studiesapathyAlzheimer's diseasedementiamild cognitive impairmentdepressionfrontal-subcortical networksanterior cingulate cortex
Type
Review Article
Information
International Psychogeriatrics , Volume 26 , Issue 2 , February 2014 , pp. 195 - 207
Copyright
Copyright © International Psychogeriatric Association 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Allman, J. M., Hakeem, A., Erwin, J. M., Nimchinsky, E. and Hof, P. (2001). The anterior cingulate cortex. The evolution of an interface between emotion and cognition. Annals of the New York Academy of Sciences, 935, 107–117. doi:10.1111/j.1749-6632.2001.tb03476.x.CrossRefGoogle ScholarPubMed
Apostolova, L. G. et al. (2007). Structural correlates of apathy in Alzheimer's disease. Dementia and Geriatric Cognitive Disorders, 24, 91–97. doi:10.1159/000103914.CrossRefGoogle ScholarPubMed
Benoit, M.et al. (1999). Behavioral and psychological symptoms in Alzheimer's disease. Relation between apathy and regional cerebral perfusion. Dementia and Geriatric Cognitive Disorders, 10, 511–517. doi:10.1159/000017198.CrossRefGoogle ScholarPubMed
Benoit, M., Clairet, S., Koulibaly, P. M., Darcourt, J. and Robert, P. H. (2004). Brain perfusion correlates of the apathy inventory dimensions of Alzheimer's disease. International Journal of Geriatric Psychiatry, 19, 864–869. doi:10.1002/gps.1163.CrossRefGoogle ScholarPubMed
Benoit, M., Koulibaly, P. M., Migneco, O., Darcourt, J., Pringuey, D. J. and Robert, P. H. (2002). Brain perfusion in Alzheimer's disease with and without apathy: a SPECT study with statistical parametric mapping analysis. Psychiatry Research: Neuroimaging, 114, 103–111. doi:10.1016/S0925-4927(02)00003-3.CrossRefGoogle Scholar
Bonelli, R. M. and Cummings, J. L. (2007). Frontal-subcortical circuitry and behavior. Dialogues in Clinical Neuroscience, 9, 141–151.CrossRefGoogle ScholarPubMed
Bruen, P. D., McGeown, W. J., Shanks, M. F. and Venneri, A. (2008). Neuroanatomical correlates of neuropsychiatric symptoms in Alzheimer's disease. Brain, 131, 2455–2463. doi:10.1093/brain/awn151.CrossRefGoogle ScholarPubMed
Clarke, D. E., Ko, J. Y., Lyketsos, C., Rebok, G. W. and Eaton, W. W. (2010). Apathy and cognitive and functional decline in community-dwelling older adults: results from the Baltimore ECA longitudinal study. International Psychogeriatrics, 22, 819–829. doi:10.1017/S1041610209991402.Google Scholar
Craig, A. H.et al. (1996). Cerebral blood flow correlates of apathy in Alzheimer disease. Archives of Neurology, 53, 1116–1120. doi:10.1001/archneur.1996.00550110056012.CrossRefGoogle ScholarPubMed
Cummings, J. L. (1997). The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology, 48 (Suppl. 6), s10–16. doi:10.1212/WNL.48.5_Suppl_6.10S.Google Scholar
Cummings, J. L., Diaz, C., Levy, M., Binetti, G. and Litvan, I. I. (1996). Behavioral syndromes in neurodegenerative diseases: frequency and significance. Seminars in Clinical Neuropsychiatry, 1, 241–247.Google Scholar
David, R.et al. (2008). Striatal dopamine transporter levels correlate with apathy in neurodegenerative diseases: a SPECT study with partial volume effect correction. Clinical Neurology and Neurosurgery, 110, 19–24. doi:10.1016/j.clineuro.2007.08.007.Google Scholar
Drijgers, R. L., Verhey, F. R., Leentjens, A. F., Köhler, S. and Aalten, P. (2011). Neuropsychological correlates of apathy in mild cognitive impairment and Alzheimer's disease: the role of executive functioning. International Psychogeriatrics, 23, 1327–1333. doi:10.1017/S1041610211001037.Google Scholar
Guimaraes, H. C., Levy, R., Teixeira, A. L., Beato, R. G. and Caramelli, P. (2008). Neurobiology of apathy in Alzheimer's disease. Arquivos de Neuro-Psiquiatria, 66, 436–443. doi:10.1590/S0004-282X2008000300035.CrossRefGoogle ScholarPubMed
Holthoff, V. A.et al. (2005). Regional cerebral metabolism in early Alzheimer's disease with clinically significant apathy or depression. Biological Psychiatry, 57, 412–421. doi:10.1016/j.biopsych.2004.11.035.Google Scholar
Jonsson, M., Edman, A., Lind, K., Rolstad, S., Sjögren, M. and Wallin, A. (2010). Apathy is a prominent neuropsychiatric feature of radiological white-matter changes in patients with dementia. International Journal of Geriatric Psychiatry, 25, 588–595. doi:10.1002/gps.2379.CrossRefGoogle ScholarPubMed
Kang, J. Y.et al. (2012). Regional cerebral blood flow abnormalities associated with apathy and depression in Alzheimer disease. Alzheimer Disease and Associated Disorders, 26, 217–224. doi:10.1097/WAD.0b013e318231e5fc.Google Scholar
Kim, J. W.et al. (2011). Microstructural alteration of the anterior cingulum is associated with apathy in Alzheimer disease. American Journal of Geriatric Psychiatry, 19, 644–653. doi:10.1097/JGP.0b013e31820dcc73.CrossRefGoogle ScholarPubMed
Lanctôt, K. L.et al. (2007). A SPECT study of apathy in Alzheimer's disease. Dementia and Geriatric Cognitive Disorders, 24, 65–72. doi:10.1159/000103633.Google Scholar
Landes, A. M., Sperry, S. D., Strauss, M. E. and Geldmacher, D. S. (2001). Apathy in Alzheimer's disease. Journal of the American Geriatrics Society, 49, 1700–1707. doi:10.1046/j.1532-5415.2001.49282.x.Google Scholar
Lavretsky, H.et al. (2008). The MRI brain correlates of depressed mood, anhedonia, apathy, and anergia in older adults with and without cognitive impairment or dementia. International Journal of Geriatric Psychiatry, 23, 1040–1050. doi:10.1002/gps.2030.Google Scholar
Levy, R. and Dubois, B. (2006). Apathy and the functional anatomy of the prefrontal cortex-basal Ganglia circuits. Cerebral Cortex, 16, 916–928. doi:10.1093/cercor/bhj043.CrossRefGoogle ScholarPubMed
Lopez, O. L., Zivkovic, S., Smith, G., Becker, J. T., Meltzer, C. C. and DeKosky, S. T. (2001). Psychiatric symptoms associated with cortical-subcortical dysfunction in Alzheimer's disease. The Journal of Neuropsychiatry and Clinical Neurosciences, 13, 56–60. doi:10.1176/appi.neuropsych.13.1.56.CrossRefGoogle ScholarPubMed
Lyketsos, C. (2007). Apathy and agitation: challenges and future directions. American Journal of Geriatric Psychiatry, 15, 361–364. doi:10.1097/JGP.0b013e31803d15c1.Google Scholar
Lyketsos, C. G., Lopez, O., Jones, B., Fitzpatrick, A. L., Breitner, J. and DeKosky, S. (2002). Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study. JAMA, 288, 1475–1483. doi:10.1001/jama.288.12.1475.CrossRefGoogle ScholarPubMed
Lyketsos, C. G., Rosenblatt, A. and Rabins, P. (2004). Forgotten frontal lobe syndrome or “Executive Dysfunction Syndrome”. Psychosomatics, 45, 247–255. doi:10.1176/appi.psy.45.3.247.Google Scholar
Lyketsos, C. G., Steinberg, M., Tschanz, J. T., Norton, M. C., Steffens, D. C. and Breitner, J. C. (2000). Mental and behavioral disturbances in dementia: findings from the Cache County Study on Memory in Aging. American Journal of Psychiatry, 157, 708–714. doi:10.1176/appi.ajp.157.5.708.Google Scholar
Marin, R. S. (1990). Differential diagnosis and classification of apathy. American Journal of Psychiatry, 147, 22–30.Google ScholarPubMed
Marshall, G. A., Fairbanks, L. A., Tekin, S., Vinters, H. V. and Cummings, J. L. (2006). Neuropathologic correlates of apathy in Alzheimer's disease. Dementia and Geriatric Cognitive Disorders, 21, 144–147. doi:10.1159/000090674.Google Scholar
Marshall, G. A., Monserratt, L., Harwood, D., Mandelkern, M., Cummings, J. L. and Sultzer, D. L. (2007). Positron emission tomography metabolic correlates of apathy in Alzheimer disease. Archives of Neurology, 64, 1015–1020. doi:10.1001/archneur.64.7.1015.CrossRefGoogle ScholarPubMed
Mega, M. S. and Cummings, J. L. (1994). Frontal-subcortical circuits and neuropsychiatric disorders. The Journal of Neuropsychiatry and Clinical Neurosciences, 6, 358–370.Google Scholar
Mega, M. S., Cummings, J. L., Fiorello, T. and Gornbein, J. (1996). The spectrum of behavioral changes in Alzheimer's disease. Neurology, 46, 130–135. doi:10.1212/WNL.46.1.130.CrossRefGoogle ScholarPubMed
Mega, M. S., Cummings, J. L., Salloway, S. and Malloy, P. (1997). The limbic system: an anatomic, phylogenetic, and clinical perspective. The Journal of Neuropsychiatry and Clinical Neurosciences, 9, 315–330.Google ScholarPubMed
Mega, M. S.et al. (2005). Metabolic patterns associated with the clinical response to galantamine therapy: a fludeoxyglucose f 18 positron emission tomographic study. Archives of Neurology, 62, 721–728. doi:10.1001/archneur.62.5.721.CrossRefGoogle ScholarPubMed
Migneco, O.et al. (2001). Perfusion brain SPECT and statistical parametric mapping analysis indicate that apathy is a cingulate syndrome: a study in Alzheimer's disease and nondemented patients. Neuroimage, 13, 896–902. doi:10.1006/nimg.2000.0741.CrossRefGoogle ScholarPubMed
Mulin, E.et al. (2011). Diagnostic criteria for apathy in clinical practice. International Journal of Geriatric Psychiatry, 26, 158–165. doi:10.1002/gps.2508.CrossRefGoogle ScholarPubMed
Onyike, C. U.et al. (2007). Epidemiology of apathy in older adults: the Cache County Study. American Journal of Geriatric Psychiatry, 15, 365–375. doi:10.1097/01.JGP.0000235689.42910.0d.Google Scholar
Ota, M., Sato, N., Nakata, Y., Arima, K. and Uno, M. (2012). Relationship between apathy and diffusion tensor imaging metrics of the brain in Alzheimer's disease. International Journal of Geriatric Psychiatry, 27, 722–726. doi:10.1002/gps.2779.Google Scholar
Ott, B. R., Noto, R. B. and Fogel, B. S. (1996). Apathy and loss of insight in Alzheimer's disease: a SPECT imaging study. The Journal of Neuropsychiatry and Clinical Neurosciences, 8, 41–46.Google ScholarPubMed
Politis, A. M., Mayer, L. S., Passa, M., Maillis, A. and Lyketsos, C. G. (2004). Validity and reliability of the newly translated Hellenic Neuropsychiatric Inventory (H-NPI) applied to Greek outpatients with Alzheimer's disease: a study of disturbing behaviors among referrals to a memory clinic. International Journal of Geriatric Psychiatry, 19, 203–208. doi:10.1002/gps.1215.Google Scholar
Robert, P. H.et al. (2006). Lack of initiative and interest in Alzheimer's disease: a single photon emission computed tomography study. European Journal of Neurology, 13, 729–735. doi:10.1111/j.1468-1331.2006.01088.x.CrossRefGoogle ScholarPubMed
Robert, P.et al. (2009). Proposed diagnostic criteria for apathy in Alzheimer's disease and other neuropsychiatric disorders. European Psychiatry, 24, 98–104. doi:10.1016/j.eurpsy.2008.09.001.CrossRefGoogle ScholarPubMed
Schroeter, M. L.et al. (2011). Dissociating behavioral disorders in early dementia – An FDG-PET study. Psychiatry Research: Neuroimaging, 194, 235–244. doi:10.1016/j.pscychresns.2011.06.009.Google Scholar
Starkstein, S. E., Petracca, G., Chemerinski, E. and Kremer, J. (2001). Syndromic validity of apathy in Alzheimer's disease. American Journal of Psychiatry, 158, 872–877. doi:10.1176/appi.ajp.158.6.872.CrossRefGoogle ScholarPubMed
Starkstein, S. E., Mizrahi, R., Capizzano, A. A., Acion, L., Brockman, S. and Power, B. D. (2009). Neuroimaging correlates of apathy and depression in Alzheimer's disease. The Journal of Neuropsychiatry and Clinical Neurosciences, 21, 259–265. doi:10.1176/appi.neuropsych.21.3.259.Google Scholar
Tanaka, M.et al. (2004). Prediction of psychiatric response to donepezil in patients with mild to moderate Alzheimer's disease. Journal of the Neurological Sciences, 225, 135–141. doi:10.1016/j.jns.2004.07.009.Google Scholar
Tekin, S.et al. (2001). Orbitofrontal and anterior cingulate cortex neurofibrillary tangle burden is associated with agitation in Alzheimer disease. Annals of Neurology, 49, 355–361. doi:10.1002/ana.72.Google Scholar
Tighe, S. K.et al. (2012). Diffusion tensor imaging of neuropsychiatric symptoms in mild cognitive impairment and Alzheimer's dementia. The Journal of Neuropsychiatry and Clinical Neurosciences, 24, 484–488. doi:10.1176/appi.neuropsych.11120375.Google Scholar
Tunnard, C.et al. (2011). Apathy and cortical atrophy in Alzheimer's disease. International Journal of Geriatric Psychiatry, 26, 741–748. doi:10.1002/gps.2603.Google Scholar
Wallis, J. D. (2007). Orbitofrontal cortex and its contribution to decision-making. Annual Review of Neuroscience, 30, 31–56. doi:10.1146/annurev.neuro.30.051606.094334.CrossRefGoogle ScholarPubMed