Hostname: page-component-cd9895bd7-gbm5v Total loading time: 0 Render date: 2024-12-25T04:35:20.608Z Has data issue: false hasContentIssue false

Anosognosia in mild cognitive impairment: Relationship to activation of cortical midline structures involved in self-appraisal

Published online by Cambridge University Press:  20 March 2007

MICHELE L. RIES
Affiliation:
Geriatric Research Education and Clinical Center, William S. Middleton VA Hospital, Madison, Wisconsin Department of Medicine, University of Wisconsin, Madison, Wisconsin
BRITTA M. JABBAR
Affiliation:
Geriatric Research Education and Clinical Center, William S. Middleton VA Hospital, Madison, Wisconsin Department of Medicine, University of Wisconsin, Madison, Wisconsin
TAYLOR W. SCHMITZ
Affiliation:
Geriatric Research Education and Clinical Center, William S. Middleton VA Hospital, Madison, Wisconsin Department of Medicine, University of Wisconsin, Madison, Wisconsin
MEHUL A. TRIVEDI
Affiliation:
Geriatric Research Education and Clinical Center, William S. Middleton VA Hospital, Madison, Wisconsin Department of Medicine, University of Wisconsin, Madison, Wisconsin
CAREY E. GLEASON
Affiliation:
Geriatric Research Education and Clinical Center, William S. Middleton VA Hospital, Madison, Wisconsin Department of Medicine, University of Wisconsin, Madison, Wisconsin
CYNTHIA M. CARLSSON
Affiliation:
Geriatric Research Education and Clinical Center, William S. Middleton VA Hospital, Madison, Wisconsin Department of Medicine, University of Wisconsin, Madison, Wisconsin
HOWARD A. ROWLEY
Affiliation:
Department of Medicine, University of Wisconsin, Madison, Wisconsin
SANJAY ASTHANA
Affiliation:
Geriatric Research Education and Clinical Center, William S. Middleton VA Hospital, Madison, Wisconsin Department of Medicine, University of Wisconsin, Madison, Wisconsin
STERLING C. JOHNSON
Affiliation:
Geriatric Research Education and Clinical Center, William S. Middleton VA Hospital, Madison, Wisconsin Department of Medicine, University of Wisconsin, Madison, Wisconsin

Abstract

Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer's disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants' activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI participants and 16 age-matched controls, examining brain regions showing conjoint or differential BOLD response during self-appraisal. Second, we used regression to investigate the relationship between awareness of deficit in MCI and BOLD activity during self-appraisal, controlling for extent of memory impairment. Between-group comparisons indicated that MCI participants show subtly attenuated CMS activity during self-appraisal. Regression analysis revealed a highly significant relationship between BOLD response during self-appraisal and self-awareness of deficit in MCI. This finding highlights the level of anosognosia in MCI as an important predictor of response to self-appraisal in cortical midline structures, brain regions vulnerable to changes in early AD. (JINS, 2007, 13, 450–461.)

Type
Research Article
Copyright
© 2007 The International Neuropsychological Society

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

REFERENCES

Amodio, D.M. & Frith, C.D. (2006). Meeting of minds: The medial frontal cortex and social cognition. Nature Reviews. Neuroscience, 7, 268277.Google Scholar
Anchisi, D., Borroni, B., Franceschi, M., Kerrouche, N., Kalbe, E., Beuthien-Beumann, B., Cappa, S., Lenz, O., Ludecke, S., Marcone, A., Mielke, R., Ortelli, P., Padovani, A., Pelati, O., Pupi, A., Scarpini, E., Weisenbach, S., Herholz, K., Salmon, E., Holthoff, V., Sorbi, S., Fazio, F., & Perani, D. (2005). Heterogeneity of brain glucose metabolism in mild cognitive impairment and clinical progression to Alzheimer disease. Archives of Neurology, 62, 17281733.Google Scholar
Ansell, E.L. & Bucks, R.S. (2006). Mnemonic anosognosia in Alzheimer's disease: A test of Agnew and Morris (1998). Neuropsychologia, 44, 10951102.Google Scholar
Babinsky, J. (1914). Contribution a l'étude des troubles mentaux dan hémiplégie organique cérébrale (anosognosie). Revista de Neurologia, 27, 845847.Google Scholar
Benedict, R. (1997). Brief Visuospatial Memory Test-Revised. Lutz, FL: Psychological Assessment Resources Inc.
Chetelat, G., Desgranges, B., de la Sayette, V., Viader, F., Eustache, F., & Baron, J.C. (2003). Mild cognitive impairment: Can FDG-PET predict who is to rapidly convert to Alzheimer's disease? Neurology, 60, 13741377.Google Scholar
Davis, H.S. & Rockwood, K. (2004). Conceptualization of mild cognitive impairment: A review. International Journal of Geriatric Psychiatry, 19, 313319.Google Scholar
Derouesne, C., Thibault, S., Lagha-Pierucci, S., Baudouin-Madec, V., Ancri, D., & Lacomblez, L. (1999). Decreased awareness of cognitive deficits in patients with mild dementia of the Alzheimer type. International Journal of Geriatric Psychiatry, 14, 10191030.Google Scholar
Duke, L.M., Seltzer, B., Seltzer, J.E., & Vasterling, J.J. (2002). Cognitive components of deficit awareness in Alzheimer's disease. Neuropsychology, 16, 359369.Google Scholar
Folstein, M.F., Folstein, S.E., & McHugh, P.R. (1975). “Mini Mental State”: A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatry Research, 12, 189198.Google Scholar
Fossati, P., Hevenor, S.J., Graham, S.J., Grady, C., Keightley, M.L., Craik, F., & Mayberg, H. (2003). In search of the emotional self: An FMRI study using positive and negative emotional words. American Journal of Psychiatry, 160, 19381945.Google Scholar
Friston, K., Holmes, A.P., Worsley, K.J., Poline, J.B., Frith, C., & Frackowiak, R.S.J. (1995). Statistical parametric maps in functional imaging: A general linear approach. Human Brain Mapping, 2, 189210.Google Scholar
Friston, K.J., Josephs, O., Zarahn, E., Holmes, A.P., Rouquette, S., & Poline, J. (2000). To smooth or not to smooth? Bias and efficiency in fMRI time-series analysis. Neuroimage, 12, 196208.Google Scholar
Gauthier, S., Reisberg, B., Zaudig, M., Petersen, R.C., Ritchie, K., Broich, K., Belleville, S., Brodaty, H., Bennett, D., Chertkow, H., Cummings, J.L., de Leon, M., Feldman, H., Ganguli, M., Hampel, H., Scheltens, P., Tierney, M.C., Whitehouse, P., & Winblad, B. (2006). Mild cognitive impairment. Lancet, 367, 12621270.Google Scholar
Good, C.D., Johnsrude, I.S., Ashburner, J., Henson, R.N., Friston, K.J., & Frackowiak, R.S. (2001). A voxel-based morphometric study of ageing in 465 normal adult human brains. Neuroimage, 14(Pt. 1), 2136.Google Scholar
Harwood, D.G., Sultzer, D.L., Feil, D., Monserratt, L., Freedman, E., & Mandelkern, M.A. (2005). Frontal lobe hypometabolism and impaired insight in Alzheimer disease. American Journal of Geriatric Psychiatry, 13, 934941.Google Scholar
Heilman, K.M., Barrett, A.M., & Adair, J.C. (1998). Possible mechanisms of anosognosia: A defect in self-awareness. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 353, 19031909.Google Scholar
Huang, C., Wahlund, L.O., Svensson, L., Winblad, B., & Julin, P. (2002). Cingulate cortex hypoperfusion predicts Alzheimer's disease in mild cognitive impairment. BMC Neurology, 2, 9.Google Scholar
Ivnik, R., Malec, J., Smith, G., Tangalos, E., & Petersen, R. (1996). Neuropsychological Test Norms Above Age 55: COWAT, BNT, MAE Token, WRAT-R Reading, AMNART, STROOP, TMT, and JLO. The Clinical Neuropsychologist, 10, 262278.Google Scholar
Ivnik, R.J., Malec, J.F., Smith, G.E., Tangalos, E.G., Petersen, R.C., Kokmen, E., & Kurland, L.T. (1992). Mayo's older Americans normative studies: WAIS-R, WMS-R, and AVLT norms for ages 56 through 97. The Clinical Neuropsychologist, 6, 1103.Google Scholar
Jastak Associates. (1993). Wide Range Achievement Test-Third Edition. Wilmington, DE: Wide Range Inc.
Jenkinson, M. (2003). Fast, automated, N-dimensional phase-unwrapping algorithm. Magnetic Resonance Medicine, 49, 193197.Google Scholar
Jezzard, P. & Balaban, R.S. (1995). Correction for geometric distortion in echo planar images from B0 field variations. Magnetic Resonance in Medicine, 34, 6573.Google Scholar
Johnson, S.C., Baxter, L.C., Wilder, L.S., Pipe, J.G., Heiserman, J.E., & Prigatano, G.P. (2002). Neural correlates of self-reflection. Brain, 125(Pt. 8), 18081814.Google Scholar
Johnson, S.C., Schmitz, T.W., Moritz, C.H., Meyerand, M.E., Rowley, H.A., Alexander, A.L., Hansen, K.W., Gleason, C.E., Carlsson, C.M., Ries, M.L., Asthana, S., Chen, K., Reiman, E.M., & Alexander, G.E. (2005). Activation of brain regions vulnerable to Alzheimer's disease: The effect of mild cognitive impairment. Neurobiology of Aging, 27, 16041612.Google Scholar
Jorm, A.F. (2004). The Informant Questionnaire on cognitive decline in the elderly (IQCODE): A review. International Psychogeriatrics, 16, 275293.Google Scholar
Kaplan, E., Goodglass, H., & Weintraub, S. (2001). Boston Naming Test (4th ed.). Philadelphia: Lippincott Williams & Wilkins.
Kelley, W.M., Macrae, C.N., Wyland, C.L., Caglar, S., Inati, S., & Heatherton, T.F. (2002). Finding the self? An event-related fMRI study. Journal of Cognitive Neuroscience, 14, 785794.Google Scholar
Kogure, D., Matsuda, H., Ohnishi, T., Asada, T., Uno, M., Kunihiro, T., Nakano, S., & Takasaki, M. (2000). Longitudinal evaluation of early Alzheimer's disease using brain perfusion SPECT. Journal of Nuclear Medicine, 41, 11551162.Google Scholar
Lopez, O.L., Becker, J.T., Somsak, D., Dew, M.A., & DeKosky, S.T. (1994). Awareness of cognitive deficits and anosognosia in probable Alzheimer's disease. European Neurology, 34, 277282.Google Scholar
Maddock, R.J., Garrett, A.S., & Buonocore, M.H. (2001). Remembering familiar people: The posterior cingulate cortex and autobiographical memory retrieval. Neuroscience, 104, 667676.Google Scholar
Manly, J.J., Bell-McGinty, S., Tang, M.X., Schupf, N., Stern, Y., & Mayeux, R. (2005). Implementing diagnostic criteria and estimating frequency of mild cognitive impairment in an urban community. Archives of Neurology, 62, 17391746.Google Scholar
Mendez, M.F. & Shapira, J.S. (2005). Loss of insight and functional neuroimaging in frontotemporal dementia. The Journal of Neuropsychiatry and Clinical Neurosciences, 17, 413416.Google Scholar
Michon, A., Deweer, B., Pillon, B., Agid, Y., & Dubois, B. (1994). Relation of anosognosia to frontal lobe dysfunction in Alzheimer's disease. Journal of Neurology Neurosurgery and Psychiatry, 57, 805809.Google Scholar
Nestor, P.J., Fryer, T.D., Ikeda, M., & Hodges, J.R. (2003). Retrosplenial cortex (BA 29/30) hypometabolism in mild cognitive impairment (prodromal Alzheimer's disease). The European Journal of Neuroscience, 18, 26632667.Google Scholar
Nichols, T., Brett, M., Andersson, J., Wager, T., & Poline, J.B. (2005). Valid conjunction inference with the minimum statistic. Neuroimage, 25, 653660.Google Scholar
Northoff, G. & Bermpohl, F. (2004). Cortical midline structures and the self. Trends in Cognitive Sciences, 8, 102107.Google Scholar
Northoff, G., Heinzel, A., de Greck, M., Bermpohl, F., Dobrowolny, H., & Panksepp, J. (2006). Self-referential processing in our brain—a meta-analysis of imaging studies on the self. Neuroimage, 31, 440457.Google Scholar
Ochsner, K.N., Knierim, K., Ludlow, D.H., Hanelin, J., Ramachandran, T., Glover, G., & Mackey, S.C. (2004). Reflecting upon feelings: An fMRI study of neural systems supporting the attribution of emotion to self and other. Journal of Cognitive Neuroscience, 16, 17461772.Google Scholar
Ott, B.R., Lafleche, G., Whelihan, W.M., Buongiorno, G.W., Albert, M.S., & Fogel, B.S. (1996). Impaired awareness of deficits in Alzheimer disease. Alzheimer Disease and Associated Disorders, 10, 6876.Google Scholar
Petersen, R.C. (2004). Mild cognitive impairment as a diagnostic entity. Journal of Internal Medicine, 256, 183194.Google Scholar
Radloff, L. (1977). The CES-D Scale: A self-report depression scale for research in the general population. Journal of Applied Psychology Measurement, 1, 385401.Google Scholar
Ready, R.E., Ott, B.R., Grace, J., & Cahn-Weiner, D.A. (2003). Apathy and executive dysfunction in mild cognitive impairment and Alzheimer disease. The American Journal of Geriatric Psychiatry, 11, 222228.Google Scholar
Reed, B.R., Jagust, W.J., & Coulter, L. (1993). Anosognosia in Alzheimer's disease: Relationships to depression, cognitive function, and cerebral perfusion. Journal of Clinical Expand Experimental Neuropsychology, 15, 231244.Google Scholar
Ries, M.L., Schmitz, T.W., Kawahara, T.N., Torgerson, B.M., Trivedi, M.A., & Johnson, S.C. (2006). Task-dependent posterior cingulate activation in mild cognitive impairment. Neuroimage, 29, 485492.Google Scholar
Salmon, E., Perani, D., Herholz, K., Marique, P., Kalbe, E., Holthoff, V., Delbeuck, X., Beuthien-Baumann, B., Pelati, O., Lespagnard, S., Collette, F., & Garraux, G. (2006). Neural correlates of anosognosia for cognitive impairment in Alzheimer's disease. Human Brain Mapping, 27, 588597.Google Scholar
Schmitz, T.W., Kawahara-Baccus, T.N., & Johnson, S.C. (2004). Metacognitive evaluation, self-relevance, and the right prefrontal cortex. Neuroimage, 22, 941947.Google Scholar
Schmitz, T.W., Rowley, H.A., Kawahara, T.N., & Johnson, S.C. (2006). Neural correlates of self-evaluative accuracy after traumatic brain injury. Neuropsychologia, 44, 762773.Google Scholar
Shah, N.J., Marshall, J.C., Zafiris, O., Schwab, A., Zilles, K., Markowitsch, H.J., & Fink, G.R. (2001). The neural correlates of person familiarity. A functional magnetic resonance imaging study with clinical implications. Brain, 124(Pt. 4), 804815.Google Scholar
Spielberger, C. (1983). Manual for the State-Trait Anxiety Inventory for Adults. Redwood City, CA: Mind Garden.
Sugiura, M., Shah, N.J., Zilles, K., & Fink, G.R. (2005). Cortical representations of personally familiar objects and places: Functional organization of the human posterior cingulate cortex. Journal of Cognitive Neuroscience, 17, 183198.Google Scholar
Tabert, M.H., Albert, S.M., Borukhova-Milov, L., Camacho, Y., Pelton, G., Liu, X., Stern, Y., & Devanand, D.P. (2002). Functional deficits in patients with mild cognitive impairment: Prediction of AD. Neurology, 58, 758764.Google Scholar
Tombaugh, T.N., Kozak, J., & Rees, L. (1999). Normative data stratified by age and education for two measures of verbal fluency: FAS and animal naming. Archives of Clinical Neuropsychology, 14, 167177.Google Scholar
Vogel, A., Hasselbalch, S.G., Gade, A., Ziebell, M., & Waldemar, G. (2005). Cognitive and functional neuroimaging correlate for anosognosia in mild cognitive impairment and Alzheimer's disease. International Journal of Geriatric Psychiatry, 20, 238246.Google Scholar
Vogel, A., Stokholm, J., Gade, A., Andersen, B.B., Hejl, A.M., & Waldemar, G. (2004). Awareness of deficits in mild cognitive impairment and Alzheimer's disease: Do MCI patients have impaired insight? Dementia and Geriatric Cognitive Disorders, 17, 181187.Google Scholar
Weissman, M.M., Sholomskas, D., Pottenger, M., Prusoff, B.A., & Locke, B.Z. (1977). Assessing depressive symptoms in five psychiatric populations: A validation study. American Journal of Epidemiology, 106, 203214.Google Scholar