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

  • MICHELE L. RIES (a1) (a2), BRITTA M. JABBAR (a1) (a2), TAYLOR W. SCHMITZ (a1) (a2), MEHUL A. TRIVEDI (a1) (a2), CAREY E. GLEASON (a1) (a2), CYNTHIA M. CARLSSON (a1) (a2), HOWARD A. ROWLEY (a2), SANJAY ASTHANA (a1) (a2) and STERLING C. JOHNSON (a1) (a2)...
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.)

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Corresponding author
Correspondence and reprint requests to: Sterling C. Johnson, Ph.D., Wm. S. Middleton VA Hospital (11G), 2500 Overlook Terrace, Madison, WI 53705. E-mail: scjohnson@wisc.edu
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This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

Amodio, D.M. & Frith, C.D. (2006). Meeting of minds: The medial frontal cortex and social cognition. Nature Reviews. Neuroscience, 7, 268277.

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.

Ansell, E.L. & Bucks, R.S. (2006). Mnemonic anosognosia in Alzheimer's disease: A test of Agnew and Morris (1998). Neuropsychologia, 44, 10951102.

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.

Davis, H.S. & Rockwood, K. (2004). Conceptualization of mild cognitive impairment: A review. International Journal of Geriatric Psychiatry, 19, 313319.

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.

Duke, L.M., Seltzer, B., Seltzer, J.E., & Vasterling, J.J. (2002). Cognitive components of deficit awareness in Alzheimer's disease. Neuropsychology, 16, 359369.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Jenkinson, M. (2003). Fast, automated, N-dimensional phase-unwrapping algorithm. Magnetic Resonance Medicine, 49, 193197.

Jezzard, P. & Balaban, R.S. (1995). Correction for geometric distortion in echo planar images from B0 field variations. Magnetic Resonance in Medicine, 34, 6573.

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.

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.

Jorm, A.F. (2004). The Informant Questionnaire on cognitive decline in the elderly (IQCODE): A review. International Psychogeriatrics, 16, 275293.

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.

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.

Maddock, R.J., Garrett, A.S., & Buonocore, M.H. (2001). Remembering familiar people: The posterior cingulate cortex and autobiographical memory retrieval. Neuroscience, 104, 667676.

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.

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.

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.

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.

Nichols, T., Brett, M., Andersson, J., Wager, T., & Poline, J.B. (2005). Valid conjunction inference with the minimum statistic. Neuroimage, 25, 653660.

Northoff, G. & Bermpohl, F. (2004). Cortical midline structures and the self. Trends in Cognitive Sciences, 8, 102107.

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.

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.

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.

Petersen, R.C. (2004). Mild cognitive impairment as a diagnostic entity. Journal of Internal Medicine, 256, 183194.

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.

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.

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.

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.

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.

Schmitz, T.W., Kawahara-Baccus, T.N., & Johnson, S.C. (2004). Metacognitive evaluation, self-relevance, and the right prefrontal cortex. Neuroimage, 22, 941947.

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.

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.

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.

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.

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.

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.

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.

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.

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Journal of the International Neuropsychological Society
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