Journal of the International Neuropsychological Society

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 c1
a1 Geriatric Research Education and Clinical Center, William S. Middleton VA Hospital, Madison, Wisconsin
a2 Department of Medicine, University of Wisconsin, Madison, Wisconsin

Article author query
ries ml   [PubMed][Google Scholar] 
jabbar bm   [PubMed][Google Scholar] 
schmitz tw   [PubMed][Google Scholar] 
trivedi ma   [PubMed][Google Scholar] 
gleason ce   [PubMed][Google Scholar] 
carlsson cm   [PubMed][Google Scholar] 
rowley ha   [PubMed][Google Scholar] 
asthana s   [PubMed][Google Scholar] 
johnson sc   [PubMed][Google Scholar] 


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.)

(Received June 20 2006)
(Revised November 6 2006)
(Accepted November 13 2006)

Key Words: Magnetic Resonance Imaging; Self assessment (Psychology); Agnosia; Alzheimer disease; Neocortex; Aging.

c1 Correspondence and reprint requests to: Sterling C. Johnson, Ph.D., Wm. S. Middleton VA Hospital (11G), 2500 Overlook Terrace, Madison, WI 53705. E-mail: