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

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.

Figure 1

Plot depicting variability in the correspondence between patient and informant ratings on the IQCODE scale. The correlation between patient and informant ratings is non-significant (r = 0.31, p = 0.24).

Figure 2

Statistical parametric map of the BOLD signal change to self-appraisal condition in reference group of 105 healthy young adults (p _FWE < .05)

Figure 3

Statistical parametric map of the BOLD signal change to self-appraisal condition in (a) non-impaired older adults and (b) individuals with mild cognitive impairment; (c) Regions of common activation between groups as determined by conjunction analysis; (d) Regions showing less activation in individuals with mild cognitive impairment. Statistical threshold for all contrasts was p _unc < 0.005.

Figure 4

Participants with Mild Cognitive Impairment: Plot of the negative correlation (r = −0.83, p_FDR < 0.05) between BOLD signal change during self-appraisal and IQCODE difference score in ventral MPFC cluster.

Figure 5

Participants with Mild Cognitive Impairment: Plot of the negative correlation (r = −0.76, p_FDR < 0.05) between BOLD signal change during self-appraisal and IQCODE difference score in PCC of MCI participants.