Neuroanatomical correlates of awareness of illness in patients with amnestic mild cognitive impairment who will or will not convert to Alzheimer's disease

Background: Awareness of cognitive deficits may be reduced in mild cognitive impairment (MCI). This may have a detrimental effect on illness course and may be a predictor of subsequent conversion to AD. Although neuropsychological correlates have been widely investigated, no evidence of a neuroanatomical basis of the phenomenon has been reported yet. This study was aimed at investigating the neuroanatomical correlates of deficit awareness in amnestic MCI to determine whether they constitute risk factors for conversion to AD.

Method: A sample of 36 first-diagnosis amnestic MCI patients were followed for five years. At the first diagnostic visit they were administered an extensive diagnostic and clinical procedure and the Memory Insight Questionnaire (MIQ), measuring a total index and four sub-indices, to investigate awareness of deficits in dementia; they also underwent a high resolution T1-weighted Magnetic Resonance Imaging (MRI) investigation. Grey matter brain volumes were analysed on a voxel-by-voxel basis using Statistical Parametric Mapping 8. Data of 10 converter patients (CONV) and those of 26 non converter patients (NOCONV) were analysed using multiple regression models.

Results: At baseline, self-awareness of memory deficits was poorer in CONV compared to NOCONV. Furthermore, reduced awareness of cognitive deficits in CONV correlated with reduced grey matter volume of the anterior cingulate (memory deficit awareness), right pars triangularis of the inferior frontal cortex (memory deficit awareness) and cerebellar vermis (total awareness), whereas in NOCONV it correlated with reduced grey matter volume of left superior (total awareness) and middle (language deficit awareness) temporal areas. Further, at baseline self-awareness of memory deficits were poorer in CONV than in NOCONV.

Conclusions: Defective awareness of cognitive deficits is underpinned by different mechanisms in CONV and NOCONV amnestic MCI patients. Our data support the hypothesis that poor awareness of cognitive deficit is a predictor of subsequent conversion to AD.