IC-P1-031: 11C PiB and structural magnetic resonance imaging in Mild Cognitive Impairment

Abstract

To date most cross modality comparisons with 11C Pittsburgh Compound B (PiB) have been with FDG PET. Our objective was to compare MRI and 11C PiB findings cross sectionally in subjects with Mild Cognitive Impairment (MCI). We included both amnestic MCI (aMCI, n=17) and non-amnestic MCI (naMCI, n=5). Subjects who were cognitively normal (CN, n=20) and subjects with probable Alzheimer's disease (AD, n=8) were included for reference purposes. All subjects were imaged with both 11C PiB and MRI in close temporal proximity. A global cortical PiB retention summary measure was derived from six cortical ROIs and normalized by forming a ratio with cerebellar 11C PiB retention. A cut off value of 1.5 of this ratio was used to separate subjects into those labeled “PiB positive” vs “PiB negative”. Hippocampal volumes were measured from MRI and corrected for age, gender and head size to form co-variate adjusted Z scores labeled “W scores”. All AD subjects were PiB positive and had atrophic hippocampi (Fig 1). While the majority of CN subjects were PiB negative and had no hippocampal atrophy, 6/20 CN were PiB positive. All 5 naMCI subjects were PiB negative; 3/5 had no hippocampal atrophy. Nine of 17 aMCI subjects were PiB positive and most (all but 2) also had atrophic hippocampi. Eight of 17 aMCI subjects were PiB negative and 5 of these also had atrophic hippocampi. Of the 17 aMCI subjects in the study, PiB and MRI were discordant in seven (Fig 2), and the most common discordance pattern was negative PiB with hippocampal atrophy. Most PiB positive aMCI subjects also have hippocampal atrophy and we suspect that this “AD-like” imaging profile indicates that with sufficient follow up all of these subjects will progress to AD. In contrast, we suspect that both the PiB negative aMCI subjects with atrophic hippocampi and the naMCI subjects with atrophic hippocampi have prodromal dementias other than AD, and with sufficient follow up will progress to non-AD dementias. However, this is an un proven hypothesis and longitudinal clinical follow up, preferably to autopsy, is required for confirmation.