In vivo assessment of amyloid-β deposition in nondemented very elderly subjects

Abstract

Objective: This study examined amyloid-β (Aβ) deposition in 190 nondemented subjects aged ≥82 years to determine the proportion of Aβ-positive scans and associations with cognition, apolipoprotein E (APOE) status, brain volume, and Ginkgo biloba (Gb) treatment.

Methods: Subjects who agreed to participate had a brain magnetic resonance imaging and positron emission tomography scan with (11) C-labeled Pittsburgh compound B (PiB) following completion of a Gb treatment clinical trial. The youngest subject in this imaging study was 82 years, and the mean age of the subjects was 85.5 years at the time of the scans; 152 (80%) were cognitively normal, and 38 (20%) were diagnosed with mild cognitive impairment (MCI) at the time of the PiB study.

Results: A high proportion of the cognitively normal subjects (51%) and MCI subjects (68%) were PiB-positive. The APOE*4 allele was more prevalent in PiB-positive than in PiB-negative subjects (30% vs 6%). Measures of memory, language, and attentional functions were worse in PiB-positive than in PiB-negative subjects, when both normal and MCI cases were analyzed together; however, no significant associations were observed within either normal or MCI subject groups alone. There was no relationship between Gb treatment and Aβ deposition as determined by PiB.

Interpretation: The data revealed a 55% prevalence of PiB positivity in nondemented subjects age >80 years and 85% PiB positivity in the APOE*4 nondemented elderly subjects. The findings also showed that long-term exposure to Gb did not affect the prevalence of cerebral Aβ deposition.

Figure 1

Scatter plot of the Global-5 SUVR values of normal cognition (NC) (○) and mild cognitive impairment (MCI) (●) subjects, highlighting the higher average values for both the NC and MCI APOE*4-positive subjects relative to the APOE*4-negative NC and MCI subjects. The horizontal line at a Global-5 SUVR of 1.57 represents the line defining PiB-positivity.

Figure 2

(A & B) Results of voxel-wise analysis of PiB retention. The t-maps show the three orthogonal views of the slice containing the point of peak significance overlaid on the MCI template. Both A & B correspond to k=50 contiguous voxels; p<0.001 uncorrected. No significant voxels are detected at p<0.001 with FDR correction. (A) Comparison of PiB retention in Gb-treated (n=95) and placebo-treated subjects (n=95); Contrast: Gb-treated > placebo-treated shown, no significant voxels for Gb-treated < placebo-treated. (B) Comparison of PiB retention in all controls (n=152) with all MCI subjects (n=38); Contrast: MCI > controls; no significant voxels for controls > MCI. (C & D) The topography of PiB retention in control (C) and MCI subjects (D). The average PiB retention (SUVR) is shown in an axial plane (top) and a sagittal plane (bottom) in PiB-negative (left) and PiB-positive subjects (right).

Figure 3

Results of VBM analyses. The t-maps show the three orthogonal views of the slice containing the point of peak significance overlaid on the MNI template. (A & B) Two-way ANOVA model with diagnosis (control, n=136; or MCI, n=35) and PiB status (negative, n=76; or positive, n=95) as grouping factors to determine voxel-wise gray matter differences. No interaction effect was found between diagnosis and PiB status. (A) Main effect of diagnosis. Contrast: Controls > MCI. (B) Main effect of PiB status. Contrast: PiB-negative > PiB-positive. (C) Comparison of PiB-negative controls (n=65) with PiB-positive MCI subjects (n=24); Contrast: PiB-negative Controls >PiB-positive MCI. (D) Comparison of PiB-negative controls with PiB-negative MCI subjects (n=11); Contrast: PiB-negative Control > PiB-negative MCI. All figures correspond to k=100 contiguous voxels and p<0.025 after FDR correction, except (B) that corresponds to k=100 contiguous voxels and p<0.01 without FDR correction. For the comparison in (B), it is important to note that no significant voxels are detected at p<0.025 with FDR correction.