Amyloid imaging in mild cognitive impairment subtypes

Abstract

Objective: We utilized the amyloid imaging ligand Pittsburgh Compound B (PiB) to determine the presence of Alzheimer's disease (AD) pathology in different mild cognitive impairment (MCI) subtypes and to relate increased PiB binding to other markers of early AD and longitudinal outcome.

Methods: Twenty-six patients with MCI (13 single-domain amnestic-MCI [a-MCI], 6 multidomain a-MCI, and 7 nonamnestic MCI) underwent PiB imaging. Twenty-three had clinical follow-up (21.2 +/- 16.0 [standard deviation] months) subsequent to their PiB scan.

Results: Using cutoffs established from a control cohort, we found that 14 (54%) patients had increased levels of PiB retention and were considered "amyloid-positive." All subtypes were associated with a significant proportion of amyloid-positive patients (6/13 single-domain a-MCI, 5/6 multidomain a-MCI, 3/7 nonamnestic MCI). There were no obvious differences in the distribution of PiB retention in the nonamnestic MCI group. Predictors of conversion to clinical AD in a-MCI, including poorer episodic memory, and medial temporal atrophy, were found in the amyloid-positive relative to amyloid-negative a-MCI patients. Longitudinal follow-up demonstrated 5 of 13 amyloid-positive patients, but 0 of 10 amyloid-negative patients, converted to clinical AD. Further, 3 of 10 amyloid-negative patients "reverted to normal."

Interpretation: These data support the notion that amyloid-positive patients are likely to have early AD, and that the use of amyloid imaging may have an important role in determining which patients are likely to benefit from disease-specific therapies. In addition, our data are consistent with longitudinal studies that suggest a significant percentage of all MCI subtypes will develop AD.

Figure 1

PiB retention in controls (red triangles), MCI patients (black circles) and patients with AD (blue squares). Non-amnestic MCI patients are indicated with filled black circles. The white bars represent cutoffs for determining amyloid status in frontal cortex and subcortical white matter. Note that the two MCI patients who only had SUVRs calculated are not included.

Figure 2

(a) Mean DVR images of amyloid-negative controls, amyloid-negative patients with a-MCI, representative group of patients with AD, amyloid-positive patients with a-MCI, and amyloid-positive patients with na-MCI. (b) Individual DVR images of the three amyloid-positive patients with na-MCI.

Figure 3

Hippocampal volumes for controls and the amyloid-positive and amyloid-negative a-MCI groups calculated with ALP. * represents p < 0.05 after correction for ICV, age, and gender. Error bars represent one SEM. black = control; gray = amyloid-positive a-MCI; white = amyloid-negative a-MCI.

Figure 4

Amyloid-positive a-MCI patients versus amyloid-negative controls VBM of MRI grey matter density. The map is corrected for multiple comparisons (FDR) and thresholded at p < 0.05. The color bar represents the value of the T-statistic.

Figure 5

Outcomes of patients with MCI based on amyloid status. Amnestic, single-domain (A-SD) and Amnestic, multiple-domain (A-MD) MCI patients are indicated with black boxes. Non-amnestic patients (all single-domain) are indicated with white boxes that also indicate the non-memory area of cognitive impairment (language or executive). The numbers beside the middle column represent the MMSE scores. The bars at the far right indicate the duration of follow-up from initial diagnosis. Note that the MCI patient with an MMSE of 21 had an isolated amnestic deficit on focused testing and was felt by consensus to qualify for an MCI designation.