Conversion of amyloid positive and negative MCI to AD over 3 years: an 11C-PIB PET study

Abstract

Background: Patients with amnestic mild cognitive impairment (MCI) represent an important clinical group as they are at increased risk of developing Alzheimer disease (AD). (11)C-PIB PET is an in vivo marker of brain amyloid load.

Objective: To assess the rates of conversion of MCI to AD during a 3-year follow-up period and to compare levels of amyloid deposition between MCI converters and nonconverters.

Methods: Thirty-one subjects with MCI with baseline (11)C-PIB PET, MRI, and neuropsychometry have been clinically followed up for 1 to 3 years (2.68 +/- 0.6 years). Raised cortical (11)C-PIB binding in subjects with MCI was detected with region of interest analysis and statistical parametric mapping.

Results: Seventeen of 31 (55%) subjects with MCI had increased (11)C-PIB retention at baseline and 14 of these 17 (82%) clinically converted to AD during follow-up. Only one of the 14 PIB-negative MCI cases converted to AD. Of the PIB-positive subjects with MCI, half (47%) converted to AD within 1 year of baseline PIB PET, these faster converters having higher tracer-retention values than slower converters in the anterior cingulate (p = 0.027) and frontal cortex (p = 0.031). Seven of 17 (41%) subjects with MCI with known APOE status were epsilon4 allele carriers, this genotype being associated with faster conversion rates in PIB-positive subjects with MCI (p = 0.035).

Conclusions: PIB-positive subjects with mild cognitive impairment (MCI) are significantly more likely to convert to AD than PIB-negative patients, faster converters having higher PIB retention levels at baseline than slower converters. In vivo detection of amyloid deposition in MCI with PIB PET provides useful prognostic information.

Figure 1 Amyloid deposition in mild cognitive impairment (MCI) subgroups Scatter plot showing the distribution of individual Pittsburgh compound B (PIB) retention values in PIB-positive MCI subgroups: fast, slow, and nonconverters compared to controls (top line = Turku control mean; bottom line = London control mean).

Figure 2 Statistical parametric mapping analysis: Localization of increased ¹¹C-PIB retention in mild cognitive impairment (MCI) converters Surface rendering is used to illustrate the cortical areas (red-yellow) where ¹¹C-PIB retention is significantly increased in MCI converters compared to MCI nonconverters. (Corrected p value at cluster level <0.001.)

Figure 3 Statistical parametric mapping: Comparison of ¹¹C-PIB retention in PIB-positive mild cognitive impairment (MCI) subgroups Sagittal (A) and coronal sections (B and C) illustrating increased ¹¹C-PIB retention in anterior cingulate, frontal, and temporal cortex in the PIB-positive MCI faster converters compared to PIB-positive slower converters and nonconverters. Corrected p value at cluster level <0.001.