Fluorodeoxyglucose positron emission tomography of mild cognitive impairment with clinical follow-up at 3 years

Abstract

Background: Alzheimer's disease (AD) is the most common dementing illness. Development of effective treatments directed at AD requires an early diagnosis. Mild cognitive impairment (MCI) often heralds AD. Thus, characterizing MCI is fundamental to the early diagnosis of AD.

Methods: 19 MCI patients referred from a memory loss clinic and 27 healthy subjects, all followed up for 3 years. Metabolism scans (MCI minus controls) were compared voxel-wise after anatomic normalization and were examined both visually and with a computerized classifier.

Results: Agreement between raters as to whether the individual scans were normal or abnormal was high. Agreement between raters of the eventual clinical diagnosis and baseline metabolic pattern was poor. A computerized classifier was unsuccessful at classifying MCI from normal; however, its performance improved when using only prototypic AD-like MCI scans, indicating the classifier worked well when shared patterns existed in the data. Outcomes on follow-up were nine of 19 AD, five of 19 remained MCI, and five of 19 developed dementias other than AD. Both MCI cases of early Lewy body dementia (LBD) showed an AD-like metabolic pattern.

Conclusions: Visual inspection proved reliable in determining normal from abnormal scans, but it proved unreliable at predicting diagnosis on follow-up. Computerized classification of MCI by using an AD-like metabolic template (such as derived from the averaged MCI images) showed potential to identify patients who will develop AD. However, the metabolic pattern in early LBD did not differ from that in AD.

Figure 1

Cluster division for SVM based on the subtraction of FDG PET scans of healthy controls from all MCI patients after age regression (i.e., MCI template). Note the similarity to AD pattern. Top of image is anterior; image left is patient’s right side. Each cluster has been colorized to aid in identification.

Figure 2

Examples of FDG PET difference images between different individual MCI patients vs. controls showing examples of presence (A) and absence (B) of an AD-like pattern as well as one with an FTD pattern (C). The numbers indicate millimeters above the AC-PC plane. Orientation same as in Figure 1.