Klunk WE, Snitz BE, Cohen AD, Price JC, Mathis CA, DeKosky ST, Lopez OL, Saxton JA.
Comparison of longitudinal changes in amyloid deposition and cerebral metabolism in early-onset familial AD.
Human Amyloid Imaging 2010 Meeting Abstracts. 2010 April 9;
Background: We have previously reported a focal, striatal-dominant pattern of Aβ deposition in early-onset,
familial Alzheimer’s disease (eFAD). We also have found that striatal amyloid may reach a peak early in the disease
process and then decline. Metabolic changes similar to those in sporadic, late-onset AD have previously been
reported in eFAD.
Objective: Compare changes in amyloid deposition with changes in cerebral metabolism over time in carriers of
Methods: Thirteen carriers of mutations in presenilin-1 (n=9), presenilin-2 (n=1) or APP (n=3) received at least two
PiB-PET and FDG-PET scans (15 mCi PiB; 7 mCi FDG, 40-60 min; ECAT HR+). We included mutation carriers with
normal cognition (n=4), mild cognitive impairment (n=4) and AD (n=5). The delta-SUVR (follow-up minus baseline
SUVR) was calculated for both PiB and FDG (using cerebellum as reference and atrophy correction). These values
were then compared by Pearson’s correlation as well as a comparison of statistically significant individual changes
using the “Reliable Change Index (RCI)”. The longest inter-scan interval was used for each subject (the interval
varied from 2-5 years). Regions of interest (ROIs) analyzed included anterior cingulate, precuneus and striatum.
We also explored larger composite ROIs.
Results: At baseline, there was a trend for a negative correlation between PiB retention and metabolism in the eFAD
subjects (r=-0.45, p=0.06). However, we found no relationship between changes in PiB retention and metabolism
in the eFAD subjects over time in any single or composite ROI. Depending on the ROI, 4-5 of the eFAD subjects
showed increased PiB retention over time and 1-3 subjects showed decreased metabolism. Only one subject
(an APP mutation carrier with AD) showed both. Although the striatum had heavy Aβ deposition, there was no
significant decrease in striatal glucose metabolism in any subject by the RCI method.
Conclusions: Although Aβ deposition and cerebral metabolism were weakly related at baseline in eFAD mutation
carriers, the changes in these parameters did not appear to be tightly coupled – except, perhaps, in the later
stages of the illness. The heavy Aβ deposition in the striatum did not appear to lead to a progressive disruption
in cerebral metabolism. The number of subjects in this study is small and confirmation from larger longitudinal
studies will be necessary.