AMYLOID-β DEPOSITION AND HYPOMETABOLISM TO EVALUATE THE PROGRESSION OF EARLY-ONSET ALZHEIMER'S DISEASE

Abstract

Patients with early-onset Alzheimer's disease (EOAD) show more rapid clinical decline. The biological mechanisms underlying the clinical differences are not well understood. The aim was to evaluate the EOAD progression using amyloid PET and FDG PET imaging. Thirty-seven EOAD patients (a mean age of 60.6±4.0) before age of 65 underwent cognitive assessment, 60-min dynamic [11C]-PIB PET and 15-min static [18F]-FDG PET at baseline and one or more over 3 years, and ApoE genotype assessment. Regions of interest were defined on co-registered MRI. A quantitative analysis for [11C]-PIB and [18F]-FDG were used with standardized uptake value ratio (SUVR) on same regions. Longitudinal changes in PIB and FDG SUVR values were evaluated. A group of late-onset AD (LOAD) after age of 80 (n=10, mean age of 82.4±1.8) was studied for comparison. EOAD patients had high global cortical PIB SUVR at baseline (1.92±2.9), similar to that in LOAD patients. In contrast, they had significantly lower global FDG SUVR at baseline (0.89±0.06, p<0.01) than LOAD patients. The lowest regional FDG SUVR was especially found in the lateral temporo-parietal cortex, followed in precuneus. Over a mean follow up of 2.1±0.8 years, an annual increase in global PIB SUVR in EOAD was 0.08±0.12 per year (n=22, p<0.05) and a 4.7% from baseline, whereas that in LOAD is 0.0003±0.096 per year and 0.3%. In contrast, an annual decrease of global FDG SUVR in EOAD (−0.01±0.03) did not significantly differ from that in LOAD (−0.01±0.02). There was no significant correlation between increase in PIB SUVR and decrease in FDG SUVR (r=0.21). The rate of decline of MMSE in EOAD was −3.0±1.9 per year (n=22, p<0.05), being significantly faster than in LOAD. The rate of decline of MMSE score in EOAD was correlated with increase rate of PIB SUVR (r=-0.42, n=22, p<0.05), but not decrease rate of FDG SUVR. There was no significant difference in ApoE gene distribution between EOAD and LOAD patients. The more rapid progression of EOAD could be associated with faster increase in cortical amyloid-β deposition that would be accompanied by more extensive and severe hypometabolism in parietal and lateral temporal cortices, and precuneus.