P2-276: Mapping of progressive loss of acetylcholinesterase activities in early- and late-onset Alzheimer’s disease

Abstract

Recent studies of postmortem brains with early stage of Alzheimer's disease (AD) suggest that there is not any or only mild cholinergic deficits in mild AD. N–[11C]methylpiperidin–4–yl acetate (MP4A) has been shown to be a useful radiotracer for quantitative measurement of AChE activity in the cerebral cortex and thalamus in vivo. To elucidate how cholinergic deficits progress in early– (EOAD) and late–onset AD (LOAD). Nineteen healthy subjects (12M and 7F, 64±12 y.o.), 27 patients with EOAD (12M and 15F, 62±5 y.o.), and 23 patients with LOAD (7M and 14F, 74±5 y.o.) took part in this study. AD patients were divided into subgroups according to MMSE scores; mildly (MMSE score 20–23, n=7 in EOAD and LOAD), moderately I (MMSE 16–19, n=7 in EOAD and LOAD), moderately II (MMSE 11–15, n=6 in EOAD and 7 in LOAD), and severely demented groups (MMSE 0–10, n=7 in EOAD and 0 in LOAD). [11C]MP4A–PET acquisition was a dynamic sequence of 14 PET scans over a 40–minute period. A three–compartment model was employed to yield voxel–by–voxel estimates of K1, k2, and k3 in the whole brain using the arterial input function. Group comparisons of k3 values (indices of AChE activity) in normal controls and each patient group were performed using two–sample t–test in SPM2 (uncorrected p<0.0001, cluster extent K> 50 voxels). The results suggest that k3 values were significantly reduced in the temporo–parietal cortices including the posterior cingulate cortex and precunei in the mild EOAD group, and more extensively reduced in the whole cerebral cortex in the moderate I, II and severe EOAD groups. In the mild LOAD group, k3 values were not significantly reduced in the brain. The k3 values were modestly reduced in the temporal cortex in the moderate LOAD I group, and moderately reduced in the fronto–temporal and cingulate cortices in the moderate LOAD II group. Our results of LOAD groups are in accord with recent studies of postmortem brains with early stage of AD. However, our results of EOAD groups suggest that there are significant cholinergic deficits even in the early stage of EOAD.