Objective: To investigate the influence of the presenilin-1 gene (PS-1) mut
ation on regional cerebral perfusion, SPECT was evaluated in 57 individuals
. The subjects were members of a large pedigree from Colombia, South Americ
a, many of whom carry a PS-1 mutation for early-onset AD. Methods: Members
of this large kindred who were cognitively normal and did not carry the PS-
1 mutation (n = 23) were compared with subjects who were carriers of the mu
tation but were asymptomatic (n = 18) and with individuals with the mutatio
n and a clinical diagnosis of AD (n = 16). Cerebral perfusion was measured
in each subject using hexamethylpropyleneamine oxime SPECT. The data were a
nalyzed in two ways: 1) Mean cerebral perfusion in each of 4320 voxels in t
he brain was compared among the groups using t-tests (t-maps); and 2) each
individual received a weighted score on 20 vectors (factors), based on a la
rge normative sample (n = 200), using a method known as singular value deco
mposition (SVD). Results: Based on t-maps, subjects with the PS-1 mutation
who were asymptomatic demonstrated reduced perfusion in comparison with the
normal control subjects in the hippocampal complex, anterior and posterior
cingulate, posterior parietal lobe, and anterior frontal lobe. The AD pati
ents demonstrated decreased perfusion in the posterior parietal and superio
r frontal cortex in comparison with the normal control subjects. Discrimina
nt function analysis of the vector scores derived from SVD (adjusted for ag
e and gender) accurately discriminated 86% of the subjects in the three gro
ups (p < 0.0005). Conclusion: Regional cerebral perfusion abnormalities bas
ed on SPECT are detectable before development of the clinical symptoms of A
D in carriers of the PS-1 mutation.