Presenilin-1-associated abnormalities in regional cerebral perfusion

Citation
Ka. Johnson et al., Presenilin-1-associated abnormalities in regional cerebral perfusion, NEUROLOGY, 56(11), 2001, pp. 1545-1551
Citations number
45
Categorie Soggetti
Neurology,"Neurosciences & Behavoir
Journal title
NEUROLOGY
ISSN journal
00283878 → ACNP
Volume
56
Issue
11
Year of publication
2001
Pages
1545 - 1551
Database
ISI
SICI code
0028-3878(20010612)56:11<1545:PAIRCP>2.0.ZU;2-3
Abstract
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.