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Presenilin-1–associated abnormalities in regional cerebral perfusion

From the Antioquia University School of Medicine Colombia (Drs. Lopera, Londono, Siegert, Arcos, Ossa, Pineda, Ardila, Roselli, and Rios, and S. Moreno and L. Madrigal), Medellin; and Brandeis University (Dr. Jones), Waltham, and Brigham and Women’s Hospital (Drs. Johnson, Sperling, and Kosik, and A. Becker and J. Hilson) and Massachusetts General Hospital (Drs. Johnson and Albert), Harvard Medical School, Boston, MA.

Address correspondence and reprint requests to Dr. Keith A. Johnson, Radiology and Neurology, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115; e-mail: keith{at}bwh.harvard.edu

Objective: To investigate the influence of the presenilin-1 gene (PS-1) mutation on regional cerebral perfusion, SPECT was evaluated in 57 individuals. The subjects were members of a large pedigree from Colombia, South America, 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 mutation but were asymptomatic (n = 18) and with individuals with the mutation and a clinical diagnosis of AD (n = 16). Cerebral perfusion was measured in each subject using hexamethylpropyleneamine oxime SPECT. The data were analyzed in two ways: 1) Mean cerebral perfusion in each of 4320 voxels in the 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 large normative sample (n = 200), using a method known as singular value decomposition (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 patients demonstrated decreased perfusion in the posterior parietal and superior frontal cortex in comparison with the normal control subjects. Discriminant function analysis of the vector scores derived from SVD (adjusted for age and gender) accurately discriminated 86% of the subjects in the three groups (p < 0.0005). Conclusion: Regional cerebral perfusion abnormalities based on SPECT are detectable before development of the clinical symptoms of AD in carriers of the PS-1 mutation.

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