Apolipoprotein E genotype and early Alzheimer's disease: A longitudinal SPECT study

Background and Purpose. To determine the association of the apolipoprotein E (APOE) genotype and longitudinal changes of regional cerebral blood flow (rCBF) in Alzheimer's disease (AD). Previous reports have yielded conflicting results concerning this association. Methods. A retrospective cohort study was performed. rCBF was noninvasively measured using Tc-99m-ethyl cysteinate dimer single-photon emission computed tomography in 23 patients with probable AD at the very early stage and at a mean interval of 24 months, as well as in 55 age-matched healthy volunteers. Patients were classified into 2 groups according to the presence of the epsilon4 allele: 11 epsilon4 carriers and 12 noncarriers. Correction for partial volume effects (PVEs) was performed in all patients using gray matter volume measured by magnetic resonance imaging. Statistical parametric mapping was used for the analysis of absolute rCBF data and the adjusted rCBF images of relative flow distribution. Results. In the baseline study, both carriers and noncarriers showed significant decreases of absolute and adjusted rCBF in the posterior cingulate gyri and precunei. After PVE correction, carriers showed a greater spread of areas with significant rCBF reduction from the parietotemporal to the frontal areas than noncarriers during the follow-up period compared to healthy volunteers. Moreover, carriers showed a significant decline of absolute rCBF in the frontal cortex from the baseline to the follow-up study. Conclusions. The authors' study suggests that the APOE epsilon4 allele is associated with the faster progression of AD, and PVE correction may be necessary for accurate assessments of SPECT studies of AD.