Apolipoprotein E genotype and early Alzheimer's disease: a longitudinal SPECT study.
OBJECTIVE
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 99mTc-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 epsilon 4 allele: 11 epsilon 4 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 psoterior cingulate gyri and precunei. After PVE correction, carriers showed a greater spread of areas with significant rCBF reduction from the parietotemporal to the frontal area 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 epsilon 4 allele is associated with the faster progression of AD, and PVE correction may be necessary for accurate assessments of SPECT studies of AD.
Department of Radiology, National Center Hospital for Mental, Nervous, and Muscular Disorders, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, 187-8551 Tokyo, Japan.
Shigeki
S
Sakamoto
Hiroshi
H
Matsuda
Takashi
T
Asada
Takashi
T
Ohnishi
Seigo
S
Nakano
Hidekazu
H
Kanetaka
Masaru
M
Takasaki
D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000503:physiopathology; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging*; D002560:Cerebrovascular Circulation; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D012039:Regional Blood Flow; D012189:Retrospective Studies; D015899:Tomography, Emission-Computed, Single-Photon
D001057:Apolipoproteins E