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Single Photon Emission Computed Tomography and Apolipoprotein E in Alzheimer's Disease: Impact of the 4 Allele on Regional Cerebral Blood Flow

Gitte Moos Knudsen, MD, PhD

Karen Husted Kjær

Ole Steen Jørgensen, MSc

Olaf B. Paulson, MD, PhD

Gunhild Waldemar, MD, PhD

The aim of this study was to examine the impact of the apolipoprotein E (APOE) 4 allele on semiquantitative regional cerebral blood flow (rCBF) in Alzheimer's disease. Single photon emission computed tomography tech netium (SPECT) with (99m)Tc d,1-hexamethyl propylenamine oxine was used to determine rCBF in 41 consecutive patients (18 males/23 females) with probable Alzheimer's disease according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria (mean age 71.0 years; range 54-85). The mean Mini-Mental State Examination (MMSE) score was 20.4 (range 10-30). After normalization of CBF to mean blood flow in the cerebellum, values for rCBF in several cortical regions of interest, side-to-side asymmetry indices, and anterior-posterior ratios were calculated. Determination of the APOE genotype from blood samples was performed using restriction enzyme polymerase chain reaction technique. Multivariate regression analyses and the Wilcoxon rank-sum test for unpaired data (Mann-Whitney) were used for statistical analysis. The patients comprised 27 APOE 4-positive and 14 APOE 4-negative individuals. Five patients were APOE 4 homozygotes. APOE 4-positive patients had significantly reduced rCBF in the right frontal and left occipital lobes. On nonparametric analysis, the most prominent differences between 4-negative and 4-positive patients were demonstrated in subregions representing the frontal association cortex (Mann-Whitney, P < .01). Age- stratified analysis suggested that these findings could be demonstrated predominantly in the elderly patients. The results of this study suggest that the APOE genotype in itself may have an impact on the pattern of rCBF deficits in Alzheimer's disease. The more pronounced reduction of rCBF in frontal association cortex observed in elderly APOE 4-positive patients might predict clinical progression. (J Geriatr Psychiatry Neurol 2001; 14:42-51).

Journal of Geriatric Psychiatry and Neurology, Vol. 14, No. 1, 42-51 (2001)
DOI: 10.1177/089198870101400110


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