Single photon emission computed tomography and apolipoprotein E in Alzheimer's disease: impact of the epsilon4 allele on regional cerebral blood flow

P Høgh, G M Knudsen, K H Kjaer, O S Jørgensen, O B Paulson, G Waldemar

Abstract

The aim of this study was to examine the impact of the apolipoprotein E (APOE) epsilon4 allele on semiquantitative regional cerebral blood flow (rCBF) in Alzheimer's disease. Single photon emission computed tomography technetium (SPECT) with (99m)Tc d,l-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 27APOE epsilon4-positive and 14APOE epsilon4-negative individuals. Five patients were APOE epsilon4 homozygotes. APOE epsilon4-positive patients had significantly reduced rCBF in the right frontal and left occipital lobes. On nonparametric analysis, the most prominent differences between epsilon4-negative and epsilon4-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 epsilon4-positive patients might predict clinical progression.

Original languageEnglish
JournalJournal of Geriatric Psychiatry and Neurology
Volume14
Issue number1
Pages (from-to)42-51
Number of pages10
ISSN0891-9887
DOIs
Publication statusPublished - 2001

Keywords

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Alleles
  • Alzheimer Disease/genetics
  • Apolipoprotein E4
  • Apolipoproteins E/genetics
  • Brain/blood supply
  • Case-Control Studies
  • Cerebrovascular Circulation/genetics
  • Dominance, Cerebral/genetics
  • Female
  • Frontal Lobe/blood supply
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Occipital Lobe/blood supply
  • Prognosis
  • Tomography, Emission-Computed, Single-Photon

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