Brain Activation During Memory Tasks in People at Genetic Risk

      To determine the relationship between brain responses to memory tasks and genetic risk for AD, Bookheimer et al. (2000) performed apo E genotyping and functional MRI while cognitively intact older persons performed memory tasks. The study included 30 participants, aged 47 to 82 years, with mild memory complaints but normal memory performance, of whom 16 were apo E-e4 carriers and 14 were not. The age and prior educational achievement in the two groups were similar. Brain-activation patterns were determined from functional MRI scanning while participants memorized and recalled unrelated word pairs. Memory performance was reassessed on 14 participants 2 years later.

     The magnitude and spatial extent of brain activation during memory performance in regions affected by AD, including left hippocarnpal, parietal, and prefrontal regions, was greater in the participants with apo E-e4 alleles, as compared with those with no apo E-e4 alleles.

     During memory performance tasks, the apo E-e4 carriers demonstrated a greater percentage increase in hippocarnpal MRIsignal intensity and a greater number of activated regions throughout the brain than did participants without apo E-e4. Longitudinal assessment after 2 years indicated that greater baseline brain activation correlated with verbal-memory decline. These results indicate that brain-activation patterns during memory tasks differ according to genetic risk for AD and may provide information that eventually predicts future cognitive decline.