Patterns of brain activation in people at risk for Alzheimer's disease

Background: The epsilon 4 allele of the apolipoprotein E gene (APOE) is the chief known genetic risk factor for Alzheimer's disease, the most common c ause of dementia late in life. To determine the relation between brain resp onses to tasks requiring memory and the genetic risk of Alzheimer's disease , we performed APOE genotyping and functional magnetic resonance imaging (M RI) of the brain in older persons with intact cognition. Methods: We studied 30 subjects (age, 47 to 82 years) who were neurological ly normal, of whom 16 were carriers of the APOE epsilon 4 allele and 14 wer e homozygous for the APOE epsilon 3 allele. The mean age and level of educa tion were similar in the two groups. Patterns of brain activation during fu nctional MRI scanning were determined while subjects memorized and recalled unrelated pairs of words and while subjects rested between such periods. M emory was reassessed in 14 subjects two years later. Results: Both the magnitude and the extent of brain activation during memor y-activation tasks in regions affected by Alzheimer's disease, including th e left hippocampal, parietal, and prefrontal regions, were greater among th e carriers of the APOE epsilon 4 allele than among the carriers of the APOE epsilon 3 allele. During periods of recall, the carriers of the APOE epsil on 4 allele had a greater average increase in signal intensity in the hippo campal region (1.03 percent vs. 0.62 percent, P<0.001) and a greater mean ( +/-SD) number of activated regions throughout the brain (15.9+/-6.2 vs. 9.4 +/-5.5, P = 0.005) than did carriers of the APOE epsilon 3 allele. Longitud inal assessment after two years indicated that the degree of base-line brai n activation correlated with degree of decline in memory. Conclusions: Patterns of brain activation during tasks requiring memory dif fer depending on the genetic risk of Alzheimer's disease and may predict a subsequent decline in memory. (N Engl J Med 2000;343:450-6.) (C)2000, Massa chusetts Medical Society.