Altered Brain Activity Visible Before AD Symptoms

In a study published January 13, 2005, in the open access journal BMC Medicine, individuals carrying the apolipoprotein E (APOE) epsilon4 allele, which has earlier been found to correlate with a high risk of developing AD, demonstrated altered brain activity compared to APOE epsilon3 homozygotes. According to the authors of the study, this supports the theory that specific areas of the brain show functional decline associated with the AOPE epsilon4 allele, and this decline begins before the onset of AD symptoms.

Dr. Mehul Trivedi and coworkers from the University of Wisconsin Medical School (Madison, USA) and the William S. Middleton Memorial VA Hospital (also in Madison) utilized functional magnetic resonance imaging (fMRI) scanning to assess the brain activity patterns of 40 apparently healthy middle-aged individuals with a family history of AD, comparing epsilon3/4 heterozygotes with epsilon3/3 homozygotes. In this study, the participants were asked to differentiate between images they were being shown for the first time and images they had already memorized previously in a pre-scan training session.

During the task, the epsilon3/4 heterozygotes demonstrated decreased activation in the medial temporal lobe (MTL) of the brain, including the right hippocampus, compared to the epsilon3/3 homozygotes. There were no differences between the two groups in age, performance during the task, education, or neuropsychologic evaluation of memory; therefore, the modified brain activation seen could not have been caused by impaired cognitive function. According to the researchers, "if compromised MTL function continues to be observed in healthy epsilon4 carriers, this group of subjects may represent a good study population for novel treatments designed to delay the onset or to prevent the development of AD.”




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University of Wisconsin Medical School