MRI and Genetic Testing Identify Early Dementia

An important aim for current AD research is to find preclinical markers of impending disease. Apolipoprotein E sigma4 (APOE epsilon4) is the chief known genetic risk factor for AD.

A number of neuroimaging studies performed by investigators from the Karolinska Institute (Stockholm, Sweden) revealed structural and functional brain alterations in non-demented APOE epsilon4-carriers. Such results have tentatively been interpreted as early signs of impending dementia, but the findings have been inconsistent across studies. To additionally address this issue, the overall aim of this study was to examine asymptomatic cognitively well-functioning APOE epsilon4-carriers with magnetic resonance imaging (MRI) techniques, together with longitudinal neuropsychologic testing.

The first study revealed that carriers of APOE epsilon4 expressed reduced functional brain activity during incidental episodic encoding. In the parietal cortex, a genetic dose-effect was seen such that the activity reduction was more pronounced for homozygous than heterozygous APOE epsilon4-carriers.

Furthermore, the researchers discovered that APOE epsilon4-carriers had structural changes in white-matter tracts in the hippocampus and the posterior corpus callosum (in the second study), and gray matter reductions in the hippocampus (the third study). The fourth study demonstrated that the level of functional activity in the parietal cortex predicted subsequent episodic memory decline within the group of APOE epsilon4-carriers.


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Karolinska Institute