Abstract
Alzheimer´s disease (AD) is the most common form of dementia. An
important goal 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 have
reported 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 further address this issue, the overall
aim of this thesis was to examine asymptomatic cognitively
well-functioning APOE epsilon4-carriers with magnetic resonance imaging
(MRI) techniques, together with longitudinal neuropsychological testing.
Study I 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. In addition, it was found that APOE epsilon4-carriers
had structural changes in white-matter tracts in the hippocampus and the
posterior corpus callosum (Study II), and grey matter reductions in the
hippocampus (Study III). Study IV demonstrated that the degree of
functional activity in the parietal cortex predicted subsequent episodic
memory decline within the group of APOE epsilon4-carriers. Collectively,
the results suggest that a combination of genetic, neuropsychological,
and neuroimaging strategies is beneficial in predicting AD development.
