Identification of Alzheimer Disease Risk by Functional Magnetic Resonance Imaging

Abstract

Background: Functional magnetic resonance imaging plays a promising role in the preclinical characterization of Alzheimer disease (AD) for use in early diagnosis and in preventive drug trials.Objective: To determine whether functional magnetic resonance imaging can reliably distinguish risk groups for AD among cognitively normal middle-aged adults.

Verbal paired-associate learning by APOE genotype in non-demented older adults: fMRI evidence of a right hemispheric compensatory response

“…These early "preclinical" memory changes are more likely to occur in those with a genetic susceptibility marker for AD, the apolipoprotein E (APOE) ε4 allele [11,37], than in those without this risk factor. In parallel with these findings, structural [32,44] and functional [4,6,15,20,34,42] neuroimaging alterations are more evident in non-demented elderly with the ε4 allele than in those without this allele type.…”

“…Given that elderly with the ε4 allele are more likely than those without the allele to be in a preclinical stage of AD, we hypothesized that the ε4 group would require more brain activation than the non-ε4 group to maintain the same level of memory performance. In addition, we expected an over-recruitment of right medial temporal lobe (MTL) activation during verbal paired-associate encoding and consolidation consistent with [26] finding that greater right MTL engagement is associated with better verbal list learning, and with the findings from a growing number of fMRI studies of at-risk older adults [4,15,16,20,25,26]. Thus, in the context of equivalent learning performance, we predicted that more right hemisphere response would be required by ε4 individuals.…”

“…This is in contrast to Bookheimer et al [6] who examined signal change from combined learning and recall periods. Previous studies from our laboratory [4,20] also have consistently reported increased MTL signal associated with the APOE ε4 allele, and ROI analyses involving the hippocampus in these and other former studies have typically been based on a standardized anatomic atlas [12], thus not allowing for consideration of individual variation with respect to hippocampal size and consequent individual hippocampal BOLD activity. In fact, most fMRI studies average groups of different subjects into standard coordinate space, and anatomic differences in brain structure create additional variance and loss of registration accuracy [46].…”

“…Task parameters were identical to those described by Fleisher et al [20]. During functional MRI scanning, participants were instructed to learn 32 pairs of associated nouns presented for 5 s each, 16 of which they had previously learned to a criterion of 10 out of 16 correct on cured recall (OLD) and 16 of which were unfamiliar (NEW).…”

“…A few studies have investigated the relationship between APOE genotype and functional neuroimaging of memory processes in non-demented elderly, but the interpretation of these results has been confounded by a number of factors. These include: (1) poorer memory in the ε4 group than in the non-ε4 group [6], (2) questions of interpretability of signal change via the subtraction method, particularly when contrasting two higher-level conditions such as novel versus familiar items, (3) no assessment for differential atrophy [6,20], or (4) the use of general standard space region of interest (ROI) analyses rather than specific individualized native space renderings [4,20] (see also Vandenbroucke et al [46] for discussion).…”