Increased fMRI signal with age in familial Alzheimer's disease mutation carriers

Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Neurobiology of aging (Impact Factor: 5.01). 12/2010; 33(2):424.e11-21. DOI: 10.1016/j.neurobiolaging.2010.09.028
Source: PubMed


Although many Alzheimer's disease (AD) patients have a family history of the disease, it is rarely inherited in a predictable way. Functional magnetic resonance imaging (fMRI) studies of nondemented adults carrying familial AD mutations provide an opportunity to prospectively identify brain differences associated with early AD-related changes. We compared fMRI activity of 18 nondemented autosomal dominant AD mutation carriers with fMRI activity in eight of their noncarrier relatives as they performed a novelty encoding task in which they viewed novel and repeated images. Because age of disease onset is relatively consistent within families, we also correlated fMRI activity with subjects' distance from the median age of diagnosis for their family. Mutation carriers did not show significantly different voxelwise fMRI activity from noncarriers as a group. However, as they approached their family age of disease diagnosis, only mutation carriers showed increased fMRI activity in the fusiform and middle temporal gyri. This suggests that during novelty encoding, increased fMRI activity in the temporal lobe may relate to incipient AD processes.

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    • "In asymptomatic APOE ε4 carriers, brain regions that are vulnerable to AD pathology have elevated resting CBF (Fleisher et al., 2009; Scarmeas et al., 2003; Thambisetty et al., 2010) and increased CBF responses during functional activation (Scarmeas et al., 2005), compared with control subjects. In addition, several functional magnetic resonance imaging studies reveal elevated blood oxygen level-dependent (BOLD) amplitudes in the mediotemporal cortex during memory encoding tasks in asymptomatic APOE ε4 carriers (Bookheimer et al., 2000; Braskie et al., 2010; Filippini et al., 2009; Fleisher et al., 2009; Trachtenberg et al., 2012). The biphasic nature of the CBF and BOLD changes during the course of the disease are illustrated in Fig. 1. "
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    Neurobiology of aging 10/2012; 34(4). DOI:10.1016/j.neurobiolaging.2012.09.011 · 5.01 Impact Factor
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    ABSTRACT: Rare autosomal dominant mutations result in familial Alzheimer's disease (FAD) with a relatively consistent age of onset within families. This provides an estimate of years until disease onset (relative age) in mutation carriers. Increased AD risk has been associated with differences in functional magnetic resonance imaging (fMRI) activity during memory tasks, but most of these studies have focused on possession of apolipoprotein E allele 4 (APOE4), a risk factor, but not causative variant, of late-onset AD. Evaluation of fMRI activity in presymptomatic FAD mutation carriers versus noncarriers provides insight into preclinical changes in those who will certainly develop AD in a prescribed period of time. Adults from FAD mutation-carrying families (nine mutation carriers, eight noncarriers) underwent fMRI scanning while performing a memory task. We examined fMRI signal differences between carriers and noncarriers, and how signal related to fMRI task performance within mutation status group, controlling for relative age and education. Mutation noncarriers had greater retrieval period activity than carriers in several AD-relevant regions, including the left hippocampus. Better performing noncarriers showed greater encoding period activity including in the parahippocampal gyrus. Poorer performing carriers showed greater retrieval period signal, including in the frontal and temporal lobes, suggesting underlying pathological processes. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
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