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Hum Brain Mapp. 2013 Dec;34(12):3308-19. doi: 10.1002/hbm.22141. Epub 2012 Jul 17.

Memory performance and fMRI signal in presymptomatic familial Alzheimer's disease.

Author information

1
Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California; Laboratory of Neuro Imaging, David Geffen School of Medicine at UCLA, Los Angeles, California.

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.

KEYWORDS:

APP; PSEN1; early onset; functional magnetic resonance imaging; hippocampus; medial temporal lobe; mutation; volume

PMID:
22806961
PMCID:
PMC3812259
DOI:
10.1002/hbm.22141
[Indexed for MEDLINE]
Free PMC Article
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