Memory performance and fMRI signal in presymptomatic familial Alzheimer's disease.
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.
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.
Meredith N
MN
Braskie
Luis D
LD
Medina
Yaneth
Y
Rodriguez-Agudelo
Daniel H
DH
Geschwind
Miguel Angel
MA
Macias-Islas
Paul M
PM
Thompson
Jeffrey L
JL
Cummings
Susan Y
SY
Bookheimer
John M
JM
Ringman
D000328:Adult; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D001921:Brain / Q000098:blood supply*; D001931:Brain Mapping; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008569:Memory Disorders / Q000175:diagnosis* / Q000209:etiology*; D011939:Mental Recall / Q000502:physiology; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010100:Oxygen; D010153:Paired-Associate Learning; D053764:Presenilin-1 / Q000235:genetics; D055815:Young Adult
D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1; D010100:Oxygen