Amyloid-Beta Deposition is Associated with Increased Medial Temporal Lobe Activation during Memory Encoding in the Cognitively Normal Elderly.
BACKGROUND
Much is unknown about changes that occur in the brain in the years preceding the cognitive and functional impairment associated with Alzheimer disease (AD). This period before mild cognitive impairment is present has been referred to as preclinical AD, and is thought to begin with amyloid-beta deposition and then progress to neurodegeneration and functional brain circuit alterations. Prior studies have shown that there is increased medial temporal lobe activation on functional magnetic resonance imaging (fMRI) early in the course of mild cognitive impairment. It is unknown, however, whether this altered fMRI activity precedes cognitive impairment. The purpose of this study is to address this question using Pittsburgh Compound-B (PiB) imaging and fMRI in a sample of cognitively normal older adults.


METHODS
Forty-four cognitively normal older adults underwent both PiB imaging and fMRI with a face-name memory task: 21 were classified as PiB(+) and 23 were PiB(-). Additionally, thorough cognitive and neuropsychological test batteries were administered outside the scanner. The main outcome measure in this study is fMRI activation in the medial temporal lobe during a face-name memory-encoding task.


RESULTS
PiB(+) subjects showed higher fMRI activation during the memory task in the hippocampus relative to PiB(-) participants.


CONCLUSIONS
The increased medial temporal lobe activation in preclinical AD, observed in this study, may serve as an early biomarker of neurodegeneration. Future studies are needed to clarify whether this functional biomarker can stratify AD risk among PiB(+) older adults.
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA.
Kathryn
K
Edelman
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA; Department of Medicine, University of Pittsburgh, Pittsburgh, PA.
Dana
D
Tudorascu
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA.
Christian
C
Agudelo
Department of Neurology, University of Pittsburgh, Pittsburgh, PA.
Beth
B
Snitz
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA.
Helmet
H
Karim
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA.
Ann
A
Cohen
Department of Radiology, University of Pittsburgh, Pittsburgh, PA.
Chester
C
Mathis
Department of Radiology, University of Pittsburgh, Pittsburgh, PA.
Julie
J
Price
Statistics Collaborative, Inc., Washington, DC.
Lisa
L
Weissfeld
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA.
William
W
Klunk
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA. Electronic address: aizen@pitt.edu.
Howard
H
Aizenstein
D000368:Aged; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D016022:Case-Control Studies; D003071:Cognition / Q000502:physiology*; D005260:Female; D059907:Functional Neuroimaging; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology*; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D013844:Thiazoles / Q000378:metabolism
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D013844:Thiazoles
Alzheimer disease; Neuroimaging; PiB; amyloid-beta; fMRI; memory