Amyloid deposition is linked to aberrant entorhinal activity among cognitively normal older adults.
Normal aging is often difficult to distinguish from the earliest stages of Alzheimer's disease. Years before clinical memory deficits manifest, amyloid-β deposits in the cortex in many older individuals. Neuroimaging studies indicate that a set of densely connected neocortical regions, referred to as the default network, is especially vulnerable to amyloid-β deposition. Yet, the impact of amyloid-β on age-related changes within the medial temporal lobe (MTL) memory system is less clear. Here we demonstrate that cognitively normal older humans, compared with young adults, show reduced ability to modulate hippocampal activations and entorhinal deactivations during an episodic memory task. Among older adults, amyloid-β deposition was associated with failure to modulate activity in entorhinal cortex, but not hippocampus. Furthermore, we show that entorhinal regions demonstrating amyloid-β-related dysfunction are directly connected to the neocortical regions of the default network. Together these findings link neocortical amyloid-β deposition to neuronal dysfunction specifically in entorhinal cortex, while aging is associated with more widespread functional changes across the MTL.
Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, Harvard Aging Brain Study, Department of Neurology, and Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114.
Willem
W
Huijbers
Elizabeth C
EC
Mormino
Sarah E
SE
Wigman
Andrew M
AM
Ward
Patrizia
P
Vannini
Donald G
DG
McLaren
J Alex
JA
Becker
Aaron P
AP
Schultz
Trey
T
Hedden
Keith A
KA
Johnson
Reisa A
RA
Sperling
D000328:Adult; D000367:Age Factors; D000368:Aged; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001931:Brain Mapping; D016022:Case-Control Studies; D003071:Cognition; D018728:Entorhinal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory; D049268:Positron-Emission Tomography
D016229:Amyloid beta-Peptides
amyloid; default network; entorhinal cortex; fMRI; memory; preclinical Alzheimer's disease