Amyloid deposition is associated with impaired default network function in older persons without dementia.
Alzheimer's disease (AD) has been associated with functional alterations in a distributed network of brain regions linked to memory function, with a recent focus on the cortical regions collectively known as the default network. Posterior components of the default network, including the precuneus and posterior cingulate, are particularly vulnerable to early deposition of amyloid beta-protein, one of the hallmark pathologies of AD. In this study, we use in vivo amyloid imaging to demonstrate that high levels of amyloid deposition are associated with aberrant default network functional magnetic resonance imaging (fMRI) activity in asymptomatic and minimally impaired older individuals, similar to the pattern of dysfunction reported in AD patients. These findings suggest that amyloid pathology is linked to neural dysfunction in brain regions supporting memory function and provide support for the hypothesis that cognitively intact older individuals with evidence of amyloid pathology may be in early stages of AD.
Sperling
Reisa A
RA
Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. reisa@rics.bwh.harvard.edu
Laviolette
Peter S
PS
O'Keefe
Kelly
K
O'Brien
Jacqueline
J
Rentz
Dorene M
DM
Pihlajamaki
Maija
M
Marshall
Gad
G
Hyman
Bradley T
BT
Selkoe
Dennis J
DJ
Hedden
Trey
T
Buckner
Randy L
RL
Becker
J Alex
JA
Johnson
Keith A
KA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D003071:Cognition; D003704:Dementia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology* / Q000648:ultrastructure; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008854:Microscopy, Electron; D009415:Nerve Net / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000648:ultrastructure*
D016229:Amyloid beta-Peptides