Amyloid Plaques Disrupt Resting State Default Mode Network Connectivity in Cognitively Normal Elderly

• Published in: Biological psychiatry (1969) Vol. 67; no. 6; pp. 584 - 587
• Main Authors: Sheline, Yvette I., Raichle, Marcus E., Snyder, Abraham Z., Morris, John C., Head, Denise, Wang, Suzhi, Mintun, Mark A.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.03.2010; Elsevier
• Subjects: Adult and adolescent clinical studies; Aged; Aged, 80 and over; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; amyloid; Amyloid beta-Peptides - metabolism; Aniline Compounds; Biological and medical sciences; Brain - blood supply; Brain - diagnostic imaging; Brain - pathology; Brain Mapping - methods; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; fMRI; Geriatric Assessment; hippocampus; Humans; Image Processing, Computer-Assisted - methods; Longitudinal Studies; Magnetic Resonance Imaging - methods; Male; Medical sciences; Nerve Net - blood supply; Nerve Net - diagnostic imaging; Nerve Net - pathology; Neurology; Organic mental disorders. Neuropsychology; Oxygen - blood; PIB; Positron-Emission Tomography - methods; precuneus; Psychiatric Status Rating Scales; Psychiatric/Mental Health; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rest - physiology; resting state; Statistics as Topic; Thiazoles; fMRI; resting state; amyloid; hippocampus; precuneus; PIB; Alzheimer's disease; Human; Nervous system diseases; Alzheimer disease; Central nervous system; Nuclear magnetic resonance imaging; Encephalon; Cerebral disorder; Rest; Central nervous system disease; Medical imagery; Degenerative disease; Amyloid; Elderly; Hippocampus; Functional imaging
• ISSN: 0006-3223; 1873-2402; 1873-2402
• DOI: 10.1016/j.biopsych.2009.08.024

Important functional connections within the default mode network (DMN) are disrupted in Alzheimer's disease (AD), likely from amyloid-beta (Aβ) plaque-associated neuronal toxicity. Here, we sought to determine if pathological effects of Aβ amyloid plaques could be seen, even in the absence of a task, by examining functional connectivity in cognitively normal participants with and without preclinical amyloid deposition. Participants with Alzheimer's disease (AD) ( n = 35) were compared with 68 cognitively normal participants who were further subdivided by positron emission tomography (PET) Pittsburgh Compound-B (PIB) imaging into those without evidence of brain amyloid (PIB−) and those with brain amyloid (PIB+) deposition. Resting state functional magnetic resonance imaging (fMRI) demonstrated that, compared with the PIB− group, the PIB+ group differed significantly in functional connectivity of the precuneus to hippocampus, parahippocampus, anterior cingulate, dorsal cingulate, gyrus rectus, superior precuneus, and visual cortex. These differences were in the same regions and in the same direction as differences found in the AD group. Thus, before any manifestations of cognitive or behavioral changes, there were differences in resting state connectivity in cognitively normal subjects with brain amyloid deposition, suggesting that early manifestation of Aβ toxicity can be detected using resting state fMRI.