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

By Yvette I. Sheline, Marcus E. Raichle, Abraham Z. Snyder, John C. Morris, Denise Head, Suzhi Wang, Mark A. Mintun. Biological Psychiatry, 2009

617 citations recorded by the source corpus.

Background 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. Methods Participants with Alzheimer’s disease (AD) (n= 35) were compared with 68 cognitively normal participants who were further subdivided by PET PIB imaging into those without evidence of brain amyloid (PIB−) and those with brain amyloid (PIB+) deposition. Results Resting state 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. Conclusions Thus, prior to 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.

Subfields: Cognitive Neuroscience, Experimental and Cognitive Psychology, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/d1b2dbb997315fd7cbaffe4eefef7990684c15bc

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Citations in the corpus

Brain imaging in Alzheimer disease. (2012, background): “Several recent studies in cognitively normal older individuals with evidence of amyloid deposition on PET imaging have shown evidence of disrupted default network activity during memory tasks and at rest (Hedden et al. 2009; Sheline et al. 2009; Sperling et al. 2009), suggesting these markers may be”
Introduction to Revised Criteria for the Diagnosis of Alzheimer’s Disease: National Institute on Aging and the Alzheimer Association Workgroups (2011, background): “Multiple groups have now reported that cognitively normal older individuals with low CSF Ab1–42 or high PET amyloid binding demonstrate disruption of functional networks [42–44] and decreased brain volume [45–49], consistent with the patterns seen in AD.”
Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus (2010, methodology): “Standard methods were used for all analyses (23, 37).”
The Restless Brain (2011, positive): “Even more interesting are three recent studies demonstrating disruption in default mode network coherence in cognitively normal older persons harboring default mode network amyloid plaques (Hedden et al., 2009; Sheline et al., 2009; Sperling et al., 2009).”
Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease (2011, result): “Multiple groups have now reported that cognitively normal older individuals with low CSF Aβ1–42 or high PET amyloid binding demonstrate disruption of functional networks [42–44] and decreased brain volume [45–49], consistent with the patterns seen in AD.”