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

doi:10.1016/j.biopsych.2009.08.024

Biological Psychiatry

Volume 67, Issue 6, 15 March 2010, Pages 584-587

https://doi.org/10.1016/j.biopsych.2009.08.024 Get rights and content

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 positron emission tomography (PET) Pittsburgh Compound-B (PIB) imaging into those without evidence of brain amyloid (PIB−) and those with brain amyloid (PIB+) deposition.

Results

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.

Conclusions

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.

Section snippets

Methods and Materials

Community-living volunteers enrolled in longitudinal studies of memory and aging at the Washington University Alzheimer's Disease Research Center (ADRC). Participants (n = 35) meeting Clinical Dementia Rating (CDR) criteria for very mild (CDR = .5) or mild (CDR = 1) dementia of the Alzheimer type were matched for age, gender, and education with 68 individuals without cognitive impairment (CDR = 0) (Table 1). All participants in the ADRC underwent an extensive battery of neuropsychological

PIB (−) Versus AD Functional Connectivity

We first examined the functional connectivity differences in patients with early AD (n = 35) versus half of the sample without amyloid plaques (PIB−) (n = 24; randomly selected from the original 48 PIB− subjects) to generate ROIs for hypothesis testing. The group difference significance map of PIB− versus AD functional connectivity was then used for hypothesis testing in a second independent sample of 24 PIB− participants compared with PIB+ participants. As expected, significant differences

Discussion

The current finding of decreased precuneus resting state functional connectivity with hippocampus, parahippocampus, anterior cingulate, dorsal anterior cingulate, gyrus rectus, and superior precuneus extends findings of disruptions in AD and highlights the importance of integrity of the default network (3, 4, 5), since all these regions fall within the default mode network. We show here that even before cognitive impairment, cognitively normal individuals with cerebral Aβ deposits had clear-cut

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

Background

Methods

Results

Conclusions

Section snippets

Methods and Materials

PIB (−) Versus AD Functional Connectivity

Discussion

Behav Brain Res

Handb Clin Neurol

Neuroimage

A default mode of brain function

Proc Natl Acad Sci U S A

[11C]PIB in a nondemented population: Potential antecedent marker of Alzheimer disease

Neurology

Default-mode network activity distinguishes Alzheimer's disease from healthy aging: Evidence from functional MRI

Proc Natl Acad Sci U S A

Network analysis of intrinsic functional brain connectivity in Alzheimer's disease

PLoS Comput Biol

Tangles and plaques in nondemented aging and “preclinical” Alzheimer's disease

Ann Neurol

Rates of progression in mild cognitive impairment and early Alzheimer's disease

Neurology

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