Disruption of functional connectivity in clinically normal older adults harboring amyloid burden

Disruption of functional connectivity in clinically normal older adults harboring amyloid burden Background: Recently developed imaging technologies allow the in vivo detection of fibrillar amyloid burden, which appears in a substantial proportion of clinically normal individuals. The presence of amyloid burden in these individuals may have subtle neurological effects despite the absence of clinical symptoms of dementia. We predicted that amyloid burden would be associated with disruption of functional connectivity within a large-scale brain network. Methods: The relationship between fibrillar amyloid burden, measured via positron emission tomography imaging using C-11 Pittsburgh Compound-B (PIB), and functional correlations within a large-scale brain network, measured via functional magnetic resonance imaging (MRI) during rest, was investigated in a cohort of 38 healthy, clinically normal, community dwelling older adults (aged from 60 to 88, M = 73.1). Participants were screened using the Clinical Dementia Rating (CDR = 0) scale and the Mini-Mental State Examination (minimum score of 27). Fibrillar amyloid burden was defined by specific binding (indexed to a cerebellar reference region) of PIB in gray matter within a large region of interest that included frontal, lateral, and retrosplenial cortices (FLR). Individuals with distribution volume ratios (DVR) within the FLR region of 1.15 or greater were classified as PIB positive, as opposed to PIB negative. Analyses treating DVR within the FLR region as a continuous measure were also conducted and confirmed the findings from the grouped analyses. Functional correlation MRI (fcMRI) was measured among regions of interest within the default network, including a priori defined regions in posterior cingulate, medial prefrontal, and lateral parietal cortices. Functional correlations were computed among these regions for scans during which participants passively viewed a fixation point (rest). Results: PIB negative individuals exhibited significantly higher estimates of fcMRI than PIB positive individuals during rest; in addition, DVR within the FLR region was significantly negatively correlated with fcMRI. The pattern of these results remained unchanged when controlling for chronological age. Exploratory analyses initiated by seeding the posterior cingulate cortex confirmed significant disruption in the default network including functional disconnection of the hippocampal formation. Conclusions: These data suggest that amyloid deposition is related to disruption of the spontaneous coherence of default network activity in clinically normal older adults.</P> http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Alzheimer's and Dementia Elsevier

Disruption of functional connectivity in clinically normal older adults harboring amyloid burden

Alzheimer's and Dementia, Volume 6 (4) – Jul 1, 2010

Loading next page...
 
/lp/elsevier/disruption-of-functional-connectivity-in-clinically-normal-older-RYdDKHbI2S
Publisher
Elsevier
Copyright
Copyright © 2010 The Alzheimer's Association
ISSN
1552-5260
DOI
10.1016/j.jalz.2010.05.525
Publisher site
See Article on Publisher Site

Abstract

Background: Recently developed imaging technologies allow the in vivo detection of fibrillar amyloid burden, which appears in a substantial proportion of clinically normal individuals. The presence of amyloid burden in these individuals may have subtle neurological effects despite the absence of clinical symptoms of dementia. We predicted that amyloid burden would be associated with disruption of functional connectivity within a large-scale brain network. Methods: The relationship between fibrillar amyloid burden, measured via positron emission tomography imaging using C-11 Pittsburgh Compound-B (PIB), and functional correlations within a large-scale brain network, measured via functional magnetic resonance imaging (MRI) during rest, was investigated in a cohort of 38 healthy, clinically normal, community dwelling older adults (aged from 60 to 88, M = 73.1). Participants were screened using the Clinical Dementia Rating (CDR = 0) scale and the Mini-Mental State Examination (minimum score of 27). Fibrillar amyloid burden was defined by specific binding (indexed to a cerebellar reference region) of PIB in gray matter within a large region of interest that included frontal, lateral, and retrosplenial cortices (FLR). Individuals with distribution volume ratios (DVR) within the FLR region of 1.15 or greater were classified as PIB positive, as opposed to PIB negative. Analyses treating DVR within the FLR region as a continuous measure were also conducted and confirmed the findings from the grouped analyses. Functional correlation MRI (fcMRI) was measured among regions of interest within the default network, including a priori defined regions in posterior cingulate, medial prefrontal, and lateral parietal cortices. Functional correlations were computed among these regions for scans during which participants passively viewed a fixation point (rest). Results: PIB negative individuals exhibited significantly higher estimates of fcMRI than PIB positive individuals during rest; in addition, DVR within the FLR region was significantly negatively correlated with fcMRI. The pattern of these results remained unchanged when controlling for chronological age. Exploratory analyses initiated by seeding the posterior cingulate cortex confirmed significant disruption in the default network including functional disconnection of the hippocampal formation. Conclusions: These data suggest that amyloid deposition is related to disruption of the spontaneous coherence of default network activity in clinically normal older adults.</P>

Journal

Alzheimer's and DementiaElsevier

Published: Jul 1, 2010

There are no references for this article.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off