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>
Alzheimer's and Dementia – Elsevier
Published: Jul 1, 2010
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