Selective changes of resting-state networks in individuals at risk for Alzheimer's disease

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder that prominently affects cerebral connectivity. Assessing the functional connectivity at rest, recent functional MRI (fMRI) studies reported on the existence of resting-state networks (RSNs). RSNs are characterized by spatially coherent, spontaneous fluctuations in the blood oxygen level-dependent signal and are made up of regional patterns commonly involved in functions such as sensory, attention, or default mode processing. In AD, the default mode network (DMN) is affected by reduced functional connectivity and atrophy. In this work, we analyzed functional and structural MRI data from healthy elderly (n ‫؍‬ 16) and patients with amnestic mild cognitive impairment (aMCI) (n ‫؍‬ 24), a syndrome of high risk for developing AD. Two questions were addressed: (i) Are any RSNs altered in aMCI? (ii) Do changes in functional connectivity relate to possible structural changes? Independent component analysis of restingstate fMRI data identified eight spatially consistent RSNs. Only selected areas of the DMN and the executive attention network demonstrated reduced network-related activity in the patient group. Voxel-based morphometry revealed atrophy in both medial temporal lobes (MTL) of the patients. The functional connectivity between both hippocampi in the MTLs and the posterior cingulate of the DMN was present in healthy controls but absent in patients. We conclude that in individuals at risk for AD, a specific subset of RSNs is altered, likely representing effects of ongoing early neurodegeneration. We interpret our finding as a proof of principle, demonstrating that functional brain disorders can be characterized by functional-disconnectivity profiles of RSNs.default mode network ͉ intrinsic brain activity ͉ mild cognitive impairment A lzheimer's disease (AD) is a neurodegenerative disorder clinically characterized by progressive dementia and neuropsychiatric symptoms (1). AD is neuropathologically defined by tau pathology and amyloid aggregations (2). Tau pathology starts in regions of the medial temporal lobe (MTL) and is well correlated with cell loss and atrophy; amyloid deposition primarily affects distributed neocortical regions but is not especially prominent in the MTL (2, 3). Atrophy of the MTL is correlated with the degree of dementia and also the extent of temporoparietal hypometabolism; both results are assumed to reflect changes in cerebral connectivity, especially between the MTL and the neocortex (3-5). In non-human primates, prominent structural connectivity between the MTL and neocortical regions as well as broad neocortical hypometabolism after ablation of parts of the MTL were demonstrated (6, 7). Evidence for disrupted structural and functional connectivity (FC) further suggests that AD includes a disconnection syndrome (5, 8-10).Mild cognitive impairment (MCI) is a syndrome with cognitive decline greater than expected for an individual's age and educational level but not interfering notably with activities of daily living; prevalence of M...

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Spontaneous brain activity observed with functional magnetic resonance imaging as a potential biomarker in neuropsychiatric disorders

“…The reduced network-related activity in the executive attention network is in line with observed attentional deficits in MCI and AD, indicating impaired interaction between the two anti-correlated networks (TPN and TNN) that prominently organize intrinsic brain activity (Sorg et al 2007). Additionally, in a recent study, both the increased FC within the salience network, which is anticorrelated with the DMN and a part of the TPN, and the decreased FC within the DMN were found in AD.…”

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“…For the lower frequencies below 4 Hz we found evidence for a reduction of functional network size across the lifespan. This result fits well into the "disconnection hypothesis" (Geschwind, 1965) and is consistent with other results demonstrating a disruption of large-scale brain systems as measured by low-frequency fMRI correlations (Andrews-Hanna et al, 2007;Bai et al, 2008;Greicius et al, 2004;Rombouts et al, 2005;Sorg et al, 2007). For the 2-4 Hz frequency range, our results suggest a continuous change of functional connectivity across adulthood between 18 and 89 years rather than a rapid drop in older age.…”