Abstract
Background We aimed to investigate how altered intrinsic connectivity networks (ICNs) affect pathologic changes of Alzheimer's disease (AD) at a network-based level. Methods Thirty normal controls (NCs), 23 patients with AD-mild cognitive impairment (MCI), and 20 patients with AD-dementia were enrolled. We compared the organization of grey matter structural covariance and functional connectivity in ICNs between NCs and all AD patients who were amyloid β (Aβ)-positive. We further used seed-based interregional covariance analysis to compare structural and Aβ plaque covariance in default mode network (DMN) between AD-MCI and AD-dementia groups. Results The patients with AD had increased functional interregional covariance among the regions of the ICN anchored to dorsal caudate (DC) seeds compared to the NCs. The increased connectivity was associated with extended patterns of reduced Aβ plaque covariance in the AD-dementia group compared to the AD-MCI group within the striatal network anchored to DC seeds. Patterns of lower Aβ plaque covariance in the AD-dementia group compared to the AD-MCI group were more extended within the network anchored to DC seeds than within the DMN, which was undergoing functional failure in the patients with AD. Significant decreased structural covariance in the AD-dementia group compared to the AD-MCI group was more extended in the DMN during functional failure. Conclusions Functional connectivity in ICNs affects the topographic spread of molecular pathologies. The temporal trajectory of pathologic alterations can be well demonstrated by pathologic covariance comparisons between different clinical stages. Pathologic covariance can provide critical support to pathologic interactions at network and molecular levels.
Highlights
The tau propagation theory [1] states that neurofibrillary tangles in Alzheimer’s disease (AD) are deposited along intrinsic connectivity networks (ICNs), and interconnected regions with high basal metabolism have been reported to be targets for accelerated pathologic accumulation [2, 3]
Regarding network anchored to dorsal caudate (DC) seeds, as the AD-dementia group had lower structural covariance and amyloid β (Aβ) plaque covariance than the AD-mild cognitive impairment (MCI) group, the decreased covariance exhibited a more extended pattern in the amyloid network (AN) anchored to DC seeds than in the structural network (SN) anchored to DC seeds
Functional failure in the default mode network (DMN) was associated with a restricted pattern of reduced Aβ plaque covariance in ANs anchored to entorhinal seeds, while the increased connectivity in functional network (FN) anchored to DC seeds was associated with an extensive pattern of decreased Aβ plaque covariance within ANs anchored to DC seeds
Summary
The tau propagation theory [1] states that neurofibrillary tangles in Alzheimer’s disease (AD) are deposited along intrinsic connectivity networks (ICNs), and interconnected regions with high basal metabolism have been reported to be targets for accelerated pathologic accumulation [2, 3]. We compared the organization of grey matter structural covariance and functional connectivity in ICNs between NCs and all AD patients who were amyloid β (Aβ)-positive. The patients with AD had increased functional interregional covariance among the regions of the ICN anchored to dorsal caudate (DC) seeds compared to the NCs. The increased connectivity was associated with extended patterns of reduced Aβ plaque covariance in the AD-dementia group compared to the AD-MCI group within the striatal network anchored to DC seeds. Patterns of lower Aβ plaque covariance in the AD-dementia group compared to the AD-MCI group were more extended within the network anchored to DC seeds than within the DMN, which was undergoing functional failure in the patients with AD. Pathologic covariance can provide critical support to pathologic interactions at network and molecular levels
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
