Preferential degradation of cognitive networks differentiates Alzheimer’s disease from ageing
Year: 2018
Type: article
Abstract: Converging evidence from structural, metabolic and functional connectivity MRI suggests that neurodegenerative diseases, such as Alzheimer's disease, target specific neural networks. However, age-related network changes commonly co-occur with neuropathological cascades, limiting efforts to disentangle disease-specific alterations in network function from those associated with normal ageing. Here we elucidate the differential effects of ageing and Alzheimer's disease pathology through simultaneous analyses of two functional connectivity MRI datasets: (i) young participants harbouring highly-penetrant mutations leading to autosomal-dominant Alzheimer's disease from the Dominantly Inherited Alzheimer's Network (DIAN), an Alzheimer's disease cohort in which age-related comorbidities are minimal and likelihood of progression along an Alzheimer's disease trajectory is extremely high; and (ii) young and elderly participants from the Harvard Aging Brain Study, a cohort in which imaging biomarkers of amyloid burden and neurodegeneration can be used to disambiguate ageing alone from preclinical Alzheimer's disease. Consonant with prior reports, we observed the preferential degradation of cognitive (especially the default and dorsal attention networks) over motor and sensory networks in early autosomal-dominant Alzheimer's disease, and found that this distinctive degradation pattern was magnified in more advanced stages of disease. Importantly, a nascent form of the pattern observed across the autosomal-dominant Alzheimer's disease spectrum was also detectable in clinically normal elderly with clear biomarker evidence of Alzheimer's disease pathology (preclinical Alzheimer's disease). At the more granular level of individual connections between node pairs, we observed that connections within cognitive networks were preferentially targeted in Alzheimer's disease (with between network connections relatively spared), and that connections between positively coupled nodes (correlations) were preferentially degraded as compared to connections between negatively coupled nodes (anti-correlations). In contrast, ageing in the absence of Alzheimer's disease biomarkers was characterized by a far less network-specific degradation across cognitive and sensory networks, of between- and within-network connections, and of connections between positively and negatively coupled nodes. We go on to demonstrate that formalizing the differential patterns of network degradation in ageing and Alzheimer's disease may have the practical benefit of yielding connectivity measurements that highlight early Alzheimer's disease-related connectivity changes over those due to age-related processes. Together, the contrasting patterns of connectivity in Alzheimer's disease and ageing add to prior work arguing against Alzheimer's disease as a form of accelerated ageing, and suggest multi-network composite functional connectivity MRI metrics may be useful in the detection of early Alzheimer's disease-specific alterations co-occurring with age-related connectivity changes. More broadly, our findings are consistent with a specific pattern of network degradation associated with the spreading of Alzheimer's disease pathology within targeted neural networks.
Source: Brain
DOI: 10.1093/brain/awy053
Authors: Jasmeer P Chhatwal, Aaron P Schultz, Keith A Johnson, Trey Hedden, Sehily Jaimes, Tammie L S Benzinger, Clifford Jack, Beau M Ances, John M Ringman, Daniel S Marcus, Bernardino Ghetti, Martin R Farlow, Adrian Danek, Johannes Levin, Igor Yakushev, Christoph Laske, Robert A Koeppe, Douglas R Galasko, Chengjie Xiong, Colin L Masters, Peter R Schofield, Kirsi M Kinnunen, Stephen Salloway, Ralph N Martins, Eric McDade, Nigel J Cairns, Virginia D Buckles, John C Morris, Randall Bateman, Reisa A Sperling, for the Dominantly Inherited Alzheimer Network
Institutions: Brigham and Women's Hospital, Harvard University, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, Washington University in St. Louis, Mayo Clinic, University of Southern California, Indiana University School of Medicine, German Center for Neurodegenerative Diseases, Ludwig-Maximilians-Universität München, Technical University of Munich, Hertie Institute for Clinical Brain Research, University of Tübingen, University of Michigan, University of California San Diego, The University of Melbourne, Florey Institute of Neuroscience and Mental Health, UNSW Sydney, Neuroscience Research Australia, UCL Queen Square Institute of Neurology, University College London, Brown University, Butler Hospital, Edith Cowan University
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Awards: Influence of Age-related Neuropathology on Functional Brain Networks, Age and genetic influence on fcMRI networks in autosomal dominant and sporadic AD, Tau, amyloid, & white matter burden interact to impact brain networks in preclinical Alzheimer's disease, Mentoring Imaging Research in Early AD, Dominantly Inherited Alzheimer Network, Alzheimer's Disease Research Center, Alzheimer Disease Research Center, NINDS Center Core for Brain Imaging, Washington University Institute of Clinical and Translational Sciences (KL2), Dominantly Inherited Alzheimer Network, NINDS CENTER CORE FOR BRAIN IMAGING, Dominantly Inherited Alzheimer Network, Impact of Amyloid and Tau on the Aging Brain: The Harvard Aging Brain Study, Washington University Institute of Clinical and Translational Sciences (KL2), Antecedent Biomarkers for Alzheimer Disease: The Adult Children Study
OpenAlex ID: W2790737276