Individual Correspondence of Amyloid-β and Intrinsic Connectivity in the Posterior Default Mode Network Across Stages of Alzheimer’s Disease

Article type: Research Article

Authors: Pasquini, Lorenzo^{a; i; 1; *} | Benson, Gloria^{e; i; 1} | Grothe, Michel J.^f | Utz, Lukas^{d; i} | Myers, Nicholas E.^{g; i} | Yakushev, Igor^{c; i} | Grimmer, Timo^{b; i} | Scherr, Martin^{b; h; i} | Sorg, Christian^{b; d; i} | for the Alzheimer’s Disease Neuroimaging Initiative²

Affiliations: [a] Memory and Aging Center, Department of Neurology, University of California at San Francisco, San Francisco, CA, USA | [b] Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany | [c] Department of Nuclear Medicine, Technische Universität München, Munich, Germany | [d] Department of Neuroradiology of Klinikum rechts der Isar, Technische Universität München, Munich, Germany | [e] Department of Neurology and NeuroCure Clinical Research Center, Charité Universitätsmedizin, Berlin, Germany | [f] German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany | [g] Department of Experimental Psychology, Oxford University, Oxford, UK | [h] Department of Neurology, Paracelsus Medical University Salzburg, and Christian Doppler Medical Centre, Salzburg, Austria | [i] TUM-Neuroimaging Center, Technische Universität München, Munich, Germany

Correspondence: [*] Correspondence to: Lorenzo Pasquini, Memory and Aging Center, Department of Neurology, University of California at San Francisco, 675 Nelson Rising Lane, San Francisco, CA 94158, USA. Tel.: +1 415 502 7187; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Note: [2] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

Abstract: In Alzheimer’s disease (AD), amyloid-β (Aβ) pathology and intrinsic functional connectivity (iFC) interact. Across stages of AD, we expected individual spatial correspondence of Aβ and iFC to reveal both Aβ accumulation and its detrimental effects on iFC. We used resting-state functional magnetic imaging and Aβ imaging in a cross-sectional sample of 90 subjects across stages of AD and healthy older adults. Global and local correspondence of Aβ and iFC were assessed within the posterior default mode network (pDMN) by within-subject voxel-wise correlations. Beginning at preclinical stages, global Aβ-iFC correspondence was positive for the whole pDMN, showing that Aβ accumulates in areas of high connectivity, and reached a plateau at prodromal stages. Starting at preclinical stages, local correspondence was negative in network centers, indicating that Aβ reduces connectivity of the pDMN as a function of local plaque concentration, and peaked at prodromal stages. Positive global correspondence suggests that Aβ accumulation progresses along iFC, with this effect starting in preclinical stages, and being constant along clinical periods. Negative local correspondence suggests detrimental effects of Aβ on iFC in network centers, starting at preclinical stages, and peaking when first symptoms appear. Data reveal a complex trajectory of Aβ and iFC correspondence, affecting both Aβ accumulation and iFC impairments.

Keywords: Alzheimer’s disease, amyloid-β, intrinsic functional connectivity, mild cognitive impairment, multimodal imaging

DOI: 10.3233/JAD-170096

Journal: Journal of Alzheimer's Disease, vol. 58, no. 3, pp. 763-773, 2017