Longitudinal Spatial Relationships Between Atrophy and Hypometabolism Across the Alzheimer’s Disease Continuum

Article type: Research Article

Authors: Stocks, Jane^{a; *} | Heywood, Ashley^a | Popuri, Karteek^{b; c} | Beg, Mirza Faisal^b | Rosen, Howie^d | Wang, Lei^{a; e} | for the Alzheimer’s Disease Neuroimaging Initiative

Affiliations: [a] Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA | [b] School of Engineering Science, Simon Fraser University, Burnaby, Canada | [c] Memorial University of Newfoundland, Department of Computer Science, St. John’s, Canada | [d] School of Medicine, University of California, San Francisco, CA, USA | [e] Department of Psychiatry and Behavioral Health, Ohio State University Wexner Medical Center, Columbus, OH, USA

Correspondence: [*] Correspondence to: Jane Stocks, MS, Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, 710 North Lake Shore Dr. #1303A, Chicago, IL 60611, USA. E-mail: janestocks2018@u.northwestern.edu.

Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (https://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: https://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf

Abstract: Background:The A/T/N framework allows for the assessment of pathology-specific markers of MRI-derived structural atrophy and hypometabolism on 18FDG-PET. However, how these measures relate to each other locally and distantly across pathology-defined A/T/N groups is currently unclear. Objective:To determine the regions of association between atrophy and hypometabolism in A/T/N groups both within and across time points. Methods:We examined multivariate multimodal neuroimaging relationships between MRI and 18FDG-PET among suspected non-Alzheimer’s disease pathology (SNAP) (A–T/N+; n = 14), Amyloid Only (A+T–N–; n = 24) and Probable AD (A+T+N+; n = 77) groups. Sparse canonical correlation analyses were employed to model spatially disjointed regions of association between MRI and 18FDG-PET data. These relationships were assessed at three combinations of time points –cross-sectionally, between baseline visits and between month 12 (M-12) follow-up visits, as well as longitudinally between baseline and M-12 follow-up. Results:In the SNAP group, spatially overlapping relationships between atrophy and hypometabolism were apparent in the bilateral temporal lobes when both modalities were assessed at the M-12 timepoint. Amyloid-Only subjects showed spatially discordant distributed atrophy-hypometabolism relationships at all time points assessed. In Probable AD subjects, local correlations were evident in the bilateral temporal lobes when both modalities were assessed at baseline and at M-12. Across groups, hypometabolism at baseline correlated with non-local, or distant, atrophy at M-12. Conclusion:These results support the view that local concordance of atrophy and hypometabolism is the result of a tau-mediated process driving neurodegeneration.

Keywords: Alzheimer’s disease, amyloid, cerebrospinal fluid, magnetic resonance imaging, multimodal imaging, neuroimaging, positron emission tomography, suspected non-Alzheimer’s disease pathology, tau

DOI: 10.3233/JAD-220975

Journal: Journal of Alzheimer's Disease, vol. 92, no. 2, pp. 513-527, 2023