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Heterogeneity of Incipient Atrophy Patterns in Parkinson’s Disease

View ORCID ProfilePedro D. Maia, View ORCID ProfileSneha Pandya, Justin Torok, Ajay Gupta, Yashar Zeighami, Ashish Raj
doi: https://doi.org/10.1101/466086
Pedro D. Maia
3Department of Radiology, Department of Radiology and Biomedical Imaging, School of Medicine, University of California at San Francisco
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Sneha Pandya
1Department of Radiology, Weill Cornell Medical College of Cornell University 407 E. 61 Street, RR106, New York, NY 10065, USA
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Justin Torok
1Department of Radiology, Weill Cornell Medical College of Cornell University 407 E. 61 Street, RR106, New York, NY 10065, USA
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Ajay Gupta
1Department of Radiology, Weill Cornell Medical College of Cornell University 407 E. 61 Street, RR106, New York, NY 10065, USA
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Yashar Zeighami
2Montreal Neurological Institute, McGill University, Montreal, Canada
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Ashish Raj
3Department of Radiology, Department of Radiology and Biomedical Imaging, School of Medicine, University of California at San Francisco
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Abstract

Parkinson’s Disease (PD) is a the second most common neurodegenerative disorder after Alzheimer’s disease and is characterized by cell death in the amygdala and in substructures of the basal ganglia such as the substantia nigra. Since neuronal loss in PD leads to measurable atrophy patterns in the brain, there is clinical value in understanding where exactly the pathology emerges in each patient and how incipient atrophy relates to the future spread of disease. A recent seed-inference algorithm combining an established network-diffusion model with an L1-penalized optimization routine led to new insights regarding the non-stereotypical origins of Alzheimer’s pathologies across individual subjects. Here, we leverage the same technique to PD patients, demonstrating that the high variability in their atrophy patterns also translates into heterogeneous seed locations. Our individualized seeds are significantly more predictive of future atrophy than a single seed placed at the substantia nigra or the amygdala. We also found a clear distinction in seeding patterns between two PD subgroups – one characterized by predominant involvement of brainstem and ventral nuclei, and the other by more widespread frontal and striatal cortices. This might be indicative of two distinct etiological mechanisms operative in PD. Ultimately, our methods demonstrate that the early stages of the disease may exhibit incipient atrophy patterns that are more complex and variable than generally appreciated.

Acknowledgements:

The authors would like to thank C. Mezias and other members of the IDEAL lab for their insightful comments. AR and PM were supported by the NIH grant R01 EB022717. AR, SP, AG and JT were supported by the NIH grant R01NS092802.

Abbreviations
PD
Parkinson’s Disease
SN
Substantia Nigra pars Compacta
PPMI
Parkinson’s Progressive Marker Initiative
NDM
Network Diffusion Model
Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted November 08, 2018.
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Heterogeneity of Incipient Atrophy Patterns in Parkinson’s Disease
Pedro D. Maia, Sneha Pandya, Justin Torok, Ajay Gupta, Yashar Zeighami, Ashish Raj
bioRxiv 466086; doi: https://doi.org/10.1101/466086
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Heterogeneity of Incipient Atrophy Patterns in Parkinson’s Disease
Pedro D. Maia, Sneha Pandya, Justin Torok, Ajay Gupta, Yashar Zeighami, Ashish Raj
bioRxiv 466086; doi: https://doi.org/10.1101/466086

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