Objective: To investigate if individual capacity in network attack tolerance moderates the relationship between striatal dopamine loss and symptom severity in PD.

Background: It was recently demonstrated that higher network attack tolerance in the fronto-parietal network was linked to relative preservation of cognition in PD (Cascone et al., 2021). However, it remains unknown, whether higher network attack tolerance of motor and cognitive networks, also acts as protective factor against the consequences of PD pathology. Here, we plan to assess the mitigating role of attack tolerance on the relation of dopamine loss and clinical symptom severity in PD.

Method: Data of healthy controls (HC), prodromal and clinical PD patients, aged between 50-85 years, were included, for whom a dopamine transporter SPECT (DaT SPECT), clinical information in the OFF state, and resting-state (RS) functional magnetic resonance imaging data (acquired on a 3T Prisma Siemens scanner with a fixed protocol) was available at PPMI. fMRI data was pre-processed using the CONN toolbox. Utilizing the Brain Connectivity Toolbox, individual RS-networks at ten different thresholds (2.5%-25%) will subsequently be constructed and attacked. When attacked, the network’s nodes will be iteratively removed in descending order of their connectedness. For each removed node, the network’s global efficiency will be computed. The ability to sustain its global efficiency to consecutive attacks defines a network’s attack tolerance. First, we will examine differences in attack tolerance between the three groups. Finally, we will test whether attack tolerance moderates the association between striatal dopamine transporter loss and motor (UPDRS-III) and cognitive function (MoCA score).

Results: Data of 17 HCs (M(Age)= 66.6, Sex= 14M/3F), 38 prodromal (M(Age)= 65.3, Sex= 17M/21F), and 69 PD patients (M(Age)= 63.5, Sex= 42M/27F) were included. RS-fMRI data has been pre-processed and quality checked. The attack tolerance analysis is currently ongoing.

Conclusion: Given the sample size, the analyses are anticipated to answer the following hypotheses: 1) Greater attack tolerance (i.e. network-based resilience) will be associated with a preservation of functionality independent of the degree of striatal dopamine loss. 2) Global and local differences in attack tolerance will distinguish healthy controls, prodromal and clinical PD patients.

References: Cascone, A. D., Langella, S., Sklerov, M., & Dayan, E. (2021). Frontoparietal network resilience is associated with protection against cognitive decline in Parkinson’s disease. Communications Biology, 4(1). https://doi.org/10.1038/S42003-021-02478-3

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MDS Abstracts - https://www.mdsabstracts.org/abstract/network-attack-tolerance-a-resilience-proxy-for-parkinsons-disease/