Clinical and imaging characteristics of Parkinson’s disease with negative alpha-synuclein seed amplification assay
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Background
The CSF alpha-synuclein (a-syn) seed amplification assay (CSFasynSAA) detects a-syn aggregation in over 90% of individuals with sporadic PD (sPD). However, the clinical characteristics of sPD with negative CSFasynSAA have not been well defined.
Objectives
Describe clinical and neuroimaging characteristics of individuals with sPD enrolled in the Parkinson’s Progression Markers Initiative (PPMI) who have a negative CSFasynSAA.
Methods
Data were from the PPMI. We compared individuals in the sPD cohort who had a negative CSFasynSAA (SAA-, n=79) to a group with positive CSFasynSAA (SAA+, n=237) propensity-score matched on age, sex, and time since clinical diagnosis at baseline assessment. Clinical parameters, DAT-SPECT, and MRI brain volumetric analyses were analyzed.
Results
The SAA- and matched SAA+ groups had similar motor performance on the MDS-UPDRS part III and similar cognitive performance on the MoCA at baseline. The proportion with severe hyposmia was 12% for SAA-versus 73% for SAA+ participants ( p < 0.001). The SAA-group showed a higher degree of atrophy in subcortical brain regions including substantia nigra. Longitudinally, the SAA-group had faster time to reach disease progression milestones, and 14.3% had a change in diagnosis, most commonly to multiple system atrophy.
Conclusions
At baseline, SAA-sPD PPMI participants have a substantially lower rate of hyposmia, but they otherwise cannot be readily distinguished from SAA+ participants based on clinical characteristics. However, SAA-participants have a greater degree of subcortical brain atrophy, faster time to reach disease milestones, and approximately 1 out of 6 received a change in research diagnosis.
