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Molecular Imaging and Computer Typing in GBA-PD and Asymptomatic GBA-mutation Carriers

Study Rationale:
People who have a mutation in the GBA gene have a higher risk of developing Parkinson’s disease (PD) and, if they have PD, are more likely to have cognitive decline and dementia. Cognitive problems in people with PD is related to dysfunction of the brain chemical acetylcholine and likely to the accumulation of the tau protein in the brain. Another observation in previous studies is that analyzing the patterns of typing into a computer can help differentiate healthy people from people with PD.

We hypothesize that people with GBA-related PD will have higher acetylcholine dysfunction and tau accumulation compared with non-GBA patients, and that these changes may start in the asymptomatic phase (i.e., people with the mutation but without symptoms of PD). We also believe that we will be able to detect subjects with higher degree of dopamine loss just by analyzing the way they type into a computer.

Study Design:
We will recruit 25 subjects with a GBA mutation (10 subjects with PD and 15 asymptomatic carriers). All the participants will have a clinical evaluation and a typing session, and subsequently will undergo a brain MRI and three PET scans with a tau tracer, an acetylcholine tracer, and a dopaminergic tracer. A blood sample will also be taken for the analysis of GCase (the enzyme related to the GBA mutation).

Impact on Diagnosis/Treatment of Parkinson’s Disease:
The results will help understand the changes that take place in the brain of people with GBA-related Parkinson’s disease, and hopefully will shed light also on the pathophysiology of non-GBA-related Parkinson’s, as well as on the molecular correlates of cognitive decline, especially in its early stage. The typing data along with dopaminergic imaging will clarify the possible role of using typing patterns to identify subjects with early stage Parkinson’s disease.

Next Steps for Development:
The findings of this study may help identify biomarkers for cognitive decline in early Parkinson’s disease, with a potential role in clinical trials. Also, if our hypothesis on the typing is confirmed, this approach may be studied in larger cohorts for early diagnosis of Parkinson’s in other at-risk populations.


  • A. Jon Stoessl, CM/MD/FRCPC/FCAHS

    Vancouver BC Canada

  • Michele Matarazzo, MD

    Vancouver BC Canada

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