Background: The C allele of the rs11136000 genetic variant of the clusterin gene has been associated with increased risk of Alzheimer's disease. However, a comprehensive characterization of the role of this genetic variant in early cognitive deterioration in PD is lacking.
Methods: Using the Parkinson's Progression Markers Initiative database, we compared baseline and 5-year cognitive performance between high-risk and low-risk clusterin genotypes.
Results: At baseline, recently diagnosed and drug-naive de novo PD patients with the high-risk clusterin genotype showed lower cognitive scores in memory and executive function tests. These differences were even higher at the 5-year follow-up, when they showed a higher prevalence of clinically diagnosed mild cognitive impairment or dementia. They also showed cortical thinning at baseline and increased annual thinning in frontal and posterior cortical regions.
Discussion: Our results provide evidence of this clusterin genotype promoting early cognitive deterioration in PD, but further research is needed to delineate the specific neurodegenerative pathways underlying this clinical association. © 2020 International Parkinson and Movement Disorder Society.
Keywords: CLU rs11136000; Parkinson's disease; cognitive impairment; cortical thinning.
© 2020 International Parkinson and Movement Disorder Society.