Session Information
Date: Wednesday, September 25, 2019
Session Title: Cognition and Cognitive Disorders
Session Time: 1:15pm-2:45pm
Location: Agora 3 East, Level 3
Objective: To investigate whether susceptibility loci for Alzheimer’s disease (AD) are associated with rates of longitudinal cognitive decline in Parkinson’s disease (PD).
Background: Parkinson’s disease is the second most prevalent neurodegenerative disease. In addition to cardinal motor symptoms, the majority of PD patients experience significant cognitive impairment long-term. Cognitive impairment can arise and progress at any point in the disease course, while also varying widely in severity between individuals. At autopsy, the presence of co-morbid AD pathology – beta-amyloid plaques and tau neurofibrillary tangles – correlates with more severe cognitive outcomes, such as dementia, in PD. However, the role of common AD-risk genetic variants in the development of cognitive decline and dementia in PD is poorly understood.
Method: 151 non-demented patients with established, idiopathic PD patients were followed for 1-9 years (mean 2.92 years). A linear mixed-effects model was used to test for associations between long-term cognitive decline (total Montreal Cognitive Assessment (MoCA) or Mattis Dementia Rating Scale-2 (DRS-2) scores) and AD-risk genotype at 19 single nucleotide polymorphisms (SNPs) previously identified by genome-wide association studies of AD. The association of clusterin protein expression in cerebrospinal fluid (CSF) on cognitive function was assessed via linear regression. Models were adjusted for APOEgenotype, sex, age, and baseline MoCA score.
Results: The risk allele at rs9331896, whose nearest gene is CLU, previously associated with increased risk for developing AD, also predicts rate of longitudinal cognitive decline in PD. In addition, a lower level of clusterin protein in CSF was associated with cognitive impairment cross-sectionally and cognitive decline longitudinally.
Conclusion: The AD-risk genotype at rs9331896 and lower CSF clusterin protein expression is associated with a faster rate of cognitive decline in PD. Future studies to validate these findings in additional PD cohorts are warranted.
To cite this abstract in AMA style:
T. Tropea, L. Baratta, K. Maddy, M. Guo, J. Rick, V. van Deerlin, J. Trojanowski, D. Weintraub, A. Chen-Plotkin. Role of Alzheimer’s Disease Genetic Risk Variant rs9331896 in Cognitive Decline in Parkinson’s Disease [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/role-of-alzheimers-disease-genetic-risk-variant-rs9331896-in-cognitive-decline-in-parkinsons-disease/. Accessed May 17, 2025.« Back to 2019 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/role-of-alzheimers-disease-genetic-risk-variant-rs9331896-in-cognitive-decline-in-parkinsons-disease/