Category: Parkinson's Disease: Cognitive functions
Objective: The aim of this study was to examine the association between kininogen cleavage in plasma and cognitive outcome in Parkinson’s disease (PD).
Background: No specific biomarkers for early diagnosis or treatment of cognitive impairment in PD exist to date. Previous work has shown increased kininogen cleavage in plasma of Alzheimer’s disease patients. Recently, our group showed that increased CSF Kininogen levels may predict early cognitive impairment in PD.
Method: Plasma samples of 129 patients with PD recruited in Stockholm and Paris, in AETIONOMY project, were analyzed. Intact and cleaved kininogen was measured with ELISA, and cognitive decline was assessed with repeated MoCA during 6 years of mean follow-up. Survival analysis was applied, and “time until MoCA score<25 or until MoCA score deterioration with 2 points” was used as outcome measure. The ration between cleaved and intact kininogen (HKc_i) was dichotomized at the 75th percentile value of 2.07.
Results: In total 118 of 129 patients with a PD diagnosis of 5 years or less at the time of plasma collection were included in this analysis. Of those, 44 (37%) were females. Cleaved kininogen levels in plasma varied between 6.9 and 221.7 mg/ml (mean 40.3; SD 47.5 mg/ml and median 22.3; IQR: 22.9 mg/ml). Intact kininogen levels varied from 3.1 to 141 mg/ml (mean 30.9; SD 21.7 mg/ml and median 28.1 IQR: 14.9 mg/ml). The ratio between cleaved and intact kininogen was calculated and the median value was 0.82, IQR 1.29.
Of 118 patents, 68 (58%) reached unfavorable cognitive outcome during a median follow-up of 6 years and 18 (26.5%) of those patients had high HKc_i, compared to 8 of 50 patients (16%) in the favorable cognitive outcome group (p=0.1).
Cox regression analysis showed that high HKc_i was associated with increased risk for unfavorable cognitive outcome (HR 1.8; 95% CI 1.06 – 3.2). after adjustment for age and sex.
Conclusion: Kininogen cleavage may be a relevant mechanism involved in cognitive impairment in PD, similarly to AD.
To cite this abstract in AMA style:
I. Markaki, T. Ntetsika, W. Paslawski, P. Tsitsi, S. Carvalho, JC. Corvol, P. Svenningsson. Cleaved plasma kininogen is associated with unfavorable cognitive outcome in Parkinson’s disease [abstract]. Mov Disord. 2024; 39 (suppl 1). https://www.mdsabstracts.org/abstract/cleaved-plasma-kininogen-is-associated-with-unfavorable-cognitive-outcome-in-parkinsons-disease/. Accessed October 5, 2024.« Back to 2024 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/cleaved-plasma-kininogen-is-associated-with-unfavorable-cognitive-outcome-in-parkinsons-disease/