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Elevations in Serum Dickkopf-1 and Disease Progression in Community-Dwelling Older Adults With Mild Cognitive Impairment and Mild-to-Moderate Alzheimer's Disease

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posted on 10.06.2021, 07:26 by Laura Tay, Pui Lam Bernard LeungPui Lam Bernard Leung, Audrey Yeo, Mark Chan, Wee Shiong Lim
Background: Disruption of Wnt signaling has been implicated in dysfunctional synaptic plasticity, the degree of which correlates with Alzheimer’s disease severity. We sought to examine whether serum levels of Dickkopf-1 (Dkk-1), a Wnt antagonist, are associated with global disease progression in older adults with mild cognitive impairment (MCI) and mild-to-moderate AD.
Methods: We prospectively followed 88 older adults with MCI and mild-to-moderate AD attending a Memory Clinic. Cognitive performance, functional performance and neuropsychological symptoms were assessed at baseline and after 1 year. We reviewed neuroimaging for white matter changes and medial temporal atrophy, and performed ApoE genotyping at baseline. Serum Dkk-1 was assayed at baseline and 1 year, along with blood biomarkers of inflammation and endocrine dysfunction. We defined global disease progression (“progressors”) as an increase in Clinical Dementia Rating Sum-of-Boxes (CDR-SB) score by >2 points at 1 year.
Results: Fifteen (17.0%) participants had global disease progression. At baseline, there was no difference in cognitive performance and neuropsychiatric symptoms between groups, although progressors were more impaired in instrumental activities of daily living (p = 0.008). Progressors had significantly greater deterioration in cognitive performance (p = 0.002), with significantly worse functional performance and more severe neuropsychiatric symptoms (p = 0.042) at follow-up. Serum inflammatory and endocrine biomarkers at baseline and 1 year were similar between progressors and non-progressors. Serum Dkk-1 had increased significantly from baseline amongst progressors, while non-progressors exhibited decremental Dkk-1 over time (Dkk-1change: 354.304 ± 670.467 vs. −173.582 ± 535.676 ng/ml, p = 0.001). Adjusting for age, gender and baseline cognitive performance, incremental Dkk-1 independently predicted global cognitive decline (p = 0.012).
Conclusion: Our results suggest progressively dysfunctional Wnt signaling through Dkk-1 antagonism contributes to disease progression amongst older adults with MCI and mild-moderate AD.

Funding

This study was funded by NHG Clinician Scientist Career Scheme CSCS 12002 and NHG CSCS 13001 to Dr Laura Tay, TTSH.

History

Journal/Conference/Book title

Frontiers in Aging Neuroscience

Publication date

2019

Version

Published

Rights statement

This is the publisher's PDF version of: Tay, L., Leung, B., Yeo, A., Chan, M., & Lim, W. S. (2019). Elevations in Serum Dickkopf-1 and disease progression in community-dwelling older adults with mild cognitive impairment and mild-to-moderate Alzheimer’s disease. Frontiers in Aging Neuroscience, 11, 278. https://doi.org/10.3389/fnagi.2019.00278. Copyright © 2019 Tay, Leung, Yeo, Chan and Lim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.