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Front. Aging Neurosci. | doi: 10.3389/fnagi.2019.00278

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

 Laura Tay1*,  Wee Shiong Lim2,  Bernard Leung2, Audrey Yeo2 and Mark Chan2
  • 1Sengkang General Hospital, Singapore
  • 2Tan Tock Seng Hospital, Singapore

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 Dickkopf-1 (Dkk-1), a Wnt antagonist, is 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, functional performance and neuropsychological symptoms were assessed at baseline and 1-year. We reviewed neuroimaging 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 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, 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 groups. Serum Dkk-1 had increased significantly from baseline amongst progressors, while non-progressors exhibited decremental Dkk-1 (Dkk-1change: 354.304+670.467 vs -173.582+535.676ng/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 in contributing to disease progression amongst older adults with MCI and mild-moderate AD.

Keywords: Dickkopf-1, Alzheimer ' s disease, Mild Cognitive Impairment, disease progression, Inflammation

Received: 29 Mar 2019; Accepted: 26 Sep 2019.

Copyright: © 2019 Tay, Lim, Leung, Yeo and Chan. 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.

* Correspondence: Dr. Laura Tay, Sengkang General Hospital, Singapore, Singapore, laura.tay.b.g@singhealth.com.sg