Elevations in Serum Dickkopf-1 and Disease Progression in Community-Dwelling Older Adults With Mild Cognitive Impairment and Mild-to-Moderate Alzheimer’s Disease
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 old...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-10-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnagi.2019.00278/full |
| _version_ | 1819169336144691200 |
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| author | Laura Tay Bernard Leung Bernard Leung Audrey Yeo Mark Chan Mark Chan Wee Shiong Lim Wee Shiong Lim |
| author_facet | Laura Tay Bernard Leung Bernard Leung Audrey Yeo Mark Chan Mark Chan Wee Shiong Lim Wee Shiong Lim |
| author_sort | Laura Tay |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T19:17:53Z |
| format | Article |
| id | doaj.art-9a971f9f415041c3aefb489c92c6e826 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-22T19:17:53Z |
| publishDate | 2019-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-9a971f9f415041c3aefb489c92c6e8262022-12-21T18:15:28ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652019-10-011110.3389/fnagi.2019.00278462825Elevations in Serum Dickkopf-1 and Disease Progression in Community-Dwelling Older Adults With Mild Cognitive Impairment and Mild-to-Moderate Alzheimer’s DiseaseLaura Tay0Bernard Leung1Bernard Leung2Audrey Yeo3Mark Chan4Mark Chan5Wee Shiong Lim6Wee Shiong Lim7Department of General Medicine, Sengkang General Hospital, Singapore, SingaporeDepartment of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore, SingaporeHealth and Social Sciences, Singapore Institute of Technology, Singapore, SingaporeInstitute of Geriatrics and Active Ageing, Tan Tock Seng Hospital, Singapore, SingaporeInstitute of Geriatrics and Active Ageing, Tan Tock Seng Hospital, Singapore, SingaporeDepartment of Geriatric Medicine, Tan Tock Seng Hospital, Singapore, SingaporeInstitute of Geriatrics and Active Ageing, Tan Tock Seng Hospital, Singapore, SingaporeDepartment of Geriatric Medicine, Tan Tock Seng Hospital, Singapore, SingaporeBackground: 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.https://www.frontiersin.org/article/10.3389/fnagi.2019.00278/fullDickkopf-1mild cognitive impairmentAlzheimer’s diseasedisease progressioninflammation |
| spellingShingle | Laura Tay Bernard Leung Bernard Leung Audrey Yeo Mark Chan Mark Chan Wee Shiong Lim Wee Shiong Lim 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 Dickkopf-1 mild cognitive impairment Alzheimer’s disease disease progression inflammation |
| title | Elevations in Serum Dickkopf-1 and Disease Progression in Community-Dwelling Older Adults With Mild Cognitive Impairment and Mild-to-Moderate Alzheimer’s Disease |
| title_full | Elevations in Serum Dickkopf-1 and Disease Progression in Community-Dwelling Older Adults With Mild Cognitive Impairment and Mild-to-Moderate Alzheimer’s Disease |
| title_fullStr | Elevations in Serum Dickkopf-1 and Disease Progression in Community-Dwelling Older Adults With Mild Cognitive Impairment and Mild-to-Moderate Alzheimer’s Disease |
| title_full_unstemmed | Elevations in Serum Dickkopf-1 and Disease Progression in Community-Dwelling Older Adults With Mild Cognitive Impairment and Mild-to-Moderate Alzheimer’s Disease |
| title_short | Elevations in Serum Dickkopf-1 and Disease Progression in Community-Dwelling Older Adults With Mild Cognitive Impairment and Mild-to-Moderate Alzheimer’s Disease |
| title_sort | elevations in serum dickkopf 1 and disease progression in community dwelling older adults with mild cognitive impairment and mild to moderate alzheimer s disease |
| topic | Dickkopf-1 mild cognitive impairment Alzheimer’s disease disease progression inflammation |
| url | https://www.frontiersin.org/article/10.3389/fnagi.2019.00278/full |
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