Circulating Dkk1 and TRAIL Are Associated With Cognitive Decline in Community-Dwelling, Older Adults With Cognitive Concerns

Ross, Ryan D.; Shah, Raj C.; Leurgans, Sue E.; Wilson, Robert S.; Sumner, Dale R.

doi:10.1093/gerona/glx252

Cited by 28 publications

(27 citation statements)

References 48 publications

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“…According to current literature, though, a possible correlation in humans is still under debate. On the one hand, reports have been published stating a positive correlation between osteocalcin levels and cognitive performance in aged women (23) and obese patients (24), but on the other hand a recent study in aged individuals with memory concerns (25) could not observe any association with either uncarboxylated or total osteocalcin levels. Considering that the initial finding is very recent, the coming years will bring more studies looking for correlations between osteocalcin levels and cognitive function.…”

Section: Introductionmentioning

confidence: 91%

Osteocalcin—A Versatile Bone-Derived Hormone

2019

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Bone has long been regarded as a static organ, simply providing protection and support. However, this mindset has changed radically in recent years and bone is becoming increasingly recognized for its endocrine function of secreting several hormones, thereby controlling various physiological pathways. One of the factors released by the skeleton is osteocalcin. Importantly, osteocalcin is secreted solely by osteoblasts but only has minor effects on bone mineralization and density. Instead, it has been reported to control several physiological processes in an endocrine manner, such as glucose homeostasis and exercise capacity, brain development, cognition, and male fertility. The aim of this review is to provide an overview of the currently known roles of osteocalcin and their underlying mechanisms. At present, one of the major goals in this field is translating basic research into therapeutic applications, therefore ongoing efforts to bring these findings to the clinics will also be discussed.

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Section: Introductionmentioning

confidence: 91%

Osteocalcin—A Versatile Bone-Derived Hormone

2019

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“…24,25 This is further underscored by recent findings that circulating DKK1 is associated with cognitive decline in older adults. 26 Moreover, in a Japanese population, DKK1 genetic variants are associated with SCZ. 27 However, there are no data whether increased DKK1 levels are associated with SCZ, TRS, and neurocognitive impairments and symptom severity.…”

Section: Dkk1mentioning

confidence: 99%

High Mobility Group Protein 1 and Dickkopf-Related Protein 1 in Schizophrenia and Treatment-Resistant Schizophrenia: Associations with Interleukin-6, Symptom Domains, and Neurocognitive Impairments

Al-Dujaili

Mousa

Al‐Hakeim

et al. 2019

Preprint

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Background: Schizophrenia and treatment-resistant schizophrenia (TRS) are associated with aberrations in immune-inflammatory pathways. Increased High Mobility Group Protein 1 (HMGB1), an inflammatory mediator, and Dickkopf-Related Protein (DKK1), a Wnt/β-catenin signaling antagonist, affect the blood-brain-barrier and induce neurotoxic effects and neurocognitive deficits.Aim of the study: The present study aims to examine HMGB1 and DDK1 in non-responders to treatments with antipsychotics (NRTT, n=60), partial RTT (PRTT, n=55) and healthy controls (n=43) in relation to established markers of schizophrenia including IL-6, IL-10 and CLL11 (eotaxin); and to delineate whether these proteins are associated with the schizophrenia symptom subdomains and neurocognitive impairments.Results: HMGB1, DKK1, IL-6 and CCL11 were significantly higher in schizophrenia patients than in controls. DKK1 and IL-6 were significantly higher in NRTT than in PRTT and controls while IL-10 was higher in NRTT than in controls. Binary logistic regression analysis showed that schizophrenia was best predicted by increased DDK1 and HMGB1 while NRTT (versus PRTT) was best predicted by increased IL-6 and CCL11 levels. A large part of the variance in psychosis, hostility, excitation, mannerism and negative (PHEMN) symptoms, and formal thought disorders was explained by HMGB1, IL-6, and CCL11 while most neurocognitive functions were predicted by HMGB1, DDK1 and CCL11. Conclusion: The neurotoxic effects of HMGB1, DKK1, IL-6 and CCL11 including effects on the blood-brain-barrier and the Wnt/β-catenin signaling pathway may cause impairments in executive functions, and working, episodic and semantic memory and explain, in part, PHEMN symptoms and a non-response to treatment with antipsychotic drugs.

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“…11 Some studies have also shown that DKK1 is associated with cognitive ability. 12,13 For over years, numerous studies have been conducted to explore the role of DKK1 in various cancers. Very interestingly, they have revealed that DKK1 changes are cancer type-specific.…”

Section: Introductionmentioning

confidence: 99%

<p>The Clinical Diagnostic and Prognostic Value of Dickkopf-1 in Cancer</p>

Li¹,

Gao²,

Yue³

2020

CMAR

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The Wnt signaling pathway extensively participates in diverse processes such as embryonic development, maintenance of homeostasis and tumor pathogenesis. Dickkopf-1 (DKK1), a Wnt inhibitor, plays a vital role for over the past decades regarding its role in the regulation of several types of cancers. However, studies have shown that DKK1 is expressed differently in cancer and plays a role as a cancer-promoting factor or a tumor suppressor, which is worthy of further exploration. We herein study whether DKK1 is highly expressed in all cancers and plays a crucial role in promoting cancer. Furthermore, we discussed as to which stages of cancer development it plays in. Finally, the present detection methods were introduced and indicated the clinical application of DKK1 in tumor development.

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Circulating Dkk1 and TRAIL Are Associated With Cognitive Decline in Community-Dwelling, Older Adults With Cognitive Concerns

Abstract: These results further confirm the link between bone and brain health and suggest that circulating levels of bone-related biomarkers may have diagnostic potential to predict worsening cognition.

Cited by 28 publications

References 48 publications

Osteocalcin—A Versatile Bone-Derived Hormone

Osteocalcin—A Versatile Bone-Derived Hormone

High Mobility Group Protein 1 and Dickkopf-Related Protein 1 in Schizophrenia and Treatment-Resistant Schizophrenia: Associations with Interleukin-6, Symptom Domains, and Neurocognitive Impairments

<p>The Clinical Diagnostic and Prognostic Value of Dickkopf-1 in Cancer</p>

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