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

ABSTRACT

Background: Osteoporosis and Alzheimer's disease are common diseases of aging that would seem to be unrelated, but may be linked through the influence of bone-derived signals on brain function. The aim of the current study is to investigate the relationship between circulating levels of bone-related biomarkers and cognition. Methods: The population included 103 community-dwelling older individuals with memory concerns but without cognitive impairment. A global cognition summary measure was collected at baseline and 6, 12, and 18 months post-enrollment by converting raw scores from 19 cognitive function tests to z-scores and averaging. Baseline plasma concentrations of bone-related biomarkers, including undercarboxylated, carboxylated, and total osteocalcin, parathyroid hormone, C-terminal telopeptide of collagen 1 (CTX-1), procollagen type 1 amino-terminal propeptide, osteoprotegrin, osteopontin, Dickkopf WNT signaling pathway inhibitor 1 (Dkk1), sclerostin, and amyloid ß peptides (Aß40 and Aß42), were measured. Results: Using sex, age, and education-adjusted mixed-effects models, we found that baseline levels of TNF-related apoptosis-inducing ligand (TRAIL; p < .001), Dkk1 (p = .014), and CTX-1 (p = .046) were related to the annual rate of change of global cognition over the 18 month follow-up. In cognitive domain-specific analysis, baseline TRAIL was found to be positively related to the annual rate of change in episodic (p < .001) and working memory (p = .016), and baseline Dkk1 was positively related to semantic memory (p = .027) and negatively related to working memory (p = .016). Conclusions: 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.