Association between osteocalcin and cognitive performance in healthy older adults

Abstract

Introductioncognitive deterioration and reductions of bone health coincide with increasing age. We examine the relationship between bone composition and plasma markers of bone remodelling with measures of cognitive performance in healthy adults.Methodsthis cross-sectional study included 225 old (52% women, mean age: 74.4 ± 3.3 years) and 134 young (52% women, mean age: 23.4 ± 2.7 years) adult participants from the MyoAge project. Whole body bone mineral density was measured by dual-energy X-ray absorptiometry. Blood analyses included a panel of bone-related peptides (dickkopf-1, osteoprotegerin, osteocalcin (OC), osteopontin, sclerostin, parathyroid hormone and fibroblast growth factor 23), as well as serum calcium and 25-hydroxy vitamin D assays. A selection of cognitive domains (working memory capacity, episodic memory, executive functioning and global cognition) was assessed with a standardised neuropsychological test battery.Resultsadjusting for covariates and multiple testing revealed that plasma OC levels were positively associated with measures of executive functioning (β = 0.444, P < 0.001) and global cognition (β = 0.381, P = 0.001) in the older women.Discussionthese correlative results demonstrate a positive association between OC, a factor known to regulate bone remodelling, with cognitive performance in older non-demented women. Further work should address possible mechanistic interpretations in humans.

Osteocalcin in the brain: from embryonic development to age-related decline in cognition

“…This notion is of fundamental importance, as too often we conceive and study functions of a given organ omitting the fact that this organ receives many, most of them still unknown, inputs from other organs. Underscoring the potential medical influence of this work, two retrospective studies performed in human subjects 40,41 after the initial paper of Oury et al, was published have suggested a correlation between decreased circulating osteocalcin levels and poor cognitive performance in healthy aged individuals. We are fully aware that these studies, because of their retrospective nature, can only be seen as encouraging, and that projective studies are now needed.…”

“…One reason for this could be that circulating levels of osteocalcin plummet beyond midlife in all species tested 2,64,65 . Finally, the aforementioned clinical studies 40,41 , which suggested an association between circulating osteocalcin levels and cognitive performance, were another reason to ask whether osteocalcin could be sufficient to restore cognitive functions in older mice. We have begun to address this question in animal models in several ways.…”

Involvement of Bone in Systemic Endocrine Regulation

“…Thus, this molecule shows some promise in the treatment of diabetes, insulin resistance and obesity (Ferron and Lacombe 2014). Moreover, a correlation study in healthy older adults showed that plasma osteocalcin levels were positively associated with global cognitive performance in healthy women (Bradburn et al 2016). Interestingly, a recent, relatively extensive study showed an association between high blood osteocalcin levels and low serum hemoglobin in elderly men (Lewerin et al 2016).…”

“…Sclerostin levels in circulation increased in the pre-hemodialysis period and declined in post hemodialysis. Sclerostin correlated with parameters of dialysis adequacy, such a creatinine levels and could represent a defensive mechanism, leading to improvement of vascular disease and bone homeostasis (Bruzzese et al 2016). From this point of view, sclerostin antagonists possess a potential role in the treatment of renal osteodystrophy.…”

Associations of Bone Turnover Markers with Cognitive Function in Patients Undergoing Hemodialysis

“…Because bone-related peptides are secreted into the circulation, there has been growing interest in their influences on the central nervous system [10]. Several bone turnover markers were found to be associated with cognitive function in general population, such as Dickkopf-related protein 1 (DKK1) [11,12], Osteocalcin (OC) [13,14], Osteopontin (OPN) [15], Osteoprotegerin (OPG) [16], and Leptin [17]. These findings suggested that there might be a convergence in mechanisms between bone and neurodegeneration and that bone may possess endocrine properties which aid in maintaining cognitive well-being.…”