Ryan D Ross1, Raj C Shah2,3, Sue Leurgans3,4, Teodoro Bottiglieri5, Robert S Wilson3,4,6, Dale Rick Sumner1,7. 1. Department of Cell and Molecular Medicine, Rush University Medical Center, Chicago, Illinois. 2. Department of Family Medicine, Rush University Medical Center, Chicago, Illinois. 3. Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois. 4. Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois. 5. Baylor Research Institute, Institute of Metabolic Disease, Dallas, Texas. 6. Department of Behavioral Sciences, Rush University Medical Center, Chicago, Illinois. 7. Department of Orthopedic Surgery, Rush University Medical Center, Chicago, Illinois.
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 β peptides (Aβ40 and Aβ42), 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.
RCT Entities:
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 β peptides (Aβ40 and Aβ42), 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.
Authors: J G Emery; P McDonnell; M B Burke; K C Deen; S Lyn; C Silverman; E Dul; E R Appelbaum; C Eichman; R DiPrinzio; R A Dodds; I E James; M Rosenberg; J C Lee; P R Young Journal: J Biol Chem Date: 1998-06-05 Impact factor: 5.157
Authors: Robert S Wilson; Laurel A Beckett; Lisa L Barnes; Julie A Schneider; Julie Bach; Denis A Evans; David A Bennett Journal: Psychol Aging Date: 2002-06
Authors: Ryan D Ross; Arnold Z Olali; Qiuhu Shi; Donald R Hoover; Anjali Sharma; Kathleen M Weber; Audrey L French; Heather McKay; Phyllis C Tien; Michael T Yin; Leah H Rubin Journal: J Acquir Immune Defic Syndr Date: 2022-10-01 Impact factor: 3.771