Potential association of bone mineral density loss with cognitive impairment and central and peripheral amyloid-β changes: a cross-sectional study

Abstract

Background There is some evidence in the literature that older adults with cognitive impairments have a higher risk for falls and osteoporotic hip fractures. Currently, the associations between bone health and cognitive health have not been extensively studied. Thus, the present cross-sectional study aims to investigate the relationship between markers of bone loss and cognitive performance in older adults with and without osteopenia as well as older adults with cognitive impairments (i.e., Alzheimer’s disease [AD]). Methods Sixty-two non-osteopenia participants and one hundred three osteopenia participants as the cohort 1 and 33 cognitively normal non-AD participants and 39 AD participants as the cohort 2 were recruited. To assess cognitive and bone health, hip bone mineral density (BMD) and cognitive performance (via Minimal Mental State Examination [MMSE] and/or Auditory Verbal Learning Test-delayed recall [AVLT-DR]) were assessed. Furthermore, in cohort 1, plasma amyloid-β (Aβ) levels, and in cohort 2, cerebrospinal fluid (CSF) Aβ levels were determined. Results We observed that (1) compared with non-osteopenia participants, BMD values (t = − 22.806; 95%CI: − 1.801, − 1.484; p < 0.001), MMSE scores (t = − 5.392; 95%CI: − 3.260, − 1.698; p < 0.001), and AVLT-DR scores (t = − 4.142; 95%CI: − 2.181, − 0.804; p < 0.001), plasma Aβ42 levels (t = − 2.821; 95%CI: − 1.737, − 0.305; p = 0.01), and Aβ42/40 ratio (t = − 2.020; 95%CI: − 0.009, − 0.001; p = 0.04) were significantly lower in osteopenia participants; (2) plasma Aβ42/40 ratio showed a mediate effect for the association between BMD values and the performance of cognitive function in osteopenia participants by mediation analysis, adjusting age, sex, years of education, and body mass index (BMI); (3) BMD values (95%CI: − 1.085, 0.478; p < 0.001) were significantly reduced in AD participants as compared with cognitively normal non-AD participants; (4) in AD participants, the interactive effects of BMD and CSF Aβ42/40 ratio on MMSE scores was found by regression analysis, controlling age, sex, years of education, and BMI; (5) BMD can distinguish AD participants from cognitively normal non-AD participants with AUC of 0.816 and distinguish participants with the cognitive impairment from cognitively normal participants with AUC of 0.794. Conclusion Our findings suggest a relationship between bone health and cognitive health. Given the correlations between BMD and important markers of cognitive health (e.g., central and peripheral pathological change of Aβ), BMD might serve as a promising and easy-accessible biomarker. However, more research is needed to further substantiate our findings.

Comparison of Eating Habits, Body Composition and Densitometric Parameters between Subjects with Normal Cognitive Function and Mild Cognitive Impairment: An Observational Study

“…Previously, it has been suggested that cognitive decline may affect the bone remodelling process [ 36 ]. Indeed, Zhang et al [ 21 ] showed a significant decrease in BMD in subjects with Alzheimer’s disease compared to NCF participants and a positive correlation between BMD and scores obtained in the Minimal Mental State Examination (MMSE) scale. In addition, the receiver operator characteristic curve analysis indicated that this densitometric variable could be used to distinguish cognitive impairment participants from NCF individuals.…”

“…Moreover, a previous meta-analysis showed that obesity and a higher body mass index (BMI) may be associated with an increased risk of dementia [ 20 ]. Some data also suggested that bone mineral density (BMD) is reduced in cognitively impaired individuals [ 21 , 22 ], but this has not been confirmed in other studies [ 23 ]. Furthermore, the underlying mechanisms for the association between cognition and body composition and densitometric parameters are not yet fully understood.…”

Association between cognitive function and body composition in older adults: data from NHANES (1999–2002)

“…Estrogen may play an important role in preventing osteoporosis and cognitive function. It delays neuronal apoptosis and atherosclerosis, inhibits the formation of amyloid b protein, prevents hyperphosphorylation of tau protein, reduces oxidative stress response in the brain, and improves brain cell metabolism ( Jett et al, 2022 ; Zhang et al, 2022 ). The findings of Loskutova et al (2010) suggested that BMD is reduced in both men and women in the early clinical stages of Alzheimer’s disease, and low BMD may be useful for identifying participants with Alzheimer’s disease or cognitive decline.…”

Potential value of serum brain-derived neurotrophic factor, vascular endothelial growth factor, and S100B for identifying major depressive disorder in knee osteoarthritis patients

“…As described in our previous study ( 18 ), the mediation analysis was utilized to determine whether serum neurotrophins could mediate the association between depressive behaviors and knee pain, which is based on a standard three-variable mediation model ( 19 ). Covariates were age, sex, pain of duration, BMI, and treatment types.…”