Bone Loss and Osteoporosis are Associated with Conversion from Mild Cognitive Impairment to Alzheimer’s Disease

Zhou, Rui; Zhou, Huadong; Li, Rui; Xu, Jianzhong

doi:10.2174/1567205011666140812115818

Cited by 60 publications

(45 citation statements)

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“…Osteoporosis and Alzheimer’s disease (AD) are common chronic degenerative disorders which are strongly associated with advanced age [1,2,3]. AD is frequently associated with fractures and reduction in bone mineral density, even at early stages of disease when patients are still active [4,5,6], indicating that AD and osteoporosis may share conserved pathogenic mechanisms. We have previously shown that there is a significant elevated expression levels of amyloid β peptide (Aβ), one of the pathological hallmarks of AD, in osteoporotic bone tissues.…”

Section: Introductionmentioning

confidence: 99%

Amyloid β Peptide Enhances RANKL-Induced Osteoclast Activation through NF-κB, ERK, and Calcium Oscillation Signaling

Yang

Teguh

et al. 2016

IJMS

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Osteoporosis and Alzheimer’s disease (AD) are common chronic degenerative disorders which are strongly associated with advanced age. We have previously demonstrated that amyloid beta peptide (Aβ), one of the pathological hallmarks of AD, accumulated abnormally in osteoporotic bone specimens in addition to having an activation effect on osteoclast (Bone 2014,61:164-75). However, the underlying molecular mechanisms remain unclear. Activation of NF-κB, extracellular signal-regulated kinase (ERK) phosphorylates, and calcium oscillation signaling pathways by receptor activator NF-κB ligand (RANKL) plays a pivotal role in osteoclast activation. Targeting this signaling to modulate osteoclast function has been a promising strategy for osteoclast-related diseases. In this study, we investigated the effects of Aβ on RANKL-induced osteoclast signaling pathways in vitro. In mouse bone marrow monocytes (BMMs), Aβ exerted no effect on RANKL-induced osteoclastogenesis but promoted osteoclastic bone resorption. In molecular levels, Aβ enhanced NF-κB activity and IκB-α degradation, activated ERK phosphorylation and stimulated calcium oscillation, thus leading to upregulation of NFAT-c1 expression during osteoclast activation. Taken together, our data demonstrate that Aβ enhances RANKL-induced osteoclast activation through IκB-α degradation, ERK phosphorylation, and calcium oscillation signaling pathways and that Aβ may be a promising agent in the treatment of osteoclast-related disease such as osteoporosis.

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Section: Introductionmentioning

confidence: 99%

Amyloid β Peptide Enhances RANKL-Induced Osteoclast Activation through NF-κB, ERK, and Calcium Oscillation Signaling

Yang

Teguh

et al. 2016

IJMS

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“…Low BMD and cognitive impairment share several common risk factors, and previous studies found an association of osteoporosis with stroke, brain atrophy, brain white matter changes, and silent infarcts [4–6]; also, it has been reported that low BMD and cognitive impairment often coexist, and that osteoporosis is associated with increased rates of progression from mild cognitive impairment to Alzheimer’s disease, as well as with incident Alzheimer disease [7, 8]. In addition, there is evidence of an increased risk of dementia in subjects with diagnosis of osteoporosis or osteoporotic fractures in Asian populations [1]; however, there are relevant racial differences in bone mass, so that Asian women have lower bone mass than Caucasian [9].…”

Section: Introductionmentioning

confidence: 99%

Bone Mineral Density and Cognitive Decline in Elderly Women: Results from the InCHIANTI Study

et al. 2015

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Osteoporosis and cognitive impairment, which are highly prevalent conditions in elderly populations, share several risk factors. This study aims at evaluating the association of bone mineral density (BMD) with prevalent and incident cognitive impairment after a 3-year follow-up. We studied 655 community-dwelling women aged 65+ participating in the InCHIANTI study, who had been followed for 3 years. Total, trabecular, and cortical BMD were estimated by peripheral quantitative computed tomography using standard transverse scans at 4 and 38 % of the tibial length. Cognitive performance was evaluated using the Mini-Mental State Examination and the Trail Making Tests (TMT) A and B; a MMSE score <24 was adopted to define cognitive impairment. The TMT A–B score was calculated as the difference between TMT-A and TMT-B times (ΔTMT). The association of cognitive performance after 3 years with baseline indices of BMD was assessed by logistic and linear regression analyses. Cortical, but not trabecular, BMD was independently associated with incident cognitive impairment (OR 0.93, 95 % CI 0.88–0.98; P = 0.012), worsening cognitive performance (OR 0.96, 95 % CI 0.92–0.98; P = 0.039), and worsening performance in ΔTMT (OR 0.96, 95 % CI 0.92–0.99; P = 0.047). Increasing cortical BMD tertiles was associated with decreasing probability of incident cognitive impairment (P for linear trend =0.001), worsening cognitive performance (P = 0.013), and a worsening performance below the median value (P for linear trend <0.0001). In older women, low BMD might represent an independent and early marker of subsequent cognitive impairment. Physicians should assess and monitor cognitive performance in the routine management of elderly women with osteoporosis.

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“…Some studies suggest that lower BMD is associated with the higher risk of AD in Western population [44]. Zhou et al [45] also report that low BMD could predict the likelihood of progression to AD in patients with mild cognitive impairment. Although there are complicated associations between AD and BMD, we performed a MR analysis and found that there was no significant causal associations of AD with BMD.…”

Section: Discussionmentioning

confidence: 99%

Schizophrenia, Bipolar Disorder, and Alzheimer’s Disease are not Causal Factors of Bone Mineral Density: A Mendelian Randomization Analysis

et al. 2019

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Until recently, it remains unclear whether schizophrenia, bipolar disorder (BD), and Alzheimer's disease (AD) is associated with bone mineral density (BMD). We aimed to investigate the causal effects of schizophrenia, BD and AD on BMD with Mendelian randomization (MR) analysis. Single-nucleotide polymorphisms (SNPs) strongly associated with these three neuropsychiatric diseases as instrumental variables were selected from genome-wide association studies in the MR Base database. We analyzed the effects of these SNPs on the femoral neck BMD (FN-BMD), lumbar spine BMD (LS-BMD) and forearm BMD (FA-BMD), and evaluated the heterogeneities and pleiotropy of these genetic variants. We also evaluated the potential confounding factors in the association between these three neuropsychiatric diseases and the BMD level. It was found that none of these genetic variants were significantly associated with BMD or confounding factors. Using these genetic variants, we did not find statistically significant causal effects of per unit increase in the log-odds of having schizophrenia, BD or AD with FN-BMD, LS-BMD and FA-BMD changes (e.g. schizophrenia and FN-BMD, MR-Egger OR 0.9673, 95% CI 0.8382 to 1.1163, p = 0.6519). The MR results also revealed that directional pleiotropy was unlikely to bias the causality (e.g., schizophrenia and FN-BMD, intercept = 0.0023, p = 0.6887), and no evidence of heterogeneity was found between the genetic variants (e.g., schizophrenia and FN-BMD, MR-Egger Q = 46.1502, I 2 = 0.0899, p = 0.3047). Our MR study did not support causal effects of increased risk of schizophrenia, BD and AD status with BMD level.

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Bone Loss and Osteoporosis are Associated with Conversion from Mild Cognitive Impairment to Alzheimer’s Disease

Abstract: Osteoporosis was associated with an increased risk of incident AD dementia. Additionally, low BMD at baseline was associated with an increased risk of AD in both women and men.

Cited by 60 publications

References 0 publications

Amyloid β Peptide Enhances RANKL-Induced Osteoclast Activation through NF-κB, ERK, and Calcium Oscillation Signaling

Amyloid β Peptide Enhances RANKL-Induced Osteoclast Activation through NF-κB, ERK, and Calcium Oscillation Signaling

Bone Mineral Density and Cognitive Decline in Elderly Women: Results from the InCHIANTI Study

Schizophrenia, Bipolar Disorder, and Alzheimer’s Disease are not Causal Factors of Bone Mineral Density: A Mendelian Randomization Analysis

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