The cause-effect relationship between bone loss and Alzheimer’s disease using statistical modeling

Loskutova, Natalia; Watts, Amber; Burns, Jeffrey M.

doi:10.1016/j.mehy.2018.10.024

Cited by 10 publications

(4 citation statements)

References 47 publications

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“…In addition, predisposing conditions for sarcopenia, such as insulin resistance, inflammation, and oxidative stress, are also associated with cognitive dysfunction 32 . Although some of these mechanisms remain uncertain, studies have shown the link between bone loss, sarcopenia, and cognitive impairment [33][34][35] . Therefore, regular physical activity with strength exercise is recommended to prevent cognitive impairment in the elderly population.…”

Section: Discussionmentioning

confidence: 99%

Body mass index trajectories and the risk for Alzheimer’s disease among older adults

Kang

Kim

Jang

et al. 2021

Sci Rep

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The effect of body mass index (BMI) changes and variability on the risk for Alzheimer’s disease (AD) remains unclear. We analyzed 45,076 participants, whose BMI were measured on phase 1 (2002–2003), phase 2 (2004–2005), and phase 3 (2006–2007), of the Korean National Health Insurance Service-Health Screening Cohort. We evaluated the effect of 2- and 4-year BMI changes and BMI variability on the risk of AD using Cox regression models. In men, association between 2-year BMI changes, BMI variability, and the risk of AD was not significant. Risk of AD was higher in men whose BMI had decreased 10.1–15.0% over 4 years. In women, aHRs and 95% CIs for AD were 1.14 (1.02–1.29), 1.44 (1.17–1.79), and 1.51 (1.09–2.09) when 2-year BMI loss was 5.1–10.0%, 10.1–15.0%, and > 15.0%. The HRs for AD in women significantly increased when 4-year BMI loss was > 5.0%. The aHR and 95% CI for AD was 1.31 (1.17–1.46) in the 4th quartile of average successive variability (ASV) compared with the 1st quartile of ASV in women. BMI loss over 2- and 4-year period was associated with increased risk for AD, and risk increased in women with higher BMI variability. Appropriate body weight management is recommended to prevent AD.

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Section: Discussionmentioning

confidence: 99%

Body mass index trajectories and the risk for Alzheimer’s disease among older adults

Kang

Kim

Jang

et al. 2021

Sci Rep

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“…(6) Further, retrospective studies have demonstrated that both low BMD and osteoporosis diagnosis were significant predictors of progression from mild cognitive impairment to diagnosed dementia, suggesting that bone loss may precede some of the clinical manifestations of AD. (7,8) Skeletal muscle has also been shown to be negatively impacted by AD, based on evidence that female and male patients progressively lose skeletal muscle mass and strength as disease progression worsens compared to age and sex-matched controls, suggesting that AD may be exacerbating age-related loss of strength. (9,10) However, whether bone and muscle loss are a direct result of the neurodegeneration or occurs due to a shared mechanism active in both brain and musculoskeletal tissues remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) R47H Variant Causes Distinct Age- and Sex-Dependent Musculoskeletal Alterations in Mice

Essex

Huot

Deosthale

et al. 2020

Journal of Bone and Mineral Research

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Previous studies proposed the Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), a receptor expressed in myeloid cells including microglia in brain and osteoclasts in bone, as a link between brain and bone disease. The TREM2 R47H variant is a known risk factor for Alzheimer's disease (AD), the most common form of dementia. To investigate whether altered TREM2 signaling could contribute to bone and skeletal muscle loss, independently of central nervous system defects, we used mice globally hemizygous for the TREM2 R47H variant (TREM2R47H/+), which do not exhibit AD pathology, and wild‐type (WT) littermate control mice. Dxa/Piximus showed bone loss in female TREM2R47H/+ animals between 4 and 13 months of age and reduced cancellous and cortical bone (measured by micro‐computed tomography [μCT]) at 13 months, which stalled out by 20 months of age. In addition, they exhibited decreased femoral biomechanical properties measured by three‐point bending at 13 months of age, but not at 4 or 20 months. Male TREM2R47H/+ animals had decreased trabecular bone geometry but increased ultimate strain and failure force at 20 months of age versus WT. Only male TREM2R47H/+ osteoclasts differentiated more ex vivo after 7 days with receptor activator of nuclear factor κB ligand (RANKL)/macrophage colony‐stimulating factor (M‐CSF) compared to WT littermates. Yet, estrogen receptor alpha expression was higher in female and male TREM2R47H/+ osteoclasts compared to WT mice. However, female TREM2R47H/+ osteoclasts expressed less complement 3 (C3), an estrogen responsive element, and increased protein kinase B (Akt) activity, suggesting altered estrogen signaling in TREM2R47H/+ cells. Despite lower bone volume/strength in TREM2R47H/+ mice, skeletal muscle function measured by plantar flexion and muscle contractility was increased in 13‐month‐old female mutant mice. Overall, these data demonstrate that an AD‐associated TREM2 variant can alter bone and skeletal muscle strength in a sex‐dimorphic manner independent of central neuropathology, potentially mediated through changes in osteoclastic intracellular signaling. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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“…It is reported that Aβ induces the differentiation and activation of osteoclasts, resulting in the promotion of bone destruction (Cui et al, 2011 ; Li et al, 2016 ). Indeed, neuronal dysfunction with the brain structure changes in AD has been suggested to reduce the bone mass (Loskutova et al, 2010 , 2019 ). This is supported by the high incidence of fracture in AD patients with a low bone mineral density (Friedman et al, 2010 ; Wang et al, 2014 ).…”

Section: Neuroinflammation In Admentioning

confidence: 99%

Inflammation Spreading: Negative Spiral Linking Systemic Inflammatory Disorders and Alzheimer’s Disease

2021

Front. Cell. Neurosci.

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As a physiological response to injury in the internal body organs, inflammation is responsible for removing dangerous stimuli and initiating healing. However, persistent and exaggerative chronic inflammation causes undesirable negative effects in the organs. Inflammation occurring in the brain and spinal cord is known as neuroinflammation, with microglia acting as the central cellular player. There is increasing evidence suggesting that chronic neuroinflammation is the most relevant pathological feature of Alzheimer’s disease (AD), regulating other pathological features, such as the accumulation of amyloid-β (Aβ) and hyperphosphorylation of Tau. Systemic inflammatory signals caused by systemic disorders are known to strongly influence neuroinflammation as a consequence of microglial activation, inflammatory mediator production, and the recruitment of peripheral immune cells to the brain, resulting in neuronal dysfunction. However, the neuroinflammation-accelerated neuronal dysfunction in AD also influences the functions of peripheral organs. In the present review, we highlight the link between systemic inflammatory disorders and AD, with inflammation serving as the common explosion. We discuss the molecular mechanisms that govern the crosstalk between systemic inflammation and neuroinflammation. In our view, inflammation spreading indicates a negative spiral between systemic diseases and AD. Therefore, “dampening inflammation” through the inhibition of cathepsin (Cat)B or CatS may be a novel therapeutic approach for delaying the onset of and enacting early intervention for AD.

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The cause-effect relationship between bone loss and Alzheimer’s disease using statistical modeling

Cited by 10 publications

References 47 publications

Body mass index trajectories and the risk for Alzheimer’s disease among older adults

Body mass index trajectories and the risk for Alzheimer’s disease among older adults

Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) R47H Variant Causes Distinct Age- and Sex-Dependent Musculoskeletal Alterations in Mice

Inflammation Spreading: Negative Spiral Linking Systemic Inflammatory Disorders and Alzheimer’s Disease

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