An Updated Mendelian Randomization Analysis of the Association Between Serum Calcium Levels and the Risk of Alzheimer’s Disease

Shi, Yuchen; Liu, Ruifei; Guo, Ying; Li, Qiwei; Zhou, Haichun; Shao-lei, YU; Liang, Hua; Li, Zeguang

doi:10.3389/fgene.2021.731391

Cited by 8 publications

(7 citation statements)

References 35 publications

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“…Calcium has been found to have a protective role in AD development, while oversupplementation of calcium has also been shown to increase the risk of AD. Extracellular accumulation of amyloid plaques and intracellular neurofibrillary tangles in the brain is present in AD, and calcium dysregulation has been shown to induce synaptic deficits and promote the accumulation of the plaques and neurofibrillary tangles [ 32 , 33 , 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

Association between the Composition of Drinking Water and Cognitive Function in the Elderly: A Systematic Review

Wasick,

Kim

2024

IJERPH

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The prevalence of dementia increases with nearly 10 million new cases each year, with Alzheimer’s disease contributing to 60–70% of cases. Environmental factors such as drinking water have been evaluated to determine if a relationship exists between trace elements in drinking water and the risk of developing cognitive disorders in the elderly. The purpose of the current systematic review was to evaluate an association between the composition of drinking water and cognitive function in the elderly. In accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines, a literature search was conducted using PubMed and CINAHL databases. A total of 10 studies were included in the current systematic review. Aluminum is the most commonly evaluated trace element in studies (n = 8), followed by silica (n = 5), calcium (n = 4), and fluoride (n = 4). Aluminum exposure showed an increased risk of cognitive decline in four studies, with no association reported in the other studies. Higher silica and pH levels were shown to be protective against a decline in cognitive function. A similar protective effect of calcium was found in two studies. Future research should measure multiple trace mineral levels in all water sources to evaluate the impact on cognitive function.

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Section: Discussionmentioning

confidence: 99%

Association between the Composition of Drinking Water and Cognitive Function in the Elderly: A Systematic Review

Wasick,

Kim

2024

IJERPH

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“…He and others selected 8 genome-wide significant and independent serum calcium genetic variants as the instrumental variables, and found that per 1 standard deviation increase in serum calcium level (about 0.5 mg/dL) contribute to a reduced risk of AD using IVW (OR = 0.57) ( He et al, 2020 ). Shi and others further conducted an updated MR analysis in both discovery stage and replication stage ( Shi et al, 2021 ). In the discovery stage, 14 independent but not genome-wide significant serum calcium genetic variants were selected as the instrumental variables ( Shi et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…Shi and others further conducted an updated MR analysis in both discovery stage and replication stage ( Shi et al, 2021 ). In the discovery stage, 14 independent but not genome-wide significant serum calcium genetic variants were selected as the instrumental variables ( Shi et al, 2021 ). In the replication stage, 166 genome-wide significant and independent serum calcium genetic variants were selected as the instrumental variables ( Shi et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…In the discovery stage, 14 independent but not genome-wide significant serum calcium genetic variants were selected as the instrumental variables ( Shi et al, 2021 ). In the replication stage, 166 genome-wide significant and independent serum calcium genetic variants were selected as the instrumental variables ( Shi et al, 2021 ). They identified the reduced trend of risk of AD as the serum calcium level increased ( Shi et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

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Identification of heel bone mineral density as a risk factor of Alzheimer’s disease by analyzing large-scale genome-wide association studies datasets

Gao,

Pan,

Fan

et al. 2023

Front. Cell Dev. Biol.

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Introduction: Both low bone mineral density (BMD) and Alzheimer’s disease (AD) commonly co_occur in the older adult. Until now, the association between AD and BMD has been widely reported by observational studies. However, Mendelian randomization (MR) studies did not support the causal association between BMD and AD. We think that the lack of significant causal association between AD and BMD identified by recent MR studies may be caused by small number of potential instrumental variables.Methods: We conduct a MR study to evaluate the causal effect of heel BMD on the risk of AD using 1,362 genome-wide significant and independent (p < 5.00E-08) heel BMD genetic variants as the potential instrumental variables, which are identified by a large-scale genome wide association study (GWAS) of heel BMD in 394,929 UK Biobank individuals. Using these 1,362 genome-wide significant and independent heel BMD genetic variants, we extracted their corresponding AD GWAS summary results in IGAP AD GWAS dataset (n = 63,926) and FinnGen AD GWAS dataset (n = 377,277). Five methods including inverse-variance weighted meta-analysis (IVW), weighted median, MR-Egger, MR-PRESSO, and MRlap were selected to perform the MR analysis. 951 of these 1,362 genetic variants are available in AD GWAS dataset.Results: We observed statistically significant causal effect of heel BMD on the risk of AD using IVW in IGAP AD GWAS dataset (OR = 1.048, 95%CI: 1.002–1.095, p = 0.04) and FinnGen AD GWAS dataset (OR = 1.053, 95% CI:1.011–1.098, p = 0.011). Importantly, meta-analysis of IVW estimates from IGAP and FinnGen further supported the causal effect of heel BMD on the risk of AD (OR = 1.051, 95% CI: 1.02–1.083, p = 0.0013).Discussion: Collectively, our current MR study supports heel BMD to be a risk factor of AD by analyzing the large-scale heel BMD and AD GWAS datasets. The potential mechanisms underlying the association between heel BMD and AD should be further evaluated in future.

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“…Ca homeostasis disruption promotes Aβ and tau pathology [ 239 ]. However, human studies have produced contradictory results, with both decreased [ 240 , 241 ] and increased Ca [ 186 , 242 ] being risk factors. In recent MR studies, higher Ca levels were shown to reduce the risk of AD [ 241 , 243 ], or no association between Ca levels and AD risk has been observed [ 218 , 220 ] ( Table 3 ).…”

Section: Essential Metals In Alzheimer’s Diseasementioning

confidence: 99%

Metals in Alzheimer’s Disease

et al. 2023

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The role of metals in the pathogenesis of Alzheimer’s disease (AD) is still debated. Although previous research has linked changes in essential metal homeostasis and exposure to environmental heavy metals to the pathogenesis of AD, more research is needed to determine the relationship between metals and AD. In this review, we included human studies that (1) compared the metal concentrations between AD patients and healthy controls, (2) correlated concentrations of AD cerebrospinal fluid (CSF) biomarkers with metal concentrations, and (3) used Mendelian randomization (MR) to assess the potential metal contributions to AD risk. Although many studies have examined various metals in dementia patients, understanding the dynamics of metals in these patients remains difficult due to considerable inconsistencies among the results of individual studies. The most consistent findings were for Zn and Cu, with most studies observing a decrease in Zn levels and an increase in Cu levels in AD patients. However, several studies found no such relation. Because few studies have compared metal levels with biomarker levels in the CSF of AD patients, more research of this type is required. Given that MR is revolutionizing epidemiologic research, additional MR studies that include participants from diverse ethnic backgrounds to assess the causal relationship between metals and AD risk are critical.

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An Updated Mendelian Randomization Analysis of the Association Between Serum Calcium Levels and the Risk of Alzheimer’s Disease

Cited by 8 publications

References 35 publications

Association between the Composition of Drinking Water and Cognitive Function in the Elderly: A Systematic Review

Association between the Composition of Drinking Water and Cognitive Function in the Elderly: A Systematic Review

Identification of heel bone mineral density as a risk factor of Alzheimer’s disease by analyzing large-scale genome-wide association studies datasets

Metals in Alzheimer’s Disease

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