Association of Serum Manganese Levels with  Alzheimer’s Disease and Mild Cognitive Impairment:  A Systematic Review and Meta‐Analysis

Du, Ke; Liu, Mingyan; Pan, Yanzhu; Zhong, Xin; Wei, Minjie

doi:10.3390/nu9030231

Cited by 50 publications

(31 citation statements)

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“…Similarly, manganese level analysis in the recent studies revealed controverted results. The most recent meta-analysis on the matter, Du et al [ 30 ], reports controversial dynamics of manganese levels presenting several studies which show a significant decrease of this parameter in demented patients' sera, while in other studies, no difference or significant increase were obtained. We also found statistical correlations between MMSE scores versus manganese levels and ADAS-COG versus magnesium and manganese levels (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Preliminary Data on the Interaction between Some Biometals and Oxidative Stress Status in Mild Cognitive Impairment and Alzheimer’s Disease Patients

Balmuș

Strungaru

Ciobîcă

et al. 2017

Oxidative Medicine and Cellular Longevity

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Increased interest regarding the biometal mechanisms of action and the pathways in which they have regulatory roles was lately observed. Particularly, it was shown that biometal homeostasis dysregulation may lead to neurodegeneration including Alzheimer's disease, Parkinson disease, or prion protein disease, since important molecular signaling mechanisms in brain functions implicate both oxidative stress and redox active biometals. Oxidative stress could be a result of a breakdown in metal-ion homeostasis which leads to abnormal metal protein chelation. In our previous work, we reported a strong correlation between Alzheimer's disease and oxidative stress. Consequently, the aim of the present work was to evaluate some of the biometals' levels (magnesium, manganese, and iron), the specific activity of some antioxidant enzymes (superoxide dismutase and glutathione peroxidase), and a common lipid peroxidation marker (malondialdehyde concentration), in mild cognitive impairment (n = 15) and Alzheimer's disease (n = 15) patients, compared to age-matched healthy subjects (n = 15). We found increased lipid peroxidation effects, low antioxidant defense, low magnesium and iron concentrations, and high manganese levels in mild cognitive impairment and Alzheimer's disease patients, in a gradual manner. These data could be relevant for future association studies regarding the prediction of Alzheimer's disease development risk or circling through stages by analyzing both active redox metals, oxidative stress markers, and the correlations in between.

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Section: Discussionmentioning

confidence: 99%

Preliminary Data on the Interaction between Some Biometals and Oxidative Stress Status in Mild Cognitive Impairment and Alzheimer’s Disease Patients

Balmuș

Strungaru

Ciobîcă

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…Studies are consistent in reporting an increased deposition of manganese in the brain of patients suffering from hepatic encephalopathy (HE) [63,64,65,66,67,68,69]. This is depicted in the form of hyperintense MRI signals, in particular in the region of the brain called the globus pallidus [70].…”

Section: Manganese In Alcoholismmentioning

confidence: 96%

“…Compromised liver function does not allow for proper detoxification, and one of the results is a free passage of neurotoxins entering the brain. As increased amounts of manganese are deposited in the brain, and in particular in the astrocytes, this causes Alzheimer type II changes, as well as selective neuronal loss in the basal ganglia [66,67,68]. Similar effects are seen in ammonia deposition in the brain [69].…”

Section: Manganese In Alcoholismmentioning

confidence: 99%

Serum iron, Magnesium, Copper, and Manganese Levels in Alcoholism: A Systematic Review

et al. 2019

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The aim of this paper was to review recent literature (from 2000 onwards) and summarize the newest findings on fluctuations in the concentration of some essential macro- and microelements in those patients with a history of chronic alcohol abuse. The focus was mainly on four elements which the authors found of particular interest: Iron, magnesium, copper, and manganese. After independently reviewing over 50 articles, the results were consistent with regard to iron and magnesium. On the other hand, data were limited, and in some cases contradictory, as far as copper and manganese were concerned. Iron overload and magnesium deficiency are two common results of an excessive and prolonged consumption of alcohol. An increase in the levels of iron can be seen both in the serum and within the cells, hepatocytes in particular. This is due to a number of factors: Increased ferritin levels, lower hepcidin levels, as well as some fluctuations in the concentration of the TfR receptor for transferrin, among others. Hypomagnesemia is universally observed among those suffering from alcoholism. Again, the causes for this are numerous and include malnutrition, drug abuse, respiratory alkalosis, and gastrointestinal problems, apart from the direct influence of excessive alcohol intake. Unfortunately, studies regarding the levels of both copper and manganese in the case of (alcoholic) liver disease are scarce and often contradictory. Still, the authors have attempted to summarize and give a thorough insight into the literature available, bearing in mind the difficulties involved in the studies. Frequent comorbidities and mutual relationships between the elements in question are just some of the complications in the study of this topic.

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“…Regarding the individual metals, more recent studies of aluminium report significantly increased mortality from AD among miners exposed to aluminium-rich dust [147] suggesting that some aspects of this hypothesis might be worth revisiting. In addition to aluminium [195], zinc [127,192], mercury [140], copper [86,144], manganese [45,186], cadmium [136,142], and magnesium [188] have all been suggested as risk factors for AD. Many of these metals have been shown to interact directly with APP metabolism or with APOE [140].…”

Section: Metalsmentioning

confidence: 99%

Risk factors for Alzheimer’s disease

Armstrong¹

2019

372

238

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Early reviews identified over 20 risk factors associated with Alzheimer's disease (AD) including age, familial inheritance, exposure to aluminium, traumatic brain injury (TBI), and associated co-morbidities such as vascular disease and infection. In the light of recent evidence, this review reconsiders these risk factors, identifies those currently regarded as important, and discusses various hypotheses to explain how they may cause AD. Rare forms of early-onset familial AD (EO-FAD) are strongly linked to causal gene mutations, viz. mutations in amyloid precursor protein (APP) and presenilin (PSEN1/2) genes. By contrast, late-onset sporadic AD (LO-SAD) is a multifactorial disorder in which age-related changes, genetic risk factors, such as allelic variation in apolipoprotein E (Apo E) and many other genes, vascular disease, TBI and risk factors associated with diet, the immune system, mitochondrial function, metal exposure, and infection are all implicated. These risk factors may act collectively to cause AD pathology: 1) by promoting the liberation of oxygen free radicals with age, 2) via environmental stress acting on regulatory genes early and later in life ('dual hit' hypothesis), or 3) by increasing the cumulative 'allostatic load' on the body over a lifetime. As a consequence, lifestyle changes which reduce the impact of these factors may be necessary to lower the risk of AD.

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Association of Serum Manganese Levels with Alzheimer’s Disease and Mild Cognitive Impairment: A Systematic Review and Meta‐Analysis

Cited by 50 publications

References 50 publications

Preliminary Data on the Interaction between Some Biometals and Oxidative Stress Status in Mild Cognitive Impairment and Alzheimer’s Disease Patients

Preliminary Data on the Interaction between Some Biometals and Oxidative Stress Status in Mild Cognitive Impairment and Alzheimer’s Disease Patients

Serum iron, Magnesium, Copper, and Manganese Levels in Alcoholism: A Systematic Review

Risk factors for Alzheimer’s disease

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