Re: 치매의 원인들 1-1. 철분, 셀레늄, 칼슘 부족증, 칼륨, 마그네슘 과잉

[문형철]

우리가 알고 있는 모든 미네랄(철분, 칼륨, 마그네슘, 셀레늄 등) 부족은 치매를 악화시키는 주요 원인

https://www.youtube.com/watch?v=z110iTx77HI

Neurology. 2013 Aug 6; 81(6): 528–533.

doi: 10.1212/WNL.0b013e31829e701d

PMCID: PMC3775683

PMID: 23902706

Anemia and risk of dementia in older adults

Findings from the Health ABC study

Chang Hyung Hong, MD, PhD, Cherie Falvey, MPH, Tamara B. Harris, MD, Eleanor M. Simonsick, PhD, Suzanne Satterfield, MD, DrPh, Luigi Ferrucci, MD, PhD, Andrea L. Metti, MPH, Kushang V. Patel, PhD, MPH, and Kristine Yaffe, MD

Author information Article notes Copyright and License information Disclaimer

This article has been corrected. See Neurology. 2013 September 3; 81(10): 939.

Abstract

Objective: 

To determine whether anemia is associated with incident dementia in older adults.

Methods: 

We studied 2,552 older adults (mean age 76.1 years; 38.9% black; 51.8% female) participating in the Health, Aging, and Body Composition study and free of dementia at baseline. We defined anemia using WHO criteria (hemoglobin concentration <13 g/dL for men and <12 g/dL for women). Dementia diagnosis was determined by dementia medication use, hospital records, or a change in Modified Mini-Mental State (3MS) score of more than 1.5 SD from mean. Discrete time Cox proportional hazard regression models were used to examine the hazard for developing dementia associated with anemia.

Results: 

Of 2,552 participants, 392 (15.4%) older adults had anemia at baseline. Over 11 years of follow-up, 455 (17.8%) participants developed dementia. In the unadjusted model, those with baseline anemia had an increased risk of dementia (23% vs 17%, hazard ratio = 1.64; 95% confidence interval 1.30, 2.07) compared to those without anemia. The association remained significant after adjusting for demographics, APOE ε4, baseline 3MS score, comorbidities, and renal function. Additional adjustment for other anemia measures (mean corpuscular volume, red cell distribution width), erythropoietin, and C-reactive protein did not appreciably change the results. There was no interaction by sex and race on risk of developing dementia.

2,552명의 참가자 중 392명(15.4%)의 노인이 기준 시점에 빈혈이 있었습니다. 11년 동안 추적 관찰한 결과, 455명(17.8%)의 참가자가 치매에 걸렸습니다. 조정되지 않은 모델에서 빈혈이 있는 사람은 빈혈이 없는 사람에 비해 치매 위험이 증가했습니다(23% 대 17%, 위험비 = 1.64; 95% 신뢰구간 1.30, 2.07). 이러한 연관성은 인구통계, APOE ε4, 기준 3MS 점수, 동반 질환 및 신장 기능을 조정한 후에도 여전히 유의미한 것으로 나타났습니다. 다른 빈혈 측정치(평균 적혈구 용적, 적혈구 분포 폭), 에리스로포이에틴, C-반응성 단백질을 추가로 조정해도 결과는 크게 달라지지 않았습니다. 치매 발병 위험에 대한 성별 및 인종별 상호작용은 없었습니다.

Conclusion: 

Among older adults, anemia is associated with an increased risk of developing dementia. Findings suggest that further study of anemia as a risk factor for dementia and a target for intervention for cognitive health is warranted.

노인의 경우 빈혈은 치매 발병 위험 증가와 관련이 있습니다. 연구 결과에 따르면 치매의 위험 인자이자 인지 건강을 위한 개입 대상인 빈혈에 대한 추가 연구가 필요하다는 것을 시사합니다.

REVIEW article

Front. Neurosci., 08 March 2021
Sec. Neuroenergetics, Nutrition and Brain Health
Volume 15 - 2021 | https://doi.org/10.3389/fnins.2021.646518

This article is part of the Research Topic

Selenium and Selenoproteins in Brain Development, Function, and Disease

View all 10 Articles 

Roles of Selenoproteins in Brain Function and the Potential Mechanism of Selenium in Alzheimer’s Disease

Zhong-Hao Zhang1,2 

Guo-Li Song1,2,3*

• 1Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China
• 2Shenzhen Bay Laboratory, Shenzhen, China
• 3Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China

Selenium (Se) and its compounds have been reported to have great potential in the prevention and treatment of Alzheimer’s disease (AD). However, little is known about the functional mechanism of Se in these processes, limiting its further clinical application. Se exerts its biological functions mainly through selenoproteins, which play vital roles in maintaining optimal brain function. Therefore, selenoproteins, especially brain function-associated selenoproteins, may be involved in the pathogenesis of AD. Here, we analyze the expression‎ and distribution of 25 selenoproteins in the brain and summarize the relationships between selenoproteins and brain function by reviewing recent literature and information contained in relevant databases to identify selenoproteins (GPX4, SELENOP, SELENOK, SELENOT, GPX1, SELENOM, SELENOS, and SELENOW) that are highly expressed specifically in AD-related brain regions and closely associated with brain function. Finally, the potential functions of these selenoproteins in AD are discussed, for example, the function of GPX4 in ferroptosis and the effects of the endoplasmic reticulum (ER)-resident protein SELENOK on Ca2+ homeostasis and receptor-mediated synaptic functions. This review discusses selenoproteins that are closely associated with brain function and the relevant pathways of their involvement in AD pathology to provide new directions for research on the mechanism of Se in AD.

셀레늄(Se)과 그 화합물은 알츠하이머병(AD)의 예방과 치료에 큰 잠재력을 가지고 있는 것으로 보고되었습니다. 그러나 이러한 과정에서 셀레늄의 기능적 메커니즘에 대해서는 알려진 바가 거의 없어 향후 임상 적용에 한계가 있습니다. Se는 주로 셀레노 단백질을 통해 생물학적 기능을 발휘하는데, 셀레노 단백질은 뇌 기능을 최적으로 유지하는 데 중요한 역할을 합니다. 따라서 셀레노 단백질, 특히 뇌 기능 관련 셀레노 단백질이 알츠하이머병의 발병에 관여할 수 있습니다. 여기에서는 뇌에서 25개의 셀레노단백질의 발현과 분포를 분석하고, 최근 문헌과 관련 데이터베이스에 수록된 정보를 검토하여 AD 관련 뇌 영역에서 특이적으로 많이 발현되고 뇌 기능과 밀접한 관련이 있는 셀레노단백질(GPX4, SELENOP, SELENOK, SELENOT, GPX1, SELENOM, SELENOS 및 SELENOW)을 선별하여 셀레노단백질과 뇌 기능과의 관계를 정리합니다. 마지막으로, AD에서 이러한 셀레노 단백질의 잠재적 기능, 예를 들어 페로펩토시스에서 GPX4의 기능 및 소포체(ER) 상주 단백질 SELENOK가 Ca2+ 항상성 및 수용체 매개 시냅스 기능에 미치는 영향에 대해 논의합니다. 이 리뷰에서는 뇌 기능과 밀접한 관련이 있는 셀레노 단백질과 이들이 알츠하이머병에 관여하는 관련 경로에 대해 논의하여 알츠하이머병에서 Se의 메커니즘에 대한 새로운 연구 방향을 제시합니다.

RESEARCH ARTICLE

Open Access

Dietary calcium and magnesium intake and risk for incident dementia: The Shanghai Aging Study

Jianfeng Luo, Chenbo Zhang, Qianhua Zhao, Wanqing Wu, Xiaoniu Liang, Zhenxu Xiao, James A. Mortimer, Amy R. Borenstein, Qi Dai, Ding Ding

First published: 05 December 2022

https://doi.org/10.1002/trc2.12362

Jianfeng Luo and Chenbo Zhang contributed equally to this study.

Abstract

Introduction

Calcium (Ca), magnesium (Mg), or the calcium to magnesium (Ca:Mg) ratio may affect the risk of dementia via complex mechanisms. The aim of this study was to eval‎uate the association of dietary Ca, Mg, and Ca:Mg ratio with dementia risk at the prospective phase of the Shanghai Aging Study.

Methods

We analyzed data from 1565 dementia-free participants living in an urban community who had measurements of dietary Ca and Mg intake derived from a food frequency questionnaire at baseline and incident dementia during follow-up.

Results

Over the 5-year follow-up, 162 (10.4%) participants were diagnosed with incident dementia by Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. Participants with the lowest tertile of dietary Ca (<339.1 mg/day) and Mg (<202.1 mg/day) had the highest incidence rates of dementia (3.3/100 person-years for Ca, 3.3/100 person-years for Mg) compared to those with higher Ca and Mg intake. In the subgroup with Ca:Mg ratios ≤ 1.69, Mg intake >267.5 mg/day was related to an increased risk for dementia (adjusted hazard ratio: 3.97, 95% confidence interval: 1.29–12.25).

결과

5년간의 추적 관찰 기간 동안 162명(10.4%)의 참가자가 정신 장애 진단 및 통계 편람 4판 기준에 따라 일차성 치매 진단을 받았습니다. 식이 칼슘(339.1 mg/일 미만)과 마그네슘(202.1 mg/일 미만) 섭취량이 가장 낮은 3분위수에 속하는 참가자는 칼슘과 마그네슘 섭취량이 높은 참가자에 비해 치매 발생률이 가장 높았습니다(칼슘 3.3/100인년, 마그네슘 3.3/100인년). 칼슘:마그네슘 비율이 1.69 이하인 하위 그룹에서는 하루 267.5mg/일 이상의 마그네슘 섭취가 치매 위험 증가와 관련이 있었습니다(조정된 위험비: 3.97, 95% 신뢰구간: 1.29-12.25).

Conclusions

Our findings suggest that high dietary intake of Mg is associated with an increased risk of dementia mainly among older adults with low Ca:Mg intake ratios. Proper balance of Ca to Mg in the diet may be critical to the relationship between Mg intake and risk of dementia.

연구 결과에 따르면 마그네슘을 많이 섭취하면 주로 칼슘:마그네슘 섭취 비율이 낮은 노인의 치매 위험 증가와 관련이 있는 것으로 나타났습니다. 식단에서 칼슘과 마그네슘의 적절한 균형은 마그네슘 섭취와 치매 위험 사이의 관계에 매우 중요할 수 있습니다.

Highlights

• Participants with the lowest tertile of dietary calcium (Ca) and magnesium (Mg) had the highest incidence rates of dementia.
• In the subgroup with Ca:Mg ratios ≤1.69, Mg intake >267.5 mg/day was related to an increased risk for dementia.
• Balance of Ca to Mg in diet may be critical to the relationship between Mg intake and risk of dementia.

J Alzheimers Dis

•  
•  
•  

. 2019;68(1):239-253.

 doi: 10.3233/JAD-181131.

Serum Potassium Is Associated with Cognitive Decline in Patients with Lewy Body Dementia

Lasse Melvaer Giil 1 2, Stein-Erik Hafstad Solvang 1 2, Malin Melvaer Giil 3, Kristoffer H Hellton 4, Ragnhild Eide Skogseth 1 5, Audun Osland Vik-Mo 2 6, Tibor Hortobágyi 7 8, Dag Aarsland 6 8, Jan Erik Nordrehaug 1 2

Affiliations expand

• PMID: 30775974
• DOI: 10.3233/JAD-181131

Abstract

Background: Epidemiological studies link serum potassium (K+) to cognitive performance, but whether cognitive prognosis in dementia is related to K+ levels is unknown.

Objective: To determine if K+ levels predict cognitive prognosis in dementia and if this varies according to diagnosis or neuropathological findings.

Methods: This longitudinal cohort study recruited 183 patients with mild Alzheimer's disease or Lewy body dementia (LBD). Serum K+ and eGFR were measured at baseline and medications which could affect K+ registered. The Mini-Mental State Examination (MMSE) was measured annually over 5 years, and mortality registered. Association between K+ and √(30 -MMSE) was estimated overall, and according to diagnosis (joint model). Associations between MMSE-decline and K+ were assessed in two subgroups with neuropathological examination (linear regression) or repeated measurements of K+ over 3 years (mixed model).

Results: Serum K+ at baseline was associated with more errors on MMSE over time (Estimate 0.18, p = 0.003), more so in LBD (p = 0.048). The overall association and LBD interaction were only significant in the 122 patients not using K+ relevant medication. Repeated K+ measures indicated that the association with MMSE errors over time was due to a between-person effect (p < 0.05, n = 57). The association between the annual MMSE decline was stronger in patients with autopsy confirmed LBD and more α-synuclein pathology (all: p < 0.05, n = 41).

결과: 기준 시점의 혈청 K+는 시간이 지남에 따라 MMSE에서 더 많은 오류와 관련이 있었으며(추정치 0.18, p = 0.003), LBD에서 더 많이 나타났습니다(p = 0.048). 전반적인 연관성과 LBD의 상호작용은 K+ 관련 약물을 사용하지 않는 122명의 환자에서만 유의미했습니다. K+를 반복 측정한 결과, 시간이 지남에 따라 MMSE 오류와의 연관성은 사람 간 효과로 인한 것으로 나타났습니다(p <0.05, n = 57). 부검을 통해 루게릭병이 확인되고 α-시누클레인 병리가 더 많은 환자에서 연간 MMSE 감소 사이의 연관성이 더 강했습니다(모두: p <0.05, n = 41).

Conclusion: Higher serum K+ predicts poorer cognitive prognosis in demented patients not using medications which affect K+, likely a between-person effect seen mainly in LBD( Lewy body dementia).

결론: 혈청 K+가 높을수록 K+에 영향을 미치는 약물을 사용하지 않는 치매 환자의 인지 예후가 나쁠 것으로 예측되며, 이는 주로 LBD에서 나타나는 사람 간 효과일 가능성이 높습니다.

Front Aging Neurosci. 2017; 9: 446.

Published online 2018 Jan 23. doi: 10.3389/fnagi.2017.00446

PMCID: PMC5810277

PMID: 29472855

Role of Copper in the Onset of Alzheimer’s Disease Compared to Other Metals

Soghra Bagheri,1 Rosanna Squitti,2 Thomas Haertlé,3,4,5 Mariacristina Siotto,6 and Ali A. Saboury3,*

Author information Article notes Copyright and License information Disclaimer

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by amyloid plaques in patients’ brain tissue. The plaques are mainly made of β-amyloid peptides and trace elements including Zn2+, Cu2+, and Fe2+. Some studies have shown that AD can be considered a type of metal dyshomeostasis. Among metal ions involved in plaques, numerous studies have focused on copper ions, which seem to be one of the main cationic elements in plaque formation. The involvement of copper in AD is controversial, as some studies show a copper deficiency in AD, and consequently a need to enhance copper levels, while other data point to copper overload and therefore a need to reduce copper levels. In this paper, the role of copper ions in AD and some contradictory reports are reviewed and discussed.

알츠하이머병(AD)은 신경 퇴행성 질환으로 환자의 뇌 조직에 아밀로이드 플라크가 생기는 것이 특징입니다. 플라크는 주로 β-아밀로이드 펩티드와 아연2+, 구리2+, 철2+를 포함한 미량 원소로 구성됩니다. 일부 연구에 따르면 알츠하이머병은 금속성 항상성 장애의 일종으로 간주될 수 있다고 합니다. 플라크에 관여하는 금속 이온 중 플라크 형성의 주요 양이온 원소 중 하나로 보이는 구리 이온에 대한 많은 연구가 진행되었습니다. 일부 연구에서는 알츠하이머병에 구리 결핍이 있어 구리 수치를 높여야 한다고 주장하는 반면, 다른 연구에서는 구리 과부하가 있어 구리 수치를 낮춰야 한다고 주장하기 때문에 알츠하이머병에 구리가 관여하는지는 논란의 여지가 있습니다. 이 백서에서는 알츠하이머병에서 구리 이온의 역할과 일부 상반된 보고를 검토하고 논의합니다.

Front Aging Neurosci. 2014; 6: 92.

Published online 2014 May 16. doi: 10.3389/fnagi.2014.00092

PMCID: PMC4030141

PMID: 24860501

Alzheimer’s disease causation by copper toxicity and treatment with zinc

George J. Brewer*

Author information Article notes Copyright and License information Disclaimer

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Abstract

Evidence will be presented that the Alzheimer’s disease (AD) epidemic is new, the disease being very rare in the 1900s. The incidence is increasing rapidly, but only in developed countries. We postulate that the new emerging environmental factor partially causal of the AD epidemic is ingestion of inorganic copper from drinking water and taking supplement pills, along with a high fat diet. Inorganic copper can be partially directly absorbed and elevate the serum free copper pool. The Squitti group has shown that serum free copper is elevated in AD, correlates with cognition, and predicts cognition loss. Thus, our inorganic copper hypothesis fits well with the Squitti group data. We have also shown that AD patients are zinc deficient compared to age-matched controls. Because zinc is a neuronal protective factor, we postulate that zinc deficiency may also be partially causative of AD. We carried out a small 6 month double blind study of a new zinc formulation and found that in patients age 70 and over, it protected against cognition loss. Zinc therapy also significantly reduced serum free copper in AD patients, so efficacy may come from restoring normal zinc levels, or from lowering serum free copper, or from both.

1900년대에는 매우 드물었던 알츠하이머병(AD)이 새로운 전염병이라는 증거가 제시될 예정입니다. 발병률이 빠르게 증가하고 있지만 선진국에서만 발생하고 있습니다. 새롭게 떠오르는 환경적 요인은 고지방 식단과 함께 식수 및 보충제 복용을 통한 무기구리 섭취가 알츠하이머병 발병의 일부 원인이라고 추정하고 있습니다. 무기 구리는 부분적으로 직접 흡수되어 혈청 내 구리 농도를 상승시킬 수 있습니다. 스퀴티 연구팀은 알츠하이머병에서 혈청 유리 구리가 증가하고, 인지력과 상관관계가 있으며, 인지력 손실을 예측할 수 있음을 보여주었습니다. 따라서 우리의 무기 구리 가설은 스퀴티 그룹 데이터와 잘 맞아떨어집니다. 또한 알츠하이머병 환자는 연령이 일치하는 대조군에 비해 아연이 결핍된 것으로 나타났습니다. 아연은 신경세포를 보호하는 인자이므로 아연 결핍이 부분적으로 알츠하이머병의 원인이 될 수 있다고 가정합니다. 새로운 아연 제형에 대한 6개월간의 소규모 이중 맹검 연구를 수행한 결과, 70세 이상의 환자에서 아연이 인지 상실을 예방하는 것으로 나타났습니다. 아연 요법은 또한 알츠하이머병 환자의 혈청 유리 구리를 현저히 감소시켰으므로 아연 요법의 효과는 정상 아연 수치를 회복시키거나 혈청 유리 구리를 낮추거나 둘 다에서 비롯될 수 있습니다.

Keywords: Alzheimer’s disease, inorganic copper, serum free copper, zinc deficiency, cognition

아연이 중요하다고 아연만 섭취하면 구리부족이 발생할 수 있음

혈청 zn/cu ratio가 깨지면 고혈압 등 문제가 발생함

혈청 zn/cu ration 불균형은 자폐증과도 관련이 있음.

또한 metabolic syndrome(비만)과도 연관!!

ORIGINAL ARTICLE

The plasma zinc/serum copper ratio as a biomarker in children with autism spectrum disorders

The Effect of Curcumin on Serum Copper and Zinc and Zn/Cu Ratio in Individuals with Metabolic Syndrome: A Double-Blind Clinical Trial

ABSTRACT

Metabolic syndrome is a complex disorder with high socioeconomic costs and a high global preval‎‎ence. The serum concentrations of some trace elements are higher in people with metabolic syndrome compared to normal individuals. Curcumin is derived from turmeric and has antioxidant and anti-inflammatory properties. Curcumin may therefore have a potential role in the management of cardiovascular risk. The aim of this study was to investigate the effects of curcumin on serum copper (Cu), zinc (Zn), and Zn/Cu ratio levels in patients with metabolic syndrome. A double-blind clinical trial was designed in which 120 individuals with metabolic syndrome were randomly assigned to one of three groups: curcumin 1gr/day, phospholipidated curcumin 1gr/day, or a placebo, each taken for 6 weeks. Serum copper and zinc were measured before and after intervention. At baseline, in addition to obtaining the anthropometric characteristics of participants, a fasting blood sample was taken from each participant, and the concentrations of serum Cu and Zn were measured by atomic absorption (Varian AA 240 FS model). Serum Zn concentrations rose significantly in the phospholipidated curcumin and curcumin groups, being significantly higher (p <.001) in the phospholipidated curcumin group than in the curcumin group (p <.05). Serum Zn concentration fell in the control group (p <.05). Changes in serum Zn level from baseline to the levels after six weeks' intervention were significantly different between the groups, but changes in serum Cu from between baseline until after intervention were not significantly different. The serum Zn/Cu level in phospholipidated curcumin and curcumin groups after intervention was higher than for the control group, but it was more significant in the group taking phospholipidated curcumin (p <.001). Curcumin and phospholipidated curcumin complex, given at a dose of 1 g per day for six weeks, were associated with an increase in serum zinc and consequently zinc-to-copper ratio.

대사증후군은 사회경제적 비용이 높고 전 세계적으로 유병률이 높은 복잡한 질환입니다. 대사증후군 환자는 정상인에 비해 일부 미량 원소의 혈청 농도가 더 높습니다. 커큐민은 강황에서 추출한 성분으로 항산화 및 항염증 작용을 합니다. 따라서 커큐민은 심혈관 질환 위험 관리에 잠재적인 역할을 할 수 있습니다. 이 연구의 목적은 커큐민(강황, 울금)이 대사증후군 환자의 혈청 구리(Cu), 아연(Zn) 및 Zn/Cu 비율 수치에 미치는 영향을 조사하는 것이었습니다. 대사증후군 환자 120명을 무작위로 커큐민 1gr/일, 인지질화 커큐민 1gr/일, 위약의 세 그룹 중 하나에 배정하여 각각 6주 동안 복용하게 하는 이중 맹검 임상시험을 설계했습니다. 중재 전후에 혈청 구리와 아연 수치를 측정했습니다. 연구 시작 시점에 참가자의 인체학적 특성을 파악하는 것 외에도 각 참가자로부터 공복 혈액 샘플을 채취하여 원자 흡수법(Varian AA 240 FS 모델)으로 혈청 Cu와 Zn의 농도를 측정했습니다. 혈청 아연 농도는 인지질 커큐민과 커큐민 그룹에서 유의하게 증가했으며, 인지질 커큐민 그룹이 커큐민 그룹보다 유의하게 높았습니다(p <.001)(p <.05). 대조군에서는 혈청 아연 농도가 감소했습니다(p <.05). 기준치에서 6주간의 개입 후 혈청 아연 농도의 변화는 두 그룹 간에 유의미한 차이가 있었지만, 기준치에서 개입 후까지의 혈청 구리 농도의 변화는 유의미한 차이가 없었습니다. 인지질 커큐민과 커큐민 섭취 그룹의 중재 후 혈청 Zn/Cu 수치는 대조군보다 높았지만, 인지질 커큐민을 섭취한 그룹에서 더 유의미했습니다(p <.001). 커큐민을 6주 동안 하루 1g씩 섭취한 결과, 혈청 아연과 결과적으로 아연 대 구리 비율이 증가했습니다.