Aluminium and Alzheimer's disease: An epidemiological approach

Epidemiological methods have an important role in the investigation of the postulated connection between exposure to aluminium and the development of Alzheimer's disease. We have examined the usefulness of existing data on prevalence and mortality as a resource for studying variations in the rate of the disease with time and geography. Unfortunately, methodological differences between prevalence surveys and errors and biases in mortality data are large. No reliable conclusions can be drawn from these data about geographical differences in rates of dementia in England and Wales nor about time trends in the disease.Aluminium salts are widely used in the UK for the treatment of drinking water. Residual aluminium concentrations vary more than ten fold between different parts of the country. We have estimated diagnostic rates of pre-senile Alzheimer's disease in seven geographical areas and examined the correlation between rates of Alzheimer's disease and water aluminium concentration.     

Aluminium and Alzheimer's disease: is there a causal connection?

At the present time there seems to be sufficient evidence to conclude that aluminium may, at least under some circumstances, be neurotoxic. Furthermore, several studies have found increased amounts of aluminium in specific brain structures of people who have died with Alzheimer's disease. From the available evidence it is not possible, however, to draw any firm conclusions regarding the possible role of aluminium in the aetiology or pathogenesis of Alzheimer's disease.Even though there is some evidence from ecological studies that exposure to aluminium at least from drinking water may be causally linked to the development of Alzheimer's disease, it is still entirely possible that the accumulation of aluminium in the brains of people with this disorder is a secondary phenomenon. There is a lack of data relating individual exposure to aluminium with subsequent risk of developing the disease.A case-control study currently being carried out in Norway will seek to collect individual exposure data with particular emphasis on aluminium exposure from drinking water sources. The design of this study is presented.     

Review of epidemiologic studies of aluminium and neurological disorders

The epidemiological study of neurological disorders is just beginning and should he continued because of the potential public health impact of these diseases on society. The most important contribution of epidemiological research is the identification of risk factors, and specific disease entities, such as Alzheimer's disease, should be studied.Ecological analysis of geographical data have associated a small increase in mortality from Alzheimer's disease and dementia with the aluminium content of drinking water. These results must necessarily be interpreted with caution because serious errors may result from inferences based on ecological analysis,e.g. the ecologic fallacy.Potential risk factors for Alzheimer's disease have been studied in case-comparison epidemiology studies conducted in Italy, Massachusetts, Colorado, Minnesota and North Carolina, but only two studies have considered aluminium exposure, through the use of antacids. Although no increased risk was found to be associated with aluminium exposure, only a small number of individuals in the studies reported antacid use, and the studies had an extremely limited statistical power to detect an association.Additional analytical epidemiology studies, either cohort or case-comparison, are required to better describe the possible relationship between aluminium and Alzheimer's disease. These studies should be designed according to well-established epidemiological principles, be conducted with no selection bias and minimum observation bias, consider potential confounding and modifying factors, and have sufficient statistical power to enable detection of low relative risks.     

Aluminium and the pathogenesis of senile plaques: studies in Alzheimer's disease and chronic renal failure

Aluminium and silicon are co-localised as aluminosilicate at the centre of the senile plaque core. These focal deposits appear to be a consistent and specific feature associated with A4 amyloid fibrils in the plaque core and are not associated with other types of amyloidosis. A pathogenic role for AI and Si is suggested by the finding of A4 amyloid deposits, immature senile plaques and an abnormal content and distribution of these elements in the brains of patients (<55 years) with chronic renal failure. Evidence suggests that AI uptake and distribution within the brain is mediated by transferrin. The distribution of transferrin receptors may account for the vulnerability of regions such as the hippocampus and cortex which are selectively involved in Alzheimer's disease.     

Microprobe studies of aluminum accumulation in association with human central nervous system disease

The neurofibrillary tangle, first described by Alzheimer in 1907, along with the senile plaque, represent the two principle neuropathologic lesions identified in the brains of patients with Alzheimer's disease. Aluminum salts inoculated into the central nervous system of certain experimental animals induces neurofilamentous lesions which are similar, but not identical to the neurofibrillary tangles seen in Alzheimer's disease. Although some reports provide evidence of increased amounts of aluminum in the brains of Alzheimer's disease victims, such bulk analysis studies have been difficult to replicate. Over the past several years we have approached this problem using a variety of microprobe techniques in order to determine the distribution of trace elements within individual nerve cells.Using scanning electron microscopy with X-ray spectrometry, we have identified accumulations of aluminum in the neurofibrillary tangle-bearing neurons of cases of Alzheimer's disease. Similar accumulations have been found in the brains of the indigenous natives of Guam who suffer from parkinsonism with dementia and from amyotrophic lateral sclerosis. Recent studies using laser microprobe mass analysis suggest that the predominance of aluminum identified within the parikaryon of neurofibrillary tangle-bearing neurons is located within the neurofibrillary tangle itself. Although this ongoing research still cannot ascribe a causal role for aluminum in the etiology and/or pathogenesis of the neurofibrillary tangle, the data suggest that certain environmental factors related to trace elemental constituents may play an important role in the formation of this type of cellular pathology.     

Spatial distribution of calcium in food, water and soil and its possible influence on rickets disease in Northern Nigeria

Since the 1990s, children of the Gbagyi tribe in Northern Nigeria have been suffering severe rickets with an incidence of up to 40% in the children's generation. The disease seems to be prevalent in an area of approximately 100 km(2) south-east of Kaduna. According to broad medical studies in that area, there is no evidence for a genetic disposition but for a nutritional cause of the disease. A lack of calcium was found in blood and was calculated to originate from diet. We therefore checked parent material, soil, maize cobs (Zea mays) and drinking water for their specific Ca contents from a region with rickets problem (study area A) and compared the results to Ca amounts in similar samples from a region where rickets is unknown among the Gbagyi population (study area B). It thereby became apparent that there are no differences in mineralogical composition of the parent material between the study areas, but that Ca contents in soil, maize cobs and drinking water are 47.6%, 26.6%, respectively, 79.1% lower in study area A compared to study area B. This result suggests that there may indeed be a nutritionally and/or environmentally influence on rickets disease. Nevertheless, further research on this topic is required.     

Assessing the health risks of aluminum

Aluminum is a ubiquitous substance with over 4,000 uses. Aluminum, as aluminum sulfate, is commonly used in the United States as a coagulant in the treatment of drinking water. For many years aluminum was not considered to be toxic to humans. However, reports associating aluminum with several skeletal and neurological disorders in humans suggest that exposure to aluminum may pose a health hazard. In 1983 the US Environmental Protection Agency (EPA) announced plans to regulate a number of substances, including aluminum, in drinking water. Aluminum was considered because of its occurrence and apparent toxicity. Upon further evaluation of the health effects data the EPA proposed not to regulate aluminum as a result of the uncertainty of the toxicity of ingested aluminum. Putative causal associations between aluminum exposure and neurological disorders such as Alzheimer's disease have yet to be substantiated. Although several issues regarding the toxicity of ingested aluminum are unresolved, aluminum has been specified in the 1986 Amendments to the Safe Drinking Water Act, as one of 83 substances in drinking water to be regulated by 1989. Additional data are needed before the potential risk of aluminum can be assessed; therefore the EPA has deferred possible regulation until 1991.     

Aluminium metabolism in chronic renat failure: Environmental influences and regional differences in Norway

Many aspects of Al metabolism in chronic renal failure are poorly understood. A longitudinal study of serum Al concentrations in predialysis patients and healthy control subjects revealed very high values during the autumn of 1984 and 1985. Renal Al clearance was low during the autumnal spike in serum Al but increased substantially when the serum Al concentration declined. A second study confirmed that by using citric acid as a chelator, the gastrointestinal absorption of Al from Al(OH)₃ may be considerably augmented as reflected by increases in both serum Al concentrations and renal Al clearance. The individual differences in Al absorption in this study were large.The first study suggests the existence of an unidentified environmental factor, possibly water borne, with profound effects on Al absorption and excretion. The citric acid/Al(OH)₃ experiment suggests that the existence of such a factor is likely. The implications of these results are not known.A histomorphometric study of bone biopsies from 138 hemodialysis and 66 predialysis patients without clinical evidence of Al related disease, revealed Al deposits after staining with aurin tricarboxylic acid in 78% of the biopsies from the former and 24% of the latter patients. Serum Al concentrations did not differ between predialysis and hemodialysis patients with Al positive biopsies. Stratification of the hemodialysis patients, who came from all parts of Norway, revealed that patients living in regions with slightly Al contaminated drinking water (Al <30 g/L) had lower serum Al concentrations than patients from regions with highly contaminated water (Al >100 g/L). The prevalence of Al-positive biopsies was the same in both regions. Patients with Al-positive biopsies did not differ in serum Al level from those with Al-negative biopsies within the same region. Predialysis patients with Al-positive biopsies had significantly higher serum Al levels than predialysis patients with Al negative biopsies.Stainable Al deposits are commonly found in the bone of patients with chronic renal failure. Cross-sectionally obtained serum Al concentrations do not reflect the prevalence of stainable bone Al in renal patients but are related to the degree of Al contamination of water of the region.     

Correlation of cadmium and aluminum in blood samples of kidney disorder patients with drinking water and tobacco smoking: related health risk

The combined exposure to aluminum (Al) and cadmium (Cd) causes more pronounced adverse health effects on humans. The kidneys are the main organs affected by internal exposure to Cd and Al via food and non-food items. The objective of present study was to measure the Al and Cd concentrations in cigarettes tobacco (branded and non-branded) and drinking water (domestic treated, ground and lake water) samples in southern part of Pakistan, to assess the risk due to ingestion of water and inhalation of cigarettes smoke containing high concentrations of both elements. The study population (kidney disorder and healthy) divided into two group based on consuming lake and ground water, while smoking non-branded cigarette as exposed, while drinking domestic treated water and smoking branded cigarette as non-exposed. Electrothermal atomic absorption spectrometry was used to determined Cd and Al concentrations in tobacco, drinking water and blood samples. The resulted data indicated that the levels of Al and Cd in lake and underground water were higher than the permissible limit in drinking water recommended by the World Health Organization. The biochemical parameters of exposed and referent patients, especially urinary N-acetyl-h-glucosaminidase, were used as a biomarkers of kidney disorder. Exposed kidney disorder patients have higher levels of Cd and Al than the exposed referents subjects, while difference was significant when compared to resulted data of non-exposed patients and referents (p = 0.01–0.001). The pearson correlation showed positive correlation between both toxic element concentrations in water, cigarettes versus blood samples of exposed subjects (r = 0.20–0.67 and 0.71–0.82), while lower values were observed for non-exposed subjects (r = 0.123–0.423 and 0.331–0.425), respectively.

     

Models of environmentally induced neurological disease: epidemiology and etiology of amyotrophic lateral sclerosis and parkinsonism-dementia in the Western Pacific

Amyotrophic lateral sclerosis (ALS) on Guam previously attained incidence rates 50 to 100 times that of the continental United States and Europe and accounted for one in five deaths among Chamorros over age 25. A second neurological disorder in high incidence, parkinsonism-dementia (PD), and the early appearance in those populations of neurofibrillary tangles such as are seen in Alzheimer's disease and normal ageing have also been noted. Incidence and mortality rates of both diseases have declined dramatically during the past 30 years, and today, the risk of developing either disease among Guamanian Chamorros is only several times higher than in non-Guamanian populations. The decline is most likely a consequence of increased acculturation over the past three decades, with a concomitant decrease in isolation, changes in dietary habits and local water supplies, and much less dependence on locally grown foodstuffs. Similar declines are evident in the remaining two Pacific foci of high- incidence ALS, namely the Kii Peninsula focus in Japan and southern West New Guinea where western contact and introduction of new foodstuffs have occurred.The accumulating epidemiological, genetic and environmental evidence, as well as the development of new and promising experimental animal models, support the hypothesis that a basic metabolic defect, provoked by chronic nutritional deficiencies of calcium, lead to increased intestinal absorption of toxic metals and the co-deposition of calcium, aluminium and silicon in neurons of patients with ALS and PD. This elemental deposition is thought to result in aberrant microtubule assembly and/or abnormal post-translational modification of the amyloid precursor protein leading to widespread formation of neurofibrillary tangles, the hallmark pathological features in these disorders. The naturalistic paradigms of these foci in the Western Pacific have provided insights to understanding not only ALS and PD but other neurological disorders, such as classical ALS, Parkinson's disease, Alzheimer's disease and early neuronal ageing.     

Disease and cell death in white syndrome of Acroporid corals on the Great Barrier Reef

White syndromes (WS) are among the most prevalent coral diseases, and are responsible for reef demise on the Great Barrier Reef. The disease manifests as a clear differentiation between tissue and exposed skeleton and results in rapid tissue loss. Fluorescence in situ hybridisation (FISH) was used in conjunction with histology and transmission electron microscopy (TEM) to investigate bacterial communities and cell death associated with WS. No evidence of bacterial communities or microbial association (using six bacterial probes, TEM and histopathology) was evident within the lesion or adjacent tissues, despite the presence of dense possible secondary invaders in the exposed skeletal regions. Despite widespread reference to necrosis in coral disease literature, there was no evidence of necrosis in any WS lesion or the adjacent tissues in this study. However, in situ end labelling, light microscopy and TEM of WS and healthy coral tissue sections showed evidence of extensive programmed cell death (PCD) exclusively in WS. This study provides the first evidence of intrinsic or PCD as a primary mechanism of cell death in WS, and may provide some explanation for the failure to isolate pathogens from over 80% of identified coral diseases, many of which show similar lesion patterns and WS characteristics.     

Distribution and Risk Assessment of Fluoride in Drinking Water in the West Plain Region of Jilin Province, China

The west plain region of Jilin province of northeast China is one of the typical endemic fluorosis areas caused by drinking water for many years. Investigations of hydrogeological and ecoenvironmental conditions as well as endemic fluorosis were conducted in 1998. Results show that the ground water, especially, the water in the unconfined aquifer is the main source of drinking water for local residents. The fluoride concentration in groundwater in the unconfined aquifers is higher than that in the confined aquifer in the west plain of Jilin province. The fluoride concentration in the unconfined aquifer can be used to classify the plain into fluoride deficient area, optimum area and excess area, which trend from west to east. High fluoride (>1.0 mg L(-1)) in drinking water resulted in dental and skeletal fluorosis in local residents (children and pregnant women). There exists a positive correlation between fluoride concentration in the drinking water and the morbidities of endemic fluorosis disease (r1 = 0.781, r2 = 0.872). Health risks associated with fluoride concentration in drinking water are assessed. It has been determined that fluoride concentration in excess of 1.0 mg L(-1) exposes residents to high health risks based on risk identification. The study area is classified into five health risk classes as shown in Figure 4. The risk indexes of this area more than 1.0 are accounted for 68% of the total west plain region.     

Chronic kidney disease in two coastal districts of Andhra Pradesh, India: role of drinking water

Chronic kidney disease (CKD) has been reported in a few coastal regions of Srikakulam district and Chimakurthy mandal (~30–40 km away from the coast) in the Prakasham district of Andhra Pradesh, India. Some medical experts and the local population have apprehensions that the drinking water is the sole reason for this disease in these areas. As the source of drinking water for these two regions is only groundwater, major ions and trace elements were measured on waters from different sources to identify the causative element(s), if any. Comparison of hydrochemical data of both the areas indicates that groundwater in Srikakulam coastal region is less mineralized than that of the Prakasham region, which may be due to geological, hydrological and climatic reasons. However, the concentrations of various inorganic chemicals are within the permissible limits of drinking water. Hence, for the inorganic chemicals to cause ill health, including CKD, is unlikely or is ruled out in the study areas.     

Characterization of dissolved organic carbon and Humic substances in the well water of the Blackfoot disease area in Taiwan

Since the early 1960s, many investigators have reported that blackfoot disease, a peripheral vascular disease, observed in southwestern Taiwan is due to drinking the higher arsenic concentration in well water. However, recent studies indicated that the relationship with blackfoot disease is not only with arsenic but also humic substances. This paper presents some results concerning the characterization (such as fluorescence, elemental composition, molecular weight and carbon distribution) of humic substances isolated from the Fuhsing well water of the blackfoot disease area. For comparison, the dissolved organic carbon (DOC) and humic substances in the normal well water from Chiuying and the Nanwan coastal water were also analyzed. In general, in the well water of the blackfoot disease area, extremely high concentrations of DOC (18.5mg/L) and fulvic acid (7.54mg/L) with high fluorescence intensity (59.1, equivalent to 0.0282uM quinine sulfate solution) and high percentages (over 50%) of low molecular weights of less than 1,000 were obtained compared with those of normal waters. C‐13 Nuclear magnetic resonance spectroscopy showed a high content (37.2%) of aromatic carbon. These higher concentrations of DOC and fulvic acid with the higher content of aromatic carbon in well water might be one of the key factors causing the blackfoot disease in Taiwan.     

大骨节病区硒元素分布的调控机理研究——以四川省阿坝地区为例

分析了阿坝地区的岩石、饮用水、农作物及其根系土中硒的不同存在形态的分布,并结合生物有效性深入研究了硒元素分布与大骨节病病因的联系和调控机理.阿坝地区的环境(岩石、土壤、水)中全硒浓度、农作物中硒的富集系数和水溶性硒占总硒的含量均远低于非病区;硒在氧化还原条件(Eh平均值143.27 mV)和酸碱度(pH 6.51—8.48)的控制下主要以亚硒酸态的稳定形式存在.元素铝、铁等的富集可能会促进硒的沉淀和络合,制约硒的生物有效利用率,进而导致人体硒摄入不足,最终激发人类微小病毒B19(HPV B19)的毒性,引发大骨节病.通过采取土壤增施硒肥、改善水质、改变膳食结构等方法可以有效地提高环境中硒的水平及其生物有效性,以缓解大骨节病的病情及发病率.     

Hydrogeochemical study of the drinking water from the Khaybar village,SW Saudi Arabia

This paper presents the results of chemical analysis of four drinking waters from the Khaybar village, SW Saudi Arabia. Four main water‐wells in the Khaybar village were investigated. The Khaybar ground water is clear without odour but its taste differs according to the amount of total dissolved solids (T.D.S.). The pH values of such water are slightly alkaline. T.D.S. of the Khaybar water is higher than the Saudi highest desired level, but it is generally within the Saudi maximum permissible level.

Good drinking quality water can be found in Al Mazaab and Al Tilah water‐wells in the Khaybar village. The other two water‐wells can be used for irrigation purposes only.

The geological features of the Khaybar area suggest a meteoric origin for the Khaybar ground water which has been stored in the fractured metamorphic and igneous rocks and in alluvial deposits.     

Chronic kidney disease of unknown etiology and the effect of multiple-ion interactions

High incidence of chronic kidney disease of unknown etiology (CKDU) prevalent in many countries (e.g., Sri Lanka, equatorial America) is reviewed in the context of recent experimental work and using our understanding of the hydration of ions and proteins. Qualitative considerations based on Hofmeister-type action of these ions, as well as quantitative electrochemical models for the Gibbs free energy change for ionpair formation, are used to explain why (1) fluoride and water hardness due to magnesium ions (but not due to calcium ions) and similarly (2) cadmium ions in the presence of suitable pairing ions can be expected to be more nephrotoxic, while arsenite in the presence of fluoride and hardness may be expected to be less nephrotoxic. No synergy of arsenic with calcium hardness is found. The analysis is applied to a variety of ionic species that may be found in typical water sources to predict their likely combined electrochemical action. These results clarify the origins of chronic kidney disease that has reached epidemic proportions in the North Central Province of Sri Lanka as being most likely due to the joint presence of fluoride and magnesium ions in drinking water. The conclusion is further strengthened by a study of the dietary load of Cd and other toxins in the affected regions and in the healthy regions where the dietary toxin loads and lifestyles are similar, and found to be safe especially when the mitigating effects of micronutrient ionic forms of Zn, Se, as well as corrections for bioavailability are taken into account. The resulting etiological picture is consistent with the views of most workers in the field who have suspected that fluoride and other ions found in the hard water stagnant in shallow household wells were the major causative factors of the disease. Similar incidence of CKDu found in other hot tropical climates is likely to have similar origins.     

Arsenic in Drinking Water and Bladder Cancer: Comparison between Studies Based on Cancer Registry and Death Certificates

Associations between arsenic in drinking water and bladder cancer in an area along the southwest coast of Taiwan have been documented for decades. Several ecologic studies were conducted to assess the dose-response relationships. Some of them used the National Cancer Registry Program to identify cancer cases, and some used death certificates. Whereas the cancer registry collects information on all patients no matter if they died of bladder cancer or not, the case ascertainment might be incomplete due to the fact that reporting of cases is not mandatory. Reporting of death, on the other hand, is strictly enforced by law, but patients who did not die of bladder cancer might not be identified. In order to assess the problems with both approaches, we conducted a study using both case identification mechanisms. A total of 243 townships with measurements of arsenic in drinking water were included in the analysis of cancer registry data, and death certificates were collected from 10 of those townships. In both analyses, the same measurements of arsenic made by the mercuric bromide stain method were adopted. Due to limitation of the method, all levels below 0.04mg L^–1 were combined as a single exposure category. The results were very much alike; both approaches detected statistically significant associations between high arsenic levels in drinking water (above 0.64mg L^–1) and occurrence of bladder cancer but did not find such associations for arsenic exposures at lower levels.     

Association between skin lesion and arsenic concentration in hair by mixed bivariate model in chronic arsenic exposure

Skin lesion is one of the important health hazards caused by high intake of arsenic through drinking water and diet, and the other hazards include several types of cancers (viz. skin, lung and urinary bladder), ischemic heart disease, hypertension, etc. Two most important biomarkers to measure arsenic intake in a human body are arsenic concentration in urine and hair. The primary interest of this paper is the association between skin lesion and arsenic concentration in hair for participants with chronic arsenic exposure from West Bengal, India, using bivariate regression model based on copula function. The result showed participants with high arsenic concentration in hair had higher incidence of developing skin lesion. Arsenic concentration in hair was significantly higher for the participants with an arsenic concentration in water?>?10 mg/L.     

Dental fluorosis associated with drinking water from hot springs in Choma district in southern province,Zambia

This study was conducted to investigate the high incidence of mottled teeth among residents of an area with hot springs in the Choma District of the Southern Province of Zambia. A survey involving 128 pupils was conducted at a Basic School to collect data on pupil’s backgrounds and their main sources of drinking water between birth and age 7. A dental specialist examined the pupils’ teeth and samples of drinking water were collected from locations where the majority of the pupils lived. It was analysed for fluorides and other drinking water quality parameters. Results of the survey showed a highly significant (P < 0.001) association between pupils’ main sources of drinking water between birth and age 7 and the incidence of discoloured teeth. All (100%) pupils who drank water from hot springs before age 7 had moderate to severe fluorosis, while the majority (96.7%) of the pupils who drank water from other sources had no dental fluorosis. Fluoride concentrations ranged from 5.95 to 10.09 mg/l in water from hot springs, and from 0.03 to 0.6 mg/l in water from other sources. Fluoride levels in water from hot spring water samples exceeded the 1.5 mg/l WHO guideline value for drinking water, while those in water from other sources were significantly (P < 0.05) lower than this. We conclude that the high prevalence of mottled teeth among residents of the study area is a case of endemic dental fluorosis associated with drinking water from hot springs containing high concentrations of fluoride.