Disturbance of cerebral function in people exposed to drinking water contaminated with aluminium sulphate: retrospective study of the Camelford water incidentBMJ 1999; 319 doi: https://doi.org/10.1136/bmj.319.7213.807 (Published 25 September 1999) Cite this as: BMJ 1999;319:807
- Disturbance of cerebral function in people exposed to drinking water contaminated with aluminium sulphate: retrospective study of the Camelford water incident
Paul Altmann, John Cunningham, Usha Dhanesha, Margaret Ballard, James Thompson, Frank MarshOxford Kidney Unit, Oxford Radcliffe Hospital, Oxford OX3 7LJ
Paul Altmann,The Royal London Hospital, Whitechapel, London E1 1BB
consultant nephrologist and physician
Frank Marsh,Paybody Eye Unit, Coventry and Warwickshire Hospital, Coventry CV1 4FH
consultant nephrologist and physician
Usha Dhanesha,Priory Hospital, Roehampton, London SW15 5JJ
Margaret Ballard,University College London Medical School, London W1N 8AA
consultant clinical psychologist
senior lecturer in psychology
Correspondence to: Paul Altmann
Objective To establish whether people exposed to drinking water contaminated with 20 tonnes of aluminium sulphate in the Camelford area of Cornwall in the south west of England in July 1988 had suffered organic brain damage as opposed to psychological trauma only.
Design Retrospective study of affected people.
Participants 55 affected people and 15 siblings nearest in age to one of the group but who had not been exposed to the contaminated water were studied.
Main outcome measures Various clinical and psychological tests to detail medical condition and anxiety levels in affected people. Assessment of premorbid IQ (pFSIQ) with the national adult reading test, a computerised battery of psychomotor testing, and measurement of the difference in latencies between the flash-pattern visual evoked potentials in all participants.
Results The mean (SE) pFSIQ was above average at 114.4 (1.1). The most sensitive of the psychomotor tests for organic brain disease was the symbol digit coding (SDC) test (normal score 100, abnormal <85). Participants performed less well on this test (54.5 (6.0)) than expected from their pFSIQ (P<0.0001) and a little less poorly on the averaged less discriminating tests within the battery (86.1 (2.5), P<0.0001). In a comparison with the 15 sibling pairs (affected people’s age 41.0 (3.3) years v sibling age of 42.7 (3.1) years, P=0.36), the exposed people had similar pFSIQ (114.7 (2.1)) to their siblings (116.3 (2.1), P=0.59) but performed badly on the symbol digit coding test (51.8 (16.6) v 87.5 (4.9) for siblings, P=0.03). The flash-pattern differences in exposed people were greater than in 42 unrelated control subjects of similar age (27.33 (1.64) ms v 18.57 (1.47) ms, P=0.0002). The 15 unexposed siblings had significantly better flash-pattern differences than their affected siblings (13.4 (2.4) ms v 29.6 (2.9) ms, P=0.0002). No effect of anxiety could be shown on these measurements from the analysis of the anxiety scores of exposed people.
Conclusion People who were exposed to the contaminated water at Camelford suffered considerable damage to cerebral function, which was not related to anxiety. Follow up studies would be required to determine the longer term prognosis for affected individuals.
On 6 July 1988, 20 tonnes of aluminium sulphate were accidentally emptied into the treated water reservoir at Lowermoor Water Treatment Works, which supplied 20<thin>000 people in the Camelford area of Cornwall. Within a few days local residents and holidaymakers started reporting rashes, gastrointestinal disturbances, and mouth ulcers, although there was much delay in informing the public of the accident. The water was heavily contaminated with aluminium (up to 620 mg/l; the European Union guideline for tap water is less than 0.2 mg/l), copper (up to 22.5 mg/l), and lead (up to 0.46 mg/l), and the pH was very low. (1) In the following weeks and months, exposed individuals complained of pain in joints and muscles, malaise, fatigue, and impairment of concentration and memory. (1) A number of veterinary reports emerged, most notably that of fish dying from aluminium poisoning in the local rivers after their contamination. (2) Two years later about 400 people were suffering from symptoms that they attributed to the incident. The standardised hospital discharge ratios in the 5 years after the incident were far greater than for other areas of Cornwall, although no single diagnosis prevailed. (3)
Considerable debate ensued as to whether the persisting complaints of memory impairment and difficulty in concentration were due to anxiety or to toxic cerebral damage. Little systematic study of the clinical effects of the incident, however, was carried out soon after the event. Several early reports of high blood aluminium concentrations have been discounted (4) because little effort was made to avoid sample contamination (a great problem when measuring concentrations of this element in any water or biological sample), and increased lead accumulation had also been described. (5) One study reported psychological changes in 10 affected people. (6) In two of these people, bone biopsies done at 6-7 months had shown presence of aluminium, which had disappeared at a second biopsy 19 months after the accident. Eight other patients who underwent biopsy 12-17 months after the incident showed no stainable aluminium. (6)
In 1991, some 3 years after the incident, we were given the opportunity to investigate 55 adults who had been exposed to the polluted water in Camelford and were considering litigation on account of its alleged effects. At the outset we considered it unlikely that we would be able to show objective abnormalities, firstly because of the time interval since exposure and, secondly, because of difficulties in assessing a self selected group, especially with subjective end points in neuropsychological tests. (7)(8)
We had previously investigated many aspects of low level aluminium exposure in patients with end stage renal disease on haemodialysis. In 1972 a fatal encephalopathy of chronic haemodialysis patients was described, quite distinct from previous reports, arising after 3-7 years' treatment. Four years later the same group suggested that this was caused by deposition of aluminium in the brain. (9) Subsequent studies have confirmed this and also the role of the element in causing bone disease (10) as well as anaemia. (11) The initial epidemic of aluminium related diseases was soon found to be related to contamination of the water used to prepare the dialysate, (12) and later the importance of gastrointestinal absorption and subsequent retention was also established. (13) (14) (15) (16) (17) (18) (19) (20) (21) Subsequent lowering of aluminium exposure has led to the disappearance of the florid forms of aluminium induced disease, except for sporadic cases.
After the largely successful efforts to reduce aluminium exposure in dialysis patients, levels of aluminium accumulation have dropped considerably. As there was still potential for toxicity from even modest aluminium accumulation, however, we studied such haemodialysis patients (with serum concentrations averaging 55 µg/l), who had no clinical evidence of cerebral impairment. They had significant inhibition of tetrahydrobiopterin metabolism due to an inhibitory effect of aluminium on dihydropteridine reductase. (22) More importantly, we showed considerable abnormalities in psychomotor function, (23)(24) with much more pronounced impairment in the symbol digit coding test than in other psychomotor tests. We also investigated visual evoked potentials (specifically the difference in latency between the flash-pattern evoked potentials), as abnormalities had been found in patients with Alzheimer's disease, (25) a condition that has similar neuropathological features, (26) and found changes that, although not as great as in Alzheimer's disease, were qualitatively similar. (23)(24) Moreover, the degree of abnormality found in our patients correlated with the severity of the psychomotor defect as measured by the symbol digit coding test, suggesting that the psychomotor defect was a valid observation even though it was only semiobjective. Finally, when the patients were analysed according to the presence or absence of aluminium deposition at the mineralisation front of the bone, symbol digit coding results were significantly worse in the former group than in the group with no aluminium deposition. (24) This suggested that a major factor in the cerebral impairment observed in these patients was indeed related to their aluminium exposure.
Therefore, in an attempt to establish whether or not the exposed people from Camelford had suffered organic damage, we undertook studies using identical techniques to the ones used in our previous studies so that comparisons might be drawn. For reasons beyond our control the studies were performed 3 years after the incident and, as they were done in the context of litigation, could not then be published until this was resolved. Studies of bone were done with dual energy x ray absorptiometry and biochemical markers, but these proved negative and are therefore not reported here for brevity.
Participants and methods
Fifty five adults claiming to have suffered cerebral damage in the Camelford incident were studied between February and August 1991. Clinical assessments (history and examination), psychological tests of anxiety, psychomotor function, and measurements of visual evoked potentials were done by separate individuals without prior knowledge of the results of any of the other tests. In addition, we studied all available siblings, each one nearest in age to one of the above group and who had not lived in the area of water contamination since before the incident. Only 15 such siblings were available, and they underwent a subset of the investigations (the National adult reading test, Bexley Maudsley automated psychological screening test, and visual evoked potential studies as described below).
Visual analogue scales for medical and self assessment
Visual analogue scales were used to score clinicians' impressions of each patient’s general appearance and affect, as well as the subjects' own views on their symptoms. The patients were given two identical visual analogue questionnaires to fill in separately, one concerning their symptoms 1 month after the incident (as perceived in retrospect) and one similarly relating to their symptoms at the time of investigation. This allowed us to assess whether they perceived symptoms to be improving or deteriorating. Symptoms studied were disturbances in appetite, sleep, taste, vision, physical energy, memory, concentration, joint pain, hearing, mood, rapid decision making, self esteem, general health, and sense of smell.
National adult reading test¾ Word reading ability is well correlated with the overall IQ in the normal population, and in patients with dementia (unless very advanced) it is maintained at its premorbid level. Therefore, the participants’ premorbid IQ was assessed with the first edition of the National adult reading test (NART), (27) the results of which may be converted to the equivalent Wechsler adult intelligence scale (WAIS) full scale IQ score (pFSIQ). This assessment was performed to establish any discrepancy between current performance and the premorbid pFSIQ derived from the national adult reading test. This tests their ability to pronounce correctly 50 words, printed in order of increasing difficulty, the number of errors being recorded. The test does not depend on the subject's comprehension of the words. The test has a much narrower range of IQ than conventional IQ testing—the maximum and minimum attainable IQ is 128 and 72 points, respectively (100 being regarded as normal). We used the first edition rather than the second edition of this test as the latter was not available at the start of these studies and we wanted to maintain consistency throughout.
Bexley Maudsley automated psychological screening¾Certain tests of cerebral function are known to be quite sensitive to even minor organic brain disease. Test results in an individual, although monitored by an observer, may depend on the subject's self motivated response to the set task. In an attempt to reduce possible interference from patient motivated voluntary bias, we used a computerised battery of tests. The second test within the battery, the symbol digit coding test, is based on the Wechsler adult intelligence scale digit symbol subtest, one of the more sensitive tests for organic brain disease. (28) Symbol digit tests have been used extensively in the assessment of cognitive impairment associated with drugs, toxins, and other conditions such as hypoglycaemia or Alzheimer's disease.
We therefore used the Bexley Maudsley automated psychological screening (BMAPS) battery of tests, (29) performed in a standard fashion with a computer. Nevertheless, bias related to the participant can alter the way in which he or she performs, even when the test is conducted in the carefully controlled manner used in this study. The package runs on an Apple II computer with a specially adapted keyboard.
The computer reports raw data as well as standardised scores around a mean of 100. In all the tests the results are regarded as abnormally low if the standardised score (calculated from normative data by the authors of the software package) is less than 85 (corresponding to 1 SD below the mean), (29) as in other neuropsychological tests. In all the tests the results quoted below are the standardised scores.
All the tests were carried out as outlined in the Bexley Maudsley automated psychological screening manual. The symbol digit coding test is a nine choice reaction time test in which the responses are the digits 1-9, represented on the special keyboard by nine numbered red buttons. The keyboard is in the form of an overlay that covers the computer's keyboard. Each digit is paired with a unique geometric shape which is continuously displayed on screen, and below these shapes appear serially in random order for 60 trials. Speed of accurate (that is, only correct) response is recorded automatically and performance is assessed according to the overall results, as well as being broken down into separate measures of the first, second, and third 20 trials. The results depend on the participants’ ability to sustain attention, motor coordination to respond quickly and accurately, visual scanning, and a memory component for the association between symbols and corresponding digits. When applied to patients known to show psychomotor slowing (by other psychological assessment techniques)—such as detoxified alcoholics—this test proved extremely sensitive (response times 2.23 (0.68) seconds v 1.76 (0.25) seconds in controls, P<0.001). (29) The test also discriminated monozygotic twins discordant for alcohol consumption. (30)
The other tests were the visual spatial ability (test No 1), whichrequires participants to make repeated right or left discriminations on a mannequin shown on the screen and rotated about two axes;visual perceptual analysis (test No 3), in which subjects are shown series of groups of three geometric block patterns on screen, one of which is, to a varying extent, different from the others and must be differentiated; verbal recognition memory (test No 4), in which subjects are required to memorise 36 nouns presented serially and subsequently recognise which of these is present in groups of three nouns presented sequentially; visual spatial recognition memory (test No 5), in which subjects are shown a block pattern on screen to memorise in 3 seconds, after which they have to recognise which one of three possible alternatives is identical to the original, after a varying interval. In all the tests, the computer records speed of response and accuracy.
In previous studies, as well as these, participants invariably commented that of all the tests within the battery the visual perceptual and spatial recognition tests were the most daunting, and so we would expect underperformance in these rather than in the symbol digit coding test if bias motivated by litigation had been operating.
Anxiety was assessed by using the symptom check list 90, which is a multidimensional self report symptom inventory designed to measure symptomatic psychological stress. (31) The results are derived from indices giving the mean level of distress for 90 symptoms, the mean intensity for the number of symptoms reported, and the total number of reported symptoms.
Visual evoked potentials
The flash-pattern stimulated visual evoked potentials were measured by standard techniques. (25) Such measurements are extremely objective and not subject to the individual's wish to underperform if the test is carefully administered. David and Wessely suggested possible areas of "bias and deliberate deception" that might have affected our results, (32) after the submission of a summary of some preliminary results to the second Clayton inquiry. We were careful to avoid these influences, however, by making sure that the patients cooperated fully and were calm before the measurements were made. The major positive P2 component of the flash and P100 component of the pattern visual evoked potentials were recorded from occipital electrodes O2 and O1, referred to central electrodes C4 and C3, respectively (according to the 10-20 system nomenclature). Fifty responses were averaged on a Cadwell 5200A averager. The flash stimulus was produced twice per second by a Grass PS22 stroboscope 33 cm from the participant. The pattern reversal stimulus, produced by a Cadwell Stimulator, was at twice per second.
There are little normative data available for the difference between the flash-pattern stimulated visual evoked potentials. In a group of 42 control subjects studied separately (mean (SE) age 44 (2) years) the mean flash-pattern difference was 18.57 (1.47) ms. Age seems to influence this with the flash-pattern difference increasing with age (r=0.35, P=0.02).
We performed duplicate measurements using 50 and 100 stimuli in a random sample of the participants studied: 23 participants for flash evoked potentials and 28 participants for pattern evoked potentials. The results were statistically indistinguishable on a paired t test (50 v 100 flash: 120.9 (2.5) v 119.8 (2.6) ms; 50 v 100 pattern: 93.6 (0.9) v 93.5 (1.0) ms) and confirmed by using the Bland and Altman method (33) for comparison of methods: for flash the mean difference was 1.0 ms (95% confidence interval –0.2 to 2.2); for pattern the mean difference was 0.1 ms (–1.2 to 1.4). This shows that the method was reliable and that there was no added benefit from using 100 stimuli.
Aluminium estimations were performed by using a well established on with a Varian AA1275 atomic absorption spectrophotometer and GTA95 electrothermal atomiser fitted with an autosampler. (34) Pyrolytically coated graphite tubes were used. We have used these methods extensively. (15) The normal range of serum aluminium concentration is less than 10 µg/l. Tap water aluminium concentration varies greatly from region to region but should comply with the European Union guideline of less than 200 µg/l. Much less is known about normal urinary aluminium excretion, but in our own studies the excretion in normal volunteers was less than 25 µg/day.
Haematology and biochemistry
Standard clinical laboratory techniques were used to measure full blood count, erythrocyte sedimentation rate, liver biochemical profile, skeletal biochemical profile, and concentrations of urea, creatinine, electrolytes, glucose, cholesterol, and triglycerides. These tests were chosen to screen for any underlying, hitherto unknown, diseases causing malaise through anaemia, chronic inflammation, renal impairment, hepatic impairment, metabolic bone disorders, diabetes, and lipid abnormalities.
Results are expressed as means (SE) unless otherwise stated. Differences between normally distributed group data were analysed by the unpaired or paired Student t test as well as one factor analysis of variance and non-parametric tests when appropriate. Correlations between different variables were performed by least squares linear regression analysis. In addition, analysis of covariance was used when age was a covariate. Two tail probability (P) values of <0.05 were regarded as significant. Some of the hypotheses examined were of course one tail in implication. All analyses were performed on an Apple Macintosh computer with the StatView statistics software package. (35)
All of the 55 adult participants (30 women and 25 men aged 15-70 years (mean (SD) 41.8 (2.1)) complained of short term memory loss and impaired concentration, and all but 11 complained of joint pains. The overall severity of the symptoms as scored by the physician assessing the subjects (blinded from the subjects' own scores) was 5.9 (0.2) (1 being normal, 10 severely affected). None of the patients had any relevant or family history, and in particular we were not made aware of any Alzheimer's disease in their families. None was on any form of psychotropic drug or consuming excess alcohol.
The participants’ self assessment visual analogue scores for memory, concentration, and overall symptoms compared with what they regarded as their own baseline are shown in table 1. Both memory and concentration ability seemed to deteriorate slightly according to the participants’ assessments, but there was little change in their overall scores, which remained negative—that is, impairment compared with the subjects' perception of their previous state.
Table 1Summary of participants' visual analogue scores for symptoms one month after incident compared with before incident (scored -5 for major deterioration, 0 for no change, and +5 for major improvement) and at time of studies ("now") compared with before incident scored as at one month questionnaire. Negative scores bad; positive scores good
One month after
The visual analogue scores for general appearance and for general affect (1 being worst, 10 best) made by the examining clinicians were 8.7 (0.1) and 7.6 (0.2), respectively, and the two measures were significantly correlated (r=0.5, P=0.0004). Both these measures were significantly related to the participants’ overall self assessed visual analogue scores (r=0.5, P=0.0001; r=0.6, P=0.0001, respectively). The results of the rest of the physical examination, in particular the neurological system, were normal in all the participants. Visual acuity, checked before the visual evoked potentials were performed, was normal in all paticipants who completed the studies.
The mean pFSIQ as assessed by the National adult reading test was above average at 114.4 (1.1). All participants used English as their native language, were educated in the United Kingdom, and were known to be free of any physical disability that could interfere with their ability to operate the special keyboard. The standardised results of the Bexley Maudsley screening are shown in figure 1. The pattern observed is more important here than the absolute scores. The group seemed to perform less well on the symbol digit coding test than the others, and it is this test that is thought most sensitive to organic brain dysfunction.
(F1) Fig 1 Summary of BMAPS test results. In all tests results are regarded as abnormal (shaded area) if standardised score is less than 85 (corresponding to 1 SD). Box plots show 10th, 25th, 50th, 75th, 90th centiles
Analysis of variance confirmed that the results of the symbol digit coding test were significantly lower than any of the other Bexley Maudsley screening test results (P=0.0001). We would not have expected the discrepancy between the participants’ pFSIQ assessed by the reading test and the mean scores of Bexley Maudsley screening tests 1,3,4,5 even though the means of these tests fell within the normal (as stated in the Bexley Maudsley manual) range (114.4 (1.1) v 86.1(2.5), P<0.0001) or the even greater discrepancy relating to the symbol digit coding test (114.4 (1.1) v 54.5 (6.0), P<0.0001). Thus the subjects performed below the level expected for their estimated premorbid IQ.
Visual evoked potentials
The mean flash-pattern difference of the Camelford subjects (age 41.8 (2.1) years) was 27.33 (1.64) ms. In a group of 42 similar aged, unrelated and unmatched control subjects (age 44.1 (2.3) years) the flash-pattern difference was 18.57 (1.47) ms. The difference (8.75 (2.27) ms) between the two groups was significant (P=0.0002). While the 2.2 year difference in age between the groups was not significant, analysis of covariance (with case and age variables entered into the model) showed that the difference in flash-pattern differences with age adjustment was a little greater at 9.45 (2.06) ms (P<0.0001).
As in our previous study there was a relation between the flash-pattern difference and the symbol digit coding response times (r=0.38, P=0.004). The association was not strong but seemed to be curvilinear, which is to be expected from what is known about the parameters in question. Symbol digit coding responses have, like all measurements of biological performance, an effective maximum speed in that performance cannot improve infinitely; and a similar situation exists with visual evoked potentials. We hypothesise that subjects with flash-pattern differences within the normal range will be likely to have symbol digit coding response times that lie within a normal range and there need not be any relation between the two parameters observed, while as results become more abnormal the line (representing their relation) moves upward in a curvilinear manner. There were no such relations between any of the other Bexley Maudsley screening tests and the flash-pattern difference.
Effects of anxiety
Thirty six of the 55 participants studied were available for anxiety testing, which was carried out at a different location and time. The mean SCL90 score was 1.0 (0.1), indicating relatively low levels of anxiety. Those below the median anxiety score (0.8) did not differ from those above it with regard to their symbol digit coding scores or flash-pattern differences (table 2).
Table 2Effects of anxiety as assessed by SCL90 on psychomotor testing (symbol digit coding test (SDC)) and visual evoked potentials
SDC test (s)
Flash-pattern difference (ms)
Sibling control study
The 15 Camelford participants who had eligible siblings were of similar age (41.0 (3.3) years) to the whole group of 55 (41.8 (2.1) years) and to their sibling pairs (42.7 (3.1) years, mean difference –1.7, P=0.36) and of similar pFSIQ as assessed by the National adult reading test (114.7 (2.1)) to the group of 55 (114.4 (1.1)). Figure 2 shows the results for the siblings and the results of the pFSIQ, Bexley Maudsley screening tests (standardised scores), and visual evoked potential flash-pattern differences. The results indicate that, although the sibling pairs were indistinguishable (paired Student t test) both in terms of age and pFSIQ, both the symbol digit coding tests and the flash-pattern differences were significantly worse (by paired Student t test) in the Camelford participants than their unexposed siblings.
(F2) Fig 2 Sibling control studies: summary of premorbid IQ (pFSIQ) assessed by National adult reading test, Bexley Maudsley automated screening test scores, and visual evoked potentials (top panel) in 15 participants and their siblings (P values refer to paired Students t test). Box plots as in figure 1
Haematology and biochemistry
Apart from few and minor abnormalities there were no significant findings. Serum aluminium concentrations were all well within the normal range, as was urinary aluminium excretion except for a minor increase in one participant. In several cases current tap water aluminium concentrations were high in specimens (containers supplied by us) forwarded by the subjects.
In experimental animals, dialysis patients, patients treated with parenteral nutrition fluids containing aluminium, and industrially exposed subjects, repeated exposure to aluminium has been shown to induce one or more of brain disease, bone disease, and anaemia. We have previously reported abnormalities of psychomotor function (symbol digit coding test) and visual evoked potentials in dialysis patients exposed chronically to low concentrations of aluminium. (23)(24)
Analyses of our group data from people exposed to aluminium and other contaminants in the Camelford incident indicate several apparent abnormalities. Their assessments of symptoms correlated with the doctors' crude but independent assessments of their general appearance and mental affect. This may add weight to the validity of the patients' complaints but throws no light on the causation.
On psychomotor testing, 42 out of 55 of the Camelford participants performed poorly, and all of these, except two, performed worse on the symbol digit coding test than on the other tests. As a group their performance was clearly worse than that predicted from their estimated premorbid IQ. Visual evoked potential tests, the results of which depend on objective measurements and are not influenced by subject or observer bias, were significantly different for the group when compared with the normal unrelated and unmatched controls.
There was a correlation between the results of the flash-pattern difference and the results of the symbol digit coding test. This suggests that the objective disturbance in signal transmission from the eye to the optic cortex, as measured by the visual evoked potential, was associated with functional changes in psychomotor performance, as measured by the symbol digit coding test. This is similar to our previous studies in dialysis patients (23)(24) and further strengthens the validity of the symbol digit coding tests in the Camelford participants. In addition, any suggestion that anxiety may have led to these abnormalities (4)(36) is rebutted effectively by the analysis of the participants grouped according to anxiety scores.
The sibling control study adds weight to the suggestion that the Camelford participants had organic brain dysfunction at the time of the study. The siblings had come from outside the area of pollution, thereby providing both out of area and genetic (phenotypic) control data. Not only were there significant differences between the siblings' symbol digit coding results and those of the Camelford participants but also quite striking differences between their flash-pattern differences (the latter measure being resistant to bias motivated by litigation in favour of their affected sibling).
The pattern of abnormalities is similar to the findings we have previously described in aluminium loaded but asymptomatic dialysis patients: normal premorbid IQ with discrepant and notably impaired symbol digit coding tests compared with other Bexley Maudsley screening tests; and prolonged flash-pattern visual evoked potential differences. These studies suggest that the participants responded to our tests, as a group, in a manner compatible with organic brain disease and in a way similar to that exhibited by dialysis patients exposed to higher than normal amounts of aluminium. As far as we are aware, there are no other known causes for the effects that we have described in the Camelford participants and so aluminium poisoning must be considered a possibility, although other contaminants may have contributed.
Effects of aluminium exposure
Aluminium poisoning has been reported sporadically since the early part of this century after acute or chronic industrial exposure, (37) (38) (39) (40) although its neurotoxicity has interested scientists since early 19th century reports referred to by von Döllken. (41) Neurodegenerative changes in animal studies proved similar to those in Alzheimer's disease, (42) and, in 1973, Crapper et al found that aluminium concentrations, approaching those found in experimental neurofibrillar degeneration induced by aluminium, were present in certain regions of the brains of patients dying with the disease. (43) Later studies supported these findings, although controversy has persisted as it has been suggested that this might be a phenomenon of ageing or an epiphenomenon. However, aluminium accumulation in the neurones containing neurofibrillary tangles (44) and increased concentrations of aluminium in serum and other tissues in patients with Alzheimer's disease (45) (46) (47) (48) (49) together with some epidemiological evidence (50) (51) (52) (53) have raised concerns about the role of aluminium in this condition, (54) (55) (56) although genetic factors predominate. (57) (58) (59) In addition, metabolic interactions occur between iron and aluminium, and evidence that disturbances in iron metabolism may be involved in the pathogenesis of Alzheimer's disease is emerging with a reduced affinity of transferrin for gallium (used as a chemical analogue of aluminium), possibly due to abnormally high transferrin-iron saturation. (60) This could account for increased absorption of aluminium from the gut in patients with Alzheimer's disease, a phenomenon that has since been documented. (47)(61) (62) (63) It is unlikely that we will ever know how much aluminium was absorbed by the people in Camelford. That some aluminium was absorbed is in little doubt, and, given the water pH and likely chemical species of aluminium salts that would have been present after the contamination, its bioavailability may well have been far greater than previously estimated.
A review of the few psychological studies on affected people from the Camelford incident concluded that the most likely explanation of the findings was that "the perception of normal and benign somatic symptoms (physical and mental) by both subjects and health professionals was heightened and subsequently attributed to an external, physical cause, such as poisoning". (32) The evidence from our study suggests that this is not the case. Although there are shortcomings in the "design" of the study, for reasons beyond our control, it seems highly probable that these people had been subjected to an environmental insult causing the effects we have reported. Through lack of funding important wider case-control studies could not be done. It has been suggested that there are some 400 other individuals who have not been studied (8) but are known to have similar symptoms. Little is known about the prognosis for affected individuals (no follow up studies have been arranged), although there is anecdotal evidence that many of the people originally affected still have symptoms 11 years later. As the effects of massive aluminium contamination of water for human consumption have not previously been described or investigated, it is possible that this neurotoxin may have been one of the causative factors, although conclusive evidence for this is unlikely ever to be forthcoming as far as the Camelford incident is concerned.
Contributors: PA (as senior registrar in renal and general medicine at the Royal London Hospital initially) designed and coordinated the studies, supervised the subjects' questionnaires, performed the NART and BMAPS psychomotor testing, drew the blood samples, carried out the data collation and analysis, and wrote the paper. FM participated in the instigation of the project and, with JC, in the study design, writing of the paper, and performed the clinical examinations. UD contributed to the study design and writing of the paper and performed all the visual evoked potential tests. MB and JT contributed to the study design and writing of the paper and performed the anxiety scoring. PA and FM are guarantors.
Funding: The studies were commissioned by lawyers acting on behalf of the plaintiffs, and funded through Legal Aid.
Competing interests: None declared.
(Accepted 9 June 1999)
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