Alzheimer's disease, dental amalgam and mercury.

Journal of the American Dental Association 1999

February 130, 191-199.

¹Saxe SR, ¹Wekstein MW, ²Kryscio RJ, ¹Henry RG, ³Cornett CR, ⁴Snowdon DA, ¹Grant FT, ⁵Schmitt FA, ⁶Donegan SJ, ⁷Wekstein DR, ³Ehmann WD, and ⁷Markesbery WR

¹College of Dentistry, ²Dept. of Statistics,   ³Dept. of Chemistry, ⁴Dept. of Preventive Medicine, ⁵Dept. of Neurology, ⁷Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY

⁶Marquette University School of Dentistry, Milwaukee, WI

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10036842&dopt=Abstract

Background. Mercury, or Hg is a neurotoxin that has been speculated to play a role in the pathogenesis of Alzheimer's disease, or AD.  Dental amalgam releases low levels of Hg vapor and is a potential source of Hg for a large segment of the adult population.

Methods. The authors studied 68 subjects with AD and 33 control subjects without AD to determine Hg levels in multiple brain regions at autopsy and to ascertain the subject's dental amalgam status and history.  The subjects were from central Kentucky and Elm Grove, Wis.  The authors conducted dental amalgam assessments during the lives of the majority of subjects  and in some subjects at the time of autopsy only.  The authors also determined three dental amalgam index scores - Event (placement, repair or removal of amalgam), Location and Time In Mouth - in addition to the numbers of and surface area of occlusal amalgam and restorations.   The authors determined Hg levels in multiple brain regions and performed full neuropathologic evaluations to confirm the normal status of the brain or the presence of AD.

Results. The authors found no significant association of AD with the number, surface area or history of having dental amalgam restorations.   They also found no statistically significant differences in brain Hg level between subjects with AD and control subjects.

Conclusions. Hg in dental amalgam restorations does not appear to be a neurotoxic factor in pathogenesis of AD.  The authors found that brain Hg levels are not associated with dental amalgam, either from existing amalgam restorations or according to subjects' dental amalgam restoration history.

Clinical Implications. Dental amalgam restorations, regardless of number, occlusal surface area or time, do not relate to brain Hg levels.

To see a few of the press releases that accompanied the publication of this study please see Press Releases.

Contrast this study published in the Journal of the American Dental Association with previous studies by the research scientists in this group when dentists were not involved

Brain trace elements in Alzheimer's disease.

Neurotoxicology 1986 Spring;7(1):195-206

Ehmann WD, Markesbery WR, Alauddin M, Hossain TI, Brubaker EH

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3714121&dopt=Abstract

    Instrumental neutron activation analysis has been used to determine the concentrations of 16 elements in selected brain regions and separated gray- and white-matter specimens from histologically verified Alzheimer's disease (AD) and age-matched control patients. Significantly different (p less than 0.05) mean concentrations of Br, Cl, Cs, Hg, N, Na, P, and Rb were observed in AD bulk brain samples compared to controls, while no significant differences were observed for Ag, Co, Cr, Fe, K, Sb, Sc, and Se. The differences that are most persistent and largest in magnitude for the pooled bulk samples, males and females, left and right hemispheres, and separated gray and white matter are the elevation of Br and Hg and the depletion of Rb in AD compared to controls. Significant interelement correlations for the latter elements in both AD and control brains are also documented. Based on these studies, the possibility of an etiological role for trace elements in AD clearly deserves further investigation.  

Regional brain trace-element studies in Alzheimer's disease.

Neurotoxicology 1988 Spring;9(1):1-7

Thompson CM, Markesbery WR, Ehmann WD, Mao YX, Vance DE

Department of Chemistry, University of Kentucky, Lexington 40506.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3393299&dopt=Abstract

    Alzheimer's disease (AD) brain trace-element imbalances in the amygdala, hippocampus and nucleus basalis of Meynert (nbM) are found in most cases to be consistent with those previously reported in samples derived principally from AD cerebral cortex (Ehmann et al., 1986). The elevation of mercury in AD nbM, as compared to age-matched controls, is the largest trace-element imbalance observed to date in AD brain. In addition to the general confirmation of imbalances for Cs, Hg, N, Na, P, and Rb noted previously in cerebral cortex samples, imbalances for Fe, K, Sc, and Zn were observed in two regions and one region also exhibited imbalances for both Co and Se. Persistent imbalances for the univalent cations Na, K, Rb and Cs support arguments for a membrane abnormality in AD. The data presented here also provide the first comprehensive simultaneous multi-element determinations in both control and AD nbM.

Trace element imbalances in hair and nails of Alzheimer's disease patients.

Neurotoxicology 1988 Summer;9(2):197-208

Vance DE, Ehmann WD, Markesbery WR

Department of Chemistry, University of Kentucky, Lexington 40506.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3205430&dopt=Abstract

    The concentrations of 17 elements in the hair and nails of 180 Alzheimer's disease (AD) and control subjects have been determined by instrumental neutron activation analysis (INAA). Comparisons of trace element levels of properly matched AD and control groups revealed significant imbalances in the concentrations of six elements (Br, Ca, Co, Hg, K, and Zn) between disease and control groups. It is noteworthy that each of these has previously been shown by our group, or others, to be altered in some AD brain region(s). Geometric means for each element in both hair and nails of AD and control subjects are presented, and significant differences noted. The significance of these alterations with regard to the possible role of trace elements in the etiology of AD is discussed.

Trace element imbalances in isolated subcellular fractions of Alzheimer's disease brains.

Brain Res 1990 Nov 12;533(1):125-31

Wenstrup D, Ehmann WD, Markesbery WR

Department of Chemistry, University of Kentucky, Lexington.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2085723&dopt=Abstract

    Concentrations of 13 trace elements (Ag, Br, Co, Cr, Cs, Fe, Hg, K, Na, Rb, Sc, Se, Zn) in isolated subcellular fractions (whole brain, nuclei, mitochondria, microsomes) of temporal lobe from autopsied Alzheimer's disease (AD) patients and normal controls were determined utilizing instrumental neutron activation analysis. Comparison of AD and controls revealed elevated Br (whole brain) and Hg (microsomes) and diminished Rb (whole brain, nuclear and microsomes), Se (microsomes) and Zn (nuclear) in AD. The elevated Br and Hg and diminished Rb are consistent with our previous studies in AD bulk brain specimens. Comparison of element ratios revealed increased Hg/Se, Hg/Zn and Zn/Se mass ratios in AD. Se and Zn play a protective role against Hg toxicity and our data suggest that they are utilized to detoxify Hg in the AD brain. Overall our studies suggest that Hg could be an important toxic element in AD. Whether Hg deposition in AD is a primary or secondary eventremains to be determined.

Imbalances of trace elements related to oxidative damage in Alzheimer's disease brain.

Neurotoxicology 1998 Jun;19(3):339-45

Cornett CR, Markesbery WR, Ehmann WD

Department of Chemistry, University of Kentucky, Lexington 40506-0055, USA.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9621340&dopt=Abstract

    Four elements that have been implicated in free-radical-induced oxidative stress in Alzheimer's disease (AD) were measured by instrumental neutron activation analysis (INAA) in seven brain regions from 58 AD patients and 21 control subjects. A statistically significant elevation of iron and zinc was observed in multiple regions of AD brain, compared with controls. Mercury was elevated in AD in most regions studied, but the high variability of mercury levels in both AD and control subjects prevented the AD-control difference from reaching significance. Selenium, a protective agent against mercury toxicity, was significantly elevated only in AD amygdala. The elevation of iron and zinc in AD brain has the potential of augmenting neuron degeneration through free radical processes.

More studies  published by other research scientists (with no dentist's involvement) showing that mercury is elevated in AD

Increased blood mercury levels in patients with Alzheimer's disease.

J Neural Transm 1998;105(1):59-68

Hock C, Drasch G, Golombowski S, Muller-Spahn F, Willershausen-Zonnchen B, Schwarz P, Hock U, Growdon JH, Nitsch RM

Department of Psychiatry, University of Basel, Switzerland.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9588761&dopt=Abstract

    Alzheimer's disease (AD) is a common neurodegenerative disorder that leads to dementia and death. In addition to several genetic parameters, various environmental factors may influence the risk of getting AD. In order to test whether blood levels of the heavy metal mercury are increased in AD, we measured blood mercury concentrations in AD patients (n = 33), and compared them to age-matched control patients with major depression (MD) (n = 45), as well as to an additional control group of patients with various non-psychiatric disorders (n = 65). Blood mercury levels were more than two-fold higher in AD patients as compared to both control groups (p = 0.0005, and p = 0.0000, respectively). In early onset AD patients (n = 13), blood mercury levels were almost three-fold higher as compared to controls (p = 0.0002, and p = 0.0000, respectively). These increases were unrelated to the patients' dental status. Linear regression analysis of blood mercury concentrations and CSF levels of amyloid beta-peptide (A beta) revealed a significant correlation of these measures in AD patients (n = 15, r = 0.7440, p = 0.0015, Pearson type of correlation). These results demonstrate elevated blood levels of mercury in AD, and they suggest that this increase of mercury levels is associated with high CSF levels of A beta, whereas tau levels were unrelated. Possible explanations of increased blood mercury levels in AD include yet unidentified environmental sources or release from brain tissue with the advance in neuronal death.

Metals and trace elements in plasma and cerebrospinal fluid in normal aging and Alzheimer's disease.

J Neural Transm Park Dis Dement Sect 1991;3(4):231-58

Basun H, Forssell LG, Wetterberg L, Winblad B.

Department of Geriatric Medicine, Huddinge Hospital, Sweden.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1772577&dopt=Abstract

    Cerebro-spinal fluid (CSF) and blood levels of aluminum, cadmium, calcium, copper, lead, magnesium, and mercury were studied in 24 subjects with dementia of the Alzheimer type (DAT) and in 28 healthy volunteers. Furthermore, arsenic, bromine, chrome, iron, manganese, nickel, rubidium, selenium, strontium, and zinc were measured only in blood. There were significant changes in the DAT group when compared to the controls. The plasma levels of aluminum, cadmium, mercury and selenium were increased and the contents of iron and manganese were lower in the DAT group as compared to control subjects. In CSF there were low levels of cadmium and calcium and increased content of copper in DAT cases. Iron and zinc levels in blood and calcium in both blood and CSF of DAT patients correlated with memory and cognitive functions. Iron, manganese and strontium levels of DAT sufferers in blood and aluminum in CSF were related with changes in behavior.

    From these results one must conclude that mercury levels are elevated in the brain and tissues of Alzheimer's disease victims ONLY when dentists are NOT involved in the studies.

Other studies by this same group of dentists

Dental amalgam and cognitive function in older women: findings from the Nun Study.

J Am Dent Assoc 1995 Nov;126(11):1495-501

Saxe SR, Snowdon DA, Wekstein MW, Henry RG, Grant FT, Donegan SJ, Wekstein DR

Geriatric Oral Health Program, College of Dentistry, Chandler Medical Center, University of Kentucky, Lexington 40536-0078, USA.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7499646&dopt=Abstract

The authors determined the number and surface area of occlusal dental amalgams in a group of 129 Roman Catholic sisters who were 75 to 102 years of age. Findings from this study of women with relatively homogeneous adult lifestyles and environments suggest that existing amalgams are not associated with lower performance on eight different tests of cognitive function.