To determine whether serum trace metals are related to abnormal cognition in Alzheimer’s disease (AD).
Methods:
We studied serum lead (Pb), cadmium (Cd), mercury (Hg), and arsenic(As) in 89 patients with AD and in 118 cognitively normal individuals. We analyzed the results of the blood tests and the food intake.
Results:
Serum Pb levels correlated with word list recall (P = .039) and word list recognition (P = .037). Without age adjustment, serum Cd levels (P = .044) were significantly higher in the AD group. After stratified age adjustment, the levels of selected trace metals did not differ significantly between AD and normal individuals. Food intakes regarding selected trace metals were not significantly different between the 2 groups.
Conclusions:
In this study, serum Pb, Cd, Hg, and As levels were not directly related to abnormal cognition in AD. Serum Pb levels were significantly negatively correlated with verbal memory scores.
CasadoAEncarnación López-FernándezMConcepción CasadoMde La TorreR. Lipid peroxidation and antioxidant enzyme activities in vascular and Alzheimer dementias. Neurochem Res. 2008;33(3):450–458.
2.
DelibasNOzcankayaRAltuntasI. Clinical importance of erythrocyte malondialdehyde levels as a marker for cognitive deterioration in patients with dementia of Alzheimer type: a repeated study in 5-year interval. Clin Biochem. 2002;35(2):137–141.
3.
AdlardPABushAI. Metals and Alzheimer's disease. J Alzheimers Dis. 2006;10(2-3):145–163.
4.
BondaDJLeeHGBlairJAZhuXPerryGSmithMA. Role of metal dyshomeostasis in Alzheimer's disease. Metallomics. 2011;3(3):267–270. doi:10.1039/c0mt00074d.
5.
HegdeMLAnithaSLathaKS. First evidence for helical transitions in supercoiled DNA by amyloid beta peptide (1-42) and aluminum: a new insight in understanding Alzheimer's disease. J Mol Neurosci. 2004;22(1-2):19–31.
6.
DaniSU. Arsenic for the fool: an exponential connection. Sci Total Environ. 2010;408(8):1842–1846. doi:10.1016/j.scitotenv.2010.01.027.
7.
DuceJABushAI. Biological metals and Alzheimer's disease: implications for therapeutics and diagnostics. Prog Neurobiol. 2010;92(1):1–18. doi:10.1016/j.pneurobio.2010.04.003.
8.
GharibzadehSHoseiniSS. Arsenic exposure may be a risk factor for Alzheimer's disease. J Neuropsychiatry Clin Neurosci. 2008;20(4):501. doi:10.1176/appi.neuropsych.20.4.501.
9.
HaraguchiTIshizuHTakehisaY. Lead content of brain tissue in diffuse neurofibrillary tangles with calcification (DNTC): the possibility of lead neurotoxicity. NeuroReport. 2001;12(18):3887–3890.
10.
LamPKKritz-SilversteinDBarrett ConnorE. Plasma trace elements and cognitive function in older men and women: the Rancho Bernardo study. J Nutr Health Aging. 2008;12(1):22–27.
11.
McClainCJMcClainMBarveSBoosalisMG. Trace metals and the elderly. Clin Geriatr Med. 2002;18(4):801–818.
AtwoodCSHuangXMoirRDTanziREBushAI. Role of free radicals and metal ions in the pathogenesis of Alzheimer's disease. Met Ions Biol Syst. 1999;36:309–364.
14.
ChowdhuryBAChandraRK. Biological and health implications of toxic heavy metal and essential trace element interactions. Prog Food Nutr Sci. 1987;11(1):55.
15.
GongGO'BryantSE. The arsenic exposure hypothesis for Alzheimer disease [published online May 13, 2010]. Alzheimer Dis Assoc Disord. 2010. doi:10.1097/WAD.0b013e3181d71bc7.
16.
WeuveJKorrickSAWeisskopfMA. Cumulative exposure to lead in relation to cognitive function in older women. Environ Health Perspect. 2009;117(4):574–580.
17.
KhalilNMorrowLANeedlemanHTalbottEOWilsonJWCauleyJA. Association of cumulative lead and neurocognitive function in an occupational cohort. Neuropsychology. 2009;23(1):10–19. doi:10.1037/a0013757.
18.
YunSHoyerS. Effects of low-level lead on glycolytic enzymes and pyruvate dehydrogenase of rat brain in vitro: relevance to sporadic Alzheimer's disease?J Neural Transm. 2000;107(3):355–368.
19.
PatraRCSwarupDSenapatiSK. Effects of cadmium on lipid peroxides and superoxide dismutase in hepatic, renal and testicular tissue of rats. Vet Hum Toxicol. 1999;41(2):65.
20.
CostaLFoxD. A selective decrease of cholinergic muscarinic receptors in the visual cortex of adult rats following developmental lead exposure. Brain Res. 1983;276(2):259–266.
21.
WebsterWSValoisAA. The toxic effects of cadmium on the neonatal mouse CNS. J Neuropathol Exp Neurol. 1981;40(3):247.
22.
GerhardssonLLundhTLondosEMinthonL. Cerebrospinal fluid/plasma quotients of essential and non-essential metals in patients with Alzheimer's disease. J Neural Transm. 2011;118(6):957–962. doi:10.1007/s00702-011-0605-x.
23.
MutterJCurthANaumannJDethRWalachH. Does inorganic mercury play a role in Alzheimer's disease? A systematic review and an integrated molecular mechanism. J Alzheimers Dis. 2010;22(2):357–374. doi:10.3233/jad-2010-100705.
24.
LlobetJFalcoGCasasCTeixidoADomingoJ.Concentrations of arsenic, cadmium, mercury, and lead in common foods and estimated daily intake by children, adolescents, adults, and seniors of Catalonia, Spain. J Agric Food Chem. 2003;51(3):838–842.
25.
AlkortaIHernández-AllicaJBecerrilJAmezagaIAlbizuIGarbisuC. Recent findings on the phytoremediation of soils contaminated with environmentally toxic heavy metals and metalloids such as zinc, cadmium, lead, and arsenic. Rev Environ Sci Biotechnol2004;3(1):71–90.
26.
ChigboFESmithRWShoreFL. Uptake of arsenic, cadmium, lead and mercury from polluted waters by the water hyacinthEichornia crassipes Environ Pollut Series A Ecol Biol. 1982;27(1):31–36.
27.
PerazaMAAyala-FierroFBarberDSCasarezERaelLT. Effects of micronutrients on metal toxicity. Environ Health Perspect. 1998;106(suppl 1):203.
28.
HwangYParkSParkGChoiSKimM. Total arsenic, mercury, lead, and cadmium contents in edible dried seaweed in Korea. Food Addit Contamin Part B. 2010;3(1):7–13.
29.
LeeHSChoYHParkSO. Dietary exposure of the Korean population to arsenic, cadmium, lead and mercury. J Food Compos Anal. 2006;19(suppl):S31–S37.
30.
McKhannGDrachmanDFolsteinMKatzmanRPriceDStadlanEM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS–ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984;34(7):939–939.
31.
WinbladBPalmerKKivipeltoM. Mild cognitive impairment—beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med. 2004;256(3):240–246.
32.
SeoEHLeeDYLeeJH. Total scores of the CERAD neuropsychological assessment battery: validation for mild cognitive impairment and dementia patients with diverse etiologies. Am J Geriatr Psychiatry. 2010;18(9):801–809.
33.
KFDA. Dietary Intake and Risk Assessment of Contaminants in Korean Foods. Seoul, Korea: Korea Food and Drug Administration; 2009.
34.
LeeJHLeeKULeeDY. Development of the Korean Version of the consortium to establish a registry for Alzheimer's disease assessment packet (CERAD-K). J Gerontol B Psychol Sci Soc Sci. 2002;57(1):P47–P53.
35.
SAS Institute. SAS Procedures Guide. Version 8. Vol 1. Cary, NC: SAS Institute; 1999.
ManterePHanninenHHernbergSLuukkonenR. A prospective follow-up study on psychological effects in workers exposed to low levels of lead. Scand J Work Environ Health. 1984;10(1):43–50.
38.
SchroterCSchroterHHuffmannG. Neurologic and psychiatric manifestations of lead poisoning in adults (case report and review of the literature) [in German]. Fortschr Neurol Psychiatr. 1991;59(10):413–424. doi:10.1055/s-2007-1000716.
39.
SchwartzBSCaffoBStewartWF. Evaluation of cumulative lead dose and longitudinal changes in structural magnetic resonance imaging in former organolead workers. J Occup Environ Med. 2010;52(4):407–414. doi:10.1097/JOM.0b013e3181d5e386.
40.
SchwartzBSStewartWBollaK. Past adult lead exposure is associated with longitudinal decline in cognitive function. Neurology. 2000;55(8):1144–1150.
41.
WeisskopfMGHuHMulkernRV. Cognitive deficits and magnetic resonance spectroscopy in adult monozygotic twins with lead poisoning. Environ Health Perspect. 2004;112(5):620–625.
42.
BleeckerMLFordDPCelioMAVaughanCGLindgrenKN. Impact of cognitive reserve on the relationship of lead exposure and neurobehavioral performance. Neurology. 2007;69(5):470–476. doi:10.1212/01.wnl.0000266628.43760.8c.
43.
WeisskopfMGProctorSPWrightRO. Cumulative lead exposure and cognitive performance among elderly men. Epidemiology. 2007;18(1):59–66.
44.
StolleryBTBanksHABroadbentDELeeWR. Cognitive functioning in lead workers. Br J Ind Med. 1989;46(10):698–707.
45.
ChangWChenJWeiQYChenXM. Effects of Brn-3a protein and RNA expression in rat brain following low-level lead exposure during development on spatial learning and memory. Toxicol Lett. 2006;164(1):63–70.
46.
WilliamsonATeoR. Neurobehavioural effects of occupational exposure to lead. Br J Ind Med. 1986;43(6):374–380.
47.
GordonJTaylorABennettP. Lead poisoning: case studies. Br J Clin Pharmacol. 2002;53(5):451–458.
KollerKBrownTSpurgeonALevyL. Recent developments in low-level lead exposure and intellectual impairment in children. Environ Health Perspect. 2004;112(9):987.
50.
SharifiAMBaniasadiSJorjaniMRahimiFBakhshayeshM. Investigation of acute lead poisoning on apoptosis in rat hippocampus in vivo. Neurosci Lett. 2002;329(1):45–48.
51.
StewartWFSchwartzBS. Effects of lead on the adult brain: a 15-year exploration. Am J Ind Med. 2007;50(10):729–739. doi:10.1002/ajim.20434.
52.
StrużyńskaLWalskiMGadamskiRDabrowska-BoutaBRafałowskaU. Lead-induced abnormalities in blood-brain barrier permeability in experimental chronic toxicity. Mol Chem Neuropathol. 1997;31(3):207–224.
53.
HwangKYLeeBKBresslerJPBollaKIStewartWFSchwartzBS. Protein kinase C activity and the relations between blood lead and neurobehavioral function in lead workers. Environ Health Perspect. 2002;110(2):133.
54.
SalthouseTA. The processing-speed theory of adult age differences in cognition. Psychol Rev. 1996;103(3):403.
55.
PetersenRCDoodyRKurzA. Current concepts in mild cognitive impairment. Arch Neurol. 2001;58(12):1985.
56.
VigEKHuH.Lead toxicity in older adults. JAm Geriatr Soc.
2000;
48(11):1501.
57.
BomboiGMarchioneFSepe-MontiM. Correlation between metal ions and clinical findings in subjects affected by Alzheimer's disease. Annali Ist Super Sanita. 2005;41(2):205–212.
58.
GerhardssonLLundhTMinthonLLondosE. Metal concentrations in plasma and cerebrospinal fluid in patients with Alzheimer's disease. Dement Geriatr Cogn Disord. 2008;25(6):508–515.
59.
BoccaBForteGPetrucciF. Monitoring of chemical elements and oxidative damage in patients affected by Alzheimer's disease. Ann Ist Super Sanita. 2005;41(2):197–203.
60.
BasunHLindBNordbergMNordstromMBjorkstenKSWinbladB. Cadmium in blood in Alzheimer's disease and non-demented subjects: results from a population-based study. Biometals. 1994;7(2):130–134.
61.
BasunHForssellLGWetterbergLWinbladB. 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):231–258.
62.
AnderssonHPetersson-GraweKLindqvistELuthmanJOskarssonAOlsonL. Low-level cadmium exposure of lactating rats causes alterations in brain serotonin levels in the offspring. Neurotoxicol Teratol. 1997;19(2):105–115.
63.
JinTLuJNordbergM. Toxicokinetics and biochemistry of cadmium with special emphasis on the role of metallothionein. Neurotoxicology. 1998;19(4-5):529–535.
64.
TjälveHHenrikssonJTallkvistJLarssonBSLindquistNG. Uptake of manganese and cadmium from the nasal mucosa into the central nervous system via olfactory pathways in rats. Pharmacol Toxicol. 2009;79(6):347–356.
