Date Published: November 12, 2015
Publisher: BioMed Central
Author(s): Yi-Hua Sun, Oswald Ndi Nfor, Jing-Yang Huang, Yung-Po Liaw.
The potential effects of amalgam fillings on the development of Alzheimer’s disease (AD) are not well understood. The aim of the study was to evaluate the association between dental amalgam fillings and Alzheimer’s disease in Taiwanese population aged 65 and older.
Data were retrieved from the Longitudinal Health Insurance Database (LHID 2005 and 2010). The study enrolled 1,943,702 beneficiaries from the LHID database. After excluding death cases and individuals aged 65 and under, 207,587 enrollees were finally involved in the study. Dental amalgam fillings are coded as 89001C, 89002C, 89003C, 89101C, 89102C, or 89103C in the national health insurance research database (NHIRD). Alzheimer’s disease was diagnosed using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes 331.0.
Individuals exposed to amalgam fillings had higher risk of Alzheimer’s disease (odds ratio, OR = 1.105, 95 % confidence interval, CI = 1.025-1.190) than their non-exposed counterparts. Further analysis showed that the odds ratio of Ahlzheimer’s disease was 1.07 (95 % CI = 0.962-1.196) in men and 1.132 (95 % CI = 1.022-1.254) in women.
Women who were exposed to amalgam fillings were 1.132 times more likely to have Alzheimer’s disease than were their non-exposed counterparts.
Dental amalgam, a material for filling prepared cavities after removing caries, consists of about 50 % mercury . Mercury vapor has been proven to be toxic to the central nervous system. In 2008, the European Commission asserted that there is no evidence showing negative effects on the human central nervous system when applying amalgam fillings as reported in previous studies. In 2009, a similar statement was made by the American Dental Association [2, 3]. The United States Food and Drug Administration, however, stated in 2008 that mercury in amalgam can increase neural risk in children and pregnant women . Some scientific experiments showed that amalgam restorations in the oral cavity keep releasing human-absorbable mercury vapor [5–8]. Other studies have reported significant associations between mercury concentration in urine or in blood and quantities of amalgam restoration or number of total faces in amalgam restoration [9–11]. Furthermore, occupational studies on mercury exposure provided a strong association between mercury metal and the degeneration of the nervous system . Inorganic mercury chloride (HgCl2) at 0.025 to 25 μM has been associated with both neuronal degeneration and perturbed excitability . Hock and colleagues have reported a two-fold increase in mercury levels among patients with Alzheimer’s disease (AD) when compared to control counterparts . The influence of mercury on AD is not well understood. However, it has been demonstrated that mercury can dramatically promote heparin–induced aggregation of R2, the Alzheimer’s tau fragment .
The study was conducted using the Longitudinal Health Insurance Databases (LHID 2005 and 2010). The databases comprise secondary data released to the public for research purposes; hence, this study was exempted from full review by the Institutional Review Board. Subjects included citizens who were ≥ 65 years at study end in 2010. The basic characteristics of the study subjects included births, gender and income. Dental amalgam fillings were coded as 89001C, 89002C, 89003C, 89101C, 89102C, and 89103C in the national health insurance research database (NHIRD), where 89001C indicates single-face amalgam restoration, 89002C indicates two-face amalgam restoration, and 89003C indicates three-face amalgam restoration. The following codes, 89101C, 89102C, and 89103C, represent single-surface, two- and three-surface amalgam restoration in specific cases. Individuals with AD were diagnosed using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 331.0.
In total, 207,587 individuals 65-years old and above were analyzed (Fig. 1). Generally, 2.76 % of men exposed to amalgam fillings and 2.8 % of their unexposed counterparts were diagnosed with AD as were 2.73 % of women exposed to amalgam fillings and 2.93 % of their unexposed counterparts. Table 1 shows the demographic characteristics of individuals with and without AD. The mean age of individuals with AD was significantly higher than of those with no AD (79.36 ± 7.14 vs. 74.87 ± 6.89, p < 0.001). There was no significant difference in the gender distributions of AD. Subjects with and without AD were categorized into four levels by income. The percentages of subjects with AD were 41.86, 25.70, 31.59, and 0.85 % by income ranging from 1–20,000, 20,001-40,000, and >40,000 respectively. Income distributions were significantly different among AD and non-AD individuals. Central, South and Taipei regions had high prevalences of the disease. Individuals exposed to amalgam fillings had a higher risk of Alzheimer’s disease [odds ratio (OR) = 1.105, 95 % confidence interval (CI) = 1.025-1.190] after adjusting for age, gender, income, and residential region (Table 2). Further analysis was made to assess disease risks by gender. The ORs for AD were 1.07 (95 % CI = 0.962-1.196) in men and 1.132 (95 % CI = 1.022-1.254) in women (Table 3).Fig. 1Flow chart showing amalgam fillings and Alzheimer’s disease (2000–2010)Table 1Baseline characteristics of study subjectsVariableAlzheimer’s diseaseNo Alzheimer’s diseasep-value(n = 5,906)(n = 201,681)No.%No.%Age (year)79.36 ± 7.1474.87 ± 6.89<.0001Sex0.1496 Men2,75546.6595,99547.60 Women3,15153.35105,68652.40Income (NT$)<.0001 Dependent2,47241.8684,74042.02 1–20,0001,51825.7044,26021.95 20,001-40,0001,86631.5969,89034.65 >40,000500.852,7911.38Region<.0001 Area 1(Taipei)1,65928.0965,57332.51 Area 2 (Northern)86814.7026,76113.27 Area 3 (Central)125621.2736,69318.19 Area 4 (Southern)1,24721.1134,69017.20 Area 5 (Kao-Ping)73912.5132,14115.94 Area 6 (Eastern)1372.325,8232.89Amalgam filling0.2274 None5,04685.44171,16284.87 Yes86014.5630,51915.13Age was mean ± S.ETable 2Logistic regression analysis of factors associated with Alzheimer’s diseaseVariableLogistic regression modelOR95 % CIAmalgam fillings None1.000- Yes1.1051.025-1.190Age1.0871.083-1.090Sex Female1.0310.976-1.088 Male1.000-Income (NT$) Dependent1.3741.287-1.466 1–20,0001.2871.195-1.386 20,001-40,0001.000- >40,0001.1750.883-1.565Region Area 1 (Taipei)0.7350.675-0.800 Area 2 (Northern)1.000- Area 3 (Central)1.1271.032-1.232 Area 4 (Southern)1.2261.120-1.341 Area 5 (Kao-Ping)0.7340.672-0.821 Area 6 (Eastern)0.7320.609-0.880Odds ratio was adjusted for age, gender, insurance level, and residential regionOR odds ratio, CI confidence intervalTable 3Characteristics of people with amalgam fillings in both gendersVariableLogistic regression modelMenWomenOR95 % CIOR95 % CIAmalgam fillings No1.00-1.00- Yes1.070.962-1.1961.1321.022-1.254Age1.091.084-1.0961.0851.080-1.090Income (NT$) Dependent1.2781.156-1.4131.4551.335-1.585 1–20,0001.1621.052-1.2841.4521.297 -1.625 20,001-40,0001.00-1.00- >40,0000.9450.656-1.3601.7701.113-2.815Region Area 1a0.8380.740-0.9500.6500.579-0.730 Area 2b1.00-1.00- Area 3c1.3021.142-1.4840.9910.878-1.118 Area 4d1.4091.234-1.6101.0870.963-1.228 Area 5e0.8010.692-0.9290.6950.606-0.796 Area 6f0.8810.685-1.1340.6110.466-0.800Odds ratio was adjusted for age, income, and residential regionaArea 1 (Taipei): Taipei City and County, Yilan County, Keelung City, Kinmen County, and Lienhiang County)bArea 2 (Northern): Taoyuan County, Hsinchu County, Miaoli County, and Hsinchu CitycArea 3 (Central): Taichung City, Taichung County, Changhua County, and Nantou CountydArea 4 (Southern): Tainan City and County, Chiayi City and County, Yunlin CountyeArea 5 (Kao-Ping): Kaohsiung City and County, Pingtung County, Penghu CountyfArea 6 (Eastern): Hualin and Taitung County
This is the first study to investigate the association between dental amalgam fillings and AD disease using large-scale data. The study results show that women exposed to mercury amalgam fillings were 1.132 times more likely to have Alzheimer’s disease than were their non-exposed counterparts. These findings are similar to those of previous studies that have reported elevated levels of plasma mercury in subjects with AD in comparison with their healthy controls [14, 27]. Moreover, mercury has been suggested as an important toxic element in AD . Since the launching of the National Health Insurance (NHI) in Taiwan, the coverage rate was 97 % by 2001 and 99 % by 2009 [29, 30]. The NHI has been responsible for the payment of amalgam fillings since 2004. The association between amalgam fillings and AD may have been underestimated considering that the number of amalgam fillings from 2001–2010 may not represent the actual fillings during the patients’ lifetimes. However, people who had multiple amalgam fillings from 2001–2010 were more likely to have subsequent fillings. The NHIRD contains dental records of every beneficiary limited to 2001 ~ 2010. Regarding the individuals without dental amalgam fillings, it is possible that this patient group may have had amalgam fillings earlier in their life, and before 2001, removed them or replaced them with other dental materials, such as gold alloys or ceramics. There are also root filled teeth in jaws. Some root fillings, especially the retrograde root fillings, often contain mercury amalgam. In this study, the control group was not a “pure” non-exposure group because its individuals may have been exposed before 2001. Of course, prior to 2001, exposure to amalgam fillings might have either been lesser or greater in the exposure than the non-exposure group, and vice versa. This also applies for replacements with other dental materials, such as gold alloys or ceramics. However, there may have been non-differential misclassification at baseline which might have resulted in underestimation. From our findings, however, the results are significant implying higher risk of exposure. Even though the NHIRD could not provide complete information on the exact number of fillings and AD, amalgam fillings from 2001–2010 could equally be representative of the total number of fillings during a patient’s life. The same assumption was made for accumulated faces. Accumulated faces are the sum of the number of faces of each amalgam filling .
After adjusting for age, income and residential region, women exposed to mercury amalgam fillings were 1.132 times more likely to have AD than were their non-exposed counterparts.