Background
Methods
Information sources
Search strategy
Screening & eligibility
Quality of evidence
Strong evidence for environmental risk factor | |
There is a reported association with dementia in the majority of published papers. | |
Moderate or weak evidence for environmental risk factor | |
Although the reported association with dementia is not seen in the majority of published papers, at least one published paper (or only one) supports the association. | |
Weak evidence may come from a single, poorly designed study. | |
No evidence for environmental risk factor | |
No association with dementia has been revealed either due to a lack of relevant research or the observed effect is not seen as significant. |
Results
Factor | N Studiesa | Overall Strength Of Evidenceb | Direction Of Associationc | ||
---|---|---|---|---|---|
C | X | R | |||
Air | |||||
Nitrogen oxides (NOx) | 2 | Strong | ↑ | ||
Carbon monoxide (CO) | 1 | Moderate | ↑ | ||
Environmental tobacco smoke | 1 | Moderate | ↑ | ||
Particulate matter (PM10&2.5) | 1 | 1 | Strong | ↑ | |
Ozone (O3) | 1 | 1 | Strong | ↑ | |
Toxic heavy metals | |||||
Arsenic | 2 | Moderate | ↕ | ||
Lead | 1 | Weak | ↑ | ||
Other metals | |||||
Aluminium | 1 | 15 | Moderate | ↕ | |
Calcium | 1 | Weak | – | ||
Cobalt | 1 | Weak | – | ||
Copper | 2 | 1 | Weak | ↕ | |
Iron | 2 | 1 | Weak | ↕ | |
Manganese | 1 | Weak | ↑ | ||
Molybdenum | 1 | Weak | – | ||
Nickel | 1 | Weak | – | ||
Uranium | 1 | Weak | – | ||
Zinc | 2 | Weak | ↕ | ||
Other trace elements | |||||
Fluoride | 1 | Weak | ↑ | ||
Selenium | 1 | Moderate | ↕ | ||
Silicon (and silica) | 2 | 2 | Strong | ↕ | |
Occupational | |||||
Aluminium (occupational exposure) | 1 | 3 | Weak | ↕ | |
Defoliants/fumigants | 1 | Weak | ↑ | ||
Diesel motor exhaust | 1 | Moderate | – | ||
Electromagnetic fields | 1 | Moderate | ↕ | ||
Excessive noise | 1 | Weak | ↓ | ||
Glues/adhesives | 1 | 1 | Weak | ↕ | |
Pesticides/fertilizers/herbicides/insecticides | 5 | 2 | 2 | Strong | ↕ |
Lead (occupational exposure) | 1 | Weak | – | ||
Metals (occupational exposure) | 1 | Moderate | ↑ | ||
Inks/dyes | 1 | Weak | – | ||
Paints/stains/varnishes | 1 | Weak | – | ||
Gasoline/fuels/oils | 1 | Weak | – | ||
Solvents/degreasers | 2 | 1 | 1 | Strong | ↕ |
Liquid plastics/rubbers | 1 | Weak | – | ||
Vibratory tools | 1 | Weak | – | ||
Radiation | 1 | Weak | ↑ | ||
Miscellaneous | |||||
Climate | 1 | Weak | – | ||
Electric and magnetic fields | 1 | 2 | Moderate | ↕ | |
Mobile phone use | 1 | Weak | ↓ | ||
Vitamin D | 3 | 1 | Strong | ↑ | |
Water pH | 1 | Weak | ↑ |
Study | Exposure | Sample description |
N
| Methodology/design | Finding | Grade |
---|---|---|---|---|---|---|
Chang et al., 2014 [28] | CO and NO2 | Comprehensive National Health Insurance database in Taiwan – people aged ≥50 years. | 29537 (NO2 29547) men and women of whom 1718 (1720) developed dementia | Retrospective cohort study: Cox PH models. Yearly average CO concentrations based on location of clinic attended. Dementia diagnoses were extracted from electronic health records. | Highest vs lowest quartile of CO and NO2 was associated with an increased risk of dementia incidence (multivariable adjusted HR, 95 % CI: 1.54, 1.34-1.77; 1.61, 1.39-1.85). Similar effects in men and women. | A |
Oudin et al., 2015 [27] | Traffic-related air pollution (NOx) | Participants from the Betula study, randomly sampled from the general population residing in the Umeå municipality | 1,806 healthy men and women of whom 302 developed dementia | Prospective cohort study: Cox PH models. Mean nitrogen oxide levels based on baseline residence and dementia outcome after 15 years. | Highest:lowest quartile of NOx revealed an increased risk of incident dementia (adjusted HR, 95 % CI 1.60, 1.02-2.10). Similar results were observed in AD and VaD. | A |
Chen et al., 2013 [29] | Environmental Tobacco Smoke | Community dwelling adults aged ≥50 years living in rural or urban areas of five provinces of China. | 5921 men and women of whom 626 had severe (O3-5) and 869 moderate (O1-2) dementia | Cross-sectional study. Smoking status and ETS exposure (at home, work, and other places) defined by self-report. Dementia was diagnosed using the GMS-AGECAT algorithm. | Multivariable-adjusted RR (95 % CI) for exposure to ETS 0.96 (0.84, 1.09) for moderate dementia and 1.29 (1.05, 1.59) for severe dementia. Risk of severe dementia increased with increasing duration and cumulative dose, particularly in never smokers. | B |
Jung et al. 2015 [33] | PM2.5 and O3 | Individuals from Taiwan entered into the longitudinal health insurance database 2000 (LHID2000) aged ≥65 in 2001. | 95,690 men and women of whom 1399 developed AD. | Prospective cohort study: Cox PH models. PM2.5 and O3 levels recorded at 70 Taiwan Environmental Protection Agency monitoring stations from 2000 to 2010. These data were controlled for secondary pollutants (CO, NO2 and SO2). AD was identified when this was recorded at least twice on the insurance database, based on a physician diagnosis. | Baseline O3 was associated with an increased risk of incident AD (multivariable-adjusted HR per interquartile range, 95 % CI: 1.06, 1.00-1.12) but baseline PM2.5 was not (1.03, 0.95-1.11). Change in both O3 and PM2.5 was associated with increased AD risk (3.12, 2.92-3.33; 2.38, 2.21-2.56). This remained after additionally adjusting for secondary pollutants. | A |
Wu et al., 2015 [34] | PM10 and O3 | 249 AD patients, 125 VaD patients (clinically diagnosed from hospital clinics) and 497 controls (from the elderly health check-up program), all ≥60 years in Taiwan. | 374 cases; 497 controls | Cross-sectional study (case–control): multiple regression. 12-year PM10 and 14-year ozone exposure were estimated from spatiotemporal models based on residential location. | Highest vs lowest tertile of PM10 and ozone exposure was associated with increased AD risk (adjusted OR, 95 % CI: 4.17, 2.31-7.54; 2.00, 1.14-3.50). Similar results were found for VaD. | B |
Study | Exposure | Sample description |
N
| Methodology/design | Finding | Grade |
---|---|---|---|---|---|---|
Fox, 2014 [35] | Arsenic | Spring Valley Community, Washington, District of Columbia. Spring Valley was built on a chemical weapons lab which caused arsenic to be distributed to the surface soil. | Population of Spring Valley 2006 – 2010: 24,762 | Comparison of annual average age-adjusted mortality rates (per 100,000) between Spring Valley, Chevy Chase (2004 – 2010) and the US (2007). No measure of arsenic concentration is given for these areas at these times. | AD mortality rate in Spring Valley (22.8; CI 20.3 – 25.4) was comparable to the Chevy Chase (22; CI 19 – 25) and US (24.70) rates. No statistically significant difference. | B |
Dani, 2010 [36] | Arsenic | Secondary analysis of country-level data. | Country-level data. | Simulation. | Slight increases in arsenic concentration in soil were related to exponential increases in dementia rates at a country level. | C |
Emard et al., 1994 [37] | Lead | The IMAGE Project covering the population of Saguenay-Lac-Saint-Jean (SLSJ), Québec. | 129 individuals with AD (clinically diagnosed by standard medical services) who were born in SLSJ. | Cross-sectional study: principal components analysis. Samples of aquatic sediment were analysed for geochemical variables. AD cases were identified from a registry. | 15 individuals with AD were born in areas with lower than average concentration of lead; 49 were born in areas with higher than average concentrations. This difference was statistically significant (P < 0.05). | B |
Study | Exposure | Sample description |
N
| Methodology/design | Finding | Grade |
---|---|---|---|---|---|---|
Rondeau et al., 2009 [39] | Aluminium | PAQUID: A community-based cohort of 3,777 elderly people aged ≥65 years in SW France. | 1925 individuals of whom 461 developed clinically diagnosed dementia (364 AD). | Prospective cohort study: Cox PH models. Mean levels of aluminium in drinking water over the previous decade based on current residential location was linked to incident dementia over 15 years follow up. | Highest:lowest quartile of aluminium in drinking water was associated with an increased risk of dementia and AD (multivariable-adjusted HR, 95 % CI: 2.34, 1.03-5.32; 3.04, 1.32-6.97). | A |
Flaten, 1990 [40] | Aluminium | The Norwegian population – mortality data provided by the Central Bureau of Statistics of Norway. | 5,642 male and 9,085 female dementia deaths were recorded 1974–1983. The denominator population is estimated at 40.6 million person-years. The population of Norway was approximately 4 million people during this period. | Cross-sectional study: Pearson’s correlation and relative risk. Four water samples (one per season) were collected in 1982–3 from 384 waterworks and analysed. Small municipalities were aggregated to regions of at least 10,000 inhabitants. Dementia was ascertained from death certification (any mention). | There was a correlation between the aluminium content of drinking water at municipality level and dementia death rates in four time periods from 1969–83 in men and women (P < 0.025 and <0.005) but not with PD or ALS death rates. This pattern was less clear at county level. | B |
Highest:lowest tertile of aluminium concentration was associated with an increased risk of dementia death in men and women (RR, 95 % CI: 1.32, 1.20-1.46; 1.42, 1.32-1.54). | ||||||
Forbes et al., 1995 [41] | Aluminium | Males from the Ontario Longitudinal Study of Aging dying between 1984 and 1991. | 3161 patients with AD or young-onset dementia. | Cross-sectional study: Poisson regression. Water quality was based on 30 years’ residential history. Dementia was identified from death certificates (underlying cause). | Highest:lowest tertile of aluminium concentration was associated with an increased risk of AD and AD plus young-onset dementia (RR, 95 % CI: 2.42, 1.42-4.11; 1.96, 1.15-3.32). Effect sizes were greater in analyses restricted to individuals aged ≥75 years. | B |
Total sample not stated. | ||||||
Some models showed a lower risk of dementia in the middle tertile of aluminium concentrations compared to the lowest. | ||||||
Neri & Hewitt, 1991 [44] | Aluminium | Patients discharged from general hospitals in Ontario, Canada in 1986. | 2344 people aged ≥55 years with a diagnosis of AD or young-onset dementia recorded and 2232 people, matched for age and sex, with a non-psychiatric diagnosis recorded. | Cross-sectional study (case–control). Aluminium concentration in drinking water based on residential location was compared with dementia diagnoses based on hospital discharge statistics. | The authors report a dose–response pattern of association (OR for quartiles 2–4 compared to lowest, 95 % CI: 1.13, 0.55-2.29; 1.26, 0.61-2.59; 1.46, 0.71-2.99) but all CIs (not reported but calculated from data reported in paper) include unity. | B |
Gillette-Guyonnet et al., 2005 [57] | Aluminium | Toulouse subset of the EPIDOS study cohort of women aged ≥75 years. | 1462 women from one centre of whom 60 developed clinically diagnosed AD. 323 had normal cognitive function and the remainder were lost to follow up. | Prospective cohort study: logistic regression. Water consumption based on self-report (at baseline and follow up) was combined with local tap water composition data. Dementia was clinically diagnosed. | It is not clear if aluminium consumption was included in logistic regression models and not found to be a predictor of dementia or if it wasn’t included. | B |
Martyn et al., 1997 [46] | Aluminium | Participants were selected from CT records of eight neuroradiology centres in the UK. | A total of 872 men (106 AD, 99 other dementia, 226 brain cancer, 441 other disease of the nervous system) | Cross-sectional study (case–control): logistic regression. Average levels of aluminium in drinking water based on residential history (after age 25 years) was related to diagnosis based on hospital records. | There were no associations identified between aluminium concentrations over three time periods (from age 25 years to diagnosis; from age 25 years to 10 years before diagnosis; and the ten years preceding diagnosis) with each of the three comparison groups. | B |
McLachlan et al., 1996 [43] | Aluminium | Participants were selected from a brain tissue bank in Ontario, Canada. | 296 participants had AD, 89 had mixed dementia, 125 had no histopathological abnormalities, and 170 had other conditions (HD, schizophrenia, MS, multiple infarcts, CJD, and other neurodegenerative diseases). | Cross-sectional study (case–control). Average aluminium concentrations in domestic water supply of residential location at death (10 year residential history was available for a subsample) were compared to dementia status (neuropathologically diagnosed). | Aluminium concentration >100 μg/L compared to <100 μg/L was associated with an increased risk of AD and dementia (OR, 95 % CI: 1.7, 1.2-2.6; 1.7, 1.2-2.5). | B |
Effect sizes were larger for the subgroup analysis based on 10-year residential history (2.6, 1.2-5.7; 2.5, 1.2-5.3). | ||||||
Frecker, 1991 [42] | Aluminium | Mortality records in Bonavista Bay, Newfoundland, 1985–86. | 191 dementia deaths in 1985, 208 deaths in 1986 | Cross-sectional study. Place of birth of all individuals dying with dementia was identified and associated with drinking water samples at those locations from 1986. | The area with the highest dementia mortality (37.5 % in 1985 and 68.8 % in 1986) also had the highest aluminium concentrations in drinking water. This association was not assessed for statistical significance, but was argued to not be confounded by age, sex or place of residence stated on death certificate. | B |
Emard et al., 1994 [37] | Aluminium | The IMAGE Project covering the population of Saguenay-Lac-Saint-Jean (SLSJ), Québec. | 129 individuals with AD (clinically diagnosed by standard medical services) who were born in SLSJ. | Cross-sectional study: principal components analysis. Samples of aquatic sediment were analysed for geochemical variables. AD cases were identified from a registry. | 44 individuals with AD were born in areas with lower than average concentration of aluminium; 41 were born in areas with higher than average concentrations. This difference is not statistically significant. | B |
Forster et al., 1995 [47] | Aluminium | Patients were drawn from a specialist service in the north of England. Controls were randomly selected from the general population. | 109 people with clinically diagnosed young-onset AD and 109 age- and sex-matched controls. | Cross-sectional study (case–control). Aluminium levels in drinking water were determined according to residential history (longest residence in the preceding 10 years plus birthplace for a subset of 80 cases and controls) at local authority district level. | There was no evidence of an association between aluminium concentration in drinking water and dementia risk (e.g. aluminium >149 mg/L OR, 95 % CI: recent residence 1.0, 0.41-2.43; birthplace 1.1, 0.38-3.35). | B |
Taylor et al., 1995 [48] | Aluminium | Same cohort as Forster et al., 1995 [47] | Water samples were obtained for 214 addresses of the 218 cases and controls. | Cross-sectional study (case–control). Aluminium concentration in water samples drawn from the place of residence at which they had lived longest within 10 years prior to onset of dementia (or equivalent date for controls). | There were no differences in aluminium concentrations in samples for cases or controls (P = 0.60). | B |
Gauthier et al., 2000 [107] | Aluminium | Random sample of individuals living in SLSJ aged ≥70 years from the provincial health plan of Quebec in 1994. | 68 participants with clinically-diagnosed AD and 68 age- and sex-matched controls. | Cross-sectional study (case–control). Aluminium concentration in drinking water was sampled four times in 1995–6 in 54 municipalities of SLSJ. Long-term exposure was estimated based on residential history. | Of all variables involved in the speciation of aluminium in drinking water (total Al, total dissolved Al, total monomeric Al, organic monomeric Al, inorganic monomeric Al, polymeric Al, as well as the main monomeric inorganic forms) based on recent and long-term exposure, only recent exposure to monomeric organic aluminium was associated with AD at conventional levels (OR, 95 % CI 2.67, 1.04-6.90). | B |
Shen et al., 2014 [49] | Aluminium | 26 provinces and 3 municipal districts of mainland China. | Not specified. | Cross-sectional study. Soil chemical levels in 1990 were related to AD mortality 1991–2000. | Higher aluminium levels in soil were associated with reduced AD mortality (highest:lowest group RR, 95 % CI: 0.267, 0.265-0.268). | B |
Vogt, 1986 [45] | Aluminium | Mortality data from the Central Bureau of Statistics (1969–1983) and dementia patients within 112 psychiatric nursing homes (as collected by Norwegian Institute for Gerontology in 1982). | Not specified. | Cross-sectional study. Drinking water quality and acidification of lakes was related to standardized dementia mortality rates. | Highest:lowest zone of aluminium concentration was associated with a raised standardised dementia mortality rate (per 10,000 inhabitants per year: 48.3 vs 32.4). The effect size was greater in women (59.4 vs 38.5) than men (36.9 vs 26.1). | B |
Wettstein et al., 1991 [108] | Aluminium | Residents of two Zurich city districts. | 775 men and women aged 82–85 years who had lived in that area for at least 15 years. | Cross-sectional study. Aluminium concentrations were measured in drinking water. The dementia outcome was measured using the truncated MMSE. | No significant difference was observed between the participant groups on mnestic or naming subscores (P = 0.962 and P = 0.567). | C |
Civita, Fiorucci, & Mie, 2001 [109] | Aluminium | AD mortality in municipalities within 20 km of Alba based on national mortality statistics. Census data were used as a reference population. | Not stated. | Cross-sectional study. A map of the location of deaths with AD was compared to levels of aluminium released from 1 kg of clay at various sampling sites. | They found an increased SMR in the municipality compared to the province or the whole of Italy. They also noted that the areas with highest dementia mortality had the highest aluminium concentrations in water. | C |
Gillette-Guyonnet et al., 2005 [57] | Calcium | Toulouse subset of the EPIDOS study cohort of women aged ≥75 years. | 1462 women from one centre of whom 60 developed clinically diagnosed AD. 323 had normal cognitive function and the remainder were lost to follow up. | Prospective cohort study: logistic regression. Water consumption based on self-report (at baseline and follow up) was combined with local tap water composition data. Dementia was clinically diagnosed. | Women who developed AD showed a decrease in daily calcium intake at follow up. It is not clear if calcium consumption was included in logistic regression models and not found to be a predictor of dementia or if it wasn’t included. | B |
Emard et al., 1994 [37] | Cobalt | The IMAGE Project covering the population of Saguenay-Lac-Saint-Jean (SLSJ), Québec. | 129 individuals with AD (clinically diagnosed by standard medical services) who were born in SLSJ. | Cross-sectional study: principal components analysis. Samples of aquatic sediment were analysed for geochemical variables. AD cases were identified from a registry. | 21 individuals with AD were born in areas with lower than average concentration of cobalt; 20 were born in areas with higher than average concentrations. This difference is not statistically significant. | B |
Emard et al., 1994 [37] | Copper | The IMAGE Project covering the population of Saguenay-Lac-Saint-Jean (SLSJ), Québec. | 129 individuals with AD (clinically diagnosed by standard medical services) who were born in SLSJ. | Cross-sectional study: principal components analysis. Samples of aquatic sediment were analysed for geochemical variables. AD cases were identified from a registry. | 18 individuals with AD were born in areas with lower than average concentration of copper; 30 were born in areas with higher than average concentrations. This difference is not statistically significant. | B |
Shen et al., 2014 [49] | Copper | 26 provinces and 3 municipal districts of mainland China. | Not specified. | Cross-sectional study. Soil chemical levels in 1990 were related to AD mortality 1991–2000. | Copper concentration correlated with annual AD mortality after three outlier provinces were removed (r = 0.449, P = 0.021). | B |
Loef & Walach, 2012 [24] | Copper | Systematic review of studies relating copper to AD from 11 databases. | 101 studies: | Systematic review. | Of relevant evidence that is reviewed, the authors conclude that “In summary, the current trials provide no conclusive evidence that depletion or supplementation of Cu is beneficial for AD… [t]he specific outcomes for Cu are more conflicting; while evidence suggests that the systemic Cu level is increased in patients with AD, further research is needed to define the alterations of Cu in the brain during AD.” (p.6). | - |
2 meta analyses, 2 systematic reviews, 11 RCTs, 2 prospective studies, 3 cross-sectional studies, 45 case–control studies, 30 autopsy studies,5 uncontrolled studies, 1 case study. | ||||||
Emard et al., 1994 [37] | Iron | The IMAGE Project covering the population of Saguenay-Lac-Saint-Jean (SLSJ), Québec. | 129 individuals with AD (clinically diagnosed by standard medical services) who were born in SLSJ. | Cross-sectional study: principal components analysis. Samples of aquatic sediment were analysed for geochemical variables. AD cases were identified from a registry. | 16 individuals with AD were born in areas with lower than average concentration of iron; 35 were born in areas with higher than average concentrations. This difference was statistically significant (P < 0.05). | B |
Shen et al., 2014 [49] | Iron | 26 provinces and 3 municipal districts of mainland China. | Not specified. | Cross-sectional study. Soil chemical levels in 1990 were related to AD mortality 1991–2000. | Higher iron levels in soil were associated with increased AD mortality (highest:lowest group RR, 95 % CI: 1.248, 1.245-1.251). Iron concentration correlated with annual AD mortality after three outlier provinces were removed (r = 0.537, P = 0.007). | B |
Loef & Walach, 2012 [24] | Iron | Systematic review of studies relating iron to AD from 11 databases. | 101 studies: | Systematic review. | “In summary, the current trials provide no conclusive evidence that depletion or supplementation of … Fe is beneficial for AD… Fe has been consistently found at elevated levels in the brains of AD sufferers by both autopsy and case–control studies.” (p.6). | - |
2 meta analyses, 2 systematic reviews, 11 RCTs, 2 prospective studies, 3 cross-sectional studies, 45 case–control studies, 30 autopsy studies,5 uncontrolled studies, 1 case study. | ||||||
Emard et al., 1994 [37] | Manganese | The IMAGE Project covering the population of Saguenay-Lac-Saint-Jean (SLSJ), Québec. | 129 individuals with AD (clinically diagnosed by standard medical services) who were born in SLSJ. | Cross-sectional study: principal components analysis. Samples of aquatic sediment were analysed for geochemical variables. AD cases were identified from a registry. | 12 individuals with AD were born in areas with lower than average concentration of manganese; 35 were born in areas with higher than average concentrations. This difference was statistically significant (P < 0.05). | B |
Emard et al., 1994 [37] | Molybdenum | The IMAGE Project covering the population of Saguenay-Lac-Saint-Jean (SLSJ), Québec. | 129 individuals with AD (clinically diagnosed by standard medical services) who were born in SLSJ. | Cross-sectional study: principal components analysis. Samples of aquatic sediment were analysed for geochemical variables. AD cases were identified from a registry. | 29 individuals with AD were born in areas with lower than average concentration of molybdenum; 16 were born in areas with higher than average concentrations. This difference is not statistically significant. | B |
Emard et al., 1994 [37] | Nickel | The IMAGE Project covering the population of Saguenay-Lac-Saint-Jean (SLSJ), Québec. | 129 individuals with AD (clinically diagnosed by standard medical services) who were born in SLSJ. | Cross-sectional study: principal components analysis. Samples of aquatic sediment were analysed for geochemical variables. AD cases were identified from a registry. | 27 individuals with AD were born in areas with lower than average concentration of nickel; 29 were born in areas with higher than average concentrations. This difference is not statistically significant. | B |
Emard et al., 1994 [37] | Uranium | The IMAGE Project covering the population of Saguenay-Lac-Saint-Jean (SLSJ), Québec. | 129 individuals with AD (clinically diagnosed by standard medical services) who were born in SLSJ. | Cross-sectional study: principal components analysis. Samples of aquatic sediment were analysed for geochemical variables. AD cases were identified from a registry. | 10 individuals with AD were born in areas with lower than average concentration of uranium; 9 were born in areas with higher than average concentrations. This difference is not statistically significant. | B |
Emard et al., 1994 [37] | Zinc | The IMAGE Project covering the population of Saguenay-Lac-Saint-Jean (SLSJ), Québec. | 129 individuals with AD (clinically diagnosed by standard medical services) who were born in SLSJ. | Cross-sectional study: principal components analysis. Samples of aquatic sediment were analysed for geochemical variables. AD cases were identified from a registry. | 29 individuals with AD were born in areas with lower than average concentration of aluminium; 30 were born in areas with higher than average concentrations. This difference is not statistically significant. | B |
Shen et al., 2014 [49] | Zinc | 26 provinces and 3 municipal districts of mainland China. | Not specified. | Cross-sectional study. Soil chemical levels in 1990 were related to AD mortality 1991–2000. | Higher zinc levels in soil were associated with increased AD mortality (highest:lowest group RR, 95 % CI: 2.289, 2.275-2.303). | B |
Study | Exposure | Sample description |
N
| Methodology/design | Finding | Grade |
---|---|---|---|---|---|---|
Still & Kelley, 1980 [51] | Fluoride | All first admissions of people aged ≥55 years to South Carolina Department of Mental Health hospitals from three counties who had lived in that county for at least 10 years. | Case records for 160 patients were examined and, based on that evidence, 67 were diagnosed with a primary degenerative dementia, i.e. AD. | Cross-sectional study. Annual incidence of dementia was calculated per county, based on the admissions data. These were then compared with fluoride concentrations in public water supplies (time of measurement is not given). | Horry County was reported to have highest levels of fluoride (4.18 ± 0.19 mg/l) compared to Anderson (0.49 ± 0.10 mg/l) and York (0.61 ± 0.12 mg/l) Counties. It also has the lowest calculated annual incidence of dementia per 100,000 population (3.6; Anderson 20.8, York 17.1). | C |
Loef, Schrauzer, & Walach, 2011 [23] | Selenium | Systematic review of studies relating selenium to AD from 8 databases. | 56 studies: 9 placebo-controlled, 4 prospective, 4 cross-sectional, 15 case–control, and 24 autopsy studies. | Systematic review. | - | |
Of 15 case–control studies, the authors comment that “four studies reported about increased levels of Se-concentration or GPx-activity while the majority found decreased levels, albeit non-significant in some studies.” (p. 87). | ||||||
Of the 24 autopsy studies, the authors conclude that “the autopsy studies do not yield a consistent picture of whether, how and where in brain Se levels become altered in subjects with AD.” (p. 87). | ||||||
Gillette-Guyonnet et al., 2005 [57] | Silica | Toulouse subset of the EPIDOS study cohort of women aged ≥75 years. | 1462 women from one centre of whom 60 developed clinically diagnosed AD. 323 had normal cognitive function and the remainder were lost to follow up. | Prospective cohort study: logistic regression. Water consumption based on self-report (at baseline and follow up) was combined with local tap water composition data. Dementia was clinically diagnosed. | Low silica consumption in water (≤4 mg vs >12 mg per day) was associated with an increased risk of dementia (multivariable-adjusted OR, 95 % CI: 2.74, 1.09-6.86). Women who developed AD had lower silica intake at baseline and showed a decrease in daily silica intake at follow up. | A |
Rondeau et al., 2009 [39] | Silica | PAQUID: A community-based cohort of 3,777 elderly people aged ≥65 years in SW France. | 1925 individuals of whom 461 developed clinically diagnosed dementia (364 AD). | Prospective cohort study: Cox PH models. Mean levels of silica in drinking water over the previous decade based on current residential location was linked to incident dementia over 15 years follow up. | Highest:lowest quartile of silica in drinking water was associated with an increased risk of dementia and AD (multivariable-adjusted HR, 95 % CI: 1.33, 1.01-1.74; 1.33, 0.98-1.80). | A |
Taylor et al., 1995 [48] | Silica | Same cohort as Forster et al., 1995 [47] | Water samples were obtained for 214 addresses of the 218 cases and controls. | Cross-sectional study (case–control). Aluminium concentration in water samples drawn from the place of residence at which they had lived longest within 10 years prior to onset of dementia (or equivalent date for controls). | There were no differences in silica concentrations in samples for cases or controls and no association between increased levels of silica and dementia (OR, 95%CI ≥3 mg/L 0.8, 0.34-1.83). | B |
Martyn et al., 1997 [46] | Silicon | Participants were selected from CT records of eight neuroradiology centres in the UK. | A total of 872 men (106 AD, 99 other dementia, 226 brain cancer, 441 other disease of the nervous system) | Cross-sectional study (case–control): logistic regression. Average levels of silicon in drinking water based on residential history (after age 25 years) was related to diagnosis based on hospital records. | There were no associations identified between silicon concentrations consistently above 6 mg/L (compared to lower levels) with each of the three comparison groups (e.g. AD vs other diagnoses (adjusted-OR, 95 % CI: 0.94, 0.39-2.26). | B |
Study | Exposure | Sample description |
N
| Methodology/design | Finding | Grade |
---|---|---|---|---|---|---|
Peters et al., 2013 [60] | Aluminium (occupational exposure) | Survey information collected from miners living in Kalgoorlie, Western Australia. Data collected in 1961,’62,’74,’75 and 2000. | 1894 ever underground gold miners linked with Western Australian Registrar General’s Mortality Database of whom 16 died with AD. | Retrospective cohort study: SMRs and Cox PH models. Exposure to aluminium dust ascertained by self-report. | Aluminium dust inhalation was associated with increased AD mortality (SMR, 95 % CI: 1.38, 0.69-2.75). There was also an association between inhaled aluminium dust and AD mortality in Cox models (HR, 95 % CI: 2.76, 0.88-8.82). | B |
Salib et al., 1996 [61] | Aluminium (occupational exposure) | Individuals referred to a psychogeriatric unit in Warrington, UK | 198 AD, 194 other dementia, 176 unmatched controls. | Cross-sectional study (case–control). Occupation based on self-report. | No association was found between working in the aluminium industry and AD (OR, 95 % CI: 0.98, 0.53-1.75). This was also the case for all dementias | B |
Graves et al., 1998 [58] | Aluminium (occupational exposure) | Subsample of Kukull et al.’s cohort [71]. | 89 AD and 89 matched controls. | Cross-sectional study (case–control). Aluminium exposure rated blind based on occupational history. | There was an association between ever exposure to aluminium and AD (OR, 95 % CI: 1.46, 0.62-3.42) but not in models which took into account intensity, duration, or age at exposure. | B |
Gun et al., 1997 [59] | Aluminium (occupational exposure) | Men and women recruited from Sydney hospitals 1986–1989. | 170 probable or possible AD and 170 controls. | Cross-sectional study (case–control). Aluminium exposure was derived from an occupational interview. | Aluminium exposure was associated with a reduced odds ratio of AD (OR, 95 % CI: 0.33, 0.01-4.16). This study has very low statistical power because only four cases and controls were exposed. Probable and Possible AD cases considered together. | C |
Tyas et al., 2001 [62] | Defoliants/fumigants | The Manitoba Study of Health and Aging – random sample from provincial health insurance records. | 694 cognitively-intact older adults followed up for five years, during which time 36 developed probable or possible AD (clinically diagnosed). | Prospective longitudinal study. Exposures based on self-report. | Exposure to defoliants/fumigants was associated with an increased risk of AD (multivariable-adjusted RR, 95 % CI: 4.35, 1.05-17.90). | A |
Koeman et al. 2015 [63] | Diesel motor exhaust (DME) | The Netherlands Cohort Study which consisted of 120,852 individuals aged 55–69 years in 1986. | 682 men and 870 women who had died with non-VaD reported on their death certificates over 17 years follow up. | Case-cohort study: Cox PH models. Exposures based on self-report. Dementia status ascertained using death certification. Person-years were calculated from a randomly-selected sub-cohort. | Exposure to DME compared to no exposure was not associated with an increased risk of non-VaD mortality in men or women. | A |
Koeman et al. 2015 [63] | Electromagnetic fields (ELF-MF and electric shocks) | The Netherlands Cohort Study which consisted of 120,852 individuals aged 55–69 years in 1986. | 682 men and 870 women who had died with non-VaD reported on their death certificates over 17 years follow up. | Case-cohort study: Cox PH models. Exposures based on self-report. Dementia status ascertained using death certification. Person-years at risk were calculated from a randomly-selected sub-cohort. | Low or high exposure to ELF-MF compared to no exposure was not associated with an increased risk of non-VaD mortality in men (adjusted HR, 95 % CI 1.26, 1.01-1.57; 1.40, 0.92-2.14) but not in women. Conversely, an association was seen for electrical shocks for women (1.25, 0.85-1.84; 11.1, 3.84-32.2) but not men. | A |
The hazard associated with cumulative ELF-MF exposure to showed no trend (P = 0.09). | ||||||
Tyas et al., 2001 [62] | Excessive noise | The Manitoba Study of Health and Aging – random sample from provincial health insurance records. | 694 cognitively-intact older adults followed up for five years, during which time 36 developed probable or possible AD (clinically diagnosed). | Prospective longitudinal study. Exposures based on self-report. | Occupational exposure to excessive noise was associated with a decreased risk of AD (multivariable-adjusted RR, 95 % CI: 0.12, 0.02-0.96). N.B. only one case was exposed to excessive noise. | B |
McDowell et al., 1994 [66] | Glues and pesticides/fertilizers | Canadian Study of Health and Aging based in 10 provinces. | 258 people clinically diagnosed with probable AD (less than three years since onset of symptoms) and 535 age-matched controls (stratified by study centre, community-/institution-dweller and clinically confirmed to be cognitively normal) | Cross-sectional study (case–control): logistic regression. Risk factor exposure gathered by questionnaire self-report. | Occupational exposure to glues and pesticides/fertilizers was associated with an increased risk of AD (multivariable-adjusted OR, 95%CI: glues 1.80, 0.99-3.27; pesticides/fertilizers 1.58, 0.81-3.10. Stratifying by education showed higher risk in those with less education. | B |
Gauthier et al., 2001 [64] | Herbicides, insecticides and pesticides | 1924 people aged ≥70 years old were screened and examined in the Saguenay–Lac Saint-Jean region (Québec, Canada). | 122 people clinically diagnosed with AD and 122 age-matched controls (±2 years). 67 case–control pairs hade complete data and were included in the models. | Cross-sectional study (case–control): logistic regression. Exposure to pesticides derived from residential history and census data (1971–91) on herbicide and insecticide spraying in the area. | No increased risk of AD with exposure to herbicides, insecticides or pesticides (multivariable adjusted OR, 95 % CI: 1.07, 0.39-2.54); 1.62 (0.64-4.11); 0.97 (0.38-2.41). | B |
Santibanez et al., 2007 [68] | Lead (occupational exposure) | Systematic review of studies linking occupational exposures and AD. | Twenty four studies: 3 cohort and 21 case–control studies. | Systematic review. | “For lead exposure there are no data supporting any association. All the studies are case–control studies, with a relatively low level of quality according to our classification.” (p. 730) | - |
Koeman et al. 2015 [63] | Metals (occupational exposure) | The Netherlands Cohort Study which consisted of 120,852 individuals aged 55–69 years in 1986. | 682 men and 870 women who had died with non-VaD reported on their death certificates over 17 years follow up. | Case-cohort study: Cox PH models. Exposures based on self-report. Dementia status ascertained using death certification. Person-years at risk were calculated from a randomly-selected sub-cohort. | Low or high exposure to metals compared to no exposure was associated with an increased risk of non-VaD mortality in men (adjusted HR, 95 % CI 1.21, 0.84-1.74; 1.35, 0.98-1.86) and women (4.55, 1.35-15.3; 1.78, 0.23-13.8). | A |
The hazard associated with cumulative exposure to metals showed a significant trend (P = 0.01). | ||||||
Hayden et al., 2010 [65] | Pesticides | The Cache County study (Utah, USA). | 3,084 individuals aged ≥65 years without dementia followed up over 10 years during which time 500 people developed clinically-diagnosed dementia (344 AD). | Prospective cohort study: Cox PH models. Exposures based on self-report. Follow-up conducted at 3, 7 and 10 years from baseline. | Pesticide exposure was associated with an increased risk of dementia (adjusted HR, 95 % CI 1.38, 1.09-1.76) and AD (1.42, 1.06-1.91). A slightly greater risk associated with organophosphates for AD was reported. | A |
Baldi et al. 2003 [70] | Pesticides | PAQUID cohort [110]. Male and female residents of Gironde, France aged ≥65 in 1987. | 96 incident cases of AD from 1,507 contactable individuals between 5- and 10-year follow-up. | Prospective cohort study. | Occupational exposure to pesticides was associated with an increased risk of AD in men (adjusted RR, 95 % CI: 2.4, 1.0-5.6). This was not the case for other pesticide variables or in women. | A |
Cumulative exposure to pesticides was calculated based on job history. AD was diagnosed by a neurologist. | ||||||
Koeman et al. 2015 [63] | Pesticides | The Netherlands Cohort Study which consisted of 120,852 individuals aged 55–69 years in 1986. | 682 men and 870 women who had died with non-VaD reported on their death certificates over 17 years follow up. | Case-cohort study: Cox PH models. Exposure based on self-report. Dementia status ascertained using death certification. Person-years at risk were calculated from a randomly-selected sub-cohort. | Exposure to any pesticides was not associated with an increased risk of non-VaD mortality in men or women. The same pattern was seen when disaggregating the effect of insecticides, herbicides, and fungicides in men. In women, high exposure to herbicides and fungicides was associated with an increased risk of non-VaD mortality (adjusted HR, 95 % CI 5.27, 1.30-21.4; 2.83, 0.87-9.16). | A |
The hazard associated with cumulative exposure showed a significant trend for all pesticides and individual types (P = 0.01) but the trend was reversed with increasing exposure associated with a lower risk. | ||||||
Povey et al., 2014 [67] | Pesticides | British farmers in the 1970s. | 1,350 individuals born before 1958. | Retrospective cohort study: logistic regression. Exposure was based on self-reported levels of organophosphate exposure. Low dose chronic exposure was defined as handling organophosphate concentrate and acute exposure as having sought advice for pesticide poisoning. Dementia was identified by a screening questionnaire. | In people who had never sought advice for pesticide poisoning, handling pesticide concentrate was not associated with dementia. However, in those who had handled pesticide concentrate, seeking advice for pesticide poisoning was associated with an increased risk of dementia (adjusted OR, 95 % CI 4.27, 1.85-9.83). | B |
Zaganas et al. 2013 [69] | Pesticides | Review of studies linking pesticide exposure and dementia. | Fourteen studies are reviewed (2 on cognitive performance, 1 mild cognitive dysfunction, 7 AD, 1 FTD, 2 VaD, and 1 PD). | Narrative review. | Of the 7 AD studies, 5 demonstrated an increased risk of AD (plus one which did so weakly) and one showed no association. | - |
“Information from the literature [on VaD] is scant; however, occupational exposure to pesticides or fertilizers conferred a two-fold increased risk of developing vascular dementia in the Canadian Study of Health and Aging.” (p. 7). | ||||||
“Due to the relative rarity of [FTD] at the population level, pesticide exposure has been studied as a contributing factor to FTD onset in relatively few studies and no association was found.” (p. 7). | ||||||
Santibanez et al., 2007 [68] | Pesticides | Systematic review of studies linking occupational exposures and AD. | Twenty four studies: 3 cohort and 21 case–control studies. | Systematic review. | “For pesticides, research of greater quality and prospective design found increased and statistically significant associations with AD. … The two case control studies assessing risk associated with pesticide exposure and with GQI above the median found evidence of smaller and non-significant associations, supporting the hypothesis that potential biases might have affected these results, decreasing the associations towards the null.” (p. 729–31) | - |
Tyas et al., 2001 [62] | Pesticides/fertilizers, inks/dyes, paints/stains/varnishes, gasoline/fuels/oils, solvents/degreasers, liquid plastics/rubbers, glues/adhesives, vibratory tools | The Manitoba Study of Health and Aging – random sample from provincial health insurance records. | 694 cognitively-intact older adults followed up for five years, during which time 36 developed probable or possible AD (clinically diagnosed). | Prospective longitudinal study. Exposures based on self-report. | Other occupational exposures were not associated with an increased risk of AD (multivariable-adjusted RR, 95 % CI: pesticides/fertilizers 1.45, 0.57-3.68; inks/dyes 0.89, 0.28-2.81; paints/stains/varnishes 1.21, 0.46-3.21; gasoline/fuels/oils 0.79, 0.29-2.20; solvents/degreasers 0.88, 0.31-2.50; liquid plastics/rubbers 1.01, 0.12-8.38; glues/adhesives 1.41, 0.49-4.05; use of vibratory tools 1.03, 0.20-5.29). | A |
Tyas et al., 2001 [62] | Radiation | The Manitoba Study of Health and Aging – random sample from provincial health insurance records. | 694 cognitively-intact older adults followed up for five years, during which time 36 developed probable or possible AD (clinically diagnosed). | Prospective longitudinal study. Exposures based on self-report. | Occupational exposure to radiation was associated with an increased risk of AD (multivariable-adjusted RR, 95 % CI: 3.57, 0.38-33.38). N.B. only one case was exposed to radiation. | B |
Kukull et al. 1995 [71] | Solvents | Individuals aged ≥60 years recruited to the Group Health Cooperative in Seattle-area clinics. | 193 cases of AD and 243 unmatched controls. | Cross-sectional study (case–control): logistic regression. Risk factor exposure was based on self-report. | Solvent exposure was associated with an increased odds ratio of dementia in men (adjusted OR, 95 % CI: 6.3, 2.2-18.1) but not in women (0.6, 0.2-1.9). In men, a significant effect of exposure duration was observed. | B |
Koeman et al. 2015 [63] | Solvents | The Netherlands Cohort Study which consisted of 120,852 individuals aged 55–69 years in 1986. | 682 men and 870 women who had died with non-VaD reported on their death certificates over 17 years follow up. | Case-cohort study: Cox PH models. Exposures based on self-report. Dementia status ascertained using death certification. Person-years at risk were calculated from a randomly-selected sub-cohort. | High exposure to any solvents compared to no exposure was associated with an increased risk of non-VaD mortality in men (adjusted HR, 95 % CI 1.20, 0.90-1.61) but not women. High exposure to aromatic solvents was associated with increased non-VaD mortality in women (3.46, 0.59-20.5) but not men. High exposure to chlorinated solvents was associated with increased risk in men (1.33, 0.96-1.83) and women (2.08, 0.60-7.14), as was low exposure in men (1.25, 0.89-1.76). | A |
The hazard associated with cumulative exposure to chlorinated solvents showed a significant trend (P = 0.01). | ||||||
Santibanez et al., 2007 [68] | Solvents | Systematic review of studies linking occupational exposures and AD. | Twenty four studies: 3 cohort and 21 case–control studies. | Systematic review. | “For solvents, only two out of the 11 studies analysing this exposure found a significant association with AD.” (p. 730) | - |
Study | Exposure | Sample description |
N
| Methodology/design | Finding | Grade |
---|---|---|---|---|---|---|
Salib & Sharp, 1999 [72] | Climate | Daily hospital admissions from North Cheshire to a single hospital. Dementia cases were identified by ICD-9 code 290. | 189/2070 psychiatric admissions during 1993 were coded as being related to dementia. | UK Meteorological Office data were collected at Manchester airport (30 miles away) every day. | There were no associations found between weather parameters and hospital admissions of people with dementia. | C |
Huss et al., 2009 [74] | Magnetic field exposure (220–380 kV) through power lines | Swiss National Cohort from 2000–5. The study population comprised 4.65 million individuals and 22,821,824 person-years. | 29,975 dementia deaths were recorded, including 9,228 AD deaths. | Prospective cohort study: Cox PH models. Exposure was based on distance of place of residence to the nearest power line and duration of exposure (5, 10, or 15 years). Dementia was ascertained from death certification. | Proximity to power lines was associated with an increased risk of dementia but this was not statistically significant at conventional levels (adjusted HR, 95 % CI closest:most distant categories 1.23, 0.96-1.59). Longer duration increased the magnitude of this association (≥15 years at this place of residence 2.00, 1.21-3.33). | A |
Vergara et al., 2013 [111] | Extremely low frequency magnetic fields | Systematic review of studies of occupational exposure to magnetic fields and neurodegenerative disease. | 20 AD and 9 dementia studies. | Systematic review and meta-analysis. | There was a small association between occupational magnetic field exposure and AD based on a meta-analysis (RR, 95 % CI 1.27, 1.15-1.40). There was no clear association with dementia (1.05, 0.96-1.14). | - |
Garcia et al., 2008 72] | Extremely low frequency electric and magnetic fields. | Systematic review and meta-analysis | Fourteen studies: 9 case–control, 5 cohort | Systematic review. | Pooled cohort risk estimates (OR, 95 % CI 1.62, 1.16-2.27). Pooled case–control risk estimates (2.03, 1.38-3.00, P = 0.004). | - |
Schuez et al., 2009 [75] | Mobile phones | All mobile phone subscriptions in Denmark, 1982–1995. | 420,095 private mobile phone subscribers of whom 532 were admitted to hospital with a dementia code during follow up. | Prospective cohort study. Mobile phone use was derived from subscription records. Dementia status was identified from hospital admission records. | Mobile phone use was associated with a decreased risk of being hospitalised with AD (Standardized hospitalization ratio, 95 % CI 0.7, 0.6-0.9). Similar results were seen for VaD and “other dementia”. | B |
Afzal et al., 2014 [76] | Vitamin D | Danish general population sample recruited to the Copenhagen Heart Study at baseline (1981 to 1983). | 10,186 participants, of whom 418 developed AD and 92 developed to VaD. | Prospective cohort study: Cox PH models. Baseline plasma vitamin D levels were related to incident AD and VaD. Dementia status was derived from diagnostic codes recorded on the national Danish Patient Registry. | Lower plasma vitamin D levels were associated with an increased risk of AD (HR, 95 % CI <25th percentile [seasonally-adjusted] vs >50th 1.29, 1.01-1.66; P = 0.03). Similar findings were reported for VaD (1.22, 0.79-1.87; P = 0.42) and all dementia (1.27, 1.01-1.60; P = 0.02). | A |
Littlejohns et al., 2014 [78] | Vitamin D | Healthy participants in the US population–based Cardiovascular | 1658 adults followed up for mean 5.6 years during which time 171 developed clinically-ascertained dementia (102 AD). | Prospective cohort study: Cox PH models. Serum vitamin D levels were measured at baseline. | Being deficient (25-50nM) or severely deficient (<25nM) in vitamin D was associated with an increased risk of incident AD (multivariable-adjusted HR, 95 % CI: 1.69, 1.06-2.69; 2.22, 1.02-4.83; Ptrend = 0.008). Similar results were seen for all-cause dementia (1.53, 1.06-2.21; 2.25, 1.23-4.13; Ptrend = 0.002). | A |
Health Study. | ||||||
Annweiler et al., 2011 [77] | Vitamin D | Toulouse subset of the EPIDOS study cohort of women aged ≥75 years. | 40 participants, of whom 6 developed non-AD (and 4 AD) at clinical assessment over 7 years follow up. | Prospective cohort study: logistic regression. Baseline serum vitamin D was related to incident non-AD dementia. | Vitamin D deficiency at baseline was associated with an increased risk of non-AD dementia (adjusted OR, 95 % CI 19.57, 1.11-343.69; P = 0.042). | A |
Wilkins et al., 2006 [79] | Vitamin D | Participants recruited from greater metropolitan St Louis, MO by the Washington University AD Research Center. | 40 people with clinically diagnosed mild AD and 40 without dementia. | Cross-sectional study (case–control): logistic regression and general linear model. Serum vitamin D levels were measured. | Vitamin D status was not associated with AD (multivariable-adjusted OR, 95 % CI: deficient vs sufficient 2.80, 0.64-12.28; insufficient vs sufficient 1.78, 0.61-5.19). Vitamin D status was associated with CDR sum of boxes (P = 0.0468); and the Short Blessed Test (P = 0.0077) but not others tests. | B |
Frecker, 1991 [42] | Water pH | Mortality records in Bonavista Bay, Newfoundland, 1985–86. | 191 dementia deaths in 1985, 208 deaths in 1986 | Cross-sectional study. Place of birth of all individuals dying with dementia was identified and associated with drinking water samples at those locations from 1986. | The area with the highest dementia mortality (37.5 % in 1985 and 68.8 % in 1986) also had the lowest pH of drinking water (5.2). This association was not assessed for statistical significance, but was argued to not be confounded by age, sex or place of residence stated on death certificate. | B |