Living near major roads or highways is linked to a higher incidence of dementia, Parkinson’s disease, Alzheimer’s disease and multiple sclerosis (MS) suggests new research published this week in the journal Environmental Health.
Researchers from the University of British Columbia analyzed data for 678,000 adults in Metro Vancouver.
They found that living less than 50 meters from a major road or less than 150 meters from a highway is associated with a higher risk of developing dementia, Parkinson’s, Alzheimer’s and MS–likely due to increased exposure to air pollution.
The researchers also found that living near green spaces, like parks, has protective effects against developing these neurological disorders.
“For the first time, we have confirmed a link between air pollution and traffic proximity with a higher risk of dementia, Parkinson’s, Alzheimer’s and MS at the population level,” says Weiran Yuchi, the study’s lead author and a PhD candidate in the UBC school of population and public health.
“The good news is that green spaces appear to have some protective effects in reducing the risk of developing one or more of these disorders.
More research is needed, but our findings do suggest that urban planning efforts to increase accessibility to green spaces and to reduce motor vehicle traffic would be beneficial for neurological health.”
Neurological disorders–a term that describes a range of disorders, including Alzheimer’s disease and other dementias, Parkinson’s disease, multiple sclerosis, and motor neuron diseases–are increasingly recognized as one of the leading causes of death and disability worldwide.
Little is known about the risk factors associated with neurological disorders, the majority of which are incurable and typically worsen over time.
For the study, researchers analyzed data for 678,000 adults between the ages of 45 and 84 who lived in Metro Vancouver from 1994 to 1998 and during a follow-up period from 1999 to 2003.
They estimated individual exposures to road proximity, air pollution, noise and greenness at each person’s residence using postal code data. During the follow-up period, the researchers identified 13,170 cases of non-Alzheimer’s dementia, 4,201 cases of Parkinson’s disease, 1,277 cases of Alzheimer’s disease and 658 cases of MS.
For non-Alzheimer’s dementia and Parkinson’s disease specifically, living near major roads or a highway was associated with 14 percent and seven percent increased risk of both conditions, respectively.
Due to relatively low numbers of Alzheimer’s and MS cases in Metro Vancouver compared to non-Alzheimer’s dementia and Parkinson’s disease, the researchers did not identify associations between air pollution and increased risk of these two disorders. However, they are now analyzing Canada-wide data and are hopeful the larger dataset will provide more information on the effects of air pollution on Alzheimer’s disease and MS.
The researchers also found that living near green spaces, like parks, has protective effects against developing these neurological disorders.
When the researchers accounted for green space, they found the effect of air pollution on the neurological disorders was mitigated. The researchers suggest that this protective effect could be due to several factors.
“For people who are exposed to a higher level of green space, they are more likely to be physically active and may also have more social interactions,” said Michael Brauer, the study’s senior author and professor in the UBC school of population and public health. “There may even be benefits from just the visual aspects of vegetation.”
Brauer added that the findings underscore the importance for city planners to ensure they incorporate greenery and parks when planning and developing residential neighborhoods.
The study was co-authored by Hind Sbihi, Hugh Davies, and Lillian Tamburic in the UBC school of population and public health.
Dementia, encompassing both vascular dementia and Alzheimer’s disease, is now reported as the leading cause of death in England and Wales, accounting for 12% of all registered deaths.1 While temporal changes in recording may have influenced how the underlying cause is now determined, more important are increases in longevity among the population at older ages, caused by declining trends in deaths from cardiovascular and cerebrovascular disease.2
In terms of years of life lost, the Global Burden of Disease in 2013 ranked all dementia as the fifth leading cause,2 noting their increasing importance as a cause of death despite little change in age-standardised rates. Therefore, primary prevention of all dementia is a major global public health concern for the coming decades.3
For Alzheimer’s disease for example, while it has been estimated that small delays in its onset and progression could significantly reduce its estimated future burden,4research has primarily focused on lifestyle factors, where a large systematic review estimated that about a third of Alzheimer’s disease may be attributable to potentially modifiable risk factors such as smoking and physical inactivity.5
More recently research has also extended to the role of environmental risk factors and dementia, where a large systematic review identified moderate evidence for an association with eight different factors including air pollution.6
While air pollution is a well-established risk factor for cardiovascular and respiratory disease,7 its role in relation to dementia is less well considered and understood.8
A recent systematic review of the epidemiological evidence linking air pollution to dementia-related outcomes identified 18 studies, with most reporting adverse associations.9
However, there was a significant variation in the size and quality of the studies involved, reiterating the noted lack of robust longitudinal or population-based studies.6 8 Subsequently, a large population-based study in Ontario, Canada, reported that living close to major roads was associated with a higher incidence of dementia,10 with a further analysis revealing corresponding associations with modelled levels of nitrogen dioxide (NO2) and mass of fine particulate matter with a median aerodynamic diameter ≤2.5 µm (PM2.5).11
These findings raise questions around the mechanisms for the early development of neuroinflammation and neurodegeneration,12 and require further exploration and replication in other large population cohorts with different exposure models, including traffic noise which has been linked to cognitive decline in adults.13
In this paper, we use modelled estimates at a fine spatial scale for modelled estimates of air and noise pollution to investigate relationships with the incidence of dementia across Greater London.
In a sample of 75 general practices across Greater London, the recording of new dementia diagnoses was positively associated with measures of NO2 and PM2.5 assigned at residential address at the beginning of the incident period. The association could not be explained by confounding and was consistent within subgroups. When we restricted to specific diagnoses, associations were still observed with Alzheimer’s disease but not vascular dementia.
Strengths and weaknesses
While we were able to link pollution exposures to the primary care record to obtain diagnoses of dementia, there are concerns around the variability of dementia diagnoses in UK primary care,24 and a recent review has concluded that dementia diagnoses on primary care databases may not be an accurate reflection of the true prevalence.25 Under-recording is thought to be a common issue, as the diagnosis is associated with a stigma for many, and GPs may be reluctant to diagnose dementia unless highly certain.26
A recent study across 23 London practices increased the prevalence on their QOF dementia registers by 9% by a simple coding review.26 To account for under-recording at baseline, a priori we decided to exclude all patients identified as living in care homes at the beginning of follow-up regardless of dementia diagnosis.
During follow-up, we observed broadly similar number of dementia subtypes being newly diagnosed, and since it is expected that about two-thirds of dementia is Alzheimer’s disease,27 this suggests the under-recording of Alzheimer’s disease in particular may be an issue. Under-recording in our study could be problematic if it was related to key practice characteristics such as deprivation, as dementia recording has been shown to be lower among more affluent practices.24 28
In our study we observed a wide range of incident rates by practice (0.2%–8.4%), and since the majority of air pollution variation was between practices we cannot discount unmeasured practice characteristics as a possible explanation for our findings. There are also known variations in the prevalence and diagnosis rates of dementia across England,24 with London being among the reported lowest,29 so we also have to acknowledge that the associations we observed may be specific within London and may not extend nationally.
Another weakness of the study is the lack of historical data surrounding exposure. Most large epidemiological studies of long-term exposure to pollution will have difficulty capturing an accurate picture of lifetime or cumulative exposure.
This may be pertinent for Alzheimer’s disease where the pathogenesis of the disease may take place over many years.30 We did not have any information relating to previous address or location, and the London population is thought to be mobile and dynamic over time.31 Thus, we are making an assumption that an annual estimate for a single year (2004) represents long-term exposure, based on the last known address for the patient at that practice.
We tested this in two ways: (1) sensitivity analyses based on patients who had been continually registered at their practice for a long time (>10 years) produced similar findings; (2) where we did have other modelled years available during follow-up (2005–2010), these were highly correlated over time (r>0.95), so alternative analyses using them made no discernible difference.
However, we cannot discount historical factors as an explanation for our findings. For example, it could be that recent exposure levels are acting as a proxy for other historical environmental factors linked to pollution, such as lead from petrol,32 where cumulative exposure has been linked to cognitive decline in later life.33
A novel aspect of our analysis was the ability to simultaneously study the modelled effects of air and noise pollution on dementia, overcoming acknowledged limitations from other studies.11 34Previous validation of the pollution models used in this study had shown low roadside correlation between them, suggesting that the independent effects of traffic pollution and road noise can be investigated.20
However, a potential limitation is that by being based within Greater London, our air pollution exposure estimates may be somewhat homogeneous, lacking the variability we would expect to see nationally when more rural geographical areas are included. Within London, the contribution of regional (background) PM2.5 and O3 to overall levels tends to dominate.17 However, we were able to make use of a dispersion model with exceptionally fine resolution (20×20 m) to estimate significant changes in exposure of air pollution such as NO2, between major roads and suburban background locations.17
Despite this, the reality was that subtle roadside changes predicted by the model were small in comparison with larger differences estimated between the areas represented by the GP practices (ICCs>0.7 for all air pollutants), suggesting most modelled air pollution variation was between (practice) areas.16While this limited statistical power to test for any within-practice effects in the study, we did not find evidence to suggest that the overall associations with NO2 and PM2.5 were entirely explained by between-practice differences in modelled exposures.
Finally, another limitation was the incomplete information on key confounders and reliance on an area-based measure (IMD) for socioeconomic status. While mid-life obesity is a risk factor for Alzheimer’s disease,5 the BMI measures we extracted around baseline showed that the risk declined with obesity in later life, a finding which has been observed elsewhere.35 However, further adjustment for IHD, stroke, diabetes and heart failure, which would be associated with earlier unmeasured risk factors, including individual socioeconomic status, did not explain our findings.
The established body of epidemiological evidence linking long-term concentrations of air pollution to adverse health effects has mainly focused on cardiovascular disease.36 The Global Burden of Disease studies, which have described the worldwide impact of air pollution, considered a wide range of outcomes (IHD, stroke, lung cancer, chronic obstructive pulmonary disease) but did not consider neurodegenerative outcomes.7 Research linking air pollution exposure to neurocognitive function has gradually increased from observational findings in 2002 from dogs in Mexico City,37 to larger studies which assessed cognitive decline,38 39 and large population cohorts that specifically investigated the association in relation to diagnoses of dementia.10 11 40–43
A 2015 review on the effect of long-term exposure to outdoor air pollution (15 studies) and noise (8 studies) on cognitive and psychological functions in adults showed that both exposures were separately shown to be associated with one or several measures of global cognitive function, but no study considered both exposures simultaneously, which they highlighted as a need for further research.34
The same authors followed with data from the Heinz Nixdorf Recall cohort study13 on 4086 adults using an additively calculated global cognitive score. They concluded ‘air pollution and road traffic noise might act synergistically on cognitive function in adults’. Our study could consider both measures (air pollution and night noise), and while both showed independent associations with dementia, in a combined model any associations with noise were diminished and of borderline statistical significance.
The largest cohort studies to date investigating dementia and long-term exposure to air pollution are from North America.10 11 43 Chen et al 10 11 used a large Canadian population-based cohort of over 2 million adults aged 55–85 years to ascertain approximately 250 000 incident dementia cases during 2001–2013. In their first analysis,10the authors found that the risk of dementia increased with nearness to a major road (adjusted HR=1.07, 95% CI 1.06 to 1.08, for people living <50 m from a major traffic road versus >300 m). Associations were stronger among urban residents, especially those who lived in major cities.
In a subsequent analysis,11 they used land-use regression models to estimate associations between incident dementia and air pollution, finding significant positive associations with both PM2.5 and NO2, and smaller negative associations with O3. An IQR increase in PM2.5 (4.8μg/m3) was associated with an HR of 1.04 (95% CI 1.03 to 1.05), while for NO2 (14.2 parts per billion) HR was estimated to be 1.10 (95% CI 1.08 to 1.12). By comparison, our estimated distribution of the same pollutants within Greater London was much less spread, with IQRs approximately one-quarter in size. Therefore, comparative HRs for similar unit changes in our study are much greater (eg, for a 1 µg/m3 change in PM2.5 the HR would be 1.07 compared with 1.01 from the Canadian study, for NO2 this would be 1.02 vs 1.00). Our estimate for PM2.5 was more in line what was found in a large US study of Medicare enrollees for first-ever hospitalisation for dementia during 1999–2010 (HR=1.08, 95% CI 1.05 to 1.11, for a 1 µg/m3 change in PM2.5).
Chen et al 11 speculate that the stronger associations observed with NO2 may be in part due to it better capturing fine-scale variability in traffic-related air pollution, whereas PM2.5 and O3 have larger regional components. However the resolution of their air pollution models was coarser (1×1 km resolution) than in our study (20×20 m) and may not capture primary emissions from road traffic. While our models were able to estimate traffic-specific components of PM2.5,17 effect estimates remained higher for NO2.
Some smaller studies have separated Alzheimer’s disease from dementia. In Europe, a 15-year longitudinal study in northern Swedish city found evidence of positive associations with both vascular dementia and Alzheimer’s disease and nitrogen oxide using a land-use regression model with a spatial resolution of 50×50 m.41 Comparison between participants in the highest quartile of residential exposure at baseline, versus those in the lowest, produced similar estimates for Alzheimer’s disease (HR=1.38) and vascular dementia (HR=1.47).
There have been recent cohort studies from Taiwan: Jung et al 40 showed long-term exposure to O3 and PM2.5 was shown to increase the risk of Alzheimer’s disease, while Chang et al 42 found associations between dementia and NO2 and carbon monoxide. A smaller case–control study by Wu et al 44 linked PM10 and O3 to an increased risk of Alzheimer’s disease and (vascular) dementia. In our study, lower O3 was negatively associated with risk of dementia, primarily as a result of the strong negative correlation with the other modelled air pollutants.45
The implications of linking exposure to air pollution such as NO2 to the development of dementia, specifically Alzheimer’s disease, raise many questions.12 The cause of these neurodegenerative diseases is still largely unknown and may be multifactorial.8 While toxicants from air pollution have several plausible pathways to reach the brain, how and when they may influence neurodegeneration remains speculative.8 30 46
Traffic-related air pollution has been linked to poorer cognitive development in young children,47 and continued significant exposure may produce neuroinflammation and altered brain innate immune responses in early adulthood.48 In later life, the risk for accelerated cognitive decline may involve gene–environment interactions, such as that with apolipoprotein E,49 where evidence comes from findings in neurotoxicological experiments with mice.50
Our observation of an association of air pollution with new dementia diagnoses among older adults living in Greater London is in contrast to an earlier analysis on these data which failed to show consistent associations between air pollution and cardiorespiratory outcomes.16
These suggest there may be a geographical pattern specific to dementia, and potentially Alzheimer’s disease, which requires further exploration nationally. In the Ontario cohort, Chen et al estimated that 6.1% of their total dementia cases were attributable to elevated air pollution exposure.11 In our study, a theoretical shift of all patients to the bottom 20% of NO2 exposure produces an attributable fraction of 7% (data not shown).
While this would be smaller than previous population attributable fraction (PAF) estimates for dementia in the UK for a range of independent risk factors such as for hypertension or obesity,5 even a small PAF for dementia would be impactful, where environmental risk factors such as air pollution can be more easily modified at the population level.30 There would be significant public health gains even if the impact was only to delay the progression of dementia.4
With the future global burden of dementia likely to be substantial,3further epidemiological work is urgently needed to confirm and understand better recent findings linking air pollution to dementia.8 30 Our results suggest both regional and urban background pollutants may be as important as near-traffic pollutants.
Future large-scale studies will need to rely on improved recording and linkage of dementia diagnoses across electronic systems, particularly Alzheimer’s disease, where multiple sources can improve diagnostic accuracy.25
Since exposure is lifelong, and most cases are diagnosed in later life, historical data are also ideally required to better estimate cumulative exposure over preceding decades. In conclusion, our findings add to a growing evidence base linking air pollution and neurodegeneration and should encourage further research in this area.