Older women exposed to higher levels of air pollution experience greater memory decline and Alzheimer

Women in their 70s and 80s who were exposed to higher levels of air pollution experienced greater declines in memory and more Alzheimer’s-like brain atrophy than their counterparts who breathed cleaner air, according to USC researchers.

The findings of the nationwide study, published today in Brain, touch on the renewed interest in preventing Alzheimer’s disease by reducing risk as well as hint at a potential disease mechanism.

Alzheimer’s is the sixth-leading cause of death in the United States, and there’s currently no cure or treatment.

“This is the first study to really show, in a statistical model, that air pollution was associated with changes in people’s brains and that those changes were then connected with declines in memory performance,” said Andrew Petkus, assistant professor of clinical neurology at the Keck School of Medicine at USC.

“Our hope is that by better understanding the underlying brain changes caused by air pollution, researchers will be able to develop interventions to help people with or at risk for cognitive decline.”

Fine particles, also called PM2.5 particles, are about 1/30th the width of a human hair.

They come from traffic exhaust, smoke and dust and their tiny size allows them to remain airborne for long periods, get inside buildings, be inhaled easily, and reach and accumulate in the brain.

Fine particle pollution is associated with asthma, cardiovascular disease, lung disease and premature death.

Previous research has suggested that fine particle pollution exposure increases the risk for Alzheimer’s disease and related dementias.

What scientists haven’t known is whether PM2.5 alters brain structure and accelerates memory decline.

For this study, researchers used data from 998 women, aged 73 to 87, who had up to two brain scans five years apart as part of the landmark Women’s Health Initiative.

The Women’s Health Initiative was launched in 1993 by the National Institutes of Health and enrolled more than 160,000 women to address questions about heart disease, cancer and osteoporosis.

Those brain scans were scored on the basis of their similarity to Alzheimer’s disease patterns by a machine learning tool that had been “trained” via brain scans of people with Alzheimer’s disease.

The researchers also gathered information about where the 998 women lived, as well as environmental data from those locations to estimate their exposure to fine particle pollution.

When all that information was combined, researchers could see the association between higher pollution exposure, brain changes and memory problems — even after adjusting to take into account differences in income, education, race, geographic region, cigarette smoking and other factors.

“This study provides another piece of the Alzheimer’s disease puzzle by identifying some of the brain changes linking air pollution and memory decline. Each research study gets us one step closer to solving the Alzheimer’s disease epidemic,” Petkus said.

Previous research has suggested that fine particle pollution exposure increases the risk for Alzheimer’s disease and related dementias. What scientists haven’t known is whether PM2.5 alters brain structure and accelerates memory decline.

In addition to Petkus, the study authors are Diana Younan, Xinhui Wang, Margaret Gatz, Helena Chui and Jiu-Chiuan Chen of USC; Keith Widaman of UC Riverside; Ramon Casanova, Mark Espeland, Stephen Rapp, Bonnie Sachs, Sarah Gaussoin, Ryan Barnard, Santiago Saldana, Daniel Beavers and Sally Shumaker of Wake Forest School of Medicine; Victor Henderson of Stanford; JoAnn Manson and Joel Salinas of Harvard Medical School; Marc Serre and William Vizuete of the University of North Carolina; and Susan Resnick of the National Institute on Aging.

Funding: The study was supported by the National Institute of Environmental Health Sciences (R01ES025888), the National Institute on Aging (R01AG033078, R21AG051113, R01AG033078, RF1AG054068 and RF1AG054068), the Southern California Environmental Health (5P30ES007048), the National Institutes of Health (P50AG047366, P50AG05142).

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Alzheimer’s disease (AD) is the most common form of dementia, with the estimated number of patients in the U.S. over 5 million, and over 35 million patients worldwide [1], [2]. AD and other dementias accounted for about 1.5 million deaths in 2015 and are currently ranked at the seventh leading cause of death worldwide [3]. These numbers will double or even triple as the aged population rapidly increases in next few decades. Such a rapid increase in AD cases will create major socioeconomic burdens for society unless effective therapeutic interventions to slow, halt, or cure this devastating disease are developed.

In lieu of conquering the disease, the most expedient and potentially actionable course to curb the predicted rise in AD cases is to identify and limit major risk factors for the disease. Aging is the single greatest risk factor for AD, and mounting evidence also indicates a strong contribution from genetic predispositions, particularly the presence of apolipoprotein E ε4 (APOE ε4) allele as, by far, the major genetic risk factor for the late-onset AD [4], [5].

While both aging and genetic risk factors are virtually perpetual within each individual, they do not fully explain the cause of every AD case, and homozygotic and heterozygotic twin studies reveal key involvement of additional environmental and modifiable risk factors in AD etiology [6], [7]. These include, but are not limited to, lifestyle, disease history, educational background, dietary habits, and exposure to environmental and occupational hazards [8], [9].

Environmental risk factors, such as metals and other toxic contaminants in drinking water, agricultural chemicals on food, and air pollution, could potentially impact large sections of the population and become public health concerns. Chronic exposure to environmental factors has been shown to increase the risk for developing AD in both epidemiological studies and in animal models [10], [11], [12].

In this review, we summarize recent evidence indicating that chronic exposure to polluted air is a major environmental risk factor for AD. There is a significant body of epidemiological works unveiling a strong correlation between exposure to particulate matter (PM) and associated air pollutants with accelerated cognitive decline across multiple stages of life, most prominently when exposed at young or old ages.

More recently, growing evidence indicates increased risk of AD and other dementias following chronic PM exposure [11], [12]. Reports examining the effects of PM exposure in cell culture, animal models, and human patients show changes in inflammatory and oxidative stress markers [13], [14], [15].

Changes in AD specific pathology, such as abnormal buildup of amyloid-beta (Aβ) plaques, have also been reported [10], [16], [17]. The purpose of this review is to discuss the recent evidence for the role of air pollutants, with a focus on PM, in AD risk at an epidemiological level, in AD pathogenesis in in vitro and in vivo models and humans, and to suggest future areas of research in this field.Go to:

Sources and chemistry of PM

Exposure to unhealthy levels of polluted air is a worldwide problem, particularly in heavily urbanized areas in developing or developed countries where the ambient levels of air pollution can be over 10 times as concentrated as health guidelines recommend [18]. Major constituents of air pollution are various sizes of PM, nitrogen oxide species (NOx), sulfur oxide species (SOx), carbon monoxide, ozone, hydrocarbons, volatile organic compounds (VOCs), metals, and other inorganic chemicals.

While pollutants from natural sources, such as volcanic activities, wildfires, dust, and coastal aerosols, are difficult to reduce, those released by human activities may be more reasonably curbed if found to adversely impact health to a sufficient degree.

The major sources of human contribution are traffic and industrial related combustion of fossil fuels, as well as mining, agricultural activities, and burning fuels for cooking and heating [19], [20], [21], [22].

PM found in the atmosphere is either generated directly from these sources as primary PM or a result of complex photochemical reactions of NOx, SOx, and ammonia released from motor vehicles, industrial combustion, and agricultural activities, respectively, as secondary PM [23].

This gas-to-particle chemical conversion occurs within water droplets and aerosols in the atmosphere and produces ammonium nitrate as a nucleation step for PM formation. The ammonium nitrate core eventually grows and ages together with other constituents to form mature PM [24]. In certain regions, ammonium nitrate could take up over 50% of all chemical mass present in PM [25].

PM includes a wide variety of microscopic liquid or solid matter in the atmosphere. Particulate contaminants include biological elements such as pollen, bacteria, viruses, and spores, as well as suspended non-biological solids such as dust and smoke.

The exact composition of PM varies considerably based on size, location, weather, the season, time of day, and a multitude of other factors. The major components of airborne particulates worldwide are sulfates, nitrates, ammonium, chlorides, elemental and organic carbons, biological materials, and minerals and dust [23], [26].

The US EPA primarily divides PM into an “ultrafine” designation for PM < 100 nm (PM_0.1), a “fine” fraction of PM of diameter 2.5 microns or less (PM_2.5), and a “coarse” fraction of PM between 2.5 and 10 microns (PM₁₀) [27].

While most components of PM can be found in all size fractions, the smaller PM fractions generally contain higher amounts of black carbon, gases, and other products of combustion, while the coarse fraction contains more metals, inorganic material, and other debris and dust from mechanical processes [28], [29] [Table 1].

Table 1

Particulate matter size fractions.

Size fraction	Designation	Diameter range (μm)	Major constituents	Minor constituents
Coarse PM	PM10	2.5–10	Metals, inorganic ions	Organic matter
Fine PM	PM2.5	0.1–2.5	Inorganic ions	Metals, organic matter
Ultra-Fine PM	PM0.1	≤0.1	Organic matter	Metals, inorganic ions

Table 1 shows the three common size fractions of PM as designated by the US EPA. Major (>25%) and minor constituents (<25%) are estimated by particle constituent mass from USC studies [28], [29]; note that composition of PM may vary considerably with time and location, and that this is only a general estimate of the components of each size fraction.

The outlined size classifications are commonly used at least in part as the size and weight of the particles plays a major role in determining inhalability and particle deposition location in the respiratory tract. While larger particles tend to deposit in and affect the upper respiratory tract, it is largely PM_2.5 and, particularly ultrafine PM that penetrate and deposit in the deep lung tissues [30], [31] [Fig. 1].

Once in the lung, these particulates are taken up by cells [32], [33], [34] and enter the blood stream [35], [36]. PM uptake by these lung cells, macrophages, and blood also facilitates the absorption of potentially toxic chemicals on the surface of the PM into the cell and tissue to exert toxicity [37], [38]. Importantly, ultrafine PM represents the majority of both the total particle number and available surface area of typical PM mixtures [39], [40], [41].

In part due to these traits, which increase relative ability to carry other agents and available surface for reactions, ultrafine PM is generally considered the most toxic form of PM [23], [40]. Research shows that the ultrafine PM fraction causes increased oxidative stress and mitochondrial damage compared to larger PM sizes in macrophages and epithelial cells [42]. Recent evidence suggests that the ultrafine PM can directly infiltrate to the brain through olfactory nerves, and potentially penetrate to the central nervous system (CNS) via systemic uptake [43], [44].

Once in the CNS, PM may lead to inflammation response and oxidative damage similar to what is seen in macrophages and the lungs [45], [46]. Vehicle exhaust is one of the most significant human contributions to PM_2.5 and PM_0.1 levels [47], [48]. As PM tends to aggregate and increase in size over time [49], sources of PM_0.1 to which people are immediately exposed, such as vehicle exhaust in traffic, have a higher impact on human exposure than more distant sources.

In the U.S., it is estimated that over 43 million people live in areas where the air concentration of PM_2.5 exceeds the EPA’s limit of 35 μg/m³ for a short periods of time, and 20 million people in the US live with exposure levels higher than the EPA long-term exposure standard of 12 μg/m³ year round [50]. These areas include major metropolitan regions such as the Los Angeles basin, which had a 2015 average PM_2.5 level of 12.4 μg/m³, with 24 h averages up to 70 μg/m³ [51]. Worldwide, the WHO estimates that 92% of the population lives in areas where WHO air quality guidelines (10 μg/m³ for maximum yearly average and 25 μg/m³ for maximum 24 h average) are not met [18].

The organization attributed an estimated 3 million premature deaths to ambient air pollution in 2012. PM levels in developing countries are still rising [52], leaving many people at risk of being exposed to unhealthy levels. Highly polluted areas such as Delhi, India, and Xingtai, China, experienced annual average PM_2.5 level of over 120 μg/m³ [52]. Together, these data indicate the importance of exploring and understanding of the health ramifications of PM exposure.

Prenatal PM exposure and its impact on cognition

The adverse effect of polluted air on cognition in young children can be caused by exposure as early as in utero. Exposure to polycyclic aromatic hydrocarbons (PAHs), a component of the PM organic carbon fraction, during pregnancy among African-American and Dominican women in New York City was found to correlate with reduced Bayley scale of infant development (BSID-II) scores in the children 3 years old and reduced verbal and full IQ at 5 years [58], [59]. Similar studies performed in Poland also reported a decrease in non-verbal IQ scores at 5 years of age and verbal IQ at 7 years of age in a group of children with high PAH exposure in utero compared to a low exposure group [60], [61].

These studies suggest that PAH exposure during development exhibits delayed impairment of performance during childhood, as in both cases negative cognitive effects were not observed at earlier time points.

In addition to PAH, motor vehicle traffic associated gases are also commonly associated with decreased cognitive ability of children if exposed in utero [62], [63], [64]. NO₂ exposure, PM_2.5 exposure, and traffic intensity are correlated with reduced IQ performance in young children, while PM₁₀, benzene, or reduced distance to roadways during pregnancy are not [63], [64]. A meta-analysis of six other European studies examining the effects of PM_2.5, PM₁₀, and NO₂ exposure during pregnancy on children 1–6 years old found the only significant association to be between NO₂ levels and psychomotor development deficit [62].

On the other hand, exposure to high levels of SO₂ and non-methane hydrocarbons, but not NO₂ and other pollutants, during 2nd or 3rd trimester pregnancy is found to be associated with reduced motor skills in infants at 6 and 18 months of age in Taiwan [65]. Verbal and social-personal scores do not appear to be correlated with any measured pollutant in this study. A recent U.S. based study found limited association between prenatal traffic related pollution exposure in late pregnancy [66]. Using distance to major roadway and EPA estimated PM and black carbon levels, and measuring cognitive ability of children at an average 8 years of age, only distance to roadway had significant effect on cognition.

Lack of personal monitoring of the specific pollutants and more generalized exposure metrics or the higher age of the tested children in this study may account for the discrepancy with other studies. Overall, these studies show that exposures to certain constituents of polluted air during pregnancy exhibit adverse effects on cognitive performance in infants. However, the inconsistency between studies of whether any given active constituent causes impaired cognitive functions requires further investigation.

Differences in study populations, the concentrations of pollutants seen in the studies, and times of exposure and endpoint testing may account for the majority of these discrepancies. Another interesting possibility raised is that the overall mixture of air pollutants, depending on the constituents and concentrations, may elicit a complex and novel toxicity in the body.

Early-life childhood PM exposure and cognition

Adverse effect of air pollution on cognition is not limited to in utero exposure. Increasing levels of NO₂ are associated with decreased gross motor skills in a 1 year longitudinal study of 5 year old male Spanish children [67]. In addition, increased levels of NO₂ at school, but not at home, are associated with a reduction in memory span among 9–11 year old school children [68].

Although the exact reason why NO₂ at school specifically correlates with the children’s cognitive performance remains unknown, the authors speculate that either additional unmeasured factors in the air at school or increased activity at school may be responsible. The same group also found that road and airway noise levels negatively affect switching attention test scores. This indicates that other environmental hazards outside of PM pollution often associated with heavy traffic may be important considerations for confounding factors in determining the effects of PM.

Two U.S. based studies in children focus on black carbon, which is often associated with diesel engines or organic matter fuels such as wood burning. Environmental levels of black carbons are inversely associated with various intellectual performances including vocabulary, composite intelligence, and visual skills of learning and memory in children [69], [70].

The finding by Suglia et al. of reduced memory ability shows that exposure to the black carbon fraction of PM can impact brain functions also affected by AD, and potentially has neurotoxic effect in the regions associated with those functions [70]. Long term studies following from childhood to senescence are highly challenging, but it is interesting to consider that early life PM exposure extends its adverse effect in later life and triggers neurodegenerative diseases like AD.

The remaining studies of air pollution exposure effects on child cognition focus primarily on using proxy measurements of air pollution exposure, such as rural versus city residence or distance of residence to roadway, rather than measurements of the individual constituents of air pollution. While these measures offer relatively simple ways to approximate all source air pollutant exposure, they leave considerable room for interference of confounding factors and exposure variance to inhibit interpreting results.

Measuring performance of children living in Mexico City, where very high levels of air pollution, including PM_2.5, are found, versus Polotitlán, a rural area of Mexico with relatively little pollution, unveils that children in Mexico City are behind age normalized levels of multiple intelligence subscales, including full scale IQ and vocabulary [45], [71]. Another study comparing children 8–10 years of age living at least 3 years in either northern or heavily polluted central Quanzhou reports that children living in the heavily polluted central area have increased risk of poor psychomotor stability, motor coordination, and response time tests [72]. Researchers also found an association between sustained attention in 13–17 year old adolescents with distance weighted traffic density-a mixture of distance to roadway and roadway traffic density used to approximate traffic related pollutant exposure [73]. Cognitive performance was, however, non-significantly impacted.

Data using the Project Viva cohort in the U.S. indicated decreased non-verbal IQ in 8 year olds whose mothers lived in residences nearer to major roadways at the time of birth to child age 6 as compared to children from mothers who lived further from major roadways [66]. In this study, prenatal or childhood exposure 1 year before the test administration were not associated with cognitive deficits. The lack of effect seen at the later exposure point may indicate that either long term or very heavy exposure is required to reduce cognition. There was no association when black carbon or PM_2.5 levels were assessed individually.

Genotype may impart particular sensitivity to air pollutants, as female, but not male, children living in Mexico City with one copy of the ApoE ε4 allele are found to perform worse than those homozygous for the APOE ε3 allele [74]. While this study did not include less polluted controls outside of Mexico City, limiting the ability to determine whether the genotype and environment are specifically interacting, this finding is critical as it indicates that certain subpopulations may be more vulnerable to the effects of air pollutants on cognition. This in turn provides possible genetic confounding factors to account for variant and sometimes conflicting results seen between many of the studies reviewed. Additional studies in this area are required to determine the strength and consistency of these effects.

Adult PM exposure and risk for dementia

Adults who are exposed to polluted air also experience accelerated cognitive impairment. In China, Mexico and the U.S., elderly residents over 65 years old who live in areas with high air pollution generally performed significantly worse on a mini-mental state examination (MMSE), one of common cognitive tests to assess dementia, than those living in cleaner areas [75], [76], [77], [78].

Black carbon [79], and PM_2.5 [80] are particularly associated with poor performance on MMSE among elderly. It is estimated that every 10 μg/m³ increase in black carbon exposure is equivalent to an extra two years of cognitive decline by aging [79]. Measuring NO₂, PM_2.5, and O₃ exposure by geocoding in the U.S. in a 1500 person sample of mean age 60, Gatto et al. found a reduction in verbal learning associated only with PM_2.5 levels [80]. PM_2.5 is also found to have a strong association with increased rate of errors in tests of working memory and orientation in adults age 55 or older [81], and with reduced episodic memory as compared to those with lower PM_2.5 exposure [82]. These associations did not carry over to overall mental status as determined by composite scores on multiple tests.

Elderly women exposed to varying PM_2.5-10 levels for up to 14 years, as estimated by modeling of US EPA environmental data, have greater decline in global cognitive function than those in the lowest exposure level [83]. PM_2.5 exposure was also linked to increase in overall disability, as determined by the World Health Organization Disability Assessment Schedule, and cognitive disability specifically in a study of populations from lower income countries [84]. Other population-based studies find that PM_2.5 and PM₁₀ levels associate with reduced memory scores in multiple tests [85], [86].

Interestingly, PM_2.5 and cognitive decline are more strongly correlated when neighborhood stressor factors, such as empty lots and abandoned buildings, are included in analysis [87]. This raises the potentially important point that other environmental factors play a role in modulating the effects of PM, and must be considered when determining the impact of PM on cognition in the elderly. It is also of note that a study focusing on younger adults, mean age approximately 37, found no significant association between PM₁₀ exposure levels and reduced cognition [88]. This could indicate that PM exposure is a more significant risk factor in vulnerable populations, such as the elderly or children, than it is in healthy adults, though additional research in this age group is required to be sure they are not vulnerable.

Recent works demonstrate a correlation between PM exposure and risk for neurological disease outcomes, with particular focus on AD. A study in Sweden observed that general dementia incidence over a 15 year period correlated to nitrogen oxide exposure levels [12]. Associations between levels of NO_x and AD or vascular dementia (VaD) specifically were non-significant, however there was significant association between the highest quartile of exposure (>26 μg/m³) and general dementia diagnosis.

Considering that the previously mentioned study evaluating cognitive changes in older groups exposed to NO₂ found no association [80], there is a possibility that additional factors impact the relation between NO_x and cognitive decline. Whether this discrepancy is due to differences in study populations and conditions, such as genetic factors or non-air pollution environmental factors, or if it is due to the specific compositions and concentrations of the air pollutants involved, is a potential area of interest for further research. Another study of elderly women (<75 years) in Germany revealed lower executive and olfactory function, and reduced Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) test scores, for those living within 50 m of a busy roadway as compared to those living further from roadways [88].

Levels of PM₁₀ were not associated with reductions in any of these measures-potentially due to reduced systemic effects resulting from the inability of coarse fraction PM to infiltrate to the bloodstream or directly to the brain.

A later study using the same study cohort found no association between overall traffic related pollution exposure and CERAD score in the general population but did see significant decreases in the figure drawing subtest associated with PM_2.5 and PM₁₀ exposure levels specifically [89]. Schikowski et al. used a larger base group, 789 participants compared to 399 in Ranft et al., presumably as more participants had responded by the later date, and so it is possible that the variations in the study cohort account for the differences. However, as very little changed in terms of average age, education level, or other descriptive statistics within the cohort between the two studies, analytical differences or exposure variations are more likely reasons for the divergent outcomes. These divergent results highlight the precarious nature of using proxy measurements for air pollution exposures when the actual composition changes daily. Increasing the body of epidemiological studies on this topic and the complimentary use of controlled animal studies that can control for such variables will be helpful in mitigating these factors.

Additional studies indirectly support a link between PM exposure and AD, one of which focuses on unspecified dementia cases and the other examining an association with mild cognitive impairment (MCI). A Canadian population based cohort of 2.2 million residents age 55–85 residing in Ontario for five or more years was examined for incidence rates of dementia and Parkinson disease (PD) related to distance of residence to the nearest major roadway, as well as dementia incidence related to PM_2.5, O_3, and NO₂ exposure [90], [91].

The adjusted hazard ratio (HR) for incident dementia was significant at 1.07 for those living within 50 m of the nearest major roadway, decreasing with distance to 1.04 at 51–100 m, 1.02 at 101–200 m, and 1 at 201–300 m compared to those living more than 300 m from the nearest major roadway. PM_2.5 and NO₂ levels were significantly associated with increased dementia incidence as well, with HR values of 1.04 and 1.1, respectively. There was no association seen between PD and distance to roadway, implying a potential vulnerability of AD-related brain regions against air pollution. Another study examined the link between various sizes of PM and nitrogen oxides with MCI in a German population-based cohort ages 47–75 from the Ruhr area [92]. PM_2.5 was significantly associated with increased overall MCI incidence and incidence of amnestic MCI at a five year follow up exam. NO₂ was only significantly associated with amnestic MCI.

This study is also notable for comparing the effects of noise level concurrently with air pollution and finding that noise was also associated with MCI incidence. This supports results seen in Ailshire et al. [86] that other environmental concerns can be a strong confounding factor with many tests of cognitive ability used in the epidemiological studies reviewed-particularly as many of these studies rely on air pollution metrics that would be associated with increased noise pollution, such as distance to major roadways.

Examination of >64 year old Medicare enrollees in multiple U.S. cities over an 11-year period, found that for every 1 μg/m³ increase in annual city wide PM_2.5 concentration, there was a 1.08 HR for all cause dementia, 1.15 HR for AD, and 1.08 HR for PD first time hospital admission [93]. A Taiwanese 9-year cohort study of individuals age 65 or higher to determine the relationship between O₃ and PM_2.5 exposure and AD risk found a 211% increased risk of AD incidence per 10.91 ppb increase in O₃ over the follow up period, and a 138% increased risk of AD incidence per 4.34 μg/m³ of PM_2.5 [11]. A case control study in Taiwan enrolling AD and VaD patients used PM₁₀ and O₃ data from the Taiwan EPA for the past 12 and 14 years, respectively, to determine exposure [94].

As with the previous study, both O₃ and PM were associated with and increased odds ratio of AD and VaD; the highest tertile exposure group for PM₁₀ (>49.23 μg/m³) had an adjusted OR of 4.17 for AD and 3.61 for VaD. The highest tertile exposure group for O₃ (>21.56 ppb) had AD an adjusted odds ratios of 2 and 2.09 for AD and VaD, respectively. Compared to Oudin et al. [12], who found no association between NO_x and either AD or VaD alone, it is interesting that both diseases are associated with PM and O₃ here, both of which are also tied to traffic related pollution. This again suggests that additional factors or specific composition of the air pollutants may affect cognitive outcomes. Together, these studies show consistent evidence that AD risk is increased with exposure to higher levels of PM. As VaD is also shown to be linked to PM exposure, it remains an open question whether AD risk is elevated more than other forms of dementia.

Genetic predisposition may play an important role in air pollution dementia risk. The APOE gene remains the strongest known genetic risk factor [4], [5], and a few studies have examined whether air pollutant exposure risk is modulated by APOE allele status. Within the Women’s Health Initiative Memory Study cohort patients living in areas of high PM_2.5 concentrations, which are over the EPA recommended long term exposure limit of 12 μg/m³, are found to have increased risk of dementia incidence [10]. The risk is exacerbated by APOE ε4 status, with increasing risk when exposed to high levels PM in carriers of one copy of the allele and the highest risk with two copies.

This strengthens the previously mentioned Mexico City study [74], which found increased risk of cognitive deficits in children when APOE ε4 carrier status and higher air pollution were both present as compared to either factor alone. While AD risk was not assessed, the ability of APOE status to modulate risk of dementia and impaired cognition strongly suggests a gene–environment interaction in determining the likelihood of developing dementia. In a study of a cohort of elderly women in Germany, there was no association between PM or NO₂ exposure and reduced overall cognition or MMSE scores regardless of APOE status [89].

However, traffic pollutant exposure, which was measured as a product of the number of cars passing and length of road close to the residence, was linked to impaired visuospatial function, but only in carriers of at least one APOE ε4 allele, further supporting that genetic factors may be critical in assessing risk for air pollution exposure.

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Source:
USCr
Media Contacts:
Leigh Hopper – USC
Image Source:
The image is credited to USC.

Original Research: Closed access
“Particulate matter and episodic memory decline mediated by early neuroanatomic biomarkers of Alzheimer’s disease “. Andrew Petkus et al.
Brain doi:10.1093/brain/awz348.