23 Feb 2012

Air pollution—already tied to asthma and heart attacks—appears also to wreak havoc in the brain. Particles that enter the body through the nose or lungs may lead to cognitive decline or strokes, suggest a trio of papers that came out in the February 13 Archives of Internal Medicine. Over the long term, exposure to both large and small particulates in the air correlated with cognitive decline, according to a study on more than 20,000 women in the U.S. Years of exposure to secondhand smoke also tracked with declining cognition for a group of women in China, according to a study by researchers there and in England. Even short-term exposure to polluted air, on the order of hours, increases the risk of ischemic stroke in hospital patients, according to another paper. The findings may point to the need for more stringent policies that prevent damage to the brain from the environment.

Particulate matter in the air comes from multiple sources, including cars and trucks, equipment that burns diesel fuel, and coal-burning factories. Each releases particulate matter categorized as fine (less than 2.5 micrometers in diameter, or PM2.5), or coarse (2.5 to 10 micrometers, or PM10), and that varies in composition, including the presence of heavy metals and organic chemicals. People who live near busy roads or industrial plants—often in urban areas—are exposed to more of this pollution. It is generally accepted that particles entering through the lungs or nasal passages can end up in the bloodstream or brain to create a host of complications, such as inflammation of the airways, vascular endothelial disturbances, and more. What has not been clear is the effect that has on cognition. Researchers previously linked coarse particulate matter to mild cognitive impairment in women older than 68 (see Ranft et al., 2009), higher ozone levels to lower cognitive scores (see Chen and Schwartz, 2009), and black carbon from traffic to cognitive decline in older men (see Power et al., 2011). In addition, living in areas of poor air quality for up to a decade correlated with decreased cognitive function in older adults in China (see Zeng et al., 2010). Until now, however, no study specifically looked at cognitive effects of fine particulate matter, or tracked cognition and air pollution longitudinally.

Researchers led by Jennifer Weuve at Rush University Medical Center, Chicago, Illinois, followed 19,409 women, aged 70-81 years, from the Nurses’ Health Study Cognitive Cohort. Beginning in 1995, the researchers assessed cognitive status over the phone, on average about every two years, using the Telephone Interview for Cognitive Status (modeled on the Mini-Mental State Examination) and with tests for delayed paragraph recall, fluency, working memory, and attention. They correlated these scores with each woman's prior estimated fine and coarse particulate matter exposure over the short term (one month), and up to 14 years prior to cognitive testing. Estimates were based on models using data from air monitors of the U.S. Environmental Protection Agency (EPA) and other local factors such as wind speed and proximity to busy roadways.

The investigators found that greater long-term exposure to both coarse and fine particles associated with faster cognitive decline. The researchers controlled for several factors, including age, education, and physical activity. Neither socioeconomic status nor the incidence of respiratory or cardiovascular conditions changed the outcome.

"It seemed that women with those highest levels of exposure experienced the worst cognitive decline over time," said Weuve. For each additional 10 μg/cubic meter exposure to fine (exposures ranged from 1.9 to 33.7 μg/cubic meter) or coarse particulate matter (0 to 69 μg/cubic meter), it looked like women performed cognitively as if they were two years older, she added. Currently, the EPA specifies the safe annual exposure to fine particulate matter to be an average of 15 μg/cubic meter per day, while the daily average for coarse particulate matter should not exceed 150 μg/m³ more than once per year.

Cognitive impairment is often a prelude to dementia. The authors note that delaying the onset of Alzheimer's disease by just two years could decrease the number of cases in the U.S. by two million over 40 years (see Brookmeyer et al., 1998). If the pollutant effect is real, environmental regulations are "a really powerful way to lower the entire population's risk of developing dementia and substantially reduce the number of cases that occur over the next few decades," Weuve said. In an e-mail to ARF, Melinda Power, Harvard School of Public Health, wrote, "Identification of modifiable risk factors is important, since we know very little about how to prevent cognitive decline or impairment, and few treatments are available."

“The EPA is currently reviewing the national ambient air quality standards for PM2.5 and PM10,” wrote Stacy Kika from the EPA Office of Media Relations in an e-mail to Alzforum. But she added, “In October 2011, after careful consideration of the scientific record and analysis by Agency scientists, EPA wrote Congress that it is prepared to propose to keep the current standard for PM10.”

Secondhand smoke may also contribute to dementia, suggest Ruoling Chen, King’s College London, U.K., and Zhi Hu, Anhui Medical University, China. In their study of 1,979 never-smoking Chinese women older than 60, they found that those exposed to secondhand smoke (predominantly from their work environment) had a greater risk of dementia than those who were not exposed (11.7 percent versus 7.4 percent, as assessed by the Geriatric Mental Status). These results are consistent with smoking being a risk factor for dementia (see ARF related news story on Rusanen et al., 2010), although a previous study found no correlation between secondhand smoke alone and dementia (see Barnes et al., 2010).

What could be the mediating factors that tie air pollution to dementia? Previous studies connected air pollution with inflammation (see Calderón-Garcidueñas et al., 2004) and cardiovascular factors (see Miller et. al., 2007), both of which have been linked to cognitive decline and dementia (see Wyss-Coray, 2006 and Breteler, 2000). Ischemic stroke could be among those cardiovascular risk factors. In their paper, Gregory Wellenius, Brown University, Providence, Rhode Island, and colleagues linked acute ischemic stroke to pollution. Several studies linked air pollution in general to stroke risk (see Villeneuve et al., 2006), but few have looked specifically at fine particulate matter and imminent risk.

Wellenius and colleagues examined the medical records of 1,705 Boston residents hospitalized for stroke at the Beth Israel Deaconess Medical Center. They estimated when strokes started and correlated those times with hourly fine particulate matter levels measured at an air monitoring station at the nearby Harvard School of Public Health. Only "good" and "moderate" days, as defined by the EPA's Air Quality Index, were analyzed. The risk of stroke was 35 percent higher during the 24-hour period following "moderate" days compared with "good" days. In addition, the number of strokes peaked 12 to 14 hours after high levels of particulate matter were registered, and correlated best with markers of traffic pollution (black carbon and nitrogen dioxide).

"Both moderate days and good days are within the current federal standards for air quality," Wellenius told ARF. "If these findings were to be replicated by other groups in other cities, the EPA should consider stricter standards, or at the very least, acknowledging that ... further reductions in air pollution are likely to have further benefits in terms of reducing adverse health effects." He and his team plan to collaborate with others to repeat the study in up to 40 other cities.

Weuve thinks the Wellenius study may explain one link between air pollution and cognitive decline. "We can imagine that these [short-term exposures to high levels of particulate matter] are just repeated small insults to the brain, even if you don't have a stroke. Over time that could contribute to cognitive decline and eventually dementia risk," she said. Mini-strokes with non-focal symptoms are a possible risk factor for AD (see ARF related news story on Bos et al., 2007), though no study has yet correlated these with air pollution. She and her team next plan to see if certain chemicals or metals in particulate matter are associated with decline.

"With the availability of improving pollutant data, future studies should aim to elucidate the health effects of sub-daily time windows of exposure," wrote Robert Brook, University of Michigan, Ann Arbor, and Sanjay Rajagopalan, Ohio State University Medical Center, Columbus, in an accompanying editorial. "If similar findings are corroborated and/or found for other diseases, those who create air quality standards might need to consider the difficult task of curbing sub-daily [particulate matter] concentrations," they added.—Gwyneth Dickey Zakaib

Comments

1. • Suzanne Tyas
     University of Waterloo
   • Posted: 09 Mar 2012
   • Paper: Passive smoking and risk of cognitive impairment in women who never smoke.

   The association between secondhand smoke and cognition is biologically plausible. These results are consistent with evidence for an association between Alzheimer’s disease and "first-hand" smoking, and an association between particulate air pollution and cognitive decline, as reported in the same issue of the Archives of Internal Medicine (Weuve et al., 2012). However, these results are not consistent with a recent article on secondhand smoke and dementia (Barnes et al., 2010). Though the results of Chen et al. are interesting, the size of the effect in adjusted models is fairly weak, only being seen at the very highest exposure levels. I also have measurement concerns. They use a self-report of passive smoking, and an insufficient adjustment for cardiovascular disease—the association between secondhand smoke and dementia may be due to the association between cardiovascular disease and dementia rather than to secondhand smoke directly (see causal pathway in Barnes et al., 2010).

   Also, the use of the Geriatric Mental Status (GMS) test and the Automated Geriatric Examination for Computer Assisted Taxonomy (AGECAT) algorithm to score it may be a problematic measurement of outcome (dementia diagnosis). According to Prince et al., 2004, "in developing countries, the GMS is a useful adjunct to diagnosis" but "the GMS on its own was never intended to provide a formal diagnosis of dementia. In developing countries and other low-education populations, the focus in the GMS/AGECAT algorithm upon educationally biased cognitive test items risks overdiagnosis. If the GMS is to be used alone in developing-country and other low-education populations, then caution is indicated in interpreting the organicity output, which may not map as closely onto clinical dementia as in a developed-country population.”

   References:

   Barnes DE, Haight TJ, Mehta KM, Carlson MC, Kuller LH, Tager IB. Secondhand smoke, vascular disease, and dementia incidence: findings from the cardiovascular health cognition study. Am J Epidemiol. 2010 Feb 1;171(3):292-302. PubMed.

   Prince M, Acosta D, Chiu H, Copeland J, Dewey M, Scazufca M, Varghese M, . Effects of education and culture on the validity of the Geriatric Mental State and its AGECAT algorithm. Br J Psychiatry. 2004 Nov;185:429-36. PubMed.

   Weuve J, Puett RC, Schwartz J, Yanosky JD, Laden F, Grodstein F. Exposure to particulate air pollution and cognitive decline in older women. Arch Intern Med. 2012 Feb 13;172(3):219-27. PubMed.

   View all comments by Suzanne Tyas

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References

News Citations

1. Risk to Your Cognition: Sepsis, Smoking Wreak Havoc Years Later 31 Oct 2010
2. Some Ministrokes Increase Risk of Dementia; Statins Leave Amyloid Untouched 25 Jan 2008

Paper Citations

1. Ranft U, Schikowski T, Sugiri D, Krutmann J, Krämer U. Long-term exposure to traffic-related particulate matter impairs cognitive function in the elderly. Environ Res. 2009 Nov;109(8):1004-11. Epub 2009 Sep 4 PubMed.
2. Chen JC, Schwartz J. Neurobehavioral effects of ambient air pollution on cognitive performance in US adults. Neurotoxicology. 2009 Mar;30(2):231-9. PubMed.
3. Power MC, Weisskopf MG, Alexeeff SE, Coull BA, Spiro A 3rd, Schwartz J. Traffic-related air pollution and cognitive function in a cohort of older men. Environ Health Perspect. 2011 May;119(5):682-7. Epub 2010 Dec 20 PubMed.
4. Zeng Y, Gu D, Purser J, Hoenig H, Christakis N. Associations of environmental factors with elderly health and mortality in China. Am J Public Health. 2010 Feb;100(2):298-305. PubMed.
5. Brookmeyer R, Gray S, Kawas C. Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset. Am J Public Health. 1998 Sep;88(9):1337-42. PubMed.
6. Rusanen M, Kivipelto M, Quesenberry CP, Zhou J, Whitmer RA. Heavy smoking in midlife and long-term risk of Alzheimer disease and vascular dementia. Arch Intern Med. 2011 Feb 28;171(4):333-9. PubMed.
7. Barnes DE, Haight TJ, Mehta KM, Carlson MC, Kuller LH, Tager IB. Secondhand smoke, vascular disease, and dementia incidence: findings from the cardiovascular health cognition study. Am J Epidemiol. 2010 Feb 1;171(3):292-302. PubMed.
8. Calderón-Garcidueñas L, Reed W, Maronpot RR, Henríquez-Roldán C, Delgado-Chavez R, Calderón-Garcidueñas A, Dragustinovis I, Franco-Lira M, Aragón-Flores M, Solt AC, Altenburg M, Torres-Jardón R, Swenberg JA. Brain inflammation and Alzheimer's-like pathology in individuals exposed to severe air pollution. Toxicol Pathol. 2004 Nov-Dec;32(6):650-8. PubMed.
9. Miller KA, Siscovick DS, Sheppard L, Shepherd K, Sullivan JH, Anderson GL, Kaufman JD. Long-term exposure to air pollution and incidence of cardiovascular events in women. N Engl J Med. 2007 Feb 1;356(5):447-58. PubMed.
10. Wyss-Coray T. Inflammation in Alzheimer disease: driving force, bystander or beneficial response?. Nat Med. 2006 Sep;12(9):1005-15. PubMed.
11. Breteler MM. Vascular involvement in cognitive decline and dementia. Epidemiologic evidence from the Rotterdam Study and the Rotterdam Scan Study. Ann N Y Acad Sci. 2000 Apr;903:457-65. PubMed.
12. Villeneuve PJ, Chen L, Stieb D, Rowe BH. Associations between outdoor air pollution and emergency department visits for stroke in Edmonton, Canada. Eur J Epidemiol. 2006;21(9):689-700. PubMed.
13. Bos MJ, van Rijn MJ, Witteman JC, Hofman A, Koudstaal PJ, Breteler MM. Incidence and prognosis of transient neurological attacks. JAMA. 2007 Dec 26;298(24):2877-85. PubMed.

Further Reading

Papers

1. Risom L, Møller P, Loft S. Oxidative stress-induced DNA damage by particulate air pollution. Mutat Res. 2005 Dec 30;592(1-2):119-37. PubMed.
2. Blum S, Luchsinger JA, Manly JJ, Schupf N, Stern Y, Brown TR, Decarli C, Small SA, Mayeux R, Brickman AM. Memory after silent stroke: hippocampus and infarcts both matter. Neurology. 2012 Jan 3;78(1):38-46. PubMed.
3. Sun Q, Wang A, Jin X, Natanzon A, Duquaine D, Brook RD, Aguinaldo JG, Fayad ZA, Fuster V, Lippmann M, Chen LC, Rajagopalan S. Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model. JAMA. 2005 Dec 21;294(23):3003-10. PubMed.
4. Calderón-Garcidueñas L, Franco-Lira M, Henríquez-Roldán C, Osnaya N, González-Maciel A, Reynoso-Robles R, Villarreal-Calderon R, Herritt L, Brooks D, Keefe S, Palacios-Moreno J, Torres-Jardón R, Medina-Cortina H, Delgado-Chávez R, Aiello-Mora M, Maronpot RR, Doty RL. Urban air pollution: influences on olfactory function and pathology in exposed children and young adults. Exp Toxicol Pathol. 2010 Jan;62(1):91-102. PubMed.
5. Calderón-Garcidueñas L, Reed W, Maronpot RR, Henríquez-Roldán C, Delgado-Chavez R, Calderón-Garcidueñas A, Dragustinovis I, Franco-Lira M, Aragón-Flores M, Solt AC, Altenburg M, Torres-Jardón R, Swenberg JA. Brain inflammation and Alzheimer's-like pathology in individuals exposed to severe air pollution. Toxicol Pathol. 2004 Nov-Dec;32(6):650-8. PubMed.
6. Calderón-Garcidueñas L, Kavanaugh M, Block M, D'Angiulli A, Delgado-Chávez R, Torres-Jardón R, González-Maciel A, Reynoso-Robles R, Osnaya N, Villarreal-Calderon R, Guo R, Hua Z, Zhu H, Perry G, Diaz P. Neuroinflammation, hyperphosphorylated tau, diffuse amyloid plaques, and down-regulation of the cellular prion protein in air pollution exposed children and young adults. J Alzheimers Dis. 2012 Jan 1;28(1):93-107. PubMed.
7. Ranft U, Schikowski T, Sugiri D, Krutmann J, Krämer U. Long-term exposure to traffic-related particulate matter impairs cognitive function in the elderly. Environ Res. 2009 Nov;109(8):1004-11. Epub 2009 Sep 4 PubMed.

News

1. Risk to Your Cognition: Sepsis, Smoking Wreak Havoc Years Later 31 Oct 2010
2. Silent Vascular Disease May Hasten Dementia Progression 10 Feb 2012
3. Some Ministrokes Increase Risk of Dementia; Statins Leave Amyloid Untouched 25 Jan 2008

Webinars

1. Vascular Factors in Alzheimer's Disease 21 Apr 2004