ASSOCIATION BETWEEN PARTICULATE MATTER
AND ALZHEIMER’S DISEASE IN ELDERLY SUBJECTS
NASIRA TAJAMAL
Loma Linda University Sc...
Alzheimer's disease (AD) in the US
• Age related dementia
• Progressive
• Irreversible
• Degeneration of brain cells
• Los...
Incidence and Prevalence
•One in nine Americans over
the age of 65 has AD.
•Affecting more than 4 million
people in US and...
Risk Factors: AGE
• Primarily affects people over age
of 65
• Incidence doubles every 5 years
after age 65
• It reaches 50...
Risk Factors: Gender
(Thies, Bleiler, & Alzheimer's, 2013)
9.1%
Men
10.2%
18.5%
12.1%
20.3%
Percentage
17.2%
Women
Age 65 ...
Risk Factors: Smoking
Smoking increases the risk of AD
The average risk of AD in smokers was
estimated to be
1.72 p< 0.000...
Risk Factors: Alcohol
According to a review article:
• Seven articles suggested alcohol
reduces the risk of AD.
• Three st...
Risk Factors: Diet
HR (95% Cl) according to tertile of
adherence to a Mediterranean diet
intake:
• Lowest tertile: 0.91 (0...
Risk Factors: Race
(Thies, Bleiler, & Alzheimer's, 2013)
2.5%
9.1%
AGE IN YEARS
Prevalence%
7.5%
10.9%
19.9.%
27.9%
30.2%
...
Risk Factors: Air Pollution
Air Pollution is a complex mixture
of:
• Gases
• Ozone, O3
• Carbone monoxide, CO
• NO2
• SO2
...
Particulate Matter
• PM is a complex mixture of
extremely small particles and
liquid droplets suspended in air.
• PM2.5-10...
PARTICULATE MATTER
• Exposure to PM2.5-10 and PM2.5
are associated with faster
cognitive decline
(Weuve J, et al, Arch Int...
PARTICULATE MATTER
Autopsy studies of people in
highly polluted areas (Mexico
city) shows the presence of
PM2.5 and PM0.1 ...
PARTICULATE MATTER
In the brain PM is associated with:
1. Increased inflammatory
changes (COX2 mRNA)
2. Accumulation of β-...
Results
STUDY SUBJECT RESULTS
(Gatto, Henderson
2014) [8]
Cross Sectional Study.
1,496 healthy
cognitively Intact
adults.
...
Results
STUDY SUBJECT RESULTS
(Weuve,Puett,2012)
[9]
Nurses’ Health Study
Cognitive Cohort
19,409 Nurses aged
70-81 years....
Results
STUDY SUBJECT RESULTS
(Ranft, Schikowski, 2009).
[6]
Cohort Study.
399 women 68 to 79
years of age with
>20 years ...
Results
STUDY SUBJECT RESULTS
(Ailshire, Clarke 2015).
[10]
Cross- Sectional study
780 non-Hispanic
black, white men
and w...
Results
STUDY SUBJECT RESULTS
(Calderon-
Garciduenas, Reed
2004) [2]
Human Autopsy
Study
Brain samples:
A. 10 from highly
...
Results
STUDY SUBJECT RESULTS
(Calderon-
Garciduenas 2003)
[11]
Case Control Study
Dogs
n=26 from
Mexico City
[MC]) or low...
Results
STUDY SUBJECT RESULTS
(Jung, Hwang
2014) [12]
Cohort Study
95,690,
individuals
aged above 65
during 2001-
2010
The...
Results
STUDY SUBJECT RESULTS
(Campbell
2005) [4]
Case control
Mice. (Male BALB/c 6
weeks old) exposed to
concentrated amb...
Results
STUDY SUBJECT RESULTS
(Calderon-
Garciduenas 2008)
[13]
Case Cohort Study
47 Children and
young adults of 2-
45 ye...
AP and AD Biological Mechanism
Pathological changes in the brain
are:
• placque formations (amyloid
beta (Aβ) protein) sur...
SUMMARY
• Ambient PM may mediate inflammation and degeneration in
brain tissues. (1)
• PM enters brain two ways: olfactory...
CONCLUSION
• health burden due to idiopathic nature of AD in the elderly
• Need to find cause and treatment of AD
• PM may...
ACKNOWLEDGEMENT
Dr Raymond Knutsen:
My special thanks are for my research advisor Dr Raymond Knutsen who have
been working...
QUESTIONS?
References
1.Moulton, P.V. and W. Yang, Air pollution, oxidative stress, and Alzheimer's disease. J Environ Public
Health,...
References
7. Power, M.C., et al., Traffic-related air pollution and cognitive function in a cohort of older men.
Environ ...
References
13. Calderon-Garciduenas, L., et al., Long-term air pollution exposure is associated with
neuroinflammation, an...
References
17.Block, M. L., Elder, A., Auten, R. L., Bilbo, S. D., Chen, H., Chen, J. C., . . . Wright, R. J. (2012). The
...
References
22)H. K. Biesalski, (2002) Free radical theory of aging,” Current Opinion in Clinical
Nutrition and Metabolic C...
References
.
27) Y. Christen (2000) Oxidative stress and Alzheimer disease, American Journal of Clinical Nutrition,
vol. 7...
References
32) H. Peery, R. Strohmeyer, and J. Rogers. (2006) Cellular and molecular mechanisms of
Alzheimer's disease inf...
References
37) Pratico, D. (2005). Peripheral biomarkers of oxidative damage in Alzheimer's disease:
the road ahead. Neuro...
References
42) Perry, G., Castellani, R. J., Smith, M. A., Harris, P. L., Kubat, Z., Ghanbari, K., . . .
Ghanbari, H. (200...
References
47) Cohen, A. J., Ross Anderson, H., Ostro, B., Pandey, K. D., Krzyzanowski, M., Kunzli, N., . . . Smith,
K. (2...
References
52) Craig, L., Brook, J. R., Chiotti, Q., Croes, B., Gower, S., Hedley, A., . . . Williams, M. (2008). Air poll...
Nasira Tajamal Presentation FINAL
Nasira Tajamal Presentation FINAL
Nasira Tajamal Presentation FINAL
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Nasira Tajamal Presentation FINAL

Published on: Mar 3, 2016
Source: www.slideshare.net


Transcripts - Nasira Tajamal Presentation FINAL

  • 1. ASSOCIATION BETWEEN PARTICULATE MATTER AND ALZHEIMER’S DISEASE IN ELDERLY SUBJECTS NASIRA TAJAMAL Loma Linda University School of Public Health CA. USA
  • 2. Alzheimer's disease (AD) in the US • Age related dementia • Progressive • Irreversible • Degeneration of brain cells • Loss of memory, thinking, language skills, and behavior (Muller et al., 2014)
  • 3. Incidence and Prevalence •One in nine Americans over the age of 65 has AD. •Affecting more than 4 million people in US and 36 million in worldwide. (Moulton & Yang, 2012)
  • 4. Risk Factors: AGE • Primarily affects people over age of 65 • Incidence doubles every 5 years after age 65 • It reaches 50 percent after 85 (Kalaria et al., 2008) 0 10 20 30 40 50 60 60 65 70 75 80 85 INCIDENCE AGE RISK OF ALZHEIMER’S WITH AGE
  • 5. Risk Factors: Gender (Thies, Bleiler, & Alzheimer's, 2013) 9.1% Men 10.2% 18.5% 12.1% 20.3% Percentage 17.2% Women Age 65 75 85
  • 6. Risk Factors: Smoking Smoking increases the risk of AD The average risk of AD in smokers was estimated to be 1.72 p< 0.0005 (Cataldo jk 2010)
  • 7. Risk Factors: Alcohol According to a review article: • Seven articles suggested alcohol reduces the risk of AD. • Three studies found increased risk of AD. • Nine reported no impact. (Piazza-Gardner, Gaffud, & Barry, 2013)
  • 8. Risk Factors: Diet HR (95% Cl) according to tertile of adherence to a Mediterranean diet intake: • Lowest tertile: 0.91 (0.83-0.98) • Middle tertile: 0.85 (0.63-1.16) • Highest tertile: 0.60 (0.42-0.87) (Scarmeas,N 2006)
  • 9. Risk Factors: Race (Thies, Bleiler, & Alzheimer's, 2013) 2.5% 9.1% AGE IN YEARS Prevalence% 7.5% 10.9% 19.9.% 27.9% 30.2% 58.6% 62.9% HISPANICS BLACKS WHITES 65-74 75-84 85+
  • 10. Risk Factors: Air Pollution Air Pollution is a complex mixture of: • Gases • Ozone, O3 • Carbone monoxide, CO • NO2 • SO2 • Particles • PM • Lead (Moulton & Yang, 2012)
  • 11. Particulate Matter • PM is a complex mixture of extremely small particles and liquid droplets suspended in air. • PM2.5-10µm = Coarse particles • PM2.5µm = PM<2.5µm = Fine particles • PM0.1µm = PM<0.1µm = Ultrafine particles
  • 12. PARTICULATE MATTER • Exposure to PM2.5-10 and PM2.5 are associated with faster cognitive decline (Weuve J, et al, Arch Intern Med 2012;172:219- 227) • Exposure to PM0.1 is associated with impaired cognitive function (Ranft U, et al, Environ Res 2009;109:1004- 1011)
  • 13. PARTICULATE MATTER Autopsy studies of people in highly polluted areas (Mexico city) shows the presence of PM2.5 and PM0.1 in: • Nasal Respiratory Epithelium • Olfactory bulb • Hippocampus • Frontal cortex • Cerebellum Calderon- Garciduenas L, et al. Toxicol Pathol 2003;31:524-538
  • 14. PARTICULATE MATTER In the brain PM is associated with: 1. Increased inflammatory changes (COX2 mRNA) 2. Accumulation of β-amyloid (Aβ42) in astrocytes 3. 1 and 2 precede the neuritic placques and neurofibrillary tangles of AD (Calderon- Garciduenas, Reed 2004)
  • 15. Results STUDY SUBJECT RESULTS (Gatto, Henderson 2014) [8] Cross Sectional Study. 1,496 healthy cognitively Intact adults. mean age 60.5 None of the pollutants (PM 2.5 , O3, NO2) were significantly associated with global cognition. Increasing exposure to PM2.5 was related to lower verbal learning β = -0.32 (95% CI: -0.63,0.00) per 10 µg/m³ PM2.5, p = 0.05
  • 16. Results STUDY SUBJECT RESULTS (Weuve,Puett,2012) [9] Nurses’ Health Study Cognitive Cohort 19,409 Nurses aged 70-81 years. Measurement period: 7-14 years Difference in 2 year change (95% CI) in global cognitive score: A. Per 10µg/m3 increment in exposure: • PM2.5-10: -0.020 (-0.032 to -0.008) • PM2.5: - 0.018 (-0.035 to -0.02) B. In highest vs lowest quintile of exposure: • PM2.5-10: -0.024 (-0.040 to -0.008) • PM2.5: -0.018 (-0.034 to -0.002)
  • 17. Results STUDY SUBJECT RESULTS (Ranft, Schikowski, 2009). [6] Cohort Study. 399 women 68 to 79 years of age with >20 years of exposure to PM. CERAD-Plus points (95% CI): A. according to traffic exposure: • Age ≤ 74: -3.8 (-7.9, 0.4) • Age > 74: 0.3 (-7.3, 7.8) B. According to distance to next busy street: -1.6 (-3.2, 00) (p≤0.05)
  • 18. Results STUDY SUBJECT RESULTS (Ailshire, Clarke 2015). [10] Cross- Sectional study 780 non-Hispanic black, white men and women age 55+ Regression of Count of Errors- PM2.5, 10 µg/m3 increment: OR=1.53 (95% CI: 1.02-2.30) Those living in areas with greater exposure to PM2.5 had an error rate 1.5 times greater than those exposed to lower PM 2.5 concentration
  • 19. Results STUDY SUBJECT RESULTS (Calderon- Garciduenas, Reed 2004) [2] Human Autopsy Study Brain samples: A. 10 from highly polluted areas (Mexico city and Monterrey) B. 9 from small cities with low level of pollution A strong positive correlation was found between: • COX2 mRNA levels and • Oxidative DNA damage by AP* sites (r = 0.89, p = 0.001, Spearman and Pearson) in frontal cortex of high- exposure group, but not in subjects of low air pollution areas. *apurinic & apyrimidinic sites (inhibits DNA replication, increases base substitution mutations and loss of genetic integrity)
  • 20. Results STUDY SUBJECT RESULTS (Calderon- Garciduenas 2003) [11] Case Control Study Dogs n=26 from Mexico City [MC]) or low levels of air pollution (n=14 from Tlaxcala [TC] Mean AP* sites/106 nucleotides in: • MC dogs: 12.5 ± 1.7 • TL dogs: 3.9 ± 0.8 • (p=0.0002). MC dogs had AD like brain changes: • Atrophy of cortex • β-amyloid plaques • Neurofibrillary tangles *apurinic/apyrimidinic sites (inhibit DNA replication, increases base substitution
  • 21. Results STUDY SUBJECT RESULTS (Jung, Hwang 2014) [12] Cohort Study 95,690, individuals aged above 65 during 2001- 2010 The data were analyzed in a Cox Regression model. The risk of AD was found to increase 138% per 4.34 µg/m3 increase in PM2.5 over the follow up period (95% Cl 2.21-2.56). Findings suggest that long term exposure to PM2.5 is associated with increased risk of Alzheimer’s disease
  • 22. Results STUDY SUBJECT RESULTS (Campbell 2005) [4] Case control Mice. (Male BALB/c 6 weeks old) exposed to concentrated ambient PM in a heavily polluted urban environment for 2 weeks vs controls Level of proinflammatory cytokines in the cytoplasmic fraction of the brain after exposure to: PM0.18 (mean 285.5µg/m3): TNF-α increased ≈ 15% (ns) IL-1α increased ≈ 2.8x (p<0.05) [PM0.18+PM2.5](mean 441.7µg/m3): TNF-α increased ≈ 50% (p<0.05) IL-1α increased ≈ 3.4x (p<0.05)
  • 23. Results STUDY SUBJECT RESULTS (Calderon- Garciduenas 2008) [13] Case Cohort Study 47 Children and young adults of 2- 45 years of age who die suddenly. N=35 from highly polluted area. N=12 from less polluted area. In highly polluted areas (MC) vs less polluted areas (control cities) significant higher levels found of: • Frontal cortex: - COX2 mRNA (p=.008) - IL-1β mRNA (p=.0002) • Olfactory bulb (OB): - COX2 mRNA (p=.0002) - IL-1β mRNA (p=.003) - CD14 rRNA (p=.04)
  • 24. AP and AD Biological Mechanism Pathological changes in the brain are: • placque formations (amyloid beta (Aβ) protein) surrounded by neurons containing neurofibrillary tangles. • Associated with the placque deposition is vascular damage and neuronal loss in the area of hippocampus and frontal cortex, These changes are associated with severe memory loss (Campbell, Oldham 2005)
  • 25. SUMMARY • Ambient PM may mediate inflammation and degeneration in brain tissues. (1) • PM enters brain two ways: olfactory pathway and systemic circulation may produce oxidative stress by releasing cytokines. (2, 3) • PM involved in ROS-production may induce amyloid beta peptides may produce senile placques &neurofibrillary tangles implicated in AD (1)
  • 26. CONCLUSION • health burden due to idiopathic nature of AD in the elderly • Need to find cause and treatment of AD • PM may increase vulnerability to AD • Few epidemiological studies on ambient PM and AD • More research needed on this topic
  • 27. ACKNOWLEDGEMENT Dr Raymond Knutsen: My special thanks are for my research advisor Dr Raymond Knutsen who have been working with me very hard throughout my project. Dr Larry Beeson: I am greatly thankful to Dr Larry Beeson who provided me valuable ideas in my power point presentation. Dr Synnove Knutsen: I thank to Dr Synnove Knutsen for her continued guidance and support throughout my work. Dr Khaled Bhajri: I am thankful to Dr Khaled Bhajri for helping me in the literature review.
  • 28. QUESTIONS?
  • 29. References 1.Moulton, P.V. and W. Yang, Air pollution, oxidative stress, and Alzheimer's disease. J Environ Public Health, 2012. 2012: p. 472751. 2. Calderon-Garciduenas, L., et al., Brain inflammation and Alzheimer's-like pathology in individuals exposed to severe air pollution. Toxicol Pathol, 2004. 32(6): p. 650-8. 3. Block, M.L. and L. Calderon-Garciduenas, Air pollution: mechanisms of neuroinflammation and CNS disease. Trends Neurosci, 2009. 32(9): p. 506-16. 4. Campbell, A., et al., Particulate matter in polluted air may increase biomarkers of inflammation in mouse brain. Neurotoxicology, 2005. 26(1): p. 133-40. 5. Campbell, A., Inflammation, neurodegenerative diseases, and environmental exposures. Ann N Y Acad Sci, 2004. 1035: p. 117-32. 6. Ranft, U., et al., Long-term exposure to traffic-related particulate matter impairs cognitive function in the elderly. Environ Res, 2009. 109(8): p. 1004-11.
  • 30. References 7. Power, M.C., et al., Traffic-related air pollution and cognitive function in a cohort of older men. Environ Health Perspect, 2011. 119(5): p. 682-7. 8. Gatto, N.M., et al., Components of air pollution and cognitive function in middle-aged and older adults in Los Angeles. Neurotoxicology, 2014. 40: p. 1-7. 9. Weuve, J., et al., Exposure to particulate air pollution and cognitive decline in older women. Arch Intern Med, 2012. 172(3): p. 219-27. 10. Ailshire, J.A. and P. Clarke, Fine particulate matter air pollution and cognitive function among U.S. older adults. J Gerontol B Psychol Sci Soc Sci, 2015. 70(2): p. 322-8. 11. Calderon-Garciduenas, L., et al., DNA damage in nasal and brain tissues of canines exposed to air pollutants is associated with evidence of chronic brain inflammation and neurodegeneration.Toxicol Pathol, 2003. 31(5): p. 524-38. 12. Jung, C.R., Y.T. Lin, and B.F. Hwang, Ozone, particulate matter, and newly diagnosed Alzheimer's disease: a population-based cohort study in Taiwan. J Alzheimers Dis, 2015. 44(2): p. 573-84.
  • 31. References 13. Calderon-Garciduenas, L., et al., Long-term air pollution exposure is associated with neuroinflammation, an altered innate immune response, di Toxicol Pathol, 2008. 36(2): p. 289-310. 14. Peters, A., Veronesi, B., Calderon-Garciduenas, L., Gehr, P., Chen, L. C., Geiser, M., . . . Schulz, H. (2006). Translocation and potential neurological effects of fine and ultrafine particles a critical update. Part Fibre Toxicol, 3, 13. doi: 10.1186/1743-8977-3-13 15. Campbell, A., Oldham, M., Becaria, A., Bondy, S. C., Meacher, D., Sioutas, C., . . . Kleinman, M. (2005). Particulate matter in polluted air may increase biomarkers of inflammation in mouse brain. Neurotoxicology, 26(1), 133-140. doi: 10.1016/j.neuro.2004.08.003 16. Thomson, E. M., Kumarathasan, P., Calderon-Garciduenas, L., & Vincent, R. (2007). Air pollution alters brain and pituitary endothelin-1 and inducible nitric oxide synthase gene expression. Environ Res, 105(2), 224-233. doi: 10.1016/j.envres.2007.06.005
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  • 33. References 22)H. K. Biesalski, (2002) Free radical theory of aging,” Current Opinion in Clinical Nutrition and Metabolic Care, vol. 5, no. 1, pp. 5–10. 23) H. Huang and K. Manton. (2004) The role of oxidative damage in mitochondria during aging: a review, Frontiers in Bioscience, vol. 9, pp. 1100–1117 24) C. Behl. (2009) Oxidative stress in Alzheimer's disease: implications for prevention and therapy, in Subcellular Biochemistry, J. Harris and F. Fahrenholz, Eds., vol. 38, pp. 65–79, Springer, New York, NY, USA, 38th ed 25) Molina-Holgado, F., Hider, R. C., Gaeta, A., Williams, R., & Francis, P. (2007). Metals ions and neurodegeneration. Biometals, 20(3-4), 639-654. doi: 10.1007/s10534-006-9033-z 26) Gil del Valle, L. (2011). Oxidative stress in aging: Theoretical outcomes and clinical evidences in humans. Biomedicine & Aging Pathology, 1(1), 1-7. doi: 10.1016/j.biomag.2011.03.001
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  • 36. References 37) Pratico, D. (2005). Peripheral biomarkers of oxidative damage in Alzheimer's disease: the road ahead. Neurobiol Aging, 26(5), 581-583. doi: 10.1016/j.neurobiolaging.2004.09.020 38) Arnold, S. E., Lee, E. B., Moberg, P. J., Stutzbach, L., Kazi, H., Han, L. Y., . . . Trojanowski, J. Q. (2010). Olfactory epithelium amyloid-beta and paired helical filament-tau pathology in Alzheimer disease. Ann Neurol, 67(4), 462-469. doi: 10.1002/ana.21910 39) T. Kovács, N. J. Cairns, and P. L. Lantos. (2001) Olfactory centres in Alzheimer's disease: olfactory bulb is involved in early Braak's stages,” NeuroReport, vol. 12, no. 2, pp. 285– 288. 40) Doty, R. L. (2008). The olfactory vector hypothesis of neurodegenerative disease: is it viable? Ann Neurol, 63(1), 7-15. doi: 10.1002/ana.21327 41) Nelson, V. M., Dancik, C. M., Pan, W., Jiang, Z. G., Lebowitz, M. S., & Ghanbari, H. A. (2009). PAN-811 inhibits oxidative stress-induced cell death of human Alzheimer's disease- derived and age-matched olfactory neuroepithelial cells via suppression of intracellular reactive oxygen species. J Alzheimers Dis, 17(3), 611-619. doi: 10.3233/JAD-2009-1078
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