Cognitive decline and neuropathology in relation to air pollution

 
   Lead Investigator:    Kyle Steenland
   Institution      :    Emory
   E-Mail           :    nsteenl@sph.emory.edu
   Proposal ID      :    235



   Proposal Description:
   Alzheimers Disease is a complex trait, with a growing list of genetic factors and as yet mostly unidentified environmental factors that mediate disease risk. Recent evidence that particulate air pollution is associated with cognitive decline has been shown in two well conducted longitudinal studies (Weuve et al. 2012, Power et al. 2011). These studies indicate that an increase in exposure to air pollution of 10 ug/m3 of particulate matter (PM2.5), or a doubling of exposure to another measure of air pollution (black carbon), is equivalent to 2 years of aging. Moreover, postmortem studies in Mexico City show that air pollution exposure is associated with AD-like neuropathology in youngsters (Calderon-Garciduenas et al. 2012, Calderon-Garciduenas et al. 2012 ). Further study of the role of environmental risk factors for cognitive decline and MCI/AD is urgently needed given the potentially modifiable nature of exposure. We propose to study this important subject further in the UDS data set, using the 3 digit zip code variable in the UDS data set. We propose to estimate the level of air pollution by zip code in terms of PM2.5 particles (particles of 2.5 micron diameter or less), using EPA and other monitoring commonly done across the US in urban areas, and evaluate associations between air pollution and cognitive decline and MCI/AD risk. We hypothesize that control subjects with normal cognition at baseline at centers with higher levels of air pollution will have lower baseline cognitive functions, faster rates of cognitive decline, and higher rates of conversion to MCI and AD after controlling for covariates such as demographic variables, APOE status, and AD-associated comorbidities). Cognitive decline would be evaluated via longitudinal data on standard neurobehavioral tests in the UDS, while transition to MCI or AD would be evaluated via survival analysis. Depending on results, we then plan for additional studies using NACC neuropathology data, to investigate whether