Particulate Air Pollutants, Brain Structure, and Neurocognitive Disorders in Older Women.

Introduction: An increasing number of studies have suggested that exposure to particulate matter (PM) may represent a novel - and potentially amendable - environmental determinant of brain aging. The current longitudinal environmental epidemiological study addressed some important knowledge gaps in this emerging field, which combines the study of air pollution and neuroepidemiology. The investigators hypothesized that long-term PM exposure adversely influences global brain volume and brain regions (e.g., frontal lobe or hippocampus) that are critical to memory and complex cognitive processing or that are affected by neuropathological changes in dementia. It was also hypothesized that long-term PM exposure results in neurovascular damage and may increase the risk of mild cognitive impairment (MCI) and -dementia. Methods: = 1,403) enrolled in the WHIMS-Magnetic Resonance Imaging (WHIMS-MRI) study (2005-2006). Residence-specific yearly exposures to PM ≤ 2.5 µm in aerodynamic diameter (PM₂.₅) were estimated using a Bayesian maximum entropy spatiotemporal model of annual monitoring data (1999-2007) recorded in the U.S. Environmental Protection Agency (U.S. EPA) Air Quality System (AQS). Annual exposures (1996-2005) to diesel PM (DPM) were assigned to each residential census tract in a nationwide spatiotemporal mapping, based on a generalized additive model (GAM), to conduct census tract-specific temporal interpolation of DPM on-road estimates given by the U.S. EPA National-Scale Air Toxics Assessment Program. Multiple linear regression and multicovariate-adjusted Cox models were used to examine the associations, with statistical adjustment for multiple potential confounders. Results: The investigators found that participants had smaller brain volumes, especially in the normal-appearing white matter (WM), if they lived in locations with higher levels of cumulative exposure (1999-2006) to PM ₂.₅ before the brain MRI scans were performed. The associations were not explained by sociodemographic factors, socioeconomic status, lifestyle factors, or other clinical characteristics. Analyses showed that the adverse effect on brain structure in the participants was driven primarily by the smaller WM volumes associated with cumulative PM₂.₅ exposures, which were present in the WM divisions of the association brain area (frontal, parietal, and temporal lobes) and corpus callosum. Increased DPM exposures were associated with larger ventricular volume, suggesting an overall atrophic effect on the aging brains. The participants tended to have smaller gray matter (GM) volumes if they lived in areas with the highest (i.e., fourth quartile) estimated cumulative DPM exposure in the 10 years before the brain MRI scans, compared with women in the first to third quartiles. This observed association was present in the total brain GM and in the association brain cortices. The associations with normal-appearing WM varied by DPM exposure range. For women with estimated cumulative exposure below that of the fourth quartile, increased DPM estimates were associated with smaller WM volumes. However, for women with increased cumulative DPM exposures estimates in the fourth quartile, WM volumes were larger. This pattern of association was found consistently in the association brain area; no measurable difference was found in the volume of the corpus callosum. These observed adverse effects of cumulative exposure to PM₂.₅ (linking exposure with smaller WM volumes) and to DPM (linking exposure in the highest quartile with smaller GM volumes) were not significantly modified by existing cardiovascular diseases, diabetes mellitus, obesity, or measured white blood cell (WBC) count. MRI measurements of the structural brain showed no differences in small-vessel ischemic diseases (SVID) in participants with varying levels of cumulative exposure to PM₂.₅ (1999-2006) or DPM (1996-2005), and no associations between PM exposures and SVID volumes were noted for total brain, association brain area, GM, or WM. For neurocognitive outcomes followed until 2007, the investigators found no evidence for increased risk of MCI/dementia associated with long-term PM exposures. Although exploratory secondary analyses showed different patterns of associations linking PM exposures separately with MCI and dementia, none of the -results was statistically significant. A similar lack of associations between PM exposures and MCI/dementia was found across the subgroups, with no strong indications for effect modification by cardiovascular diseases, diabetes mellitus, obesity, or WBC count. Conclusions: The investigators concluded that their study findings support the hypothesized brain-structure neurotoxicity associated with PM exposures, a result that is in line with emerging neurotoxicological data. However, the investigators found no evidence of increased risk of MCI/dementia associated with long-term PM exposures. To better test the neurovascular effect hypothesis in PM-associated neurotoxic effects on the aging brain, the investigators recommend that future studies pay greater attention to selecting optimal populations with repeated measurements of cerebrovascular damage and address the possibility of selection biases accordingly. To further investigate the long-term consequence of brain-structure neurotoxicity on pathological brain aging, future researchers should take the pathobiologically heterogeneous neurocognitive outcomes into account and design adequately powered prospective cohort studies with improved exposure estimation and valid outcome ascertainment to assess whether PM-associated neurotoxicity increases the risks of pathological brain aging, including MCI and dementia.