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Air pollution and dementia: An epidemiological approach integrating multimodal biomarkers

Award Number: K23AG101527
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 07/01/2026
PERIOD OF PERFORMANCE END DATE: 03/31/2031

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Air pollution and dementia: An epidemiological approach integrating multimodal biomarkers - PROJECT SUMMARY Although long-term air pollution is an established dementia risk factor, the biological basis of this association remains poorly understood. Long-term exposure to fine particles less than 2.5 microns in diameter (PM2.5) may increase dementia risk through pathways that include inflammation, neurodegeneration and the accelerated production and deposition of amyloid-b (Ab) plaques, through accumulation of cerebrovascular disease burden, or some combination thereof. An understanding of the biological basis of the air pollution-dementia association is essential to inform future research and interventions that target underlying disease mechanisms. A mechanistic understanding of the air pollution-dementia association is essential to inform future research as well as public health and clinical interventions aimed at primary and secondary prevention. Informed by existing theory and prior research, the overarching hypothesis of this proposal is that the magnitude and duration of long-term air pollution exposure increases dementia through co-existent pathways that include increased Alzheimer disease (AD) pathology and cerebrovascular disease. This proposal will leverage detailed, patient-level measures of disease biology from two ongoing prospective cohort studies. In Aims 1–3 I will use data from the Penn Alzheimer’s Disease Research Center (ADRC) Cohort, with findings from Aims 1 compared with and validated against the Penn Medicine Biobank (PMBB) Cohort. In Aim 1 and 2, I will use g-computation, a novel causal inference method that flexibly models the dose-response association at varied magnitude and duration of exposure to examine how long-term PM2.5 exposure influences levels of plasma-based biomarkers of AD neuropathology and neuroinflammation (Ab42/40, pTau217, GFAP and NfL) and neuroimaging measures of neurodegeneration and cerebrovascular disease (hippocampal volume, global cortical thickness, white matter hyperintensity volume), respectively. In Aim 3, I will use a simulation-based approach to examine whether plasma-based and neuroimaging biomarkers mediate the relation between long- term PM2.5 exposure and cognitive function. The proposed research aims to address critical gaps in the existing literature on air pollution and dementia and will be complemented by dedicated training in ADRC clinical research, selection and implementation of multimodal biomarker data for epidemiologic research, and the application of novel causal inference methods in environmental epidemiology. Collectively, the applied research and dedicated training will build upon my strong quantitative foundation as an epidemiologist prepare me for independence as a physician-scientist whose work aims to characterize the biological mechanisms linking environmental exposures with the onset and exacerbation of neurological diseases in populations with an emphasis on dementia.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $196,020 )
2026	2026	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Aging Research	000	1	7/1/2026	NEW	$196,020
														Subtotal = $196,020

Grand Total All Awards = $196,020

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Air pollution and dementia: An epidemiological approach integrating multimodal biomarkers

Award Number: K23AG101527

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 07/01/2026

PERIOD OF PERFORMANCE END DATE: 03/31/2031

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