Estimated long-term environmental dioxin exposure and cognitive and brain health in the adult changes in thought study

The National Institute of Environmental Health Sciences awarded Kaiser Foundation Hospitals $853,447 on September 1, 2026, under the Environmental Health program (CFDA 93.113) to examine long-term environmental dioxin exposure and cognitive and brain health outcomes in the Adult Changes in Thought Study.

The research leverages existing data resources from ACT, a population-based prospective cohort study established in 1994 that follows cognitively healthy members aged 65 and older for incident dementia, Alzheimer's disease diagnosis, or study withdrawal. The project analyzes extensive longitudinal cognitive function data, residential address history, and occupational records for 6,522 participants to assess whether dioxin exposure at population-characteristic levels is associated with dementia incidence. For a subset of 1,801 participants, the award funds analysis of clinical and research magnetic resonance imaging scans for common data elements, quantitative volumetric measures, and diffusion-weighted imaging sequences. For 1,037 participants, the work leverages comprehensively characterized brain autopsy data.

Kaiser Foundation Hospitals, operating through its Kaiser Foundation Research Institute division and doing business as Kaiser Permanente, serves as the recipient. Place of performance is Seattle, Washington. The period of performance runs through June 30, 2031. This project grant funds epidemiological investigation of point-source hazardous air pollutants, specifically dioxins emitted as combustion by-products, as modifiable exposures potentially associated with late-life cognitive decline.

Abstract

Opportunities exist to reduce dementia incidence among older adults by addressing modifiable exposures. While late life air pollution exposure is associated with dementia, studies have almost exclusively focused on particulate matter or traffic-related air pollution, and have mostly overlooked point source hazardous air pollutants, such as dioxins, which are emitted as combustion by-products. In vivo and in vitro studies provide compelling evidence that dioxin exposure could plausibly lead to either direct or indirect injury to the brain or increase its vulnerability to neurodegeneration. Epidemiologic studies in special populations suggest that occupational dioxin exposure during the life course may be associated with adverse cognitive outcomes in the ensuing one to two decades. However, no study has examined effects of dioxin exposure at levels more characteristic of the general population on dementia incidence. We will fill this GAP by leveraging rich existing data resources from the adult changes in thought (act) study, a population-based prospective cohort study established in 1994 that randomly recruits cognitively healthy members of a large health plan aged ≥65 years, and follows them every two years to dementia onset, death or study withdrawal. In act, we have extensive longitudinal data on cognitive function, consensus diagnoses of incident alzheimer's disease (ad) and dementia, residential address history and longest-held occupation for 6,522 participants. For 1,801 participants, we will leverage in vivo clinical (currently N=2,400 scans) and research (currently N=530 scans) mris for common data elements (CDES) and quantitative volumetric measures, and research scan sequences for diffusion weighted images. For 1,037 participants, we will leverage the exceptional resource of comprehensively characterized brain autopsies collected using standard neuropathologic assessments for the diagnosis of neurodegenerative neuropathology. We will use geocoded historical residential addresses linked in a validated state-of-the-art GIS-based model to estimate long-term airborne dioxin emissions from industrial sources. We will evaluate the impact of long-term dioxin exposure on: 1) risk of incident ad and of all-cause dementia and accelerated global and domain-specific cognitive decline; 2) neuroimaging indicators global and regional brain atrophy and white matter hyperintensities and microinfarcts and with grey and white matter microstructural abnormalities; 3) prevalence of dementia-related neuropathological outcomes including ad neuropathic change (ADNC), lewy bodies, hippocampal sclerosis and cerebral microinfarcts and with greater neurofibrillary tangle distribution, cortical neuritic plaque density, AΒ plaque distribution, cerebral amyloid angiopathy, atherosclerosis, macroscopic infarcts and phosphorylated TDP-43. We will conduct a multi- exposure mixture analysis to estimate associations for CO-exposure to dioxin emissions and air pollutants. This research will inform public health approaches such as regulations of industrial source emissions and is particularly salient to communities who bear a greater burden of exposure to environmental hazards.