Highlight
1. Older adults with end-stage kidney disease living in areas of high fine particulate matter (PM2.5) exposure have a 44% higher risk of developing dementia compared to those in low-exposure areas.
2. Combined environmental pollution and racial/ethnic segregation markedly increase dementia risk, with a 2.28-fold higher hazard observed.
3. Minority populations residing in highly segregated, polluted neighborhoods are disproportionately affected, demonstrating the impact of compounded social and environmental injustices.
4. These findings underscore the urgent need for targeted public health interventions and policy reforms addressing environmental and social determinants of health.
Study background
End-stage kidney disease (ESKD) is a severe condition involving irreversible loss of kidney function requiring dialysis or transplantation. Older adults with ESKD are at increased risk of cognitive impairment and dementia, contributing to poor outcomes and quality of life. Racial and ethnic disparities in dementia prevalence are well documented, but the underlying drivers remain insufficiently understood. Environmental factors such as air pollution (particularly fine particulate matter, PM2.5) and social determinants including residential racial/ethnic segregation have emerged as key contributors to health inequities. Investigating how these intersecting injustices influence dementia risk in the vulnerable ESKD population is critical for informing equitable healthcare strategies.
Study design
This study analyzed data from the United States national ESKD registry comprising 884,950 older adults aged 55 years and above who initiated dialysis between 2003 and 2019. Researchers linked individual patient data with environmental exposure metrics by matching residential ZIP codes at dialysis initiation to annual average PM2.5 concentrations. Social injustice was quantified using Theil’s H segregation index reflecting racial/ethnic neighborhood segregation. The primary endpoint was incident dementia diagnosis during follow-up. Adjusted Cox proportional hazards models with shared state-level frailty terms evaluated dementia risk associations with PM2.5 exposure and segregation, adjusting for demographic, clinical, and neighborhood-level confounders. Interaction analyses examined effect modifications by race, ethnicity, and sex.
Key findings
The cohort’s mean age was 70.5 years, comprising 44.2% females; racial/ethnic composition included 3.8% Asian, 24.5% Black, 11.0% Hispanic, and 60.7% White individuals. Diabetes and hypertension were common ESKD etiologies, and over half had pre-ESKD nephrology care.
During a median follow-up of 2.2 years, 79,165 dementia cases were identified. Older adults in neighborhoods with high PM2.5 exposure (n=598,778) had a significantly increased dementia risk with an adjusted hazard ratio (aHR) of 1.44 (95% CI: 1.41–1.47) compared to those in low PM2.5 areas. Notably, the PM2.5-dementia association varied across racial/ethnic groups (P_interaction <0.0001), with highest risk in Black patients (aHR=1.63, 95% CI: 1.57–1.68) and lower, though still significant, elevations in Asian (aHR=1.26), Hispanic (aHR=1.25), and White patients (aHR=1.44). There was no significant interaction by sex.
Cumulative incidence of (A) all-type dementia, (B) Alzheimer’s disease, (C) vascular dementia, (D) other/mixed-type dementia stratified by residential neighborhood PM2.5 and segregation levels among older adults (age ≥55) with end-stage kidney disease (ESKD) who initiated dialysis (2003–2019).
Critically, in neighborhoods characterized by both high PM2.5 and high racial/ethnic segregation (n=232,708), the dementia risk was profoundly elevated (aHR=2.28, 95% CI: 2.21–2.36). Within these areas, predominantly minority neighborhoods had the highest risk (aHR=2.85, 95% CI: 2.75–2.95) compared to those in low PM2.5 and low segregation areas.
Table 3.
Residential neighborhood PM2.5 and segregation levels and dementia diagnosis (all-type dementia, Alzheimer’s disease, vascular dementia, and other/mixed-type dementia) among older adults (aged ≥55) with end-stage kidney disease (ESKD) initiating dialysis (2003–2019; N = 884,950).
| Adjusted hazard ratio (aHR) (95% confidence interval)a
|
||||||
|---|---|---|---|---|---|---|
| Low PM2.5
|
High PM2.5
|
|||||
| Low segregation | Medium segregation | High segregation | Low segregation | Medium segregation | High segregation | |
| All-type Dementia | Reference | 1.30 (1.25–1.34) | 1.46 (1.40–1.52) | 1.20 (1.16–1.24) | 1.73 (1.67–1.79) | 2.28 (2.21–2.36) |
| Alzheimer’s disease | Reference | 1.43 (1.33–1.54) | 1.67 (1.53–1.81) | 1.18 (1.09–1.27) | 1.59 (1.48–1.70) | 2.23 (2.07–2.39) |
| Vascular dementia | Reference | 1.23 (1.14–1.34) | 1.39 (1.26–1.53) | 1.22 (1.13–1.32) | 1.81 (1.68–1.95) | 2.35 (2.18–2.54) |
| Other/mixed-type dementia | Reference | 1.29 (1.24–1.34) | 1.42 (1.37–1.48) | 1.19 (1.15–1.24) | 1.73 (1.67–1.79) | 2.28 (2.20–2.36) |
The unadjusted 5-year cumulative incidence of dementia was 13.4% in high PM2.5 neighborhoods versus 11.8% in low PM2.5 neighborhoods (P_log-rank <0.0001), underscoring the public health impact.
Expert commentary
This comprehensive national registry study robustly links exposure to environmental pollution and social segregation with heightened dementia risk among older adults with ESKD, emphasizing how environmental and social determinants synergize to exacerbate health disparities. The use of ZIP code–level PM2.5 data enhances exposure precision, while adjustment for multiple potential confounders bolsters causal inference. The differential racial/ethnic vulnerability signals complex interactions between biology, social context, and structural inequalities requiring in-depth exploration.
Limitations include reliance on registry diagnosis codes for dementia ascertainment, which may underdetect cases or introduce misclassification bias, and observational design precluding definitive causality. The median follow-up of 2.2 years may underestimate long-term dementia risks. Nevertheless, this study provides compelling evidence of how injustices embedded in environmental and social frameworks disproportionately jeopardize cognitive health in a high-risk clinical subgroup.
These findings align with emerging mechanistic insights implicating chronic PM2.5 exposure in neuroinflammation, microvascular injury, and accelerated neurodegeneration, which may compound preexisting vulnerabilities from ESKD-related uremia and vascular pathology. The exacerbation of risk in segregated minority neighborhoods reflects systemic factors such as resource deprivation, healthcare access barriers, and chronic psychosocial stress that compound vulnerability.
Future research should focus on interventional studies testing pollution reduction and social policy reforms as dementia prevention strategies in this and broader populations. Clinicians should consider environmental and social context as part of holistic risk assessment and advocate for policies addressing these upstream determinants.
Conclusion
Older adults with ESKD exposed to high levels of fine particulate air pollution and living in racially segregated neighborhoods face substantially increased risks of developing dementia. Environmental and social injustices are critical drivers of observed racial and ethnic disparities in dementia incidence within this vulnerable population. This evidence underscores an urgent need for multifaceted interventions and health policies addressing pollution control and social inequity to mitigate cognitive decline risks and promote equitable health outcomes for older adults with kidney disease.
Funding and clinicaltrials.gov
This study was supported by the National Institutes of Health. There was no clinical trial registration associated with the observational registry analysis.
References
Li Y, Menon G, Long JJ, Wilson M, Kim B, Bae S, DeMarco MP, Wu W, Orandi BJ, Gordon T, Thurston GD, Purnell TS, Thorpe RJ Jr, Szanton SL, Segev DL, McAdams-DeMarco MA. Environmental and social injustices impact dementia risk among older adults with end-stage kidney disease: a national registry study. Lancet Reg Health Am. 2025 Oct 15;52:101269. doi: 10.1016/j.lana.2025.101269 IF: 7.6 Q1 . PMID: 41141567 IF: 7.6 Q1 ; PMCID: PMC12550583 IF: 7.6 Q1 .