Five papers worth your time — May 28–29, 2026

Five papers from the May 28–29 window: two neurological early-detection signals (Alzheimer's and auditory neurodegeneration), a genetic-metabolic atlas that revises a causal assumption about diabetes, a reframing of suicide risk in veterans with cancer, and the first mechanistic breakdown of how traffic pollutants drive chronic sinusitis via divergent inflammatory pathways.

Journal: The Lancet (IF ~169) · Prospective cohort study · Published May 28, 2026 1

Study design: CARDIA (Coronary Artery Risk Development in Young Adults) longitudinal sub-cohort — 1,350 dementia-free adults (mean age 61; 58% female; 45% Black, 55% white). Blood was drawn at CARDIA Year 35 (2020–2022) using the FDA-cleared Fujirebio Lumipulse assay measuring plasma p-tau217, Aβ42, and Aβ40. Cognition was assessed at Years 30 and 35.

Key findings: 6% (86/1,350) were positive for Alzheimer's pathology based on the p-tau217/Aβ42 ratio. Pathology-positive individuals already scored lower on processing speed and executive function at baseline; global cognition and memory remained intact at that point. At five-year follow-up, baseline pathology-positive status predicted:

Effect modification was present: associations were stronger in women, Black participants, and APOE4 carriers.

Lead author/affiliation: Kristine Yaffe, MD (UCSF).

Clinical implication: The biomarkers identify presymptomatic Alzheimer's pathology roughly a decade before expected symptom onset, and predict differential cognitive trajectories even in a cognitively normal population. The concurrent Lancet editorial by Tiia Ngandu and Anna Rosenberg (Finnish Institute for Health and Welfare) flags the population-screening risk: in low-pretest-probability groups, positive predictive value drops and false positives accumulate. Ngandu and Rosenberg: "A positive biomarker result should not be used as a stand-alone indicator without other biological or clinical information. Therefore, these blood biomarkers are not suitable for large-scale, untargeted screening for Alzheimer's disease pathology in cognitively unimpaired populations or in the community." 2 Yaffe notes the tests are intended for symptomatic patients but widely used off-label: "There's a possibility of false positives and they can only be used for Alzheimer's, not other dementias, meaning about 60% to 70% of all dementia cases." 2

Peer review status: Published in The Lancet.

Journal: Nature (IF ~64) · GWAS / metabolomic association study · Published May 28, 2026 · DOI: 10.1038/s41586-026-10532-5 3

Study design: University of Tartu team (Ralf Tambets, Kaur Alasoo, Priit Palta) merged Estonian Biobank and UK Biobank data: 619,372 individuals, 249 circulating metabolites, producing 88,604 genetic variant–metabolite associations. Advanced analytical methods were applied to separate direct genetic effects from indirect associations. 4

Key finding: The headline result revises a widely cited association: elevated circulating amino acids had been considered a likely causal factor in type 2 diabetes risk. This analysis indicates that relationship is likely not causal — implying that drugs targeting those amino acids would probably not prevent diabetes. 3 The dataset also provides a base for identifying causal factors and drug targets in cardiovascular disease and MASLD (metabolic dysfunction-associated steatotic liver disease).

Lead authors/affiliation: Kaur Alasoo (Associate Professor of Bioinformatics) and Priit Palta (Professor of Translational Genomics), University of Tartu, Estonia.

Research implication: Palta: "Metabolic markers found in blood, such as different types of cholesterol, are very useful for creating personalized risk scores because they reflect a person's health status and lifestyle choices. This is information that genetic data alone cannot reveal." 4 Alasoo adds the epistemic note that runs through the paper: "Large datasets alone are not enough to uncover causal relationships — you also need a very good understanding of biological mechanisms." 4 The dataset is publicly available for secondary interrogation across metabolic disease pipelines.

Peer review status: Published in Nature.

Journal: JAMA Oncology (IF ~28) · Retrospective longitudinal cohort · Published May 28, 2026 · DOI: 10.1001/jamaoncol.2026.1459 5

Study design: 292,271 veterans diagnosed with invasive solid or hematologic malignancies, January 2014–December 2023 (mean age 69; 98% male; 75% white). Primary outcome: suicidal self-directed violence (SSDV), capturing both fatal and nonfatal attempts. 6

Key findings: 2,400 SSDV events (overall rate: 203/100,000 person-years; 22 fatal, 181 nonfatal per 100,000 PY). Adjusted hazard ratios within six months of diagnosis:

Five-year risk remained elevated for younger veterans (≤45 vs. 46–64: aHR 1.58), unmarried veterans (aHR 1.48), and CNS cancer patients (aHR 1.63). 5 Most common method: poisoning at 26% (anxiolytics, muscle relaxants, opioids), followed by firearms at 23%.

Lead author/affiliation: Donald R. Sullivan, MD (Oregon Health & Science University).

Clinical implication: Including nonfatal attempts — 95% of all SSDV events — surfaces risk subgroups that studies limited to completed suicides miss. Sullivan: "It's no secret that patients with cancer suffer from higher suicide rates. What this study challenges is the idea of who is most at risk for suicide." 6 The aHR of 2.55 for Asian veterans — a group not previously flagged in cancer–suicide literature — and the five-year persistent risk elevation argue for longer routine screening windows. The poisoning-dominant method profile has direct relevance for prescribers managing anxiolytics and opioids in this population.

Limitations: Female veterans are only 2% of the cohort; generalizability to women is limited.

Peer review status: Published in JAMA Oncology.

Journal: JAMA Otolaryngology–Head & Neck Surgery (IF ~12) · Longitudinal observational study · Published May 28, 2026 7

Study design: 312 cognitively normal older adults (mean age 73.5; 54% female) from the Australian ASPREE (ASPirin in Reducing Events in the Elderly) trial sub-cohort. Baseline speech-in-noise ability assessed via LiSN-S (Listening in Spatialized Noise-Sentences); peripheral hearing measured by pure-tone audiometry. T1-weighted MRI tracked cortical thickness and regional brain volumes over three years. 8

Key findings: Poorer baseline speech-in-noise performance was associated with accelerated cortical thinning across four regions over three years, after adjustment for hearing thresholds and hearing aid use:

Only central auditory processing deficits — not peripheral hearing loss or hearing aid use — drove these associations. 7

Lead author/affiliation: Julien Zanin, PhD (University of Melbourne).

Clinical implication: Zanin: "We found that speech-in-noise impairment was more closely related to structural brain change than hearing thresholds alone. These associations remained after accounting for peripheral hearing loss, suggesting speech-in-noise ability may capture broader neural vulnerability." 8 No global cognitive decline was detected over the three-year follow-up, suggesting these structural changes precede what standard cognitive screens can detect. Standard audiometry will not capture this risk signal; the finding points toward LiSN-S or equivalent speech-in-noise testing as a more sensitive neurodegeneration screen.

Peer review status: Published in JAMA Otolaryngology–Head & Neck Surgery.

Journal: JAMA Otolaryngology–Head & Neck Surgery (IF ~12) · Case-control study · Published May 28, 2026 · DOI: 10.1001/jamaoto.2026.1176 9

Study design: 62 CRS (chronic rhinosinusitis) patients undergoing endoscopic sinus surgery vs. 30 controls (endonasal endoscopic skull-base surgery without CRS), at a California tertiary referral center (March 2017–August 2021). Five-year average residential pollutant concentrations estimated via validated land-use regression. 10

Key findings: Per standard deviation increment in pollutant concentration, associations with CRS diagnosis and observed cytokine pathway:

Lead author/affiliation: Jivianne T. Lee, MD, and colleagues (UCLA).

Clinical implication: The pathway divergence is directly relevant to biologics selection. NO2 activates the type 2 barrier alarmin axis — the same pathway targeted by dupilumab and other biologics now used in refractory CRS. Benzene and atmospheric lead drive a distinct innate neutrophilic pathway for which targeted biologics are not yet established. Lee et al.: "These findings potentially advance understanding of how distinct pollutants contribute to [chronic rhinosinusitis] heterogeneity and may help inform future directions for targeted prevention, therapeutic innovation, and clinical management." 9 For clinicians managing CRS with biologics, residential exposure profile — particularly proximity to high-combustion traffic — may become a relevant stratification variable.

Limitations: Case-control design precludes causal inference; exposure estimates reflect residential-address ambient levels, not personal exposure.

Peer review status: Published in JAMA Otolaryngology–Head & Neck Surgery.