Geriatrics

Using blood-based Alzheimer biomarkers without losing clinical perspective

This JAGS review offers practical guidance on applying blood-based Alzheimer’s disease (AD) biomarkers in everyday cognitive assessments. Plasma tests align more closely with amyloid PET than p-tau PET, so positivity does not necessarily indicate symptomatic AD. The authors emphasize that dementia remains a clinical diagnosis; biomarkers only clarify whether AD pathology likely contributes. They highlight that predictive value depends on test characteristics and disease prevalence, requiring thoughtful pretest probability estimation. Clinicians must also be prepared to interpret results for patients and families, including direct-to-consumer testing outputs. 1

Proteomic frailty score as a biomarker of biological aging

In 50,506 UK Biobank participants, 1,339 of 2,911 measured plasma proteins were significantly associated with a 35-item frailty index. Investigators derived a proteomic frailty score (PFS) that strongly predicted 199 incident diseases across 13 categories and responded to 84 modifiable risk factors. PFS progression accelerated with advancing age and greater baseline frailty, supporting its role as a biological aging biomarker. Mendelian randomization highlighted five proteins as potentially causal, suggesting novel targets for frailty interventions. An online tool enables PFS calculation from proteomic data, but current applications are research oriented rather than routine clinical practice. 2

Sleep EEG brain-age index predicts dementia in community cohorts

This individual participant data meta-analysis pooled 7,105 adults from five community-based cohorts with home polysomnography. A machine learning–derived brain age index (BAI) quantified the gap between sleep EEG–estimated brain age and chronological age. Across cohorts, each 10-year increase in BAI was associated with a 39% higher risk of incident dementia after accounting for competing mortality. Follow-up ranged from roughly 3 to 17 years, with higher BAI consistently linked to greater dementia incidence. Findings support sleep EEG microstructure as a scalable digital biomarker for preclinical brain aging and dementia risk stratification. 3