Concurrent cognitive, behavioral and systemic physiological features mark preclinical Alzheimer's disease

In a medically managed cohort of 644 older adults with intact cognition, 20% had elevated plasma p-tau217, including 93 cognitively unimpaired individuals, showing concurrent multidomain features.

• Why it matters: AD pathology can precede symptoms by years, but the multidomain phenotype of biomarker-defined preclinical disease is unclear, partly due to comorbidities.
• What they did: The study assembled risk-factor–controlled participants without systemic or neurological diseases, measured plasma p-tau217, and compared cognitive, behavioral, physiological measures, and biomarkers including GFAP and NfL.
• The result: The p-tau217-high subgroup showed subtle concurrent cognitive/behavioral differences and higher GFAP and NfL, and a proof-of-concept AI classifier using routine multidomain data improved identification versus cognitive screening alone.

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