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Updated: May 29, 2026

The 4 Mountains Test: A Short Test of Spatial Memory with High Sensitivity for the Diagnosis of Pre-dementia Alzheimer's Disease
Published on: October 13, 2016
Scalable markers for early cognitive decline: Plasma p-tau217, subjective cognitive concerns, and digital testing:
Babak Khorsand1, Devin Teichrow1, Elham Ghanbarian1
1Department of Neurology, University of California, Irvine, California, USA.
Introduction:
Amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers confirm Alzheimer's disease (AD) pathology but are impractical for large-scale screening. Plasma phosphorylated tau at threonine 217 (p-tau217), subjective cognitive concerns, and computerized cognitive testing are non-invasive, scalable, and feasible to implement in large populations. We assessed their separate and combined predictive value for cognitive decline.
Methods:
We analyzed 1064 cognitively unimpaired adults (ages 65-85 years) from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4; amyloid-positive) and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN; amyloid-negative) studies. Baseline assessments included apolipoprotein E (APOE) ε4 status, hippocampal volume, amyloid PET, plasma p-tau217, Cognitive Function Index (CFI), and Cogstate Computerized Battery (CCB). Cognitive impairment was defined as conversion from a Clinical Dementia Rating Global Score (CDR-GS) of 0 to ≥0.5 over 240 weeks.
Results:
During the follow-up, 34.1% developed cognitive impairment. Higher p-tau217, higher CFI, and lower CCB were associated with higher odds of converting to CDR-GS >0 across all cohorts.
Discussion:
P-tau217, CFI, and CCB each independently predict cognitive decline, offering practical, non-invasive tools for early AD risk stratification and trial enrichment.
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