- Plasma phosphorylated tau 217 (pTau217) is a promising, scalable, minimally invasive blood-based biomarker of Alzheimer's disease (AD) pathology.

- pTau217 is correlated with amyloid and tau PET and clinical diagnosis, and is increasingly used to index AD pathology.

- Its domain-specific associations with cognitive change in preclinical stages remain poorly characterized; most studies use global composites (mPACC, MMSE).

Aim. Test bidirectional associations between pTau217 and ~6-year change across five cognitive domains in older men, and assess whether pTau217 change is associated with cognitive change.

 

## Sample

- N = 1,261 community-dwelling men, waves 3 & 4 of the *Vietnam Era Twin Study of Aging (VETSA)* .
- Plasma + cognition at age 68 (baseline; 2016--2019; n=1,196) and age 73 (2021--2024; n=941); mean interval 5.63 yrs (SD=0.60).
- ~80% reported no combat exposure; at study entry similar to U.S. men of the same age cohort.

## Measures

- Cognition: factor scores for 5 domains — executive function, verbal fluency, episodic memory, processing speed, visuospatial ability — standardized to wave-1 means/SDs (higher = better).
- pTau217: ALZpath assay on Quanterix Simoa HD-X (USC ATRI Biomarker Core). Box--Cox transformed across waves; site and storage time regressed out within wave (umx).

# Conclusion

- From late midlife to early old age, plasma pTau217 change tracked cognitive change in 4 of 5 domains (all but verbal fluency), supporting its use to monitor disease progression.

- A single early (age 68) pTau217 measure predicted ~6-year decline most reliably in processing speed and visuospatial ability.