# Comparison of amyloid chronicity and EYO in autosomal dominant Alzheimer's disease

## TL;DR

The study compares amyloid chronicity and estimated years to onset in autosomal dominant Alzheimer's disease to understand preclinical phases and symptom progression.

## Contribution

The study introduces SILA, a method to estimate age at amyloid positivity with high accuracy in autosomal dominant Alzheimer's disease.

## Key findings

- SILA estimates age at amyloid positivity with a mean absolute error of less than 2 years.
- Estimated years to symptom onset (EYO) better predicts symptom onset than amyloid chronicity.
- APP mutation carriers show atypical amyloid accumulation patterns.

## Abstract

Preclinical Alzheimer's disease (AD) can be described relative to biomarker positivity onset time.

We estimated time from amyloid positivity (A+) using sampled iterative local approximation (SILA) in a longitudinal autosomal dominant AD (ADAD) sample (N = 379) with amyloid positron emission tomography. We compared (1) predicted age at A+ to imputed age, (2) estimated age at A+ to estimated age at symptom onset, and (3) variance in cognitive performance explained.

Mean error between imputed and SILA‐estimated age at A+ (N = 26) was 1.15 years. Age at A+ explained 39% of estimated years to symptom onset (EYO) variance. Time from A+ explained 19% of cognitive composite variance and 14% of Clinical Dementia Rating Sum of Boxes CDR‐SB variance; EYO explained 43% and 57%, respectively.

SILA estimates A+ age in ADAD with reasonably good accuracy. SILA‐estimated time from A+ describes the start of pathology, but the time from A+ onset to symptoms is variable in ADAD and better described by EYO.

Amyloid chronicity predicts a 14‐year preclinical AD phase in ADAD.SILA accurately estimates age at A+ (MAE < 2 years).EYO outperforms chronicity in predicting symptom onset.APP mutation carriers show atypical amyloid accumulation.Chronicity models help reveal AD heterogeneity in preclinical stages.

Amyloid chronicity predicts a 14‐year preclinical AD phase in ADAD.

SILA accurately estimates age at A+ (MAE < 2 years).

EYO outperforms chronicity in predicting symptom onset.

APP mutation carriers show atypical amyloid accumulation.

Chronicity models help reveal AD heterogeneity in preclinical stages.