# Age‐related amyloid‐β dynamics modeled with the generalized additive model for location, scale, and shape (GAMLSS) across diverse populations: cross‐sectional trajectories and longitudinal validation

## TL;DR

This study models how amyloid-beta levels change with age in different populations and finds that non-Hispanic Whites show steeper increases compared to Koreans.

## Contribution

The study introduces a validated statistical model for age-related amyloid-beta trajectories using cross-sectional data and validates it with longitudinal data.

## Key findings

- Amyloid-beta levels increase with age in the upper percentiles for both Koreans and non-Hispanic Whites.
- Non-Hispanic Whites showed steeper amyloid-beta accumulation trajectories, especially among APOE ε4 carriers.
- The statistical model was validated using longitudinal data, confirming its reliability.

## Abstract

Alzheimer's disease is characterized by early amyloid‐β (Aβ) accumulation, even in cognitively unimpaired (CU) individuals, yet age‐related Aβ trajectories remain poorly understood. We developed and validated age‐related Aβ positron emission tomography ( trajectories using a statistical model in CU individuals, and examined the effects of sex and APOE ε4.

We analyzed 849 CU Korean participants and 521 CU non‐Hispanic Whites (NHWs) after propensity score matching. Age‐related Aβ PET trajectories were modeled using the generalized additive model for location, scale, and shape (GAMLSS) based on cross‐sectional data and validated with longitudinal data. Subgroup analyses explored the influence of APOE ε4 and sex on age‐related Aβ PET trajectories.

The age‐related centile curves of Aβ PET centiloid values showed stable distributions in the lower percentiles. Aβ values increased with age in the upper percentiles for both Koreans and NHWs. NHWs demonstrated steeper trajectories of Aβ accumulation, particularly among APOE ε4 carriers, compared to Koreans. The reliability of this cross‐sectional method was confirmed through robust calibration using the study's own longitudinal dataset.

Our study developed a statistical model of age‐related Aβ PET trajectories using cross‐sectional data, validated with longitudinal data. NHWs had steeper trajectories of AB accumulation compared to Koreans. The results suggest differences in population‐specific patterns of Aβ accumulation.