1. extract image-related features

2. train model on normative dataset to predict age

 3. obtain predicted ages on test set

 4. compute
brain-predicted age difference (brainPAD)

 5. make inference: accelerated/
delayed aging

select voxels/ROIs

structural MRI

predicted brain age

DNA-methylation

epigenetic age

- real age

- real age

automated ML

\Delta

epigenetic age

(regularized NPDR)

 ~  genetic variants

epigenetic age

\Delta

Dimensions and stages of aging

Aim 3

Aim 2

Aim 2 + 3

select CpG sites

time

automated ML

brain age

\Delta

brain age

\Delta

Aim 1

Develop and evaluate NPDR

select voxels/ROIs

structural MRI

predicted brain age

DNA-methylation

epigenetic age

- real age

- real age

automated ML

\Delta

epigenetic age

 ~  genetic variants

epigenetic age

\Delta

Dimensions and stages of aging

select CpG sites

time

automated ML

brain age

\Delta

brain age

\Delta

Biological
processes

Accelerated
aging

Disease progression

?

?

\(allele_i \) carrier

\(allele_i \) non-carrier

time

composite \(\Delta\) age