To make things even more complicated, it may also depend on the trait you are interested in. On average FSL VBM does a good job, but for some traits like Alzheimer's disease or maternal smoking, FreeSurfer may yield more significant associations.

We also demonstrated that each processing step captures a unique signal. So we cannot claim that a single processing (among the ones we considered) is the best. Some are better, but none is perfect.

Elise's results also confirm that the choices of processing have important consequences on the results, which contributes to the reproducibility crisis. See results below for the same individuals and same trait (maternal smoking around birth - associated regions vary depending on processing)

I have always wondered if there is a best method/software to process T1w image (at a vertex/voxel wise level). Elise Delzant has some answers in her first published paper from her PhD. She compared FreeSurfer, CAT12 and FSL across several traits and analyses (association, prediction).

Lastly, we showed that the brain-based predictor of Alzheimer's could also predict early AD, mild cognitive impairment, cognition, tau levels or genetic risk. Our predictor is on par with some of the best ones that can predict progression to AD, which could help with early intervention

Interestingly, the brain regions associated with Alzheimer's, disease progression and cognition overlapped suggesting some of the same regions are implicated. Some regions stand out being associated with many traits.

We have also estimated that there should be at least 5 times more regions that remain to be identified (difference between the morphometricity and variance currently explained by the identified regions). Even more data will be needed!

Even better with a GIF (showing the regions with reduced thickness associated with Alzheimer's across the left subcortical structures)! Made with our R package brainMapR. github.com/baptisteCD/b...

Our high-resolution approach makes it possible to identify sub-regions of the hippocampus (or of the amygdala) that are involved, which can orient research towards specific brain regions/networks or cell populations.

This is the largest study of its kind in terms of the number of participants (>9,000 subjects from 10 clinical cohorts+ the UK Biobank), and we have identified 103 grey matter regions associated with Alzheimer's, including some in ‘known’ regions, such as the hippocampus.

Likewise for medical conditions, which are associated with future risk of neurodegenerative disorders.

Here is a summary of the drug classes, whose frequency of use differs in individuals who are going to receive a neurodegenerative diagnosis within 5-10 years.