API ADAD Colombia Trial

The API ADAD Colombia Trial tested whether the anti-amyloid antibody crenezumab could delay cognitive decline when started before symptoms in autosomal dominant Alzheimer disease. It enrolled members of the Colombian kindred that carries the PSEN1 E280A (Glu280Ala) mutation, whose carriers develop mild cognitive impairment at a median age of about 44. Banner Alzheimer's Institute, the University of Antioquia and Genentech/Roche ran it at a single site in Medellín from December 2013 to March 2022. Crenezumab did not change the primary cognitive outcomes or the biomarker outcomes. Clinical data and trial imaging are requested through the LONI Image and Data Archive.

Composition

252 cognitively unimpaired people aged 30 to 60 at screening: 85 mutation carriers on crenezumab, 84 carriers on placebo and 83 non-carriers from the same families, all on placebo, enrolled so that nobody learned their genotype. 160 are women. Carriers were younger on average (about 37 years) than non-carriers (about 43). Around 55% of carriers had a positive amyloid PET scan at baseline. Treatment lasted 5 to 8 years and 237 participants completed the trial.

Acquisition

All MRI was done on one 3T Siemens Tim Trio, with safety, structural and functional sequences. The volumetric scan is a 3D T1 MP-RAGE with 1.25 x 1.25 mm in-plane resolution and 1.2 mm slices. MRI was repeated at weeks 12, 24, 36 and 52 and then every six months. Florbetapir amyloid PET and FDG PET were acquired on a Siemens Biograph mCT at baseline, year 2, year 5 and study end. GTP1 tau PET was an optional substudy added after the trial began, so it has no baseline scan. CSF was optional, and plasma was collected every year.

Annotations

No image annotations are described. Safety reads recorded ARIA: new ARIA-H in four carriers on crenezumab and two on placebo, and no ARIA-E. Volumes of the whole brain, hippocampus and lateral ventricles were derived with FreeSurfer.

Known limitations

• The trial's own data page says the clinical dataset is available without imaging and that imaging is coming soon, while the results paper states that trial imaging is hosted at LONI. Check with the API data team what is released.
• The safety, FLAIR or T2*-weighted sequences are not described in the papers, so only T1w is listed.
• One kindred and one mutation, at one site, so the cohort is genetically and geographically narrow.
• Every publication must be reviewed by the API Administrative Review Committee before submission.