# The Down Alzheimer Barcelona Neuroimaging Initiative (DABNI): Ten Years of Progress in Understanding Alzheimer's in Down Syndrome

## TL;DR

The DABNI study tracks Alzheimer's in people with Down syndrome over ten years, revealing disease progression patterns and biomarkers for better treatment strategies.

## Contribution

DABNI is one of the largest longitudinal studies on Alzheimer's in Down syndrome, offering insights into disease progression and biomarkers.

## Key findings

- AD progression is rare before age 40 but increases significantly after age 50.
- Neuropsychological assessments and biomarkers show strong diagnostic performance for symptomatic AD.
- A prolonged and predictable preclinical phase of AD was observed, similar to autosomal dominant AD.

## Abstract

Down syndrome (DS) is a form of genetically determined Alzheimer's disease (AD). Understanding the natural history and biomarker specificities in this population can offer insights into AD pathogenesis and potential treatment targets.

The Down Alzheimer Barcelona Neuroimaging Initiative (DABNI) is a prospective longitudinal cohort of adults with DS that builds on a population‐based health plan screening for neurological conditions (Figure 1). Conducted at the Alzheimer‐Down Unit, the study aims to elucidate the natural history of AD in DS through multimodal biomarker investigations and support clinical trials. Participants undergo neurological and neuropsychological evaluations, blood and cerebrospinal fluid collection, structural 3T brain MRI, PET imaging ([18F]FDG‐PET, amyloid‐PET or tau‐PET), as well as electroencephalography and video‐polysomnography examinations.

The DABNI cohort included 1,135 participants with a mean age of 42.82 years (SD = 11.56), 46.3% of whom are female. At baseline, 673 participants were asymptomatic or cognitively stable, 113 had prodromal AD, 239 had AD dementia, and 110 were uncertain due to non‐AD conditions. The cohort's intellectual disability level distribution was 20% mild, 50% moderate, 20% severe, and 7% profound. Over 10,000 visits have demonstrated that AD progression is rare before age 40, but high thereafter (57.5% of individuals over 50 progress within 5 years). Neuropsychological assessments and biomarkers have shown strong diagnostic performance for symptomatic AD, and a prolonged and predictable preclinical phase similar to autosomal dominant AD. The initiative is actively participating in three clinical trials and has yielded a robust body of work, with nearly 100 publications. Table 1 shows the number of clinical visits and biomarker studies in the whole sample and stratified by clinical diagnosis.

In 10 years, the DABNI study has become one of the largest multimodal initiatives on AD in adults with DS and has provided critical insights into disease progression and biomarkers, advancing interventions and clinical research