Sequential grey matter atrophy related to Alzheimer’s disease in adults with Down’s syndrome

Abstract

AbstractBackgroundDue to the triplication of the APP gene on chromosome 21, virtually all individuals with Down’s syndrome (DS) present AD neuropathological hallmarks by the age of 40, and have a lifetime risk of developing dementia >90%. However, whether DS follows a stereotypical pattern of AD atrophy has not been investigated. Here, we aimed at defining the sequential grey matter (GM) volume loss across the whole AD continuum in adults with DS.MethodCross‐sectional design. 248 adults with DS (n = 145 asymptomatic [preclinical], n = 93 prodromal/demented AD) and 181 euploid cognitively unimpaired (CU) individuals from the Down Alzheimer Barcelona Neuroimaging Initiative underwent a 3T‐MRI protocol (Table.1). T1‐weighted images were preprocessed using CAT12. GM volumes adjusted for demographics (age, sex) and nuisance variables (TIV, MRI scanner) were computed for each cortical region of the Hammer Atlas and for each DS participant, using the CU group as a reference. Adjusted volumes (W‐scores) were binarized using a threshold of ‐2.33 (corresponding to a regional volume <99th percentiles of the CU group) to examine the brain regions most frequently atrophied in DS compared to CU. Conditional probability analyses were additionally performed in DS to assess if a brain region was more likely to present with atrophy than another.ResultAdults with DS most frequently showed atrophy in the medial temporal lobe, anterior cingulate, and temporo‐parietal regions. This pattern remains essentially similar when using a dynamic range of thresholds (Fig1.A) and across clinical AD stages (Fig1.B), even though the proportion of individuals showing atrophy increased with disease progression (Fig1.C). Interestingly, the anterior cingulate was the most frequently atrophied region in asymptomatic but not prodromal/demented DS. Conditional probability analyses revealed that the hippocampus, amygdala, and anterior cingulate have a significantly higher probability of showing GM loss before any other regions. A second cluster of tempo‐parietal regions appears more likely to show atrophy than most other regions.ConclusionIn DS, GM atrophy appears to follow a stereotypical pattern that strongly resembles the one of sporadic AD. Brain developmental specificities (e.g., anterior cingulate) are coupled with AD‐like atrophy early in the disease and become less predominant with AD progression.