Imaging of onset and progression of Alzheimerʹs disease with voxel-compression mapping of serial magnetic resonance images

Background Early diagnosis and monitoring of the progression of Alzheimerʹs disease is important for the development of therapeutic strategies. To detect the earliest structural brain changes, individuals need to be studied before symptom onset. We used an imaging technique known as voxel-compression mapping to localise progressive atrophy in patients with preclinical Alzheimerʹs disease Methods Four symptom-free individuals from families with early-onset Alzheimerʹs disease with known autosomal dominant mutations underwent serial magnetic resonance imaging (MRI) over 5–8 years. All four became symptomatic during follow-up. 20 individuals with a clinical diagnosis of probable Alzheimerʹs disease and 20 control participants also underwent serial MR imaging. A non-linear fluid matching algorithm was applied to register repeat scans onto baseline imaging. Jacobian determinants were used to create the voxel-compression maps. Findings Progressive atrophy was revealed in presymptomatic individuals, with posterior cingulate and neocortical temporoparietal cortical losses, and medial temporal-lobe atrophy. In patients with known Alzheimerʹs disease, atrophy was widespread apart from in the primary motor and sensory cortices and cerebellum, reflecting the clinical phenomenology. Interpretation Voxel-compression maps confirmed early involvement of the medial temporal lobes, but also showed posterior cingulate and temporoparietal cortical losses at presymptomatic stage. This technique could be applied diagnostically and used to monitor the effects of therapeutic intervention.