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We measured hippocampi on baseline-, 6- and 12-month scans in a group of AD (n=36) and control subjects (n=20). We found that mean annualised atrophy rates using 6-month intervals were comparable at a group level to those generated from a 12-month interval. Higher variance was seen using shorter intervals, although this was only significant in the control group. This has implications where shorter inter-scan intervals may be advantageous, such as rapid diagnosis, and tracking of disease progression including in a clinical trial.

We describe a method of automatically calculating hippocampal atrophy rates on T1-weighted MR images without manual delineation of hippocampi. This method was applied to a group of Alzheimer's disease (AD) (n=36) and control (n=19) subjects and compared with manual methods (manual segmentation of baseline and repeat-image hippocampi) and semi-automated methods (manual segmentation of baseline hippocampi only). In controls, mean (S.D.) atrophy rates for manual, semi-automated, and automated methods were 18.1 (53.5), 15.3 (50.2) and 11.3 (50.4) mm3 loss per year, respectively. In AD patients these rates were 174.6 (106.5) 159.4 (101.2) and 172.1 (123.1) mm3 loss per year, respectively. The automated method was a significant predictor of disease (p=0.001) and gave similar group discrimination compared with both semi-automated and manual methods. The automated hippocampal analysis in this small study took approximately 20 min per hippocampal pair on a 3.4 GHz Intel Xeon server, whereas manual delineation of each hippocampal pair took approximately 90 min of operator-intensive labour. This method may be useful diagnostically or in studies where analysis of many scans may be required.

Background: Early diagnosis and monitoring of the progression of Alzheimer's 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 Alzheimer's disease., Methods: Four symptom-free individuals from families with early-onset Alzheimer's 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 Alzheimer's 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 Alzheimer's 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.