The extent to which cerebral atrophy in Alzheimer's disease changes with time is unknown. We used multiple MRI scans to measure progression of cerebral atrophy in 12 patients with Alzheimer's disease who were followed up from a presymptomatic stage through to moderately severe dementia. Analysis with hierarchical regression models with quadratic terms in time provided evidence of increasing yearly percentage losses in brain volume. At the time when patients were judged to have mild dementia (mini-mental state examination score MMSE=23), mean yearly loss of brain volume was 2·8% (95% CI 2·3-3·3), which rose by 0·32% per year (0· 15-0·50). Our findings reinforce the need for early diagnosis and therapeutic intervention in Alzheimer's disease.
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