Visualisation and quantification of rates of atrophy in Alzheimer's disease

Background Definitive diagnosis of Alzheimer's disease requires histological examination of brain tissue. In life, brain atrophy can be visualised by computed tomography or magnetic resonance (MR) imaging, but the atrophy due to the disease is difficult to distinguish from that caused by normal ageing. We have investigated use of accurate positional matching (registration) and digital subtraction of serially acquired MR brain scans to allow determination of rates of global and regional atrophy. Methods This technique was applied to eleven patients with clinically diagnosed Alzheimer's disease and eleven age-matched controls. Each individual had two scans approximately 1 year apart; scan intervals were matched between the groups. Findings The median rate atrophy was significantly greater in the Alzheimer's disease group than in the control group (12 . 3 [range 5 . 8 to 23 . 6] vs 0 . 3 (-1 . 2 to 1 . 7) mL per year; p<0 . 0001). There was no overlap between the groups. Furthermore, three non-demented individuals at risk of familiar Alzheimer's disease had scans 6-14 months apart and showed greater rates of volume loss than the controls; these three individuals have subsequently developed symptoms. Interpretation This technique may be useful for the diagnosis of Alzheimer's disease, the assessment of disease progression, and the evaluation of potential treatments.