Visualisation and quantification of rates of atrophy in Alzheimerʹs disease

Background Definitive diagnosis of Alzheimerʹs 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 Alzheimerʹs 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 of atrophy was significantly greater in the Alzheimerʹs 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 familial Alzheimerʹs 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 Alzheimerʹs disease, the assessment of disease progression, and the evaluation of potential treatments.