Serial magnetic resonance imaging of cerebral atrophy in preclinical Alzheimer's disease

Abstract

Quantitative cross-sectional magnetic resonance imaging (MRI) studies of Alzheimer’s disease have shown that atrophy is already present even in mildly affected individuals. 1 However, single measures of structures with a wide normal range are not as sensitive as repeated measures in progressive disorders such as Alzheimer’s disease. Subtraction of registered serial MRI provides an accurate method of measuring small amounts of diffuse cerebralvolume change. In this way rates of atrophy have been found to be ten to 40 times greater in mild to moderate Alzheimer’s disease than in normal ageing. 2,3 We have used this technique to assess whether rates of atrophy were increased at an even earlier stage of the disease. We did a prospective longitudinal study of symptomless individuals at risk of familial Alzheimer’s disease. Individuals were defined as at risk if they had a family history of autosomal dominant early-onset (<65 years) Alzheimer’s disease and were within 5 years of the age at onset in their family. Patients were regarded as symptomless if they and their close informants felt there were no symptoms of memory loss or other cognitive decline. 28 (15 female) at-risk individuals underwent serial (about yearly) clinical and neuropsychological assessments and volumetric brain MRI. 26 (14 female) age-matched cognitively normal individuals were recruited from volunteers including spouses of study participants and were similarly studied. Informed consent was obtained from all individuals and the study received ethical approval from participating centres. Five at-risk patients developed symptoms of cognitive decline during follow-up and subsequently progressed to fulfil established criteria for probable Alzheimer’s disease. 4