Poster Session P2 - Diagnosis and Disease Progression - Neuroimaging

Monday, July 19, 2004

Abstract: P2-170

Citation: NeuroBiology of Aging, Volume 25, Number S2 , July 2004, Page 274

Patterns of Atrophy on MRI in Histologically-Proven Sporadic Alzheimer's Disease and Genetically-Proven Familial Alzheimer's Disease

Jennifer L. Whitwell1, Alison K. Godbolt1, Keith A. Josephs1,2, John M. Stevens3, Martin N. Rossor1,4, Nick C. Fox1

1 Institute of Neurology, University College London, London, United Kingdom; 2 Mayo Clinic, Rochester, MN, USA; 3 Department of Radiology, Queen Square, London, United Kingdom; 4 Division of Neuroscience and Psychological Medicine, Imperial College London, London, United Kingdom. Contact e-mail:

Background: Studies of familial Alzheimer's disease (FAD) have provided significant insights into the pathophysiology of this disease. How generalisable this is to the much more common sporadic cases of AD (SAD) remains uncertain. Both SAD and FAD are associated with progressive cerebral atrophy, however very few studies have compared the two conditions. Objective(s): To compare the patterns of atrophy on MRI in 'definite' cases of FAD and SAD. Methods: We studied 13 patients with histologically-proven early-onset SAD, and 20 patients with FAD, all with genetic confirmation, an autosomal dominant family history and who fulfilled the criteria for probable AD. Groups were matched by MMSE and gender. Mean MMSE in both groups was 15 (range of 7 to 22 in FAD, and 5 to 23 in SAD (p = 0.77)). Mean (±SD) age was 52±7.7 years in FAD and 60±8.0 years in SAD (p = 0.006). Mean disease duration was 5.5±3.1 years in FAD and 4.0±2.7 years in SAD (p = 0.25). These were matched to a group of 20 controls. Each subject had one volumetric MRI scan. Brain volumes were measured on every scan. Voxel-based morphometry (VBM), an automated unbiased technique, was used to assess the regional patterns of cerebral atrophy in each group. Age and gender were included as nuisance variables. Results: Mean brain volume was 1023±124ml in FAD and 1038±131ml in SAD (p = 0.77). VBM revealed significant grey matter losses in FAD across a wide range of regions. After correcting for multiple comparisons, significant losses were particularly seen bilaterally in the hippocampus, superior temporal gyrus, posterior part of cingulate gyrus, precuneus, cuneus and the parietal and occipital lobes (p < 0.05). To a lesser degree atrophy was also present in an apparently patchy distribution in both frontal lobes. Some predilection for the left hemisphere was shown. SAD showed a similar pattern but less atrophy compared to controls (corrected, p < 0.05). Conclusions: Both FAD and SAD appear to have the same topographic distribution of atrophy. However, for a similar MMSE the FAD group had more widespread areas of significant loss than the SAD group, perhaps reflecting relative preservation of MMSE scores in these younger patients despite longer disease duration.