Background: Previous analysis using voxel based morphometry (VBM) of the familial Alzheimer's disease (FAD) cohort from the Dominantly Inherited Alzheimer's Network (DIAN) indicated local grey matter (GM) and white matter (WM) changes associated with very mild symptoms. VBMfindings are driven by a combination of shape and intensity or contrast effects, typically after substantial smoothing (typically 6-8 mm FWHM). These factors make it difficult to interpret the precise location and potential cause of observed differences. Here, we perform separate analyses on shape and intensity features to better characterize the underlying components of our VBM findings. Methods: Volumetric MRI scans were analysed from 191 subjects (non-carriers, presymptomatic carriers, and symptomatic carriers) in the DIAN study (see Table). Two features were extracted: (1) regional volume, characterized by the Jacobian determinants from nonlinearly registering each subject to the groupwise average; (2) intensity features, based on spatially normalized, bias corrected images, rescaled to a fixed average intensity over a region in the pons. Statistical parametric maps were generated for group-differences in these features using permutation testing (n=10000), with total intracranial volume, sex, acquisition site, and APOE genotype as covariates and an interaction term between group and years to expected symptom onset. Results were corrected for multiple comparisons, controlling Family-Wise Error at p<0.05. Results: Local contraction is observed in similar areas to VBM GM and WM results (temporal lobe, cingulate gyrus, precuneus, putamen). Local expansion and intensity decreases are observed in temporal and parietal sulcal areas, lateral, and third ventricles. Near the hippocampus, both contraction and intensity decrease are present more posteriorly than near the head (see Figure). Thalamic intensity changes are restricted medially to the third ventricle, while shape differences extend laterally throughout the structure. As with VBM, we find no evidence of intensity or shape differences between non-carriers and presymptomatic mutation carriers. Conclusions: Most differences observed between non-carriers and symptomatic carriers appear related to volume change rather than change in tissue contrast, even in regions like the thalamus and putamen whose boundaries on T1-weighted MRI are very sensitive to contrast changes. Future work will explore whether longitudinal data allow localized presymptomatic differences to be discerned. (Table Presented).
Cash, D., Ridgway, G., Modat, M., Ryan, N., Kinnunen, K., Cardoso, J., … Fox, N. (2013). P3-134: Dissociating volume and intensity differences in familial Alzheimer’s disease. Alzheimer’s & Dementia, 9, P603–P603. https://doi.org/10.1016/j.jalz.2013.05.1205