IC‐P‐085: Spatial heterogeneity of patterns of cortical amyloid deposition in healthy aging and its relationship to memory decline (2012)

The recent development of amyloid imaging compounds has allowed in vivo PET imaging of amyloid. Generally, sensorimotor and occipital areas remain relatively free of amyloid, while the frontal lobe and precuneus are affected early (Braak 1997). Using pseudo-temporal image analysis algorithms of spatial progression of amyloid deposition, we demonstrate similar patterns using 11 C-PiB (Pittsburgh Compound B) PET data from the Baltimore Longitudinal Study of Aging (BLSA). Moreover, spatial patterns were significantly different between memory decliners and non-decliners. To examine the pseudo-temporal spatial patterns of amyloid deposition from cross-sectional data, we used a method that quantifies regional tissue sparing relative to total amyloid burden (defined as the cortical distribution volume ratios (cDVR) (Sojkova 2011)). 64 non-demented subjects (35 men, aged 76.61 ± 6.89 years) from the BLSA neuroimaging sub-study were included. For each voxel, a piece-wise linear curve was fitted to the PiB signal across the group as a function of total amyloid load. The location of the inflection point determines the cDVR magnitude that needs to be reached before amyloid plaques start to accumulate at that voxel. Furthermore, we analyzed subjects grouped into top and bottom 20% California Verbal Learning Test (CVLT) slopes (Table 1). The significance was quantified using a permutation test on sensorimotor and temporal ROIs. Spatial patterns demonstrate relative sparing of sensorimotor and occipital areas, while the frontal lobe and precuneus begin to accumulate amyloid earlier, i.e., need minimal cDVR before they begin to be affected (Figure 1). The spatial patterns for CVLT subgroups diverge, such that the “cognitively stable” subgroup had relative sparing of sensorimotor and temporal areas compared to the “cognitively declining” group (Figure 2). Permutation testing revealed that left hemisphere differences between subgroups are significant (Table 2). (a) The inflection point at which the voxel-wise PiB signal begins increasing demonstrates relative sparing in select cortical areas. Higher cDVR needs to be reached before blue/green regions are affected. Similar to previous finding, occipital and sensorimotor areas are relatively spared. Units are cDVR at which the signal begins increasing at a particular voxel. (b) The amount of amyloid accumulations at a given voxel is reflected via integration of the curve after the inflection point. Relatively spared areas are similar to those found by spatial analysis of the inflection point, i.e., sensorimotor and occipital areas. Units are signal intensity increase multiplied by cDVR. Cognitive status and relative sparing of cortical areas with respect to amyloid load appear to be related. Shown are the relative sparing (inflection) and amyloid accumulation (area under the curve). (a) Relative Sparing – in the “cognitively stable” group, the sensorimotor and temporal cortices are relatively spared compared to the “cognitively declining” group. Units are cDVR at which the signal begins increasing. (b) Accumulation – The amount of amyloid accumulation does not have divergent patterns between the “cognitively declining” and “cognitively stable” group. However, the trend of higher cDVR values for the “cognitively declining” group is apparent via the increased signal intensity. Units are signal intensity increase multiplied by cDVR. The implication is that although the spatial distribution of amyloid accumulation is not very different between these groups, the estimated pseudo-temporal maps (a) indicate that the pattern of relative sparing is the most important discriminant. We have quantified spatial patterns of progression of amyloid deposition in healthy older adults using pseudo-temporal image analysis methods applied to cross-sectional amyloid PET images. When our approach was applied to subgroups based on cognitive performance, the spatial patterns diverged. This finding has implications for prediction of cognitive decline from amyloid data, suggesting that it is the spatial pattern rather than total amyloid burden that might be more relevant.