Patterns of amyloid plaque better signal slumping memory

Rather than looking at the global deposition of beta-amyloid in the brain, it may be more valuable to analyze its spatial pattern, now thought to have a stronger association with memory decline, according to a study published July 15 in Neurobiology of Aging.

Rachel A. Yotter, PhD, from the Center for Biomedical Image Computing and Analytics, University of Pennsylvania in Philadelphia, and colleagues used a new methodology to assess amyloid plaque deposition with C-11 PiB PET and found that the temporal progression of amyloid was more meaningful than total amyloid burden when assessing changes in cognition. Patients were grouped according to longitudinal alterations in memory performance. These subgroups were found to have substantially varying spatial patterns of amyloid deposition.

“Our results indicate that the spatial pattern of amyloid deposition is related to cognitive performance and may be more informative than a biomarker reflecting total amyloid burden, the use of which is the current practice,” the authors wrote. “This finding has broad implications for our understanding of the relationship between cognitive decline/resilience and amyloid deposition, as well as for the use of amyloid imaging as a biomarker in research and clinical applications.”

For this study, a total of 64 participants with a mean age of 77 years were included from the Baltimore Longitudinal Study of Aging (BLSA) and were observed for an average of 12 years. They were  imaged annually and also underwent extensive neuropsychological tests. Patients were subgrouped according to cognitive level and an amyloid permutation analysis was conducted and spatial mapping created according to inflection points of plaque burden.

“We obtained estimates of the spatial progression of amyloid deposition in older adults using C-11 PiB PET imaging and an image analysis method that assumed that the total amyloid burden would be a reasonable approximation of the stage of the pathology. This assumption allowed the approximation of spatiotemporal patterns from cross-sectional data, leading to an estimation of relative sparing of certain brain regions, as reflected by relatively later inflection points in regional amyloid signal.”

The spatial patterns were remarkable because they visualized data that have been followed in histological studies as well as imaging data, according to the researchers. Occipital and sensorimotor areas were largely spared at early stages and researchers found frontal and precuneus regions had more amyloid deposition in the beginning stages with burden in the occipital and sensorimotor cortices developing later in the progression of neurodegenerative disease.

“Furthermore, there are some noteworthy new findings,” the researchers wrote. “Histologically, it was found that subjects exhibited amyloid deposition in a basal-to-apical pattern, but there was no detectable basal-to-apical pattern in the analysis of C-11 PiB PET imaging, a finding similar to that in other imaging studies. This discrepancy could be due to divergent approaches to quantifying amyloid load.”