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Should a global or a regional measure of amyloidosis be used in a longitudinal study?

      Background

      Global amyloid burden is widely used as measurement to assess the brain amyloidosis in many studies, but its reliability in a longitudinal study is yet to be fully understood. In this study we developed a surface based technique to assess the relationship between amyloidosis and neurodegeneration measured by hypo-metabolism across diagnosis stages of Alzheimer’s disease. We hypothesize that the regional effects of amyloid retention on the rate of hypo-metabolism depend on the diagnosis stage. We will further investigate whether a consolidated measure of amyloidosis (global SUVR) can capture the effects shown in the regional analysis.

      Methods

      The study included 213 subjects (65 Cognitively Normal [CN], 111 Early Cognitive Impairment [EMCI], 19 Late Cognitive Impairment [LMCI], 18 Alzheimer’s Disease [AD]) taken from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Their [18F]Florbetapir and [18F]FDG PET images were acquired 24 months apart and the SUVR maps were subsequently generated using cerebellar grey/white matter and pons as reference regions for [18F]Florbetapir and [18F]FDG PET images, respectively. The effects of [18F]Florbetapir on yearly rate of metabolism were computed using vertex-based regression models including the baseline glucose metabolism, age, gender and APOE genotype as covariates.

      Results

      During the 24-month observation period, for the subjects in CN and EMCI stages, the regional rates of hypo-metabolism did not show a linear relationship to the localized amyloid burden. However, at LMCI and AD stages, regional amyloid load shows a linear relationship to the rate of metabolic decline in precuneus and temporo-parietal areas (Figure 1). In contrast, the global measure of amyloid burden showed a linear relationship with metabolism only in temporal regions.

      Conclusions

      Based on the results it is evident that in LMCI and AD stages, the rates of hypo-metabolism at temporo-parietal areas as well as in the precuneus depend on the local tissue amyloid burden, while in CN and EMCI stages, it is independent. Absence of a relationship in similar regions with the global measure amyloidosis suggests that a consolidated measure cannot represent the brain amyloid burden in all disease stages, and perhaps, a new consolidation masks need to be generated based on disease stage.
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      Figure 1Vertex-based multivariate linear regression model showing the effect of amyloid load on the rate of hypo-metabolism in each disease stage, corrected for baseline glucose metabolism, age, gender and apoe genotype. Only LMCI and AD stages show positive effect from amyloid load on hypo-metabolism in temporo-parietal and precuneus regions.