Our study has a number of potential limitations. First, given the small sample size, our findings should be regarded as preliminary. Second, the 11C-PIB healthy controls were age matched to the AD group, and so were older than the TBI group. Although two separate age-matched control groups would have been preferable, Aβ pathology increases with age and so a comparison with older healthy controls is likely to have reduced our sensitivity to detect a relative increase in the younger TBI group. Therefore, the presences of abnormalities in a relatively young TBI group is even more striking. Third, it is possible that GM tissue differences such as atrophy, associated with AD or aging, could have biased our group contrast results. A number of analysis steps were used to minimize this possibility: an advanced algorithm for optimised registration of brain images into standard space (DARTEL); 11C-PIB binding was only assessed in regions where the GM probability was high; and ROI analyses, based on both automated segmentations, were used to provide confirmatory results, To control for the possible effects of focal injury after TBI, we also excluded lesioned areas from the analysis. It is possible that the extent of focal lesions was underestimated as we used T1 imaging to segment the lesions. However, since 11C-PIB binding was reduced in visible lesions, this possibility would have biased the analysis against detecting increases in 11C-PIB. We provide 11C-PIB PET evidence for the presence of amyloid pathology many years after injury in non-demented TBI patients. The distribution of 11C-PIB binding partially overlapped with that seen in typical AD but also affected the cerebellum, unlike in AD. This suggests a different mechanism for amyloid plaque genesis. Our findings support the hypothesis that amyloid plaque pathology is related to the presence of axonal damage produced subsequent to the TBI.
Our study has a number of potential limitations. First, given the small sample size, our findings should be regarded as preliminary. Second, the 11C-PIB healthy controls were age matched to the AD group, and so were older than the TBI group. Although two separate age-matched control groups would have been preferable, Aβ pathology increases with age and so a comparison with older healthy controls is likely to have reduced our sensitivity to detect a relative increase in the younger TBI group. Therefore, the presences of abnormalities in a relatively young TBI group is even more striking. Third, it is possible that GM tissue differences such as atrophy, associated with AD or aging, could have biased our group contrast results. A number of analysis steps were used to minimize this possibility: an advanced algorithm for optimised registration of brain images into standard space (DARTEL); 11C-PIB binding was only assessed in regions where the GM probability was high; and ROI analyses, based on both automated segmentations, were used to provide confirmatory results, To control for the possible effects of focal injury after TBI, we also excluded lesioned areas from the analysis. It is possible that the extent of focal lesions was underestimated as we used T1 imaging to segment the lesions. However, since 11C-PIB binding was reduced in visible lesions, this possibility would have biased the analysis against detecting increases in 11C-PIB. We provide 11C-PIB PET evidence for the presence of amyloid pathology many years after injury in non-demented TBI patients. The distribution of 11C-PIB binding partially overlapped with that seen in typical AD but also affected the cerebellum, unlike in AD. This suggests a different mechanism for amyloid plaque genesis. Our findings support the hypothesis that amyloid plaque pathology is related to the presence of axonal damage produced subsequent to the TBI.
NeurologyTBIAmyloid_Revision_Manuscript.docx