TBI and PTSD as Risk Factors for Alzheimer's Disease

What is it about?

Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) have both been identified as potential risk factors for the development of dementia including Alzheimer's disease (AD) in later life. The findings of epidemiological and imaging studies investigating this question in more depth are inconsistent though. The overall goal of this project was to try to find an explanation for these inconsistencies by answering two questions. 1. Are there subgroups within groups of older persons with PTSD and TBI of which some have a higher risk to develop AD and if so, how are they different from subgroups without increased risk? 2. Does a history of PTSD or TBI affect the typical tau load/brain atrophy pattern typically seen in AD? These questions were addressed using MRI and PET data of 89 subjects with or without previous TBI and/or PTSD from the DoD ADNI database. Gray matter and tau load were extracted from 94 regions of interest and used to calculate an age-corrected gray matter tau mismatch metric (ageN-T mismatch-score and matrix) for each subject. This metric provides a measure to what degree regional tau accumulation drives regional gray matter atrophy and can be used to calculate a summary score reflecting the severity of AD pathology in an individual. The ageN-T mismatch summary score was positively correlated with whole brain beta-amyloid load and general cognitive function but not with PTSD or TBI severity. Hierarchical cluster analysis identified five different spatial patterns of tau-gray matter interactions. These clusters reflected the different stages of the typical AD tau progression pattern. None was exclusively associated with PTSD and/or TBI. Subjects assigned to the cluster with the highest degree of AD pathology had not only a history of TBI but also of PTSD and were often ApoE4 carriers. This suggests that TBI and PTSD have to occur in combination with other brain insults and risk factors to raise the risk to develop AD pathology. Finally, there was no evidence that TBI or PTSD modify the typical AD distribution pattern.

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Why is it important?

The findings reported here support the hypothesis that only a subset of the patients with PTSD and/or remote TBI develop AD pathology. There is no evidence that TBI or PTSD modify tau binding patterns and create PTSD or post TBI specific patterns. This suggests that a history of TBI or a PTSD diagnosis alone is not sufficient to put a subject at risk for AD but rather that TBI and PTSD represent one of several factors that need to come together for this to happen.