Tau Imaging in Late Traumatic Brain Injury: A [18F]MK-6240 Positron Emission Tomography Study.

Epidemiological studies have identified prior traumatic brain injury (TBI) as a risk factor for developing Alzheimer's disease (AD). Neurofibrillary tangles (NFTs) are common to AD and chronic traumatic encephalopathy following repetitive mild TBI. However, it is unclear if a single TBI is sufficient to cause accumulation of NFTs. We performed a [18F]MK-6240 positron emission tomography (PET) imaging study to assess NFTs in patients who had sustained a single TBI at least 2 years prior to study inclusion. Fourteen TBI patients (49 ± 20 years; 5 M/9 F; 8 moderate-severe, 1 mild-probable, 5 symptomatic-possible TBI) and 40 demographically similar controls (57 ± 19 years; 19 M/21 F) underwent simultaneous [18F]MK-6240 PET and magnetic resonance imaging (MRI) as well as neuropsychological assessment including the Cambridge Neuropsychological Test Automated Battery (CANTAB). A region-based voxelwise partial volume correction was applied, using parcels obtained by FreeSurfer v6.0, and standardized uptake value ratios (SUVR) were calculated relative to the cerebellar gray matter. Group differences were assessed on both a voxel- and a volume-of-interest-based level and correlations of [18F]MK-6240 SUVR with time since injury as well as with clinical outcomes were calculated. Visual assessment of TBI images did not show global or focal increases in tracer uptake in any subject. On a group level, [18F]MK-6240 SUVR was not significantly different in patients versus controls or between subgroups of moderate-severe TBI versus less severe TBI. Within the TBI group, One Touch Stockings problem solving and spatial working memory (executive function), reaction time (attention), and Mini-Mental State Examination (MMSE) (global cognition) were associated with [18F]MK-6240 SUVR. We found no group-based increase of [18F]MK-6240 brain uptake in patients scanned at least 2 years after a single TBI compared with healthy volunteers, which suggests that no NFTs are building up in the first years after a single TBI. Nonetheless, correlations with cognitive outcomes were found that warrant further investigation.

Relationship between psychosocial and psychiatric risk factors and poor long-term outcome following mild traumatic brain injury: A systematic review.

BACKGROUND AND PURPOSE: Mild traumatic brain injury (mTBI) has an estimated worldwide incidence of >60 million per year, and long-term persistent postconcussion symptoms (PPCS) are increasingly recognized as being predicted by psychosocial variables. Patients at risk for PPCS may be amenable to closer follow-up to treat modifiable symptoms and prevent chronicity. In this regard, similarities seem to exist with psychosocial risk factors for chronicity in other health-related conditions. However, as opposed to other conditions, no screening instruments exist for mTBI. METHODS: A systematic search of the literature on psychological and psychiatric predictors of long-term symptoms in mTBI was performed by two independent reviewers using PubMed, Embase, and Web of Science. RESULTS: Fifty papers were included in the systematic analysis. Anxiety, depressive symptoms, and emotional distress early after injury predict PPCS burden and functional outcome up to 1 year after injury. In addition, coping styles and preinjury psychiatric disorders and mental health also correlate with PPCS burden and functional outcome. Associations between PPCS and personality and beliefs were reported, but either these effects were small or evidence was limited. CONCLUSIONS: Early psychological and psychiatric factors may negatively interact with recovery potential to increase the risk of chronicity of PPCS burden after mTBI. This opens opportunities for research on screening tools and early intervention in patients at risk.