In order to perform their duties, airline pilots must have no clinical diagnosis of mental illness or any substance use disorder. However, provisions have been in place since the 1970s that provide for a return to work for airline pilots with alcohol problems. To date, over 5,000 airline pilots have undergone rehabilitation for Alcohol Use Disorder (AUD) and successfully returned to work. An important gap in the literature remains with regard to what extent improvements in cognitive performance may be experienced by airline pilots who complete treatment and to what extent age influences the amount of change. This study examined the archival data of 95 male Caucasian pilots who were assessed for cognitive performance shortly after entry to 30-day inpatient treatment and approximately 5 months later during the return to work evaluation. A nonexperimental within subjects design compared pre- and post-treatment scores on the Wechsler Adult Intelligence Scale-IV (WAIS-IV) full scale and 4 index scores as well as differences for age groups (25 to 44, 45 to 54, and 55 to 64). Repeated measures ANOVA revealed that there were significant gains on all WAIS-IV measures pre-post treatment for AUD. MANOVA results indicated no differences between age groups. These findings support current Federal Aviation Administration program practices with regard to returning airline pilots to work following rehabilitation and a sufficient period of abstinence. The potential of this study to promote the agenda of social change may be substantive for raising awareness of the cognitive deficits associated with AUD and how these may impact the safety of flight operations.

Every year over 2.5 million traumatic brain injuries (TBI) occur and are the leading cause of death and disability among adolescents. There are no approved treatments for TBI. Survivors suffer from persistent cognitive impairment due to posttraumatic tissue damage and disruption of neural networks which significantly detract from their quality of life. Posttraumatic cognitive impairment depends in part on the brain's limited ability to repair or replace damaged cells. Immature neurons in the hippocampus dentate gyrus, a brain region required for learning and memory, are particularly vulnerable to TBI. Insulin-like growth factor-1 (IGF1) is a potential therapeutic for TBI because it is a potent neurotrophic factor capable of mediating neuroprotection, neuro-repair, and neurogenesis. We hypothesized that conditional IGF1 overexpression in the mouse hippocampus following experimental controlled cortical impact injury (CCI) would enhance posttraumatic neurogenesis chronically. To this end, conditional astrocyte-specific IGF1 overexpressing mice (IGFtg) and wild-type (WT) mice received CCI or sham injury. The proliferation marker BrdU was used to label neurons born the first week after injury. Six weeks after injury, when surviving posttrauma-born neurons would be fully developed, we counted proliferated cells (BrdU+) and the subset expressing a mature neuronal marker (NeuN+/BrdU+) in the hippocampus. We also assessed cognitive performance during radial arm water-maze reversal (RAWM-R) testing, a neurogenesis-sensitive assay. IGF1 promoted end-stage maturity and decreased mis-migration of neurons born after trauma. These effects coincide with IGF1 induced improvements in performance on neurogenesis sensitive cognition following TBI. Mammalian target of rapamycin (mTOR), an early signaling molecule downstream of IGF1, has been identified as a potential target for TBI interventions because of its regulatory role in neuronal plasticity and neurogenesis. However, recent studies have also reported maladaptive plasticity and recovery associated with posttraumatic mTOR activation. It is imperative to elucidate the mechanism of action of IGF1 during pre-clinical evaluations. We hypothesized that IGF1 mediates posttraumatic neurogenic effects through IGF1 induction of mTOR activation. We injured cohorts of IGFtg and WT mice and harvested their brains for immunohistochemistry to assess IGF1 overexpression effects on posttraumatic mTOR activation at 1, 3, and 10 days post-injury (dpi). We found that IGF1 upregulated mTOR activation following TBI in a region-specific manner at 1 and 3dpi. To determine if IGF1 regulated differentiation and arborization through the mTOR pathway, injured WT and IGFtg mice received daily i.p. injections of rapamycin (10mg/kg), the inhibitor of mTOR, or its vehicle for 7 days. Vehicle and rapamycin administration began 3dpi, after the cells dividing at the peak of posttraumatic proliferation were labeled with BrdU. IGF1 enhancement of posttraumatic neurogenesis was not dependent on mTOR activation. In summary, IGF1 directs newborn neuron localization, promotes end-stage maturation, and chronically improves cognition. IGF1 can stimulate posttraumatic neurogenesis and plasticity independent of mTOR activation. These data suggest that IGF1 can stimulate neuron replacement following trauma-induced hippocampal neuron loss and cognitive improvement. Further studies should investigate IGF1 and mTOR inhibition as a combination therapy for neurorehabilitation.