Sleep apnea, apolipoprotein epsilon 4 allele, and TBI: Mechanism for cognitive dysfunction and development of dementia

Abstract

Abstract-Sleep apnea is prevalent among patients with traumatic brain injuries (TBIs), and initial studies suggest it is associated with cognitive impairments in these patients. Recent studies found that the apolipoprotein epsilon 4 (APOE epsilon 4) allele increases the risk for sleep disordered breathing, particularly sleep apnea. The APOE epsilon 4 allele is associated with cognitive decline and the development of dementia in the general population as well as in patients with TBI. These findings raise the question of whether patients with TBI who are APOE epsilon 4 allele carriers are more vulnerable to the negative effects of sleep apnea on their cognitive functioning. While few treatments are available for cognitive impairment, highly effective treatments are available for sleep apnea. Here we review these different lines of evidence, making a case that the interactive effects of sleep apnea and the APOE epsilon 4 allele represent an important mechanism by which patients with TBI may develop a range of cognitive and neurobehavioral impairments. Increased understanding of the relationships among sleep apnea, the APOE epsilon 4 allele, and cognition could improve our ability to ameliorate one significant source of cognitive impairment and risk for dementia associated with TBI.

Sleep Apnea and the Risk of Dementia: A Population-Based 5-Year Follow-Up Study in Taiwan

“…Third, both SA and dementia are complex diseases that involve complex genetic and environmental interactions. Recent studies have shown that the apolipoprotein epsilon 4 (APOE4) allele increases the risk of SA, particularly that which is obstructive in mechanism [14]. The APOE4 allele is associated with cognitive decline and the development of dementia in the general population.…”

Sleep Hygiene Program Implementation in Patients with Traumatic Brain Injury

“…The direct medical cost and indirect cost of TBI in lost productivity is estimated at $60 billion (Corso, Finkelstein, Miller, Fiebelkorn, & Zaloshnja, 2006). The impact of TBI on the individual is multifaceted and includes neurocognitive, behavioral, and psychiatric disturbances as well as greater predisposition for dementia (DeKosky, Ikonomovic, & Gandy, 2010;O'Hara, Luzon, Hubbard, & Zeitzer, 2009;Zeitzer, Friedman, & O'Hara, 2009). The significant individual and societal cost has increased awareness of TBI as a serious health risk for all age groups, but especially in individuals who participate in athletics at both the professional and recreational levels and in U.S. military service personnel.…”

Dementia Risk in Posttraumatic Stress Disorder: the Relevance of Sleep-Related Abnormalities in Brain Structure, Amyloid, and Inflammation

“…Similarly, individuals with PTSD have a high rate of high risk health-related behaviors such as smoking [132] and heavy alcohol use [133] and a high prevalence of obstructive sleep apnea (OSA) [134, 135]. These factors could elevate risk of dementia in PTSD via mechanisms separate from or complimentary to those discussed above [94, 136], as described by the glucocorticoid vulnerability hypothesis referenced above [57]. …”