Logo for the Journal of Rehab R and D

Volume 46 Number 6, 2009
   Pages 837 — 850

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

Ruth O'Hara, PhD;1-2* Avinoam Luzon, BS;2 Jeffrey Hubbard, BA;1-2 Jamie M. Zeitzer, PhD1-2

1Sierra-Pacific Mental Illness Research, Education, and Clinical Center, Department of Veterans Affairs Palo Alto Health Care System, Palo Alto, CA; 2Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA

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.

Key words: Alzheimer disease, apolipoprotein epsilon 4, cognition, daytime sleepiness, dementia, mild cognitive impairment, obstructive sleep apnea, sleep apnea, sleep disordered breathing, traumatic brain injury.

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