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Sleep Apnea May Be Key to Apo E4 and Alzheimer's Link


 

DENVER — The well-documented association between the apolipoprotein E4 allele and development of cognitive decline and Alzheimer's disease may be mediated at least in part by obstructive sleep apnea, Ruth O'Hara, Ph.D., said at the annual meeting of the Associated Professional Sleep Societies.

This is an exciting possibility, because although there are no therapies to delay the onset of dementia, continuous positive airway pressure (CPAP) offers a highly effective treatment for obstructive sleep apnea. It may be that identifying and treating this disorder in apo E4-positive patients could delay or even prevent the onset of cognitive decline and Alzheimer's dementia, said Dr. O'Hara of Stanford (Calif.) University.

She presented a cross-sectional study of 36 community-dwelling nondemented older adults—mean age 70 years—half of whom possessed the apo E4 allele. All were assessed for cognitive performance status by the Mini-Mental State Examination and Rey Auditory Verbal Learning Test. The presence and severity of obstructive sleep apnea were assessed using home ventilatory polygraphy, she said. The most striking study finding was that although there was no difference in cognitive function between the apo E4-positive and -negative groups overall, apo E4-positive individuals with sleep apnea as defined by a higher apnea/hypopnea index had lower memory scores as reflected by worse performance on the delayed recall and short-term recall components of the Rey test. The higher an apo E4-positive subject's apnea/hypopnea index, the lower their memory scores. In contrast, the apnea/hypopnea index was unrelated to memory function in individuals who did not carry the apo E4 allele. Daytime sleepiness was unrelated to cognitive performance in either group.

Dr. O'Hara observed that it's impossible to tell from a cross-sectional study such as this whether sleep apnea is mediating the effect of the apo E4 allele as a risk factor for development of cognitive decline and Alzheimer's disease. That's a question that can be addressed only in a longitudinal study. On the strength of the provocative cross-sectional study findings, the National Institute of Mental Health has granted funding for Dr. O'Hara and coworkers to conduct a 150-subject prospective study.

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