The conclusion from the recent APPLES study was that CPAP did not improve neurocognitive function in sleep apnea patients. This study, conducted by some of the best scientists in the field, enrolled 1,516 subjects, followed a rigorous clinical trial design, came to a conclusion that surprised us all.
After 6 month comparison of CPAP versus sham treatment, in three measures of neurocognitive function including attention and psychomoter function, learning and memory, and executive and frontal-lobe function, there was no difference observed.
Unlike in cardiovascular clinical research, where large-scale randomized controlled trial is the norm to evaluate most treatments, it is rare to have randomized controlled trial in sleep apnea treatment evaluation. The APPLES study is probably the most rigorous trial to date to evaluate the standard of care --- CPAP.
There are abundant evidence of neurocognitive impairment associated with sleep apnea. In a systematic review of published literature, Dr, Ellen RL found persons with sleep apnea had 2 to 3 times car accident rate compared to those without sleep apnea. It also seemed to be clear that CPAP treatment could reduce car accidents. In another review, Dr. Antonopoulos CN showed CPAP use reduced car accident rate by about 20%.
What do these studies tell us?
There is a possibility that the association between sleep apnea and neurocognitive function is indeed weak as reported in the APPLES study. Our body may have incredible cognitive reserve to protect from sleep loss. These compensatory processes may be especially active during test conditions such as those used in the APPLES study. This is essentially the conclusion from authors of the APPLES study that sleep apnea is a multifaceted disorder and this study suggested the existence of a complex OSA-neurocognitive relationship.
The other big question is the effectiveness of CPAP, especially the adherence of therapy. The APPLES study did report on adherent adjusted outcome measures, which did not differ from main findings of the trial. Examining the adherence data more closely, there is a number that is quite alarming. In subjects with CPAP treatment at one month prior to the 6-month visit, the percent of regular users, greater than 4 hours per night for 5 nights per week, is 39%.
This has been the elephant in the room for sleep apnea patient care ever since the introduction of CPAP more than 20 years ago. Most patient could not adhere to treatment.
A study from Harvard Medical School and McKinsey estimated total economic cost of moderate-severe sleep apnea to be $65 to 165 billion annually in the US. We need to either improve adherence of CPAP significantly or to find new treatment options that are effective and much less intrusive for patient’s life.
