Alzheimer's disease, sleep apnea, and positive pressure therapy

Numerous lines of evidence converge in suggesting that sleep apnea may play a causal role in severe cognitive impairment, most likely Alzheimer's Disease (AD) but also including vascular dementia. Until recently, most of these studies have been based on small samples of clinic patients or population-based, descriptive studies of sleep apnea and cognition. Although randomized clinical trials have been completed for treating sleep apnea in middle-aged cognitively intact patients with sleep apnea using continuous positive airway pressure (CPAP), systematic intervention studies in well-characterized AD patients are very rare and have been published from only a single research group. Results suggest some very modest improvement in selected aspects of cognition over a very limited period of time. There is, thus, a lack of conclusive evidence that treating sleep apnea in AD is likely to have a major impact on dementia, although it may benefit daytime hypersomnolence, excessive napping, and lethargy so common in many dementia patients. In addition, anecdotal evidence suggests that in some selected cases, treatment can have relatively dramatic effects. At this point in time, the best indications for pursuing treatment for sleep apnea with nasal CPAP in AD patients would be factors promoting adherence, such as presence of a caregiver/family member invested in treatment, and a realistic appraisal of what goals of intervention should be expected (eg, increasing daytime functionality by enhancing alertness) over a reasonable window of time. Speculative factors implicating a potentially causal role for sleep apnea in dementing illness would be comorbid diseases well-established to be associated with both sleep apnea and dementia (cardiovascular disease, diabetes) and presence of the Apolipoprotein-E4 genotype. None of these factors have been shown conclusively to influence CPAP efficacy in dementia, but to the extent that they lie on a putative causal pathway for sleep apnea and dementia (either as moderators or mediators of CPAP efficacy), their presence might be expected to enhance, rather than mitigate, a more favorable response in the domain of cognition.