A recent article in the New York Times, How Poor Sleep Affects Your Risk of Dementia, summarizes some recent findings showing both excessively short and long sleep, as well as sleep disorders such as sleep apnea, insomnia, and rapid-eye movement (REM) behavior disorder, may be linked with risk for Alzheimer’s disease (AD) or other forms of dementia. Our recent findings from multiple studies at UCI are consistent with this interpretation.For example, in our most recent study , in collaboration with Alzheimer Biomarkers Consortium — Down Syndrome (ABC-DS) and UCI MIND investigators, we found symptoms of insomnia were more prevalent in adults with Down syndrome with dementia compared to adults with Down syndrome that did not have dementia. We also found that symptoms of insomnia were associated with the severity of impairments in social function, regardless of dementia status. Of interest, these findings were stronger in women than men, hinting that links between sleep disturbance and dementia risk may contribute to sex differences in dementia risk. However, these findings do not tell us if sleep disturbances cause dementia.
Whether sleep abnormalities can cause dementia is central to the New York Times article, and it remains a central issue in the field. We now know the biomarkers of AD can build up for 1-2 decades before clinical symptoms are observed. Most studies of sleep and dementia risk examined sleep well within this 10-20 year window, complicating interpretations of causality. Two important papers from the 90+ study at UCI provide important insight into this issue. Both papers examined sleep and nap duration from individuals 24-30 years prior to death. In the first study , short sleep conferred an increased risk for developing dementia 25 years later, and again this risk was more specific to women, further highlighting the role of sex differences in sleep and dementia relationships. In the second study , longer sleep duration was associated with lower amounts of brain pathology 30 years later, specifically fewer amyloid plaques and TAR DNA-binding protein 43 (TDP-43), both of which are known to contribute to dementia and cognitive decline. These findings are among the first to show that sleep duration may impact dementia risk even before the onset of brain pathology. This means that the effects of sleep duration and sleep disorders on dementia risk may be more than an early warning sign of dementia. Sleep disturbance may actually facilitate the onset of dementia.
In another paper we recently published, consistent with the findings reported in the New York Times article, we showed that the sleep apnea, and specifically the severity and frequency of hypoxemia, which refers to dips in blood oxygen levels, during sleep were associated with memory impairment, particularly in individuals with genetic risk or family history of AD. Of note, it was the frequency of hypoxemia during REM sleep that mattered the most. This is particularly important, since the severity and frequency of hypoxemia during REM sleep is often higher than hypoxemia observed during NREM sleep. However, most clinical estimates of hypoxemia are averaged across sleep stages and NREM sleep makes up 75% of the sleep period. This means that one can have a high frequency of hypoxemia during REM sleep but may appear to have a low frequency overall if events are rare during NREM sleep. Moreover, most of REM sleep occurs in the early morning, after many patients take off their positive airway pressure masks by this time of the night. This means that detection and treatment of sleep apnea during REM sleep can often be overlooked.
Collectively, our findings at UCI show that sleep duration and the presence of sleep disturbance may be more than an early indicators of oncoming dementia. This is critically important, because if sleep disturbance contributes to dementia risk, then treatment should help reduce risk. If true, this provides a hopeful avenue for future interventions since sleep duration, insomnia, and sleep apnea are all modifiable with current treatments. Exploring this possibility is a core mission of our work here at UCI.
