Snoring link to Alzheimer’s disease unproven

"Snoring linked to Alzheimer's," the Mail Online reports. A US study reported an association between sleep-disorder breathing and Alzheimer's disease in later life. But no definitive link between the two has been proven.

Sleep-disordered breathing is a general term to describe pauses in breathing during sleep that restrict oxygen supply to the body. At the most severe end of the spectrum is obstructive sleep apnoea, which can itself range in severity.

In this latest study, researchers looked at data regarding sleep in 1,750 middle aged and older adults. They then looked at whether problems with sleep breathing were associated with their performance in cognitive testing.

Researchers in the current study found a link between certain measures of sleep-disorder breathing and worse attention, short term memory and information processing speed. However, there was no link with overall cognitive function (which also includes aspects such as language, judgement, fluency of speech and visual thinking). The reason for this was unclear but it suggests the evidence of any link is inconclusive.

Some of the links were stronger in people who carried a form of a gene called APOE-e4, which is a known genetic risk factor for Alzheimer's.

In conclusion, this study does not prove that sleep-disorder breathing is a risk factor for Alzheimer's disease. This study did not specifically look at whether people developed dementia or not. It only looked at their performance on cognitive tests at a single point in time.

These limitations aside, it is important to see your GP for a diagnosis if you suspect you may have sleep apnoea. Left untreated, sleep apnoea may increase the risk of more serious conditions, such as heart attack and stroke.

Where did the story come from?

The study was carried out by researchers from Brigham and Women's Hospital (Boston), Harvard Medical School, Beth Israel Deaconess Medical Center (Boston), University of Washington, Wake Forest School of Medicine, US Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, and Stanford University School of Medicine. It was funded by the National Heart, Lung, and Blood Institute in the US.

The study was published in the peer-reviewed medical journal Annals of the American Thoracic Society. Both the Mail and The Sun suggest a link between snoring and Alzheimer's has been found, but this is not the case. A cohort study analysis, where people are assessed for dementia over the course of many years, would be a better way to look at the question.

Also, while it looked at performance on cognitive tests it did not investigate whether people went on to develop dementia. The media also did not mention that it's not possible to say from this type of study whether the breathing problems during sleep are actually the cause of the problems with brain function, because both were measured at around the same time. They also didn't mention that the size of the effect of sleep problems on brain function was small.

What kind of research was this?

This was a cross-sectional analysis of data from the ongoing Multi-Ethnic Study of Atherosclerosis (MESA) cohort study in the US. The main goal of MESA is to look at how various lifestyle factors impact on the risk of developing atherosclerosis (hardening of the arteries).

The researchers aimed to see if breathing problems during sleep (sleep-disordered breathing or SDB) were associated with problems in brain functions such as attention and memory. The researchers say that previous studies examining this question have had mixed findings – some showing a link and others not.

They also looked at whether the presence of a variant of the apolipoprotein-E gene called e4 (APOE-e4) also affected the risk of developing problems with brain function. The APOE-e4 variant is a known risk factor for Alzheimer's disease. The Alzheimer's Society report that people with one copy of the variant gene have twice the risk of developing Alzheimer's disease compared to the population at large.

While a cross-sectional analysis can identify a link between two different factors, it cannot prove that one causes the other, as we can't be sure which factor came first. Links identified using this type of study need to be followed up by studies that can identify the sequence of events.

What did the research involve?

Researchers analysed sleep and brain function data from participants of the MESA study They looked at whether people with breathing problems during sleep had poorer performance on cognitive tests.

The MESA study involved adults aged between 45 and 84 years old. Study participants underwent a sleep study at home. This involved attaching various monitors to their body overnight to record:

episodes of shallow breathing (called hypopneas)
episodes of stopping breathing completely (called apnoeas)
the levels of oxygen in the blood (oxygen saturation) – as sleep breathing problems can reduce these levels
the total time of sleeping
the timing of the different stages of sleep

The participants also filled out the Epworth Sleepiness Scale (ESS) questionnaire, which asks various questions to assess whether someone has excessive sleepiness during the day. The minimum score is 0 (no daytime sleepiness) and the maximum score is 24 (most daytime sleepiness).

For each participant the researchers calculated the:

apnoea-hypopnea index (AHI) – a measure of how many apnoea and hypopnea episodes a person has per hour of sleep
percentage of time during sleep when the oxygen levels in their blood were under 90%

Participants with an AHI score of 15 or more were considered to have moderate to severe sleep disordered breathing. People with an AHI of five or more, and an ESS score of more than 10 were considered to have sleep apnoea.

The cognitive assessment involved three tests that assessed:

overall brain function, including areas such as attention, concentration, short and long-term memory and language using the Cognitive Abilities Screening Instrument
how quickly the brain could perform tasks (processing speed) and attention using the Digit Symbol-Coding test
memory and attention using the Digit Span Test (DST)

The researchers also carried out genetic testing to identify participants with at least one APOE-e4 gene variant (an Alzheimer's "risk gene").

They then compared the cognitive performance of people with the quality of breathing during sleep. They looked at whether results were any different for those people with the APOE-e4 variant. The researchers took into account a number of factors that could affect the results (potential confounders) in their analysis, including:

race
age
body mass index (BMI)
level of education
smoking
high blood pressure
depression
use of benzodiazepines (a class of drugs used as sleeping pills and tranquilisers)
diabetes

What were the basic results?

The sleep studies showed that 9.7% of the participants had sleep apnoea, and 33.4% had moderate to severe sleep disordered breathing.

There was no association between AHI score and any of the cognitive outcomes. There was also no link between any of the sleep breathing measures and one of the more challenging cognitive tests used (The DST Backward), or with the test of overall brain function.

Lower oxygen levels in the blood and being more sleepy during the daytime were associated with a small reduction in attention and short-term memory on one cognitive test (the DST Forward). Having sleep apnoea and greater daytime sleepiness were also associated with small reductions in attention and the speed that the brain could process simple mental tasks on another cognitive test.

Some – but not all – of these links were stronger in people carrying at least one copy of the e4 form of the APOE gene (the links were between having lower levels of oxygen in the blood and poorer attention and memory, and between greater daytime sleepiness and poorer attention and speed of brain processing).

How did the researchers interpret the results?

The researchers concluded that their results "suggest that more severe overnight [low blood oxygen levels] and sleepiness may be related to poorer cognitive function, especially attention, concentration, and process speed in middle-aged to older adults, and that the risk is greater among carriers of the APOE-ε4 alleles, a known risk factor for Alzheimer's disease."

Conclusion

This relatively large cross-sectional analysis has found a link between certain measures of breathing problems during sleep and poorer cognitive function in middle-aged to older adults.

The strengths of this study include its size and use of a prospective sleep study to assess whether people had sleep apnoea or other problems with breathing during sleep. The use of standard cognitive tests is also a strength.

However, the study does have its limitations:

The study did have mixed findings – while certain measures of problems with breathing during sleep (e.g. oxygen levels) were associated with cognitive outcomes, others (e.g. Apnea-Hypopnea Index) were not. This suggests that findings are not conclusive. In addition, previous studies have also had mixed results. This suggests that a systematic review which brings together all of the available evidence on this question would be helpful to assess whether, on balance, the research suggests a true link.
It's not possible from this type of cross-sectional analysis to prove that breathing problems during sleep cause the differences in brain function seen. This is largely because it's not possible to establish whether participants only developed problems with brain function after they experienced sleep breathing problems. It's also difficult to be sure that the effect of all potential confounders has been removed.
The study measured brain function at one time point and did not assess whether people had (or went on to develop) dementia. Therefore we don't know if the brain function differences were temporary or long lasting, whether it had any impact on the participants' lives, or whether there is a link between problems with breathing during sleep and dementia.
Sleep was only assessed on one night and may not be indicative of longer term sleep breathing problems.
The participants were older and middle aged adults so it may not be possible to generalise these results to younger adults.

Some of the risk factors for sleep apnoea are similar to some of those for dementia. These include being overweight or obese, smoking, and drinking excessive amounts of alcohol.

So maintaining a healthy weight, giving up smoking, and limiting your alcohol intake are likely to reduce both your risk of developing sleep apnoea and dementia.