Wednesday June 3 2015
Alzheimer's is linked to abnormal clumps of protein in the brain
"Sleepless nights … could raise your odds of developing Alzheimer's," is the claim in the Daily Mail. A new US study did find a link between poor sleep quality and higher levels of clumps of abnormal proteins in the brain (known as beta-amyloid plaques), but no cause and effect relationship between sleep quality and Alzheimer’s disease was proven.
This small study involved 26 healthy older adults who were analysed with a brain scan to measure the amount of protein plaques in their brain. The researchers did find an association with increased amounts of plaques and reduced deep sleep during the night. This in turn was associated with reduced ability to remember word-pair associations from the night before.
It is important to note that these are just associations as this was a cross-sectional study. The study cannot prove that the plaques caused the poor sleep or poor performance on the memory test, or that poor sleep caused plaque development. Various unmeasured factors could account for the results, such as difficulty sleeping in a laboratory.
Additionally, despite the media headlines, this study cannot show whether improving the quality of sleep would reduce the risk of Alzheimer's disease or slow its progression. The participants did not have any symptoms of dementia and were only assessed at one time point.
Where did the story come from?
The study was carried out by researchers from the University of California, California Pacific Medical Center and the Lawrence Berkeley National Laboratory. It was funded by the US National Institutes of Health.
The study was published in the peer-reviewed medical journal Nature Neuroscience.
Some of the UK media’s reporting of the study was inaccurate. For example, the Daily Mirror reported that adults "deprived of regular sleep had the highest levels of beta-amyloid" when this was not assessed in the study. The participants’ sleep pattern was only monitored for one night; the researchers did not formally assess their usual sleep pattern or use this in their calculations. Their claim that the "the study also revealed a 'vicious cycle' in which the protein not only corrodes memory, but also disrupts sleep further" was not found in the study – it was a speculation by the authors.
The Daily Mail also overstated the findings of the study and neither reported on the limitations.
What kind of research was this?
This was a cross-sectional study looking for a link between beta-amyloid plaques, poor sleep and memory deficits. This type of study cannot prove cause and effect but can further our knowledge of associations between these factors.
Beta-amyloid precursor protein is a large protein that is found on the surface of cells and is essential for growth and repair of nerve cells. However, it can be broken up into fragments, one of them called beta-amyloid. These beta-amyloid proteins attach to each other, forming long fibrils that accumulate to form plaques. This occurs in normal ageing, but to a much greater extent in Alzheimer’s disease. The plaques usually start to appear in the grey matter, called the cerebral cortex. The plaques are associated with memory loss but the exact mechanisms for this are not known.
The researchers wanted to explore their theory that the plaques may be causing memory loss through interrupting non-rapid eye movement (NREM) sleep. This part of the sleep cycle occurs during:
- Stage one: when you start to go to sleep
- Stage two: light sleep
- Stage three: deep sleep, when the body repairs and regrows tissues and the immune system
During a night’s sleep, after around 90 minutes, NREM sleep changes into rapid eye movement (REM) sleep for about 10 minutes. REM sleep is when dreams occur. The cycle is then repeated, going back to NREM sleep, with progressively longer periods of REM sleep as the night progresses.
What did the research involve?
The researchers recruited 26 older adults with no cognitive impairment. The study involved participants having a brain scan to measure the amount of beta-amyloid plaques, and performing a word-pair task before and after a night of sleep in the laboratory to test their ability to lay down memory.
The study participants did not have any symptoms of dementia, mental health conditions or reported sleep problems. Each participant underwent a positron emission tomography (PET) brain scan to estimate the amount of beta-amyloid protein build-up in the grey matter of the brain.
The participants then performed a word-pair task before and after a night of sleep in the laboratory. The amount of REM and NREM sleep was measured using an electroencephalogram (EEG) – a test that measures the electrical activity of the brain. The word-pair task consisted of learning a series of word pairs. Short-delay memory was tested by asking the participants to remember some of the word pairs after 10 minutes. Long-delay memory was tested the following day when they were asked to remember the rest of the word pairs. This was performed at the same time as a behavioural and functional magnetic resonance imaging (fMRI) scan, so that the researchers could look at which areas of the brain were active, such as the hippocampus, which is involved in memory.
What were the basic results?
Increased beta-amyloid protein in the medial prefrontal cortex of the brain, was associated with reduced NREM sleep. In particular, it was associated with less slow wave activity of below one hertz (Hz) – a measurement of frequency, which is believed to be when memory is consolidated. These results remained significant after adjusting for age and volume of grey matter. Beta-amyloid protein in other areas of the brain was not associated with NREM sleep of slow wave activity below one Hz.
Reduced NREM slow wave sleep and increased beta-amyloid protein in the medial prefrontal cortex of the brain was associated with poorer overnight memory. It was also associated with an increase in the activity of the hippocampus area of the brain.
The amount of beta-amyloid protein was not directly associated with poorer ability to form new memories. The link was only formed when reduced NREM sleep was included in the statistical analyses.
How did the researchers interpret the results?
The researchers concluded that their data "implicate sleep disruption as a mechanistic pathway through which β-amyloid [beta-amyloid] pathology may contribute to hippocampus-dependent cognitive decline in the elderly". They say that "cortical Aβ [beta-amyloid] pathology is associated with impaired generation of NREM slow wave oscillations that, in turn, predict the failure in long-term hippocampus-dependent memory consolidation".
The researchers go on to speculate from previous animal studies that NREM sleep disruption increases the build-up of beta-amyloid plaques and that this then reduces the amount of NREM sleep, creating a vicious cycle. However, they are clear that this is a hypothesis and has not been proven by this study.
This small study of 26 healthy older adults has found a link between the build-up of protein plaques in the brain, poor quality sleep and difficulty in laying down memory overnight.
The main limitations of this study are the cross-sectional study design. This means that the study cannot prove that the increased beta-amyloid plaques caused the poor NREM sleep or that either caused the memory difficulties. Similarly it does not show that poor sleep quality increases plaque build-up and so could be associated with Alzheimer’s development. Other factors could have accounted for the results seen, such as poor sleep from trying to sleep in a laboratory setting.
Additionally, despite the media claims, the study was taken at one point in time and so cannot show that increased NREM sleep would reduce the risk of dementia such as Alzheimer’s disease or slow its progression.
Overall this is an interesting piece of research, but further studies over a long period of time are needed to better understand the associations seen. That said, improving the quality of your sleep may have numerous health benefits, and tips can be found on our Better sleep hub