April 20, 2021

expert reaction to observational study looking at sleep duration in middle age and dementia risk

An observational study published in Nature Communications looks at sleep duration in middle and old age and incidence of dementia.

Prof Derk-Jan Dijk, Professor of Sleep and Physiology, Director, Surrey Sleep Research Centre, University of Surrey and UK Dementia Research Institute (UK DRI) Group Leader, said:

“It is a solid piece of research adding to the growing evidence for a link between sleep and dementia. It is often stated that the link is bidirectional, i.e. abnormal sleep may predict incidence dementia and dementia or prodromal dementia may affect sleep. Particular strengths of this study are the long follow up period ( 25 years), repeated assessment of sleep and objective assessments of sleep in a subsample. The data show that short sleep duration defined as less than 6 hours on ‘week nights’ was associated with increased risk for dementia. This association persisted even when it was controlled for potential confounders such as depression. The latter is important because mental health problems such as depression may in themselves be risk factor for dementia and also influence sleep. In several previous studies long sleep was also a risk factor for dementia but there was no strong evidence for this in the present study. This may be related to the long-follow up period. In studies with shorter follow up periods the association with long sleep may reflect what is referred to as ‘reverse causality’: changes in the brain which may ultimately lead to dementia already affect sleep. An alternatively explanation for the discrepancy may be the different definitions used for long sleep. In the current study the criterion for long sleep was longer than 8 h whereas in previous studies the cutoff may have been 9 or even 10 h.   Overall, a valuable contribution to  sleep-dementia research. To further our understanding in this area will require objective assessments of not only sleep duration but also sleep physiology. This will allow for an assessment of the contribution of the various sleep stages such as slow wave sleep and REM sleep, and also sleep continuity to brain health and failure thereof.”

Dr Sara Imarisio, Head of Research at Alzheimer’s Research UK said:

“Many of us have experienced a bad night’s sleep and probably know that it can have an impact on our memory and thinking in the short term, but an intriguing question is whether long-term sleep patterns can affect our risk of dementia.

“We know that the diseases that cause dementia start up to two decades before symptoms like memory loss start to show, so midlife is a crucial time for research into risk factors. In this study, sleep duration was largely measured through study volunteers self-reporting their sleep duration, and while this group of volunteers was not reflective of the UK population, it does offer insight into the relationship with sleep and dementia in mid to later life.

“This study cannot tease apart cause and effect and while it suggests that persistent lower sleep duration was linked with an increased risk of dementia, it did not find an association between longer than average sleep duration and dementia risk.

“While there is no sure-fire way to prevent dementia, there are things within our control that can reduce our risk. The best evidence suggests that not smoking, only drinking in moderation, staying mentally and physically active, eating a balanced diet, and keeping cholesterol and blood pressure levels in check can all help to keep our brains healthy as we age.”

Dr Elizabeth Coulthard, Consultant Senior Lecturer in Dementia Neurology at the University of Bristol, said:

“There is intense interest in whether poor sleep could cause or worsen dementia and, therefore, whether improving sleep might help prevent dementia. Before this study there was already strong evidence that sleep becomes abnormal before dementia is diagnosed. But this still does not tell us whether sleep triggers or exacerbates dementia because the brain changes that cause dementia start many years before a diagnosis. We know that established dementia is associated with poor sleep.

“This study adds new information to the emerging picture because sleep is reported in a middle-aged cohort who are then followed over 30 years. This means that at least some of the people who went on to develop dementia probably did not already have it at the start of the study when their sleep was first assessed. So, it strengthens the evidence that poor sleep in middle age could cause or worsen dementia in later life.

“There are several limitations to the study most of which are acknowledged by the authors. These limitations mean we still have work to do to understand whether we can treat sleep to avoid dementia and maintain brain health. Limitations –

1. The main information about sleep in this study comes from the participants’ report of their own sleep duration on a typical weeknight. People’s views of their own sleep are notoriously unreliable and can become worse as people develop dementia. Actigraphy, used as an objective measure of sleep, was carried out too late in the study to tell us about sleep before the onset of dementia.
2. The story emerging for sleep is that slow oscillations during slow wave sleep, that predominate at the start of the night, are particularly important for maintaining brain health and possibly preventing dementia. As far as we know, people cannot assess their own slow oscillations and slow oscillations are not measured by wrist-worn actigraphs.  So, this study does not probe the critical features of sleep that might be really important for our brains. To better understand sleep, we need large cohorts who have electroencephalographic recording of slow oscillations and other sleep architecture.
3. The definition of dementia was based on health records such as Hospital Episode Statistics (HES). The authors claim these are 78% and 92% sensitive and specific, respectively. This estimate compares the accuracy of HES data to mental health clinic records as a gold standard. However, we know that only around 60% of people with dementia in the UK are diagnosed during their lives. This is a major drawback of using routinely collected health data to ascertain dementia cases and limits the conclusions we can make.
4. Dementia is not a single disease. Rather, it is a set of different currently untreatable illnesses that cause cognitive, behavioural and social decline. The commonest of these diseases is Alzheimer’s disease and other types of dementia include vascular dementia and Lewy body dementia. Sleep may have different effects in each of these different diseases. We cannot tell here how sleep affects the different diseases that cause dementia. To target treatment we need to know which aspects of sleep are important for each different disease. So, we need to test populations that have been characterised in much more detail to understand the relationship between sleep and the brain diseases that cause dementia.”

Prof Robert Howard, Professor of Old Age Psychiatry, UCL, said:

“The study showed that 50-year-olds, who slept for less than 6 hours per night, were at a very slightly (the difference only just reached statistical significance) increased risk of later developing dementia. It’s always difficult to know what to conclude from these kinds of studies. We know that the first signs of Alzheimer’s disease appear in the brain 20 years before detectable cognitive impairment, so it is always possible that poor sleep might be a very early symptom of the condition, rather than a treatable risk factor. Insomniacs – who probably don’t need something else to ruminate about in bed – shouldn’t worry that they are heading for dementia unless they get off to sleep immediately. ”

Prof Tom Dening, Professor of Dementia Research and Head of the Centre for Dementia at the Institute of Mental Health, University of Nottingham, said:

“As dementia results from changes in the brain, it is unsurprising that people with dementia often have disrupted sleep patterns. Changes in sleep pattern may occur before a person has enough other symptoms to acquire a diagnosis of dementia. Previous research has shown that disrupted sleep patterns may occur several years before dementia becomes manifest.

“This important study contributes to the existing literature in several ways. The authors have used data from the UK Whitehall II cohort – civil servants who were first interviewed between age 35 and 55 and then followed up for about 25 years. There were nearly 8000 participants with data on their self-reported sleep, of whom just over 500 had developed dementia by the end of the period being studied. Men and women with shorter sleep duration (6 hours a night or less) at the age of 50 or at the age of 60 had a higher rate of developing dementia than those who slept 7 hours per night. The findings for people sleeping 8 hours plus were less clear. Given that the mean age of dementia diagnosis was 77, then these changes occurred many years before the condition was diagnosed.

“What this study adds is the large sample size, the full assessments and the long period of follow-up. The study has made repeated measures of sleep duration over the years. Although most of the sleep data were based on self-report, which can be unreliable, a small subset of participants did have objective sleep measures with an accelerometer and the findings were consistent with the rest of the observations. The study team were able to use NHS data to determine whether participants had eventually been diagnosed with dementia. While NHS data have their limitations, this method will correctly pick up the great majority of cases. Finally, the research team undertook several sensitivity analyses, that is analyses to discount other possible hypotheses;  for example, they were able to establish that the effects of sleep on the future risk of dementia were not due to mental illness, such as depression or anxiety, as these also play havoc with sleep.

“What’s the message for us all? Evidence of sleep disturbance can occur a long time before the onset of other clinical evidence of dementia. However, this study cannot establish cause and effect. Maybe it is simply a very early sign of the dementia that is to come, but it’s also quite likely that poor sleep is not good for the brain and leaves it vulnerable to neurodegenerative conditions like Alzheimer’s disease.

“Turning off mobile phones and avoiding caffeine before bed are good habits to have as we already know the importance of good sleep on health more generally, however we would need further studies to know if longer sleep in itself could reduce the risk of dementia later in life.”

Prof Tara Spires-Jones, UK Dementia Research Institute at The University of Edinburgh & Deputy Director, Centre for Discovery Brain Sciences, University of Edinburgh, said:

“This study by Sabia and colleagues found an association between short sleep duration in midlife and a 30% increase in dementia risk.  Sleep is important for normal brain function and is also thought to be important for clearing toxic proteins that build up in dementias from the brain.  This study looked at data from over 7,900 people over 25 years and authors carefully considered many potential confounding factors like smoking, exercise, and weight.

“However, as the authors point out, these results do not conclusively prove that less sleep leads to dementia. It is possible, for example, that brain changes associated with very early disease are instead disrupting sleep.” 

‘Association of sleep duration in middle and old age with incidence of dementia’ by Séverine Sabia et al. was published in Nature Communications at 16:00 UK time on Tuesday 20 April.

DOI: https://doi.org/10.1038/s41467-021-22354-2

Declared interests

Dr Elizabeth Coulthard: “No conflicts.”

Prof Robert Howard: “No conflicts.”

Prof Tara Spires Jones: “I have no conflicts of interest with this study.”

None others received