Nature | Outlook
Neurodegeneration: Amyloid awakenings
Moheb Costandi
Published online22 May 2013
Sleep disturbances may be an early sign of neurodegenerative diseases — but could sleep deficits cause these conditions in the first place?
...So sleep disturbances might be one of the earliest manifestations of Alzheimer's disease, raising the tantalizing possibility of early intervention to help prevent or slow the inevitable march into the cognitive fog.
Sleep disturbances might be an early sign of other neurodegenerative conditions as well. Last year, Roxanne Sterniczuk, a neuroscientist at Dalhousie University in Halifax, Canada, looked at data collected from approximately 14,600 people as part of the Survey of Health, Ageing and Retirement in Europe (SHARE), a long-term study of people aged 50 and over across 12 countries.
People who experienced sleep disturbances were more likely to be diagnosed with Alzheimer's within two to four years, according to the SHARE data. In particular, increased daytime sleepiness was the best predictor of the disease. The data also showed that daytime fatigue, a sleep disturbance that leads to exhaustion during the day, predicted those who went on to develop Parkinson's disease.
Parkinson's involves the progressive degeneration of midbrain neurons that produce dopamine — a neurotransmitter involved in regulating the sleep–wake switch. The drugs amphetamine and modafinil, for example, increase wakefulness by increasing dopamine signalling.
Conversely, even one night of sleep deprivation reduces the number of dopamine receptors in the striatum, a region of the basal ganglia that is severely affected by the disease. Thus the sleep disturbances associated with Parkinson's may be caused by the degeneration of dopaminergic midbrain neurons.
Sterniczuk plans to analyse the SHARE data again to see if there are subtle differences between the sleep disturbances in presymptomatic Alzheimer's and Parkinson's patients. “If we can characterize the changes before symptoms appear then we can use them as diagnostic markers,” she says. “That might permit earlier treatment.”
The evidence is building for a correlation between disturbed sleep and neurodegenerative diseases, but the next step — discovering whether sleep disturbances are a cause of these conditions — will take considerably more research. In particular, establishing a causal relationship will require longitudinal studies that assess the sleeping patterns of large numbers of people over long periods of time, and link specific types of sleep disorder with the incidence of each disease. But to diagnose the diseases accurately, researchers must look for the tell-tale signs in the brains of study participants...
Broken dreams
Sleeping difficulties and neurodegeneration seem to reinforce one another in a vicious cycle. “Abnormal sleep in mid-life might cause protein aggregation that starts the disease off,” Holtzman says, “and the damage that causes may further disrupt sleep.”
“A lot of early data suggest that modifying sleep could actually delay the onset of disease.”
But could that dynamic be reversed? If disrupted sleep can predispose people to neurodegeneration, then might healthy sleeping patterns help protect the brain against it? Holtzman's group is testing this idea — essentially, whether it is possible to turn the vicious cycle virtuous. “A lot of early data suggest that modifying sleep could actually delay the onset of disease,” he says. “I think that's where the field should be going now, but it's not trivial translating all the animal studies directly into people.”
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...Sleep apnoea, which is characterised by abnormally shallow and interrupted breathing, may almost double the risk of dementia
7. Sleep apnoea is treatable, so early intervention could delay the onset not only of neurodegeneration, but also of normal age-related cognitive decline. “Once it is corrected, patients are much brighter and have better memory function,” says Saper, “but it's still not clear whether sleep loss itself increases neurodegeneration.”
Nevertheless, once clinicians wake up to the fact that sleep is so intimately linked to the most common neurodegenerative diseases, they may be in a better position to detect these debilitating neurological conditions at an early stage, and perhaps stop them in their tracks.
