With age, sleep comes not so easily. Waking up in the middle of the night, trouble falling asleep, and then tiredness in the afternoon. A normal consequence of age? Or is it more? This could also be a first indication that the mind slowly but surely is dying away. Not only with Alzheimer’s but also with other neurological degenerative diseases such as Parkinson or Huntington’s disease, the internal clock and its regular sleep and wake cycles are lost early in the course of the disease.
Apnea therapy improves cognitive performance
This is not only tragic for the ageing person himself or herself, but also for his or her environment. If the partner must also dispense with his or her night’s sleep, energy reserves for maintenance and care soon run out and the nursing home is the only way out. All this is also associated with high costs: reason enough to look for markers of a connection between degenerative neurological diseases and the disturbed biorhythms, its causes and possible treatment.
The matter is however not quite as simple as that. Data on terminally ill apnea patients indeed says clearly that the degradation of nerves in the brain can be slowed down when the oxygen supply or prevention against respiratory-cutouts improves. “Once corrected, the patients are much clearer in the head, and remember things more easily,” says Clifford Saper, a neurologist from Harvard, “but it is far from clear whether the loss of sleep itself promotes the neurodegeneration”.
Risky midday nap?
In 2009, David Holtzman from the University of St. Louis in the US reported in Science on a study of mice which showed a daily rise and fall in ß-amyloid levels of the interstitial liquid in the brain. Lack of sleep in the mice allowed the concentration to increase to such an extent that the protein was deposited and led to characteristic plaques. The administration of an antagonist to receptors of the sleep hormone orexin delayed the plaque formation. What’s more, the mice’s normal sleep-wake cycle itself was impaired with the amyloid deposits, being then stabilised again through an active amyloid immunisation.
A recent study from the Holtzman lab involving about 150 participants, some with a family background of Alzheimer’s disease, showed the intricate patterns of interdependence. About a fifth had deposits in their brains and clearly showed more restless sleep than those without this pattern of degeneration. With regard to total sleep time the researchers found no differences between the groups. However people who indulged in a midday nap several times a week more frequently had amyloid plaques.
Sleep disorders promote Alzheimer’s – or vice versa?
That memory function should decrease with age is taken to be quite normal. Just as normal with seniors is sleep which is not as effective as it was in the first half of life. The further a pathological process, such as Alzheimer’s disease, has advanced, the more extensive the disturbances in sleep-wake rhythm are. In 2012, Roxanne Sterniczuk from Halifax, Canada, undertook a data analysis of 14,000 participants who had taken part in the European long-term age study SHARE, from which it emerged that among those people with extensive sleep disorders a greatly increased risk of Alzheimer’s showed up during the next two to four years.
In the mouse model of Alzheimer’s disease, the author also found out however that the degeneration process itself leads to the destruction of the control centres of the body clock. Particularly in the important nucleus suprachiasmaticus of the hypothalamus, damage is detectable soon after the first plaques are present in the neural connections. In the other centres which control the switching of sleep and waking, the degradation caused by Alzheimer’s inflicts damage as well, which steers the patients out of their usual sleep pattern. These processes are also observed of patients in hospitals.
However, it is only through using mice that the researchers could be provided with more detailed information on the mechanisms and possibilities for intervention. Which protein patterns are altered in the control centres? Might one be able to counteract them with the appropriate medications or gene therapy? This is what Sterniczuk wants to elucidate over the next few years.
Huntington’s disease: Altered rhythm genes
However, other diseases in which nerve tissue in the brain is the source of the problem are closely associated with the function of circadian rhythms. In Huntington’s disease the symptoms begin with mobility or cognitive disorders, until gradually ever larger areas of the nervous system begin to lose their functions as part of the motor control centre. Huntington’s patients at a very early point also lose their control over day and night activities. Looking at Huntington’s disease mice, researchers have demonstrated a significant change in the pattern of expression of two key genes of the body clock mechanism. It still remains unclear whether this loss is due to the Huntington’s gene defect itself or to the spreading neurodegeneration. Apparently, the disturbed rhythm does contribute to the outcome, whereby the brain continues to lose its control function. Since sleep hygiene measures bring at least some improvement in symptoms, there is hope at least that the disease process can thus be somewhat delayed.
Sleep aid against Parkinson’s disease?
Things look very similar with regard to Parkinson’s disease. Here, dopaminergic neurons die particularly in the midbrain. Dopamine also plays a crucial role in the sleep-wake rhythm and its management. Thus, the “stimulants” amphetamine and modafinil, for instance, increase the dopamine level. As with the other neuronal disorders double feedback also occurs here: sleep deprivation leads to a strong reduction of dopamine receptors in the striatum in the region of basal ganglia. In Parkinson’s patients this region is strongly affected by degeneration. Dysfunction of the circadian clock could constitute an important marker for the disease, because it often occurs many years before the first typical symptoms. Apart from the motor symptoms many profile characteristics of Parkinson’s patients overlap with those of disrupted circadian rhythm cases without Parkinson’s disease’s pathological processes being present. For many experts, this is an indication that the broken inner clock could also be driving the disease process itself. This in turn means that sleeping pills and behavioral training should at least help to improve things.
So far, experiments with higher light doses in nursing homes and treatment with melatonin have only achieved moderate success in the fight against cognitive deficits and serve primarily as a remedy for depression. Nevertheless, poor sleep seems to accelerate the onset of Parkinson’s and Alzheimer’s. David Holtzman puts it this way: “Disturbed sleep during midlife could cause the aggregation of proteins and thus the onset of the disease. The respective damage in turn causes further disturbed sleep“. In the mouse model, sleeping aids improve the cognitive function of animals with induced Alzheimer’s or Huntington’s disease. Regular outdoor exercise and self-discipline help suppress the symptoms of neurodegenerative diseases, but stopping the deterioration of the nervous system is something they probably cannot do.