scrutinize REM sleep to identify people at risk? ⋅ Inserm, Science for health

In Alzheimer’s disease, sleep disturbances occur long before the diagnosis has been made. Are they caused by the very first stages of the disease, or are they on the contrary a risk factor, which promotes neurodegeneration? To explore these questions, researchers from the GIP Cyceron, in Caen, studied the modifications paradoxical sleep, associated with the dreams of elderly people, as well as the presence of neurotoxic deposits in their brains.

Alzheimer’s disease is mainly due to the accumulation of amyloid protein in the brain. While memory problems are the most common and well-known symptom, people with the disease also have sleep disorders that often begin early, well before the onset of dementia. But the link between these sleep alterations and the neurotoxic deposits observed in the brain is not clearly established: is there an association between the two and, if so, could one be the consequence of the other ? The issue is important because if sleep disorders promote the development of amyloid protein deposits, they would constitute a risk factor for dementia. Tracking them could make it possible to identify people at risk and offer them preventive approaches.

In order to explore this hypothesis, Géraldine Rauchs’ team focused on disorders that specifically affect REM sleep, this phase of sleep particularly conducive to dreams. The Inserm researcher explains: Most of the studies conducted on the subject have been more interested in slow-wave sleep, because it corresponds to an intense recovery period, and because it is during this period that the toxic waste produced by our neurons is eliminated. This work has shown an association between the accumulation of amyloid proteins and slow-wave sleep disorders. But REM sleep is interesting for two main reasons: First of all, it involves neurons which are affected early in Alzheimer’s disease, cholinergic-type neurons. In addition, changes in REM sleep are observed in the early stages of the disease, before those affecting slow-wave sleep. “, she continues.

Slow or paradoxical, the architecture of our sleep

A night’s sleep is made up of successive cycles which themselves consist of an alternation between “slow” sleep and “paradoxical” sleep. These two types of sleep are distinguished by the brain activity associated with them. When measuring brain activity by electroencephalography during slow sleep, electrical waves of high amplitude and low frequency are observed. During REM sleep, brain activity is close to that of the waking phase, with shorter and more frequent waves.

To learn more about sleep

The researcher and her team analyzed the sleep architecture of a cohort of elderly people without cognitive impairment. At the same time, imaging examinations (by PET scan and MRI) were carried out to look for the possible presence of amyloid deposits in their brains and to assess their cerebral structure and functioning. ” We first demonstrated that the power of the cerebral waves which characterize paradoxical sleep, the theta waves, is all the lower as the amyloid deposits in the cortex are numerous. “, reports Geraldine Rauchs. The researchers did not find this correlation with any other wave among those that characterize slow, light or deep sleep. ” This supports the hypothesis of a link between early changes in REM sleep and the risk of progression to dementia. » she underlines. To confirm this, follow-up studies will be necessary, in order to study in the same volunteers the evolution of sleep disorders, cognitive disorders and amyloid aggregation over time.

From correlation to causation

« During this work, we were surprised to observe that the decrease in theta brain wave power, and therefore in neuronal activity, is accompanied by an increase in cerebral perfusion. [c’est-à-dire du débit sanguin] at the level of several regions of the brain, in particular in the fronto-parietal areas “says the scientist. However, the decrease in activity of a cerebral area is logically associated with a lower need for oxygen, and therefore with a decrease in blood flow. Géraldine Rauchs and her team therefore hypothesize that the fronto-parietal areas could constitute the epicenter of an early mechanism that would eventually lead to cognitive decline and then spread to other areas. ” The increased cerebral perfusion in regions with more amyloid deposits could reflect a transient compensatory mechanism to help maintain habitual neuronal activity there. But it could be harmful in the longer term, since neuronal hyperactivity is known to promote the accumulation of amyloid protein “, she offers.

To confirm these hypotheses, the researcher and her team wish to conduct similar work with larger groups of elderly people in good cognitive health, but also with volunteers who suffer from cognitive disorders of varying severity. ” Until then, we will continue to follow the participants of the cohort already formed. We will therefore be able to study their cognitive evolution and assess whether their sleep disorders have a predictive value of progression to Alzheimer’s disease », concludes Géraldine Rauchs.

Géraldine Rauchs is a researcher on the team Neuropresage