Can a sleep disorder predict Parkinson's years before its obvious manifestation?

About 70% of Parkinson's patients have sleep-related problems, especially linked to early awakening and sleep fragmentation, according to data from the Spanish Foundation for Parkinson's Research Assistance.

The inverse relationship is not as well known.

That is, how a certain sleep disorder can be the first symptom of this neurodegenerative disease that manifests itself (in patients over 55 years of age) between five, ten or fifteen years before the most well-known symptoms of the disease appear: tremors, stiffness and slowness of movement.

A prospective study recently published in the scientific journal

(

), which followed up almost 4,000 men over the age of 67, with an average age of 77, for an average of 7.3 years, has concluded that those patients who reported frequent distressing dreams (more than one a week ) at baseline had a threefold increased risk of developing Parkinson's disease during the first five years.

"The most important contribution of the study is to show that we can identify people who are at increased risk of developing Parkinson's disease simply by asking older people in the general population about what they dream about at night," explains Dr. Abidemi I. Otaiku, author of the study and member of the Department of Neurology at Birmingham City Hospital, who based on the results of his research, considers that the high frequency of distressing dreams could be considered a "prodromal symptom" of Parkinson's disease.

Dr. Alex Iranzo, a neurologist at the Hospital Clínic de Barcelona and one of the most prolific Spanish researchers in the field of this sleep-Parkinson's relationship, points out that, although the results of the study "are credible", it has several limitations.

On the one hand, by focusing on men and based on a cohort with a mean age of 77 years, it excludes a significant part of the population.

On the other, that the concept of "distressing dreams" is very undefined, since, as he explains, the only nightmares that have been related to Parkinson's and other neurodegenerative diseases such as dementia with Lewy bodies and multiple system atrophy are those that are associated with REM sleep behavior disorder.

“They are nightmares of violent and unpleasant content, of suffering, in which the patients stir in self-defense when they feel attacked.

The patient dreams that he is fighting, arguing, that someone wants to rob or harm him, that someone is chasing him, that an animal is attacking him”, explains Dr. Carles Gaig, a member of the sleep and wakefulness study group of the Spanish Society of Neurology (SEN), which adds that what is surprising about these nightmares is that, despite occurring in the REM sleep phase, in which we dream but the body is immobilized, patients affected by this disorder sleep as if they were performing a play: they move excessively, hit, kick, argue loudly, insult and even fall out of bed.

“Many times people who suffer from this disorder are not aware of it, they do not realize it.

The one who usually realizes it is the one who sleeps next to him, who is the one who takes the hits and many times who ends up motivating the consultation, ”says Gaig.

REM sleep behavior disorder

The correct diagnosis of this sleep disorder -which must be carried out by means of a video polysomnogram in a hospital sleep unit, since it can be confused in your clinic with other pathologies such as severe obstructive sleep apnea-, is essential, since if positive, it is a disorder that, in turn, is also an almost certain diagnosis of Parkinson's, dementia with Lewy bodies, or multiple system atrophy.

This has been demonstrated by Dr. Iranzo himself.

In 2006, together with other Spanish researchers, he published a study in

based on the follow-up of 44 patients with this disorder.

After five years of follow-up, 45% of them had developed a neurological disease.

Eight years later, in 2014, he published in the scientific journal

a continuation of the first investigation to which 130 more patients were incorporated.

The results left no room for speculation: the estimated risk of a definite neurodegenerative syndrome from the time of REM sleep behavior disorder diagnosis was 33.1% at five years, 75.7% at ten years and 90.9% at 14 years.

“Then we wondered why some people developed neurological disease before others.

We discovered that those patients we diagnosed with a REM sleep behavior disorder who also had a loss of smell -research published in the

or had altered levels of dopamine in the brain -study published in the

of the American Association of Neurology - were also the ones who developed the disease the fastest”, adds Iranzo.

An open door to a future healing?

Parkinson's, dementia with Lewy bodies and multiple system atrophy are included among the group of diseases known as synucleinopathies, a proper name that derives from a protein, Alpha-synuclein, whose abnormal expansion by brain cells is responsible for these neurodegenerative diseases.

“Last year we published an article in

in which, through a lumbar puncture, we showed that 90% of our patients diagnosed with REM sleep behavior disorder who had not yet developed the most typical symptoms of Parkinson's, already presented an abnormal presence of this protein”, explains Iranzo.

The prevalence of REM sleep behavior disorder is relatively low (0.74% according to an epidemiological study carried out in the province of Lérida with patients over 60 years of age who attended routine consultations in two primary care centers) and, as points out Dr. Carles Gaig, only in approximately a third of patients with these neurodegenerative diseases does the REM sleep behavior disorder appear years before their more well-known symptoms.

But could this sleep disorder be a pathway for the future cure of diseases such as Parkinson's?

“Today there is no treatment, but if we can identify people three to five years before they develop movement problems,

In this sense, for Carles Gaig, this group of patients is "very special", since being in a very early and mild phase of neurodegenerative disease, it constitutes a "perfect target" to carry out tests that can help prevent or stop it. .

“Generally, when we diagnose this disease it is when there are already mobility or memory problems and many neurons in the brain have already been lost.

Here we would be talking about a much more initial phase and with many more neurons to save”, he adds.

Dr. Alex Iranzo recalls that for several years trials have already been carried out with patients diagnosed with Parkinson's with vaccines that attack the abnormal production of alpha-synuclein.

“Ideally, it would also be offered to patients a few years after they develop Parkinson's.

And those are patients like ours.

After four years of work, we are about to start a trial to offer this vaccine to patients with REM sleep behavior disorder.

The idea would be to eliminate alpha-synuclein when it is still only located in a single area of ​​the brain, the one that controls REM sleep, with the hope of being able to slow down and even end these neurodegenerative diseases”, he concludes.

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