ALS Disturbs Sleep Prior to onset of ALS Symptoms and associated genetic mutations

This seems to be a plausible connection! Do not older people get less sleep and sometimes less quality sleep (e.g. reduced rapid eye movement or REM)?

Unfortunately, the study did not investigate whether sleep disturbances cause ALS. We are left with a kind of a chicken and egg problem.

Therefore, I also suspect, the pre onset sleep disturbances are not a good indicator for developing ALS.

This mix of sleep disturbances and genetic mutations make this study confusing. More research is probably needed.

"Sleep disturbances are commonly reported by people with neurodegenerative conditions that damage motor neurons. Some of these disorders, including amyotrophic lateral sclerosis (ALS), affect nonmotor functions of the brain, including sleep, which is regulated by the hypothalamus. ...

The researchers started by investigating differences in sleep quality between individuals who had early-stage ALS, a period before the onset of respiratory problems, and people without ALS or other motor deficits. They observed that people with ALS took longer to fall asleep and had increased bouts of wake and rapid eye movement (REM) sleep but reduced deep sleep non-REM (NREM) stages.

In a second cohort of individuals with an immediate relation to someone with ALS but who had not developed motor symptoms, the researchers recorded their sleep and collected DNA samples to determine which individuals carried a genetic mutation associated with ALS.

Compared to individuals with no ALS mutations, presymptomatic ALS carriers demonstrated altered sleep patterns that were dependent on the mutation that they carried: 

one mutation was associated with less overall time asleep and reduced deep sleep NREM, while a 

second mutation led to a longer time to fall asleep and more time in REM, but less time in total in NREM stages. Both mutations were associated with increased times in the wake period. ...

The team confirmed the sleep changes they saw in their human studies using three different animal models of ALS with mutations in either an RNA-binding protein, a DNA-binding protein, or superoxide dismutase, all shown to be affected in the disorder. Although the onset of sleeping changes varied by genetic mutation, the researchers saw an overall decrease in NREM and REM and increased wake periods in animals; these changes occurred prior to motor deficits in one model. Thus, although the effects to REM sleep differed between mice and humans, ALS caused similar changes to sleep-wake patterns in both species. ..."

From the editor's note and abstract:

"Editor’s summary

Patients with amyotrophic lateral sclerosis (ALS) often experience poor sleep, but whether these disturbances are caused by alterations in sleep regulating brain circuits or triggered by motor symptoms remains unclear.

Guillot et al. found that patients with ALS and presymptomatic carriers of ALS risk genes show increased wakefulness and reduced non–rapid eye movement sleep. Disruptions in sleep architecture were also found in three mouse models of ALS and partially normalized by intraventricular injection of melanin-concentrating hormone or oral administration of an orexin antagonist.

These results suggest that sleep disturbances occur before symptom onset and can be ameliorated by targeting neuropeptides involved in sleep/wake regulation. ...

Abstract

Sleep alterations have been described in several neurodegenerative diseases yet are currently poorly characterized in amyotrophic lateral sclerosis (ALS).

This study investigates sleep macroarchitecture and related hypothalamic signaling disruptions in ALS. Using polysomnography, we found that both patients with ALS as well as asymptomatic C9ORF72 and SOD1 mutation carriers exhibited increased wakefulness and reduced non–rapid eye movement sleep.

Increased wakefulness correlated with diminished cognitive performance in both clinical cohorts. Similar changes in sleep macroarchitecture were observed in three ALS mouse models (Sod1G86R, FusΔNLS/+, and TDP43Q331K).

A single oral administration of a dual-orexin receptor antagonist or intracerebroventricular delivery of melanin-concentrating hormone (MCH) through an osmotic pump over 15 days partially normalized sleep patterns in mouse models. MCH treatment did not extend the survival of Sod1G86R mice but did decrease the loss of lumbar motor neurons. These findings suggest MCH and orexin signaling as potential targets to treat sleep alterations that arise in early stages of the disease."

ALS Disturbs Sleep Prior to Symptom Onset | The Scientist "Humans and mice with a predisposition for ALS displayed altered sleep patterns before symptoms began, offering a potential novel diagnostic and treatment approach."

Early-onset sleep alterations found in patients with amyotrophic lateral sclerosis are ameliorated by orexin antagonist in mouse models (no public access)