People with Parkinson’s disease more often have bad dreams and nightmares

0
59

Every night when we go to sleep, we spend a couple of hours in a virtual world created by our brains in which we are the main protagonist of an unfolding story we did not consciously create. In other words, we dream.

For most people, dreams are mainly pleasant, sometimes negative, often bizarre, but rarely terrifying. That is, if they are remembered at all. Yet for about 5% of people, highly memorable and terrifying nightmares (bad dreams that make you wake up) happen on a weekly or even nightly basis.

Recent studies have shown that people with Parkinson’s disease have bad dreams and nightmares more often than people without the disease. Studies suggest that between 17% and 78% of people with Parkinson’s have nightmares weekly.

A study I conducted in 2021 found that people newly diagnosed with Parkinson’s who experience recurring dreams with “aggressive or action-packed” content, have more rapid disease progression in the years following their diagnosis, compared with those without aggressive dreams. As such, my study, alongside similar studies, strongly suggests that the dreams of people with Parkinson’s can predict future health outcomes.

This made me wonder, might the dreams of people who don’t have Parkinson’s predict future health outcomes, too? My latest study, published in The Lancet’s eClinicalMedicine journal, shows that they can. Specifically, it showed that developing frequent bad dreams or nightmares in older age could be an early warning sign of imminent Parkinson’s disease in otherwise healthy people.

I analyzed data from a large U.S. study that contained data over 12 years from 3,818 older men living independently. At the beginning of the study, the men completed a range of questionnaires, one of which included a question about bad dreams.

The participants who reported bad dreams at least once a week were then followed at the end of the study for an average of seven years to see whether they were more likely to be diagnosed with Parkinson’s.

During this period, 91 people were diagnosed with Parkinson’s. Those who reported having frequent bad dreams at the beginning of the study were twice as likely to develop Parkinson’s compared with those who had them less than weekly.

Intriguingly, a significant proportion of the diagnoses happened during the first five years of the study. During this period, the participants with frequent bad dreams were more than three times as likely to develop Parkinson’s disease.

Years before

These results suggest that older adults who will one day be diagnosed with Parkinson’s disease may start to experience bad dreams and nightmares a few years before developing the characteristic symptoms of Parkinson’s, including tremors, stiffness and slowness of movement.

The study also shows that our dreams can reveal important information about our brain structure and function and may prove to be an important target for neuroscience research.

However, it is important to highlight that only 16 of the 368 men with frequent bad dreams in this study developed Parkinson’s. Since Parkinson’s is a relatively rare condition, most people who have frequent bad dreams are unlikely to ever get the disease.

Still, for those who have other known Parkinson’s risk factors, such as excessive daytime sleepiness or constipation, the finding could be important. Being aware that frequent bad dreams and nightmares (particularly when they start suddenly in later life) may be an early indicator of Parkinson’s, could lead to earlier diagnoses and earlier treatment. One day, doctors may even be able to intervene to stop Parkinson’s disease from developing at all.

My team now plans to use electroencephalography (a technique to measure brainwaves) to look at the biological reasons for dream changes in people with Parkinson’s. This may help us identify treatments that could simultaneously treat bad dreams, and also slow down or prevent the onset of Parkinson’s in people at risk of developing the condition.


Parasomnias

NREM Parasomnias 

NREM parasomnias are undesired events characterized by an incomplete arousal from NREM sleep and include confusional arousals, sleepwalking, and sleep terrors (Table ​(Table3)3) (11). The prevalence of NREM parasomnias in PD is not clear. A questionnaire study on 661 PD patients showed that sleepwalking had a prevalence of 1.8% while night terrors 3.9% (81). In PD patients with RBD, the prevalence of NREM parasomnias (parasomnia overlap disorder) is higher, reaching respectively, 4.3 and 8.7% (81). Somnambulism in PD is associated with higher incidence of depression and advanced PD stage (82). Probably, the neurodegenerative changes of advanced PD influence not only the control of muscle tone but also the mechanisms of state transition (83).

Table 3

Diagnostic criteria for NREM parasomnias (International Classification of Sleep Disorders).

Criteria A–E must be met:
A – Recurrent episodes of incomplete awakening from sleep.
B – Inappropriate or absent responsiveness to efforts of others to intervene or redirect the person during the episode.
C – Limited (e.g., a single visual scene) or no associated cognition or dream imagery.
D – Partial or complete amnesia for the episode.
E – The disturbance is not better explained by another sleep disorder, mental disorder, medical condition, medication, or substance use.

The first approach to a patient with NREM parasomnias, independently of its causes, is to secure the bedroom in which the patient sleeps, closing and locking doors or windows, blocking stairways, and removing all potentially dangerous objects. It is also important to reduce all the possible precipitating and predisposing factors such as alcohol consumption, stress, fever, sleep deprivation, sleeping in unfamiliar or noise-exposed bedrooms. If present, it is necessary to treat OSA and reduce or withdraw psychotropic drugs such as phenothiazines, anticholinergic agents, and sedative/hypnotic agents (11). Clonazepam (CNZ) (0.25–2 mg at bedtime) is the first line pharmacologic treatment for NREM parasomnias in adults, but its efficacy has not been proved in randomized controlled trials (84–87). CNZ was effective in 90% of a series of 20 patients with parasomnia overlap disorder (88), but there are no studies in PD patients. Only four sleepwalkers were identified in a set of 165 PD patients. After a 2-year follow-up, two patients have had a spontaneous remission of sleepwalking, one patient responded to topiramate treatment (100 mg/day) and one patient showed a resolution of the episodes after clozapine treatment (25/mg die) (89).

REM Parasomnias

Nightmares 

Nightmares are vivid and unpleasant dreams recurring in REM sleep and causing awakening (Table ​(Table4)4) (11). Their prevalence in PD patients seems to be 17.2%, but these data are only based on questionnaires (81). Dream contents in PD patients seem to be different from controls in particular regarding violence, misfortune, and presence of animals. Some authors explain these contents in relation to the cognitive and frontal impairment of PD patients instead of therapy, mood disorders, hallucinations, and the presence of RBD (90). Traumatic events, stress, use of antidepressants, alpha-agonists, beta-blockers, and cholinergic antagonists are all predisposing and precipitating factors for nightmares (91).

Table 4

Diagnostic criteria for nightmares (International Classification of Sleep Disorders).

Criteria A–C must be met:

  1. Repeated occurrences of extended, extremely dysphoric, and well-remembered dreams that usually involve threats to survival, security, or physical integrity.
  2. On awakening from the dysphoric dreams, the person rapidly becomes oriented and alert.
  3. The dream experience, or the sleep disturbance produced by awakening from it, causes clinically significant distress or impairment in social, occupational, or other important areas of functioning as indicated by the report of at least one of the following:
    1. Mood disturbance (e.g., persistence of nightmare affect, anxiety, and dysphoria).
    2. Sleep resistance (e.g., bedtime anxiety, fear of sleep/subsequent nightmares).
    3. Cognitive impairments (e.g., intrusive nightmare imagery, impaired concentration, or memory).
    4. Negative impact on caregiver or family functioning (e.g., nighttime disruption).
    5. Behavioral problems (e.g., bedtime avoidance, fear of the dark).
    6. Daytime sleepiness.
    7. Fatigue or low energy.
    8. Impaired occupational or educational function.
    9. Impaired interpersonal/social function.

The first-line treatment for nightmares is cognitive behavioral therapy, in particular, the imagery rehearsal therapy (IRT), but these techniques have not been systematically tested in PD patients and need to be confirmed. A placebo-controlled study showed that prazosin (9.5 mg/at bedtime) reduced nightmares in 10 Vietnam veterans. Other studies proved prazosin efficacy, but its real effectiveness needs to be tested in larger placebo-controlled trials (92–95). Side effects such as orthostatic hypotension could discourage its use in PD patients.

REM Sleep Behavior Disorder 

REM sleep behavior disorder is a REM parasomnia characterized by complex, sometimes violent, and dangerous motor behaviors during which the patient acts out the content of his/her dream (Table ​(Table5)5) (11). RBD is present in 30% of patients with PD and often precedes the onset of motor symptoms (1). The association between PD and RBD may be explained considering the brainstem abnormalities in regions that control REM sleep such as the peduncle pontine nucleus and the laterodorsal tegmental nuclei, which are affected during Braak’s stages 1 and 2 (96). Independent of pharmacological therapy, in order to guarantee the patient and bed partner’s safety, securing the bedroom is necessary (Figure ​(Figure4)4) (97). It is also necessary to withdraw or reduce drugs potentially causing RBD, such as monoamine oxidase inhibitors, antidepressants, beta blockers (bisoprolol), opioids (tramadol), and centrally acting alpha-agonist hypotensive agents (clonidine) (98–108).

If RBD causes sleep disruption or if it influences the patient and bed partner’s safety, pharmacological treatment is indicated (97). CNZ, 0.25–2 mg 30 min prior to bedtime has been a first-line therapy for RBD (97). Several large case series proved the efficacy of CNZ in 87–90% RBD patients with or without PD, also if no randomized placebo-controlled studies have been performed (85, 109–111). Sedation and increased risk of fallings are CNZ possible side effects. CNZ is contraindicated in moderate and severe OSAS (85, 110, 112). The mechanism of action of CNZ is unknown.

Considering that it does not suppress REM sleep and it does not influence REM muscle tone, probably it could modify dream contents or inhibit brainstem locomotor pattern generators (113, 114). Recent studies proved that CNZ moderately increases total sleep time, sleep efficiency, NREM sleep stages (except stage 1), and decreases wake after sleep onset (WASO) (115). In PD patients in which CNZ is contraindicated (for example, patient with OSAS, cognitive impairment, and a high baseline risk of falling), melatonin (3–12 mg, before sleeping) could be the treatment of choice.

CNZ and melatonin appear comparably effective for RBD symptoms and injury prevention. Melatonin’s favorable safety and tolerability profile is very useful for patients receiving polytherapy and for neurologically impaired RBD patients who are more sensitive to adverse drugs effects (116, 117). A recent meta-analysis of randomized clinical trials suggested that exogenous melatonin, improving sleep quality in patients with neurodegenerative disorders can be considered as a possible mono or add-on therapy in patients with RBD (118).

Table 5

Diagnostic criteria for REM sleep behavior disorder (International Classification of Sleep Disorders).

Criteria A–D must be met:Repeated episodes of sleep-related vocalization and/or complex motor behaviors.These behaviors are documented by polysomnography to occur during REM sleep or, based on clinical history of dream enactment, are presumed to occur during REM sleep.Polysomnographic recording demonstrates REM sleep without atonia.The disturbance is not better explained by another sleep disorder, mental disorder, medication, or substance use.

An external file that holds a picture, illustration, etc.
Object name is fneur-08-00042-g004.jpg

Figure 4

Treatment algorithm for REM sleep behavior disorder.

Melatonin mechanisms of action are still not completely known, but its use seems to reduce RBD and decrease muscle tone during REM sleep. Side effects (morning headache, morning sleepiness, and delusions/hallucinations) are usually related to high doses (117, 119, 120). Pramipexole (0.2–1 mg/night), paroxetine (10–40 mg), donepezil (10–15 mg), and rivastigmine (4.5–6 mg) may be effective in some refractory cases, but the evidence of their efficacy is inconclusive due to the lack of randomized controlled trials (97, 121–123). Two studies have been carried out on rivastigmine.

Rivastigmine compared to placebo induced a reduction in the frequency of RBD episodes in a pilot placebo-controlled crossover trial on 25 patients with mild cognitive impairment (but without PD). Similar results have been found in a double-blind, crossover trial in 12 patients with PD and RBD resistant to CNZ and melatonin (124, 125). Very limited evidence has been reported for zopiclone, benzodiazepines other than CNZ, yi-gan san, desipramine, clozapine, carbamazepine, and sodium oxybate (97). Ramelteon was effective in RBD in PD patients in two recent open trials, conducted, respectively, in 24 and 12 PD patients, but these promising results could be confirmed in larger population and for longer follow-up. Daytime sleepiness, nausea, delirium, giddiness, and worsening of constipation are possible ramelteon side effects (40, 126).

reference link :https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5311042/


More information: Dr Abidemi I. Otaiku, Distressing dreams and risk of Parkinson’s disease: A population-based cohort study, eClinicalMedicine (2022). DOI: 10.1016/j.eclinm.2022.101474

LEAVE A REPLY

Please enter your comment!
Please enter your name here

Questo sito usa Akismet per ridurre lo spam. Scopri come i tuoi dati vengono elaborati.