Category Archives: MSA

On June 22nd, the Lewy Body Dementia Association (lbda.org) hosted a good one-hour webinar on sleep problems in Lewy Body Dementia (LBD).  This post provides the Brain Support Network notes about the webinar.

Most of the webinar is of relevance to sleep issues in Multiple System Atrophy (MSA) as well.

The presenter, a sleep disorders neurologist at UCLA, addressed these topics:
* function of sleep
* how much sleep do we need
* obstructive sleep apnea (OSA)
* REM sleep behavior disorder (RBD)
* restless legs syndrome (RLS)
* insomnia
* conclusions about RBD and DLB

I was surprised that excessive daytime sleepiness was not addressed during the presentation. I suppose since the sponsoring pharmaceutical company is studying a drug for RBD, that was really the focus.

The highlight of the webinar was the question-and-answer session, which was well-facilitated by Angela Taylor of the LBDA. The questions were about:
* RLS and diabetic neuropathy
* excessive daytime sleepiness
* napping
* melatonin dosage
* neurodegenerative disease risk

Note that the presenter sometimes uses the term Dementia with Lewy Bodies.  “Lewy body dementia” is a term that includes both DLB and Parkinson’s Disease Dementia.

My detailed notes from the webinar (including the question-and-answer session) are below.

The presentation is here:
lbda.org/downloads/lbda-sleep-webinar-slides.pdf

The webinar recording is here:
youtube.com/watch?v=bnHQwduxGSA
(Note: there’s a problem with the slides for the first eight minutes or so.)

Robin

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Robin’s Notes from

LBDU Webinar: Sleep Issues in LBD
June 22, 2017

Presenter: Dr. Alon Y. Avidan, MD, MPH, Professor of Neurology, Director of the UCLA Sleep Disorders Center.

Theory that sleep is restorative. Memory is consolidated. If you don’t sleep well, your memory and cognitive abilities may decline.

Sleep is rejuvenative. Brain’s glymphatic system is most active during sleep. The brain “takes out the trash” while we sleep. Trash = byproducts and toxins. The function of the glymphatic system was only characterized in the last few years. Lack of good sleep puts the patient at risk for more disease and poor health.

14:13 Most adults need 7-8 hours. If less than 4 hours, you are putting yourself at risk for heart disease, depression, diabetes, and cardiovascular disease. Sleep needed varies by age groups. National Sleep Foundation recommends 7-9 hours for adults. Later, the American Academy of Sleep Medicine recommends 7-8 hours; less or more than that is not good. Healthy sleep duration is 7 hours or more each night (regularly). Good sleep on weekends is important.

Less than 7 hours/night regularly, puts you at risk for weight gain and obesity, diabetes, hypertension, heart disease, stroke, depression, increased risk of death, depressed immune function, increased pain, poor performance, increased risk, and increased accidents.

16:48 Sleep is often affected by aging process but it doesn’t have to be this way. As we age, we have more pain, more sleep apnea, more RLS, more comorbid disorders, and take more medications. Don’t be satisfied with 4-5 hours of sleep. Make an effort to improve sleep quality and duration.

OSA
18:10 Obstructive sleep apnea is affected by age, weight, alcohol. Alcohol can convert someone from simple snoring to sleep apnea. 20-80 times to stop breathing in one hour! CPAP therapy is gold-standard treatment.

RBD
20:20 This is the most important sleep disorder in those with LBD. REM sleep behavior disorder is a type of parasomnia (abnormal behavior in sleep). Muscles are supposed to be paralyzed when dreaming. In RBD, patients act out dreams. Concerns are self-injury or injury of bed partner. Incomplete transition from REM sleep to non-REM sleep (where you are nearly awake). REM sleep without atonia.

RBD is common in alpha-synucleinopathies (PD, DLB, MSA). RBD can present before the onset of neurodegenerative disease. Usually 2/3 of patients will develop neurodegenerative disease within 10 years.

Sleep neurologists should tell patients diagnosed with RBD that they are “at risk for dementia later in life.”

RBD is part of the diagnostic criteria for DLB.

Dreams in RBD are rarely pleasant.

26:10 Treatment focuses on safety: bedroom safe; remove hard/sharp objects; sleep in padded mattress; place mattress on floor; cover windows with heavy curtain; use pillow barricades. Until managed, sleep alone. Sleep in sleeping bag until treated. Medications: melatonin (he prefers because it’s the safesty; 5mg up to 15mg), clonazepam (.25 to .5mg; had side effects, such as grogginess).

RBD could be a window of opportunity in DLB. Nelotanserin clinical trial is ending at the end of June 2017. Lead institution is Mayo.

RLS
28:19 Restless legs syndrome. Urge to move the legs occur primarily in the evening. Many LBD patients have this condition. Very bothersome. Often physicians don’t know how to diagnose RLS. Symptoms get worse with inactivity. Difficult to relieve leg discomfort. Driving or flying long distances – especially difficult. Effective treatments available.

Insomnia
29:46 One-third of patients with neurodegenerative disease are affected by insomnia, particularly middle-of-the-night insomnia. Alcohol is not a good idea for insomnia. Get out of bed; avoid staying in bed awake. Talk to your MD about potential treatments.

30:40 Conclusions
* sleep disorder increases odds of DLB by 5x over Alzheimer’s
* RBD is strongest prognosticator of dementia, including DLB

Future research into RBD will focus on:
* benefit of exercise
* role of dietary factors (dairy products, saturated and animal fat, lower use of Mediterranean diet and of non-steroid drugs)
* role of melatonin as a neuroprotective agent
* establish guideline about agents that can help prevent phenoconversion from RBD to DLB

31:48 Notes from Question-and-Answer session:

Q: RLS and diabetic neuropathy
A: Common situation. The medication gabapentin can address both problems. Talk to a PCP. RLS diagnosis must be validated.

Q: Excessive daytime sleepiness is common. How do you know if sleepiness is excessive?
A: Well-validated measures of EDS to assess what is abnormal and what is not. Epworth Sleepiness Scale (ESS) can be used. You can find the scale online. Falling asleep immediately upon watching TV at any time of day, for example, is excessive.

Q: What is the maximum number of nap-time that will not disrupt nighttime sleep?
A: If “hours,” it’s already not good. Naps should be short (15-20 minutes) and strategic (1-3pm). Sleep is not like a bank account.

Q: What treatments are there for EDS?
A: Stimulants should not be the focus. We should use good sleep to give us energy. Exception to the “avoid medications” rule is narcolepsy, which is very rare. Shift workers or patients with sleep apnea who are still fatigued could be given stimulants. But I would never give someone with EDS a stimulant because this doesn’t address the problem of poor sleep. First find out what is causing the sleep disruption. One thing that can be helpful in treating LBD sleepiness is light. Light exposure, especially early in the day, is important. We don’t have good data on wake-promoting agents in LBD.

Q: Dosage of melatonin for LBD for sleep or RBD?
A: Melatonin for RBD – high-dose melatonin (3mg, increasing by 3mg every two weeks up to 12mg). We have good data on RBD. Could consider 5mg sustained release melatonin. This increases by 5mg every two weeks up to 15mg. If 12mg or 15mg don’t work, consider adding clonazepam. If that doesn’t work, look again into the cause of RBD. Often RBD is due to other substance patient is taking but forgot reporting initially to MD.

Low-dose melatonin (.5mg) – circadian rhythm problems. Middle-dose melatonin – insomnia.

Q: Is RLS or sleep apnea associated with neurodegenerative diseases?
A: No data whatsoever that RLS puts you at risk for neurodegenerative disease. Nor is it a prognosticator.

Untreated sleep apnea puts you at risk for accelerated neurodegeneration, if you already have a predisposition for development of Alzheimer’s.

Q: If you have RBD and receive treatment for it, can you reduce risk of neurodegenerative disease?
A: We don’t know. If you use clonazepam, you are probably not going to reduce risk of disease. We don’t know for sure about melatonin. Some believe that melatonin is neuroprotective. But patients taking melatonin don’t have slower progression towards neurodegeneration. Disease process isn’t reversed.

RBD is a great biomarker. This means that we can use it to test neuroprotective agents.

Angela Taylor, LBDA:
LBDA research page — lbda.org/participate-in-research

Enrollment for one RBD study has been extended.

The Lewy Body Dementia Association (lbda.org) is hosting a webinar this Thursday 6/22 at 11:30am California time on sleep issues in Lewy body dementia (LBD).  The content also applies to those in the multiple system atrophy (MSA) and Parkinson’s Disease (PD).

Sleep issues to be addressed by a UCLA sleep disorders specialist include REM sleep behavior disorder, daytime sleepiness, restless leg syndrome, insomnia, obstructive sleep apnea, and periodic limb movement.  There is no charge to attend.  Details below.

Updated, 6/23/17:  See our blog post of the notes from this webinar:

www.brainsupportnetwork.org/webinar-notes-sleep-issues-in-lbd-msa-and-pd/

Robin

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lbda.org/sleep

Webinar – Sleep Issues in LBD
Thursday, June 22, 2017
2:30 pm Eastern Time

Did you know that most people with LBD have at least one sleep disorder?
From REM sleep behavior disorder, which causes frightening dreams that sufferers often act out, to daytime sleepiness, restless leg syndrome, insomnia, obstructive sleep apnea, and periodic limb movement, those with LBD often have sleep issues that dramatically effect their quality of life and can lead sometime lead to injuries to themselves and others. In addition, the sleep disorders associated with LBD can begin years to decades earlier than other common LBD symptoms such as memory loss or confused thinking.

Join LBDU and Dr. Alon Y. Avidan, MD, MPH, Director of the UCLA Sleep Disorders Center for a free, informative webinar on sleep issues in Lewy Body Dementia.

Dr. Avidan will explain changes in sleep patterns with aging specific to Lewy Body Dementia. He also will share information about the management of LBD-related sleep disorders, as well as treatment strategies, ongoing research and clinical trials.

Presenter:
Dr. Alon Y. Avidan, MD, MPH
Professor of Neurology
Vice Chair Clinical and Educational Affairs
Department of Neurology
Director of the UCLA Sleep Disorders Center
David Geffen School of Medicine at UCLA

This article on last week’s Live Science (livescience.com) is about REM sleep behavior disorder (RBD), which is acting out dreams. This symptom in common in Parkinson’s Disease, Dementia with Lewy Bodies, and Multiple System Atrophy. The vast majority of those with RBD have one of these three disorders and often one of these neurological disorders comes to light years (or decades) after the first signs of RBD.

Here’s a link to the full article:
http://www.livescience.com/59300-brain-cells-linked-to-dreaming-found.html

Live Science
Health
Dreams and Brain Disease: REM Sleep Cells Linked to Disorders
By Tracy Staedter, Live Science Contributor
May 30, 2017 07:06pm ET

There’s been quite a bit published this year about those with “Pure Autonomic Failure” converting to Parkinson’s Disease (PD), Dementia with Lewy Bodies (DLB), or Multiple System Atrophy (MSA).  (All three disorders are alpha-synucleinopathies.)

PAF is a disorder of the autonomic system.  The autonomic system controls things that the body generally handles automatically such as blood pressure, heart rate, eye blink, body temperature, sweating, digestion, etc.

This article, published in February 2017, is authored by the Autonomic Disorders Consortium, a group made up of the key autonomic specialists in the US.

In this study of 74 subjects at five US medical centers (NYU, Vanderbilt, Mayo Rochester, NIH, and Harvard), about one-third (34%) developed DLB (n=13), PD (n=6), or MSA (n=6) over four years. Overall, 14% of people converted from PAF to one of the three alpha-synculein disorders each year.  Many of those who converted had REM sleep behavior disorder (RBD).

Other symptoms were associated with who got MSA, DLB, or PD:

* “Patients who phenoconverted to multiple system atrophy had younger age at onset of autonomic failure, severe bladder/bowel dysfunction, preserved olfaction, and a cardiac chronotropic response upon tilt > 10 beats per minute.”  The “younger age” was early 50s.  On average, those in the PAF group who converted to MSA had PAF symptoms for fewer than five years.

* “Those who phenoconverted to Parkinson disease or dementia with Lewy bodies had decreased olfaction, a lesser chronotropic response to tilt, and a longer duration of illness.”  “Longer duration of illness” refers to the fact that, on average, those in the PAF group who converted to PD or DLB had PAF symptoms for nearly ten years.

And:  “The small group of patients retaining the pure autonomic failure phenotype had very low plasma norepinephrine levels, slow resting heart rate, no REM sleep behavior disorder, and preserved smell.”

Here’s a link to the full article (available at no charge online):

www.ncbi.nlm.nih.gov/pmc/articles/PMC5323269/

The abstract is copied below.

Robin

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Annals of Neurology. 2017 Feb;81(2):287-297.

Natural history of pure autonomic failure: A United States prospective cohort.

Kaufmann H, Norcliffe-Kaufmann L, Palma JA, Biaggioni I, Low PA, Singer W, Goldstein DS, Peltier AC, Shibao CA, Gibbons CH, Freeman R, Robertson D; Autonomic Disorders Consortium.

Abstract
OBJECTIVE:
To define the clinical features and biomarkers that predict which patients with pure autonomic failure will develop Parkinson disease, dementia with Lewy bodies, or multiple system atrophy.

METHODS:
One hundred patients who presented with pure autonomic failure were recruited at 5 medical centers in the United States. Seventy-four patients agreed to be followed prospectively. Patients underwent clinical evaluations including neurological rating scales, sleep questionnaires, smell test, and sympathetic and parasympathetic cardiovascular autonomic function tests.

RESULTS:
At enrollment, patients were 68 ± 12 years old (median ± interquartile range) and had had autonomic failure for 5 ± 7 years. Within 4 years of follow-up, 25 of 74 subjects (34%) developed dementia with Lewy bodies (n = 13), Parkinson disease (n = 6), or multiple system atrophy (n = 6). The presence of probable rapid eye movement (REM) sleep behavior disorder was strongly associated with the development of a manifest central nervous system (CNS) synucleinopathy (odds ratio = 7.1). Patients who phenoconverted to multiple system atrophy had younger age at onset of autonomic failure, severe bladder/bowel dysfunction, preserved olfaction, and a cardiac chronotropic response upon tilt > 10 beats per minute. Those who phenoconverted to Parkinson disease or dementia with Lewy bodies had decreased olfaction, a lesser chronotropic response to tilt, and a longer duration of illness. The small group of patients retaining the pure autonomic failure phenotype had very low plasma norepinephrine levels, slow resting heart rate, no REM sleep behavior disorder, and preserved smell.

INTERPRETATION:
Patients presenting with pure autonomic failure are at high risk of phenoconverting to a manifest CNS synucleinopathy. Specific clinical features predict future diagnosis.

© 2017 American Neurological Association.

PMID: 28093795
www.ncbi.nlm.nih.gov/pubmed/28093795

We posted earlier this week about the Mayo Rochester research into lifespan for Parkinson’s Disease, Parkinson’s Disease Dementia, Dementia with Lewy Bodies, and Multiple System Atrophy, as compared to those without these disorders.

This is a good Alzforum explanation of the same research:

www.alzforum.org/news/research-news/synucleinopathy-how-long-you-live-depends-which-one-you-have

Here are a few excerpts from the Alzforum article:

* “Prior studies have reported survival rates for various parkinsonian disorders; however, most of these recruited from hospitals rather than the general population, and none compared α-synucleinopathies side by side.”

* David Irwin, University of Pennsylvania wrote to Alzforum:  “The comparison of survival…highlights the powerful effect of cognitive impairment and dementia to predict a poor prognosis across the PDD/DLB spectrum.  Further, there is limited data on the natural history of MSA, and this paper provides new insight into the relatively rapid progression of this disease.”

* “[Mayo Rochester researcher] Savica said his group has submitted one autopsy study for publication, and will expand on pathology in an upcoming project.”