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LBDA Issues Position Statement on Aducanumab

Key Highlights:

The FDA approved marketing of aducanumab for the treatment of Alzheimer’s disease under a special accelerated approval process.

Aducanumab has not yet been proven to slow the progression of Alzheimer’s disease or provide clinical benefit.

Dementia expertise is required to determine who may potentially benefit from aducanumab and who may be at greater risk for brain swelling and/or bleeding.

Clinical trials are needed in people with co-existing LBD and AD to determine if aducanumab is safe and effective for those with LBD.

The biggest dementia-related news this month was the Food and Drug Administration’s (FDA) decision to approve the marketing of Biogen’s aducanumab (brand name Aduhelm) for the treatment of Alzheimer’s disease (AD) under the “accelerated approval process.” Federal law allows the FDA to accelerate the approval of a drug intended for a serious disease, when it improves a measure of a disease and is “reasonably likely” that the measure predicts clinical benefit.

Aducanumab may have the potential to slow down progression of AD. This is the first FDA-approved drug that may be able to do more than just treat symptoms. This new treatment option may be a very important next step for treating people with Alzheimer’s disease.

The FDA decision was quite controversial, in part because research has not yet convincingly proven this treatment will slow down the progression of Alzheimer’s disease. What the studies did prove is that aducanumab shows dose-dependent effects on lowering amyloid plaque burden in the brain, a protein-related change in the brain of people with AD. As amyloid plaques are considered an important biological marker of AD, removal of amyloid was determined by the FDA to meet the requirement of a surrogate endpoint. Surrogate biomarkers are measurements that may predict positive clinical benefits. Removal of amyloid from the brain therefore might predict slowing of cognitive decline in Alzheimer’s.

Because the long-term benefit of aducanumab treatment has not been fully determined, the FDA has issued an approval that is contingent on Biogen carrying out additional studies to confirm that amyloid reduction is associated with clinically measured slowing of Alzheimer progression.

Relevance to Lewy Body Dementias

Research has shown that people with co-existing Lewy body dementia (LBD) and Alzheimer’s disease have a faster rate of progression and worse health outcomes. Studies of people with LBD who have come to autopsy support that most people with LBD have at least some Alzheimer’s changes in their brain. As such, aducanumab may offer some potential benefits to people with LBD. However, aducanumab has not been studied in LBD yet and we do not know whether it is effective or safe in people with LBD.

The Lewy Body Dementia Association is issuing this position statement to ensure the LBD community and healthcare professionals receive clear, expert guidance on aducanumab: People with LBD can have severe medication side effects that are not common in people with Alzheimer’s. As such, clinical trials are needed to determine if aducanumab is safe and effective in people with LBD who also have co-existing Alzheimer’s disease.

Considerations for Clinicians

The drug has only been studied in people with mild cognitive impairment due to Alzheimer’s disease and mild dementia due to Alzheimer’s disease.

Expert panelists on the Alzheimer’s Association’s recent 4-hour webinar, Dialogue: Current Perspectives on Aducanumab, emphasized that AD expertise is needed to determine if an individual is an appropriate candidate for this treatment.

Periodic MRIs reviewed by physicians trained and experienced in MRI scan interpretation is critical to monitor for brain inflammation, including brain swelling, bleeding or both, which may occur in up to 40% of individuals treated with aducanumab. It is not known what impact dose titration has on efficacy and side effects.

There may be major financial barriers to anyone being evaluated for and treated with aducanumab right now.

  • Pre-Treatment Testing: A person must first have to undergo tests to confirm they have biological signs of Alzheimer’s disease, via a lumbar puncture (“spinal tap”) or an amyloid PET scan. While Biogen is providing assistance to cover the cost of the measurement of amyloid following lumbar puncture, there will still be out of pocket costs to the patient. Measurement of amyloid with a PET scan would be entirely at the expense of the patient.
  • Treatment: If a person is determined to be eligible for treatment, the annual price of Aduhelm as reported by Biogen is $56,000, plus the cost of administering the infusion. Eventually insurers, including Medicare, will decide whether the drug and its associated diagnostic and monitoring tests should be covered.
  • Follow-Up Tests: Periodic safety monitoring with clinicians, MRI scans, etc., will also be necessary, and these costs also need to be considered.

Receiving aducanumab treatments may exclude people from participating in certain research studies.

Aducanumab Clinical Trials in LBD Needed

To be clear, LBDA strongly advocates for the study of aducanumab in individuals with LBD who have coexisting AD.  There are extremely important unanswered questions about safety and potential long-term benefits in LBD that must be answered. LBDA supports a network of experts in LBD through its Research Centers of Excellence Program. If there is a decision to conduct a study of aducanumab in LBD, LBDA and its Research Center of Excellence Program is prepared to participate in such a study.

In the meantime, LBDA is pleased to offer answers to some Frequently Asked Questions about aducanumab, what is known, and what is not known about its benefit to people with Alzheimer’s disease and other dementias.


Plan a Virtual Fundraising Event

Get Involved

Take action and get involved in the fight against Lewy body dementia.  You can host a meaningful event that all can attend to raise awareness and support individuals and families who are battling Lewy body dementia. Your efforts will ensure that LBDA will continue to provide vital support, up-to-the-minute education, and help push LBD research forward.

We encourage you to be creative with your event! Below are some ideas for your virtual fundraising event.

  • Host a virtual run/walk
  • Plan a virtual paint/craft party
  • Host a virtual cooking party
  • Plan a virtual game night

…the ideas don’t stop here! Have a unique idea for your own virtual event? Let us know and we will help you get started.

Get Started 

We are here to help you plan your own virtual fundraising event, or create your personal web page to raise support those affected by LBD.

Use FrontStream.com to create your personal web page. LBDA has partnered with FrontStream.com, a widely-trusted online service, to allow you to create your own web page to raise awareness and support. Once you create your web page, upload a photograph and share a special message with your family and friends so they can visit your page to see your progress and contribute to support your efforts.

Host a Virtual Run/Walk

Join the LBDA community of fundraisers and help LBDA do even more to provide valuable support and resources. Whether your goal is to raise $200 or $2,000 your efforts are going to make a major difference in the lives of many people. We have provided three easy steps to help you with your event:

Step 1 – Get Creative

Make your virtual event exciting and memorable by incorporating lives or pre-recorded videos for the event. Create your own hashtag for friends and family to share their participation during the event!

Step 2 – Get Others Involved

Share your event with friends and family. Ask them to share their pictures with your hashtag.

Share details of your event and encourage others to create their own teams. Using social media is also a quick and easy way to spread the word. Be sure to include information and links about how donations to LBDA can be made.

Create an account with frontstream.com, share your about why you want others to support LBDA, and provide family and friends with direct links to your page. Donations come straight to the organization, so you don’t have to worry about managing them.

Step 3 – Share Your Success

Let all your participants and donors know how their donations and efforts impact the lives of those affected by Lewy body dementia.

Tag us on Facebook in your photos and videos on Facebook or email them to us at specialevents@lbda.org. Photos may be shared on our social media pages.

Create your own unique hashtag and ask them to share their pictures using the tag.

Set up a live video or zoom call for your event. Share the link to the live call on your FrontStream.com page.

Thank you for considering hosting a virtual fundraising event to benefit LBDA.


LBD and Coronavirus: Prevention is the Best Medicine

LBDA Corona prevention Logo
With all of the news about the coronavirus and the condition “COVID-19,” here are some things that LBD families should keep in mind in the coming weeks and months.

  • This is a rapidly evolving situation; visit the U.S. Centers for Disease Control (CDC) website for the most up-to-date information.
  • Older adults and those with serious, chronic health conditions are at increased risk for getting very sick from this illness. Some people with LBD fall into both categories, so it is especially important to reduce the risk of exposure for some people with LBD. For more information, visit the CDC website for information for people who are at higher risk.
  • According to the CDC, the best way to prevent illness is to avoid being exposed to this virus. Here are steps you can take to protect yourself:
    • Clean your hands often: Wash your hands often with soap and water for at least 20 seconds especially after you have been in a public place, or after blowing your nose, coughing, or sneezing. If soap and water are not readily available, use a hand sanitizer that contains at least 60% alcohol. Cover all surfaces of your hands and rub them together until they feel dry.
    • Avoid close contact: Avoid close contact with people who are sick. Put distance between yourself and other people if COVID-19 is spreading in your community
  • In consultation with several LBD experts, here are some additional things LBD families should consider to reduce possible exposure:
    • People with Lewy body dementia may have a harder time understanding public health messages about coronavirus. Instructions to reduce risks, such as self-isolation or handwashing, may be more difficult for them to follow. Care partners can help by staying calm, providing reassurance, and providing help to reduce exposure risks.
    • Be understanding of any limitations placed on visits to long term care facilities. Limits may be put in place to minimize the risk to all residents who are at a heightened risk from the virus.
    • Minimize in-person attendance for medical appointments. Contact your physician’s office to see if the appointment can be done by phone or video. If you have questions whether or not to come in for an appointment, contact your doctor’s office.
    • If you are in a research study, schedules for study visits may be disrupted; study coordinators may contact participants regarding upcoming visits. If you have concerns or questions about attending an upcoming appointment, contact the study coordinator.

For our Support Services Volunteers/Support Group Facilitators: Many of you meet in senior facilities/healthcare locations and have already had your meetings cancelled. We are recommending cancelling your in-person meetings and consider meeting via phone/video conferencing if possible. There are a few free options for you to use such as freeconferencecall.com. Contact LBDA’s Support Services if you have any questions/concerns about providing support to your members during this time.


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The importance of early treatment is supported by recent data suggesting that patients with LBD, might respond better to cholinesterase inhibitors than patients with AD. In addition, an early diagnosis of DLB will help treating physicians know which medications to avoid or use cautiously, especially the antipsychotics (aka neuroleptics).

IMPORTANT NOTE: It is estimated that a high percentage of DLB patients exhibit worsening parkinsonism, sedation, immobility, or even neuroleptic malignant syndrome (NMS) after exposure to antipsychotics. NMS is a rare, life-threatening medical emergency characterized by fever, generalized rigidity, and breakdown of muscle tissue that can cause renal failure and death. The heightened risk of NMS in DLB mandates that typical or traditional antipsychotics (such as haloperidol, fluphenazine. or thioridazine) should be avoided. Atypical antipsychotics have been available for treating mental illness for 25 years and may be safer to use in patients with DLB, but only with extreme caution. Patients with PDD appear to have a lower risk of an adverse reaction to antipsychotics, but all patients with LBD should be carefully managed with any antipsychotic drug.

Goals of Care

Comprehensive, palliative management of LBD should begin at diagnosis to promote the best quality of life for the person with LBD and the family and caregivers. An early, wide-ranging discussion of symptoms and goals of treatment will proactively inform both the provider and the primary family care partner about important future decisions.

The goals of care may change as the illness progresses due to emerging or evolving issues of safety, caregiver burden, or comorbid illness. An ongoing dialogue between the healthcare providers, patient and family about management, especially in regard to later, end-of life decisions, should occur regularly throughout the course of the illness.

First-Line Medications

Cognitive impairment and fluctuations

Acetylcholinesterase inhibitors (AChEIs): AChEIs are the current standard of care for treating cognitive and psychiatric symptoms of LBD. Three have been approved by the FDA for treatment of AD; donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne). Rivastigmine is the only one of the three that is FDA-approved for treating LBD, specifically PDD. The other two are used “off label.” There is no compelling evidence that any one of the three is superior to the other two in treating LBD1.

AChEIs are generally well-tolerated by patients with LBD, but not always. For example, in a study of rivastigmine in PDD, approximately 10% of patients experienced worsening of tremor, but it was not usually clinically significant.Healthcare providers and patients/caregivers must always be on guard for the development of adverse effects of any drug.

Memantine (Namenda) is another drug (with a different pharmacological mechanism of action) approved for AD but not LBD and is also used off label as an add-on therapy to AChEIs, typically in patients with more severe dementia. Only a few studies of memantine have been done in LBD, with mixed results.3,4


Levodopa is an effective and relatively safe drug for treating motor symptoms in PD; most patients with LBD respond with improvement in motor function, without side effects, as long as the dosing is kept at the lowest, most effective level.However, all patients with LBD are vulnerable to the development of medication-induced behavioral or psychotic symptoms. Not everyone with LBD requires anti-parkinsonian treatment, particularly those with DLB. In fact, some patients with DLB may go years before showing signs of parkinsonism. Given the potential for adverse effects, healthcare providers should use levodopa in this setting only when symptoms are truly bothersome and should start with a low dose and titrate up slowly.

Dopamine agonists are less effective than levodopa for treating motor symptoms and are more likely to cause non-motor side effects, especially drug-induced psychosis even at low doses. Dopamine agonists may also cause excessive daytime sleepiness and swelling of the legs. Other PD medications such as amantadine, COMT inhibitors, MAO inhibitors, and anticholinergics, likewise, can induce psychosis and exacerbate cognitive impairment and should be avoided in DLB. Furthermore, dementia is a contraindication to deep brain stimulation, even when the patient is an otherwise good candidate.6,7

Behavioral changes

The overarching goal of managing psychotic and behavioral disturbances in LBD is to improve outcome without compromising safety of the patient and others. If hallucinations (usually visual) are not frightening to the patient, even if they are considered bothersome by the family, treatment with a drug may not be needed, especially if the patient understands that the hallucinations are not real. On the other hand, delusions (a false belief held with strong conviction despite evidence to the contrary), are often socially disruptive and in most cases, should be treated, most productively by a mental health professional.

The first line intervention should be non-pharmacologic measures including evaluation for acute physical ailments that may be provoking behavioral disturbances (e.g., fecal impaction, pain, decubitus ulcers, urinary tract infection and other febrile illnesses). Medications that can potentially cause agitation, especially those with anticholinergic properties, including amantadine, certain antidepressants, and those antihistamines with significant anticholinergic effects should be reviewed for need and stopped if possible. It may be necessary to reduce or discontinue all PD medications other than low dose levodopa.

Although little evidence exists to guide specific pharmacotherapy for hallucinations and behavioral symptoms in LBD, the following background literature review should be helpful.

AChEI for behavioral symptoms

Deficits in the brain’s supply of the neurotransmitter acetylcholine probably contribute to cognitive impairment and psychosis in LBD. Visual hallucinations may predict a favorable response to treatment with an AChEI. By comparison, a meta-analysis of 6 large trials in AD, which also causes depletion of acetylcholine in the brain, showed a small but significant benefit of AChEI treatment in decreasing neuropsychiatric symptoms. Moreover, AChEIs may selectively ameliorate psychosis and anxiety compared with other psychiatric symptoms.

A few published reports have shown behavioral improvement in patients with LBD treated with the AChEI rivastigmine. In a large multicenter trial, rivastigmine resulted in improvement by 30% from baseline in psychiatric symptoms.8 In a comparator study of rivastigmine in patients with clinical diagnoses of DLB and AD, treatment was associated with improvement in hallucinations, anxiety, and sleep disturbances only in the DLB group.9

Behavioral medications to avoid:
  • Typical antipsychotics (neuroleptics) should always be avoided in the management of patients with LBD, especially DLB, who risk severe worsening of all symptoms, and, as mentioned above, may develop potentially fatal NMS.10
  • Atypical antipsychotics, especially those with high D2 receptor antagonism (such as olanzapine and risperidone), should also be avoided due to the risk of severe neuroleptic sensitivity reactions,  neuroleptic malignant syndrome, worsening parkinsonism, somnolence and orthostatic hypotension.11,12 Quetiapine and clozapine are two from this class of drugs that have been shown to be well tolerated in low doses for treatment of psychosis (see below).
  • Benzodiazepines and benzodiazepine-like sedative hypnotic medications (such as zolpidem) should not be first-line agents given their risk of sedation and paradoxical agitation. (One exception is clonazepam at night for management of REM sleep behavior disorder.)
  • Opiates or tramadol should be avoided; alternatives for pain management include nonsteroidal anti-inflammatory agents and acetaminophen.
Atypical Antipsychotics

If long-term treatment with AChEIs is ineffective, or more acute symptom control of behavior is required, it may be difficult to avoid a cautious trial of an atypical antipsychotic. When medications are needed to modify behaviors, they should be used for the shortest duration possible.

Quetiapine and clozapine are preferred when psychosis warrants drug treatment. Clozapine has been demonstrated to be effective for PD psychosis in several randomized clinical trials. However, due to the infrequent but serious risk of potentially fatal agranulocytosis (severe depression of white blood cells), and the corresponding need for intrusively frequent blood monitoring to prevent such a reaction, clozapine is not the drug of first choice. Quetiapine is a safer alternative atypical antipsychotic in PDD and DLB, typically in the dose range of 6.25 mg to 50 mg a day, although higher doses may be used if tolerated and necessary. As with any drug in this setting the low slow approach is required. Pimavanserin, now FDA-approved for the treatment of psychosis in PD13, has not yet been studied in DLB.

Black box warning: The FDA’s ‘black box warning’ indicates both typical and atypical antipsychotics are associated with an increased risk of mortality and morbidity in elderly patients with dementia-related psychosis. However, if used carefully according to the guidelines mentioned above, the risk of mortality is extremely low. Physicians should discuss the risks and benefits of these types of medications, so that patients with LBD and caregivers can weigh the impact of the symptoms against the potential risks associated with these medications.

Non-pharmacological methods to managing behavioral changes

Refer to LBDA’s publication, Understanding Behavioral Changes in Dementia, which can be downloaded at https://lbda.org/content/understanding-behavioral-changes-dementia

Emergency room treatment of psychosis

Refer to LBDA’s publication, Emergency Room Treatment of Psychosis, which can be downloaded at https://lbda.org/go/er

REM Sleep Behavior Disorder and Insomnia

 Melatonin is a safe, over-the-counter natural substance that may also offer benefit either as monotherapy without risk or in conjunction with clonazepam. Prescription medications may be prescribed.

For insomnia, treatment can be attempted with antidepressants, low doses of benzodiazepines or specific sedative-hypnotic agents. These medications have not been extensively studied in LBD, and worsening confusion and daytime sedation is a potential side effect of sedative-hypnotics.

Autonomic Dysfunction

Orthostatic hypotension (drop in blood pressure) is a common manifestation of LBD, often presenting as lightheadedness or fainting, mainly when standing. Initial management consists of simple measures such as arising slowly from a reclining or seated position, leg elevation when sitting, elastic stockings, increasing salt and fluid intake, and if possible avoiding medications that are known to exacerbate orthostasis. If simple measures fail, medications can be used.

Medications with anticholinergic activity can be used to treat urinary urgency, frequency and urge incontinence. They should be used cautiously however, given their risk of exacerbating cognitive problems because of their anticholinergic properties.

Constipation can usually be treated by exercise and modifications of the daily diet to include foods with high fiber content (fruits and vegetables) and bran cereal. Laxatives, stool softeners and mechanical disimpaction may be needed.

Erectile dysfunction (ED), loss of libido and impotence in LBD is likely multifactorial. While autonomic dysfunction is a possible cause, other factors often contribute, such as depression, poor bed mobility, pain and co-morbid illnesses. Treatment can be complex, requiring a urologic and/or psychiatric consultation. Medications for ED include three inhibitors of phosphodiesterase-5 (sildenafil, tadalfil, and vardenafil), the natural substance yohimbine, or the intracavernal injectables phentolamine and prostaglandid E. If immobility in bed is a major problem, a bedtime dose of levodopa is worth a try. If mood disturbances are associated with sexual dysfunction, psychotherapy or a trial of an antidepressant can be considered, although antidepressants often cause ED.

Other Drugs to Avoid

  • Anticholinergics, as mentioned above, may worsen cognitive impairment, confusion, and hallucinations.
  • Benzodiazepines are best avoided unless specifically indicated, given their risk of sedation, increasing risk of falls, worsening cognition, and potentially paradoxical agitation.
  • Inhaled anesthetics should be avoided when possible to minimize delirium and a decrease in functional ability.
  • OTC sleep agents such as Tylenol or Advil PM and bladder-control medications may cause agitation. Many of these drugs contain diphenhydramine, an antihistamine with anticholinergic effects.

1. Bhasin, M., Rowan, E., Edwards, K. & McKeith, I. Cholinesterase inhibitors in dementia with Lewy bodies—a comparative analysis. Int. J. Geriatr. Psychiatry 22, 890–895 (2007).
2. Emre, M. et al. Rivastigmine for dementia associated with Parkinson’s disease. N. Engl. J. Med. 351, 2509– 2518 (2004).
3. Wang, H.-F. et al. Efficacy and safety of cholinesterase inhibitors and memantine in cognitive impairment in Parkinson’s disease, Parkinson’s disease dementia, and dementia with Lewy bodies: systematic review with meta-analysis and trial sequential analysis. J. Neurol. Neurosurg. Psychiatry 86, 135–143 (2015).
4. Stinton, C. et al. Pharmacological management of Lewy body dementia: a systematic review and metaanalysis. Am. J. Psychiatry 172, 731–742 (2015).
5. Goldman, J. G., Goetz, C. G., Brandabur, M., Sanfilippo, M. & Stebbins, G. T. Effects of dopaminergic medications on psychosis and motor function in dementia with Lewy bodies. Mov. Disord. 23, 2248–2250 (2008).
6. Rothlind, J. C. et al. Neuropsychological changes following deep brain stimulation surgery for Parkinson’s disease: comparisons of treatment at pallidal and subthalamic targets versus best medical therapy. J. Neurol. Neurosurg. Psychiatry 86, 622–629 (2015).
7. Weaver, F. M. et al. Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. JAMA 301, 63–73 (2009).
8. McKeith, I. et al. Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study. Lancet 356, 2031–2036 (2000).
9. Rozzini, L. et al. Cognitive and psychopathologic response to rivastigmine in dementia with Lewy bodies compared to Alzheimer’s disease: a case control study. Am. J. Alzheimers Dis. Other Demen. 22, 42–47 (2007).
10. McKeith, I., Fairbairn, A., Perry, R., Thompson, P. & Perry, E. Neuroleptic sensitivity in patients with senile dementia of Lewy body type. BMJ 305, 673–678 (1992).
11. Walker, Z. et al. Olanzapine in dementia with Lewy bodies: a clinical study. Int. J. Geriatr. Psychiatry 14, 459–466 (1999).
12. Culo, S. et al. Treating neuropsychiatric symptoms in dementia with Lewy bodies: a randomized controlled-trial. Alzheimer Dis. Assoc. Disord. 24, 360–364 (2010).
13. Cummings, J. et al. Pimavanserin for patients with Parkinson’s disease psychosis: a randomised, placebocontrolled phase 3 trial. The Lancet 383, 533–540 (2014).
14. Aurora, R. N. et al. Best practice guide for the treatment of REM sleep behavior disorder (RBD). J. Clin. Sleep Med. JCSM Off. Publ. Am. Acad. Sleep Med. 6, 85–95 (2010).


LBD has variable presentations that include cognitive difficulties associated with motor dysfunction, perceptual disturbances, and/or sleep/wake cycle alterations.


Cognitive impairment in DLB is often misdiagnosed as AD. While memory may be relatively intact in early DLB, the cognitive profile of DLB includes:

  • Early and significant deficits in executive function, such as impaired planning, problem solving and judgment.
  • Visuospatial dysfunction, resulting in difficulty recognizing familiar people or objects, problems with depth perception, or impaired hand-eye coordination.
  • Reduced attention or ability to concentrate, which may mimic memory deficits.
  • Slowed thinking (bradyphrenia) and speech difficulties may also occur.
  • Fluctuating cognition is common and refers to changes in levels of attention, concentration and functional ability. Fluctuations may present as staring spells or confusion that lasts from minutes to hours. Transient episodes of unresponsiveness may also occur.

Mild cognitive impairment or unexplained delirium may be the earliest signs of impending LBD.


The onset timing of spontaneous parkinsonism in LBD varies and may be subtle at first. Signs and symptoms include:

  • Reduced facial expression (masked facies)
  • Soft voice (hypophonia)
  • Stiffness (rigidity)
  • Postural instability
  • Gait difficulty and falls
  • Slowness of movement (bradykinesia)
  • Tremor at rest


Recurrent visual hallucinations occur in up to 80% of people with LBD, and their appearance early in the course of dementia strongly suggests LBD3. People with LBD frequently report seeing people, animals or insects and can often describe them in great detail. Delusions are also common and may relate to visual hallucinations. Apathy, anxiety and depressive symptoms and signs are also frequently seen in LBD patients. Unfortunately, a severe sensitivity to antipsychotics is also a common symptom of LBD.


REM sleep behavior disorder (RBD) may present years or even decades before other signs of LBD. RBD results from the absence of sleep paralysis that normally occurs during REM sleep, leading people to physically move about in their dreams. Patients may experience vivid nightmares and can shout, thrash, punch or kick during their dreams, sometimes injuring themselves or their bed partners. Idiopathic RBD is highly associated with the development of Lewy body disorders, both DLB and PD, but not AD.
Other sleep disorders include excessive daytime sleepiness, restless leg syndrome, insomnia, obstructive sleep apnea and periodic limb movement. A formal sleep study and treatment is recommended to resolve significant disruptions of sleep.


Severe autonomic dysfunction may occur in LBD, including orthostatic hypotension (a form of low blood pressure that happens when standing after sitting or lying down), syncope (fainting), erectile dysfunction, urinary incontinence and constipation. Other signs of autonomic dysfunction include excessive saliva and drooling (sialorrhea), altered sweating and a chronic, scaly skin condition (seborrhea). An impaired sense of smell (hyposmia) is also common, occurring earlier in LBD than in AD.

About LBD

The LBD Spectrum

Lewy body dementia (LBD) is a brain disease characterized by a spectrum of symptoms involving disturbances of movement, cognition, behavior, sleep and autonomic function. Two related clinical disorders make up the LBD spectrum: dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD).
Individuals with DLB present with dementia as the early disabling symptom, plus other LBD symptoms, one of which may be parkinsonism. Others will present with motor symptoms resulting in a diagnosis of Parkinson’s disease (PD) and may also have some mild cognitive impairment initially or in the early stages of the disease; over time, usually several years or more, some will progress to dementia (PDD).
Did you know?  LBD affects an estimated 1.4 million Americans. LBD is often misdiagnosed as a psychiatric disorder or another form of dementia.

Dementia with Lewy Bodies

DLB is the second most common form of degenerative dementia in the elderly next to Alzheimer’s disease (AD). Recent estimates suggest that DLB represents 4 to 16% of cases of dementia seen in the clinic,1 but the true prevalence is probably higher.2 The most common features of DLB are progressive cognitive impairment leading eventually to full-blown dementia, parkinsonian motor symptoms (tremor, slowed mobility, stiffness of muscles, stooped posture, shuffling gait), visual hallucinations, and fluctuations in levels of alertness and cognitive acuity. Other symptoms include acting out dreams (REM sleep behavior disorder) and disturbances of autonomic function (low blood pressure, constipation and urinary frequency).3 Severe sensitivity or over-reaction to antipsychotic drugs (aka neuroleptics) are also common.
DLB is often misdiagnosed as AD, especially in those individuals who have few, if any signs of motor parkinsonism.4 Diagnosis is challenging because the order of symptom appearance, their relative severity and the combination of features present varies among individuals.5

Parkinson’s Disease Dementia

PD is a common movement disorder that affects 1 in 100 individuals over the age of 60 and 4-5% of adults over age 85 (up to 1 million Americans).5,6 Original descriptions of PD in the medical literature did not recognize cognitive problems as an important clinical feature. More recently, clinicians have come to realize that PDD occurs often and is among the most debilitating symptoms associated with disease progression. Each year an estimated 14% of PD patients over age 65 will develop at least mild dementia. In one study, almost 80% of PD patients developed dementia over an 8-year period.7,8

Cause and Pathology

The cause of LBD is unknown. Brain pathological changes in LBD involve selective damage and loss of nerve cells in certain regions of the brain (example: substantia nigra in the brainstem). Affected, but less damaged cells contain Lewy bodies, which are a microscopic aggregation of a specific protein (α-synuclein). The Lewy body is the pathological signature of LBD that overwhelms the cell’s normal biological functions and causes it to die.9 There are many possible causes of LBD but researchers are just beginning to understand the reasons why some people are more susceptible to developing LBD. One important reason that has recently come to light is the discovery of an increasing number of genetic variants that increase the likelihood that a person will develop LBD.
DLB and PDD are clinically similar, except for the timing of onset of cognitive impairment, but the pathology of the two is almost identical. This is both a surprise and a mystery, since there is no good explanation for the variability of the motor-cognitive interval among people with LBD. In other words, why do some people develop serious cognitive impairment at the earliest stage of a Lewy body disorder, whereas others remain cognitively normal for many years before impairment develops or never develop dementia?
Another puzzling fact is the frequent coexistence of the pathology of AD (amyloid plaques and neurofibrillary tangles) in DLB compared with PDD. AD differs from LBD clinically because of its distinctive cognitive profile (mostly a disorder of memory without the other features typical of LBD) and its lack of parkinsonian features except in late stages. The clinical overlap between AD and DLB in the absence of a specific diagnostic test leads to misdiagnosis in a significant minority of patients. Currently, the only way to definitively diagnose LBD is with an autopsy. These facts underscore the current concept of a neurodegenerative continuum with boundaries that are frequently blurred. It is only through research that these and other fundamental questions will be answered.

Risk Factors

Older age is the greatest risk factor for LBD, with most diagnoses being made in individuals over the age of 50. There is some evidence that the age of onset of the symptoms of DLB is younger than in PDD and the rate of progression/duration of disease is slightly faster in DLB.10
 Rapid eye movement (REM) sleep behavior disorder (RBD), a condition characterized by dream enactment, is a common risk factor for DLB, PD and other synucleinopathies, often occurring many years before the onset of parkinsonism or cognitive impairment.11 Pre-Parkinson’s RBD is thought to increase the risk of cognitive impairment when the motor phase of PD evolves, compared with PD that has no RBD prodrome.
Parkinson’s disease is a risk factor for developing dementia, since the majority of those with PD will eventually suffer from cognitive impairment


Mutations in over a dozen genes have been shown to “cause” PD.12,13 Individuals with such rare genetic variants have a very high risk of developing PD during their lifetime, and many of them will later develop dementia. Mutations in one of these genes (SNCA) can occasionally result in a clinical picture that resembles DLB.14 However, no more than 2% of patients with PD, and likely even fewer with DLB, carry a disease-causing mutation in a known gene. In most instances PD and DLB are thought to arise through a complex interaction between common genetic and environmental factors, each one with a small-to-modest effect. Two important common genetic risk factors that have recently come to light are variants in the APOE and GBA genes. The APOE ε4 allele has long been known to increase the risk of developing AD, but there is now strong evidence that it does the same for DLB.15,16 Furthermore, patients with PD who carry APOE ε4 have (on average) more severe cognitive problems.17 A number of variants in the GBA gene have been shown to increase risk for both PD and DLB.18–20 In addition, patients with PD who have one of these GBA variants have a more rapid cognitive decline and are more likely to develop dementia.21,22
Since mutations that cause LBD are rare, and no treatments have been discovered to reverse the effects of known genetic risk factors, genetic testing is not currently recommended for routine screening.
However, if a family has multiple individuals with PD (with or without dementia) and/or DLB, it is reasonable to consider genetic testing for some or all of the known genes. The rationale for considering such testing would be to (1) confirm a diagnosis and (2) provide genetic counseling for family members, if the results are positive. These decisions need to be made carefully with family members and the individual’s healthcare provider. It is prudent to undergo pre- and post-testing counseling so that the individual fully understands the risks and benefits of learning about their genetic status. In addition, certain research centers at academic institutions and the National Institutes of Health are investigating genetic risk and are actively seeking people who would like to volunteer as research subjects.


In 2013, the National Institutes of Health organized a summit that resulted in the first national research strategy for LBD. Updated in 2016,23 research priorities for LBD include:

  • Developing new drugs for clinical trials.
  • Establishing longitudinal studies culminating in autopsy studies to improve diagnosis of DLB.
  • Determining which individuals with PD have a high risk of progressing to dementia.
  • Developing a better understanding of the disease mechanisms through brain mapping and genetics.
  • Identifying validated biological and imaging biomarkers to detect disease presence, measure progression and advance the development of safe and effective symptomatic and disease modifying therapies.

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