Tag: Featured

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 by planning a Virtual Fundraising Event!
We are in this together! Putting our hearts and minds together we can still create fun, meaningful ways to raise awareness and support individuals and families who are battling with Lewy body dementia.

We encourage you to be creative with your event, below are some ideas of a few ways you may host a virtual event.

  • Host a Virtual Run/Walk
  • Plan a Virtual Paint/Craft Party
  • Host a Virtual Cooking Party

…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!

Below are steps to help you here to get information on hosting a Virtual Event.
We are here to help you plan your own virtual fundraising event, or simply create your personal Web page to raise support for families affected by LBD.

Use FrontStream.com to create your personal Web page to raise support and awareness about Lewy body dementia. LBDA has partnered with FrontStream.com, a long-established, widely trusted online service, to allow you to create your own, personalized web page to raise awareness and support for the cause.

Once you create your personal web page, you can upload a photograph and share a special message with your family and friends that will appear on your web page. Family and friends can visit your page to see your progress and contribute to support your efforts and the cause.

Contact Us Today for Additional Information! You will work one-on-one with a representative from LBDA who will answer all your questions and help ensure the success of your event! Email us at specialevents@lbda.org

Host a Virtual Run/Walk

Thank you for choosing to raise awareness and participate in a fundraiser for LBDA. You are helping thousands of individuals and their families receive 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/Walk 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.

Promote
Share details of your event with friend and family and encourage them to create their own teams. Social Media is also a quick and easy way to spread the word. Be sure to include information and links on how donations can be made.

Donate
LBDA uses Firstgiving, a free and easy tool for you to manage your fundraising efforts. Simply create an account, share your mission, and provide family and friends with direct links to your page for them to show their support. Donations come straight to the organization, so you don’t have to worry about managing the donations. Click here to get started.

Step 3 – Share Your Success

Let all your participants and donors know how their donations and efforts impacted your event.

Don’t forget, we want to see all the fun too! 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.

Plan a Virtual Paint/Craft Party

Thank you for choosing to raise awareness and participate in a fundraiser for LBDA. You are helping thousands of individuals and their families receive 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 – Pick a Paint Kit or Craft Project

Get creative! Choose a paint/craft project that you would like your participants to create. Add suggested paint colors or supplies that will be needed to complete the project

Step 2 – Get Others Involved

Share your event with friends and family. Create your own unique hashtag and ask them to share their pictures with your hashtag!

Promote
Share details of your event with friend and family and encourage them to participate. Social Media is also a quick and easy way to spread the word. Be sure to include information and links on how donations can be made.

Donate
LBDA uses Firstgiving, a free and easy tool for you to manage your fundraising efforts. Simply create an account, share your mission, and provide family and friends with direct links to your page for them to show their support. Donations come straight to the organization, so you don’t have to worry about managing the donations. Click here to get started.

Step 3 – Live Video/Zoom

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

Step 4 – Share Your Success

Let all your participants and donors know how their donations and efforts impacted your event.
Don’t forget, we want to see all the fun too! 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.

Host a Virtual Cooking Party

Join with family members, friends or colleagues from any location for a virtual cooking class in your home kitchen!
Thank you for choosing to raise awareness and participate in a fundraiser for LBDA. You are helping thousands of individuals and their families receive 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 – Chose a Menu

Chose a menu of dishes or one simple recipe with an adaptable ingredient list. Share a shopping and equipment list with your attendees.

Step 2 – Get Others Involved

Share your event with friends and family. Create your own unique hashtag and ask them to share their pictures with your hashtag!

Promote
Share details of your event with friend and family and encourage them to participate. Social Media is also a quick and easy way to spread the word. Be sure to include information and links on how donations can be made.

Donate
LBDA uses Firstgiving, a free and easy tool for you to manage your fundraising efforts. Simply create an account, share your mission, and provide family and friends with direct links to your page for them to show their support. Donations come straight to the organization, so you don’t have to worry about managing the donations. Click here to get started.

Step 3 – Live Video/Zoom

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

Step 4 – Share Your Success

Let all your participants and donors know how their donations and efforts impacted your event. Don’t forget, we want to see all the fun too! 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.

ACADIA Pharmaceuticals Submits Supplemental New Drug Application to U.S. FDA

ACADIA Pharmaceuticals has submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) to support a potential new indication for NUPLAZID® (pimavanserin) for the treatment of hallucinations and delusions associated with dementia-related psychosis (DRP). The FDA previously granted Breakthrough Therapy Designation for pimavanserin for the treatment of hallucinations and delusions associated with DRP.
The submission was based on positive results from the Phase 3 HARMONY study which showed a statistically significant 2.8 fold reduction in the risk of relapse of psychosis.
NUPLAZID was approved in the U.S. in 2016 as the first and only treatment for hallucinations and delusions associated with Parkinson’s disease psychosis. If approved by the FDA, NUPLAZID would be the first drug approved to treat the hallucinations and delusions associated with dementia-related psychosis.
Read the full press release from ACADIA Pharmaceuticals.

New Research Definition of Mild Cognitive Impairment with Lewy bodies (MCI-LB)

Most people with Lewy body dementia (LBD) will experience mild changes in thinking; over time, these symptoms, referred to as mild cognitive impairment (MCI), worsen and may become dementia. As the understanding of LBD has grown, people in this pre-dementia stage are being included in research studies.

LBD is an umbrella term for two related disorders: dementia with Lewy bodies (DLB) and Parkinson’s disease dementia. Although MCI in Alzheimer’s disease and Parkinson’s disease have both been well-described for some time, defining MCI in DLB has not been formally defined. A global panel of experts in DLB has just published the first formal research criteria to aid in the study of the MCI stage of DLB, referred to as MCI with Lewy bodies (MCI-LB).

The authors also outline two lesser-known, but potentially important patterns of DLB onset that need further study. For some people the earliest sign of possible DLB is a sudden onset of confusion, like cloudy thinking, episodes of daytime sleepiness and disorientation, similar to delirium. A different subset of people may have psychiatric features like depression and hallucinations that may precede cognitive changes. This suggests a possible psychiatric-onset of DLB.

The authors stress that these new proposals require further testing in research studies before being adopted for wide clinical use; they carefully evaluate available evidence and suggest where new advances might be made.

MCI with Lewy bodies

The new research criteria describe how to categorize possible and probable MCI-LB, based on specific combinations of MCI, other DLB symptoms and abnormal biomarker test results. MCI-LB requires an observed change in cognition made by the person themselves, a close friend or family member, or their healthcare professional. The individual still maintains their prior level of independence, though more effort or time may be needed to carry out certain tasks.
An objective assessment must confirm a decline in one or more cognitive domains, such as language, attention or memory. The cognitive changes in the MCI-LB criteria are similar to DLB, but less pronounced. These typically involve difficulties with attention and doing complex mental tasks like multi-tasking and problem solving. The person may not be able to process visual input correctly, including spatial orientation or recognizing objects correctly due to lighting/shading or angle of view. Some individuals with MCI-LB may present with only memory loss, which is also seen in early Alzheimer’s disease.

In addition to MCI, one or more of the core features of DLB are required for a diagnosis of MCI-LB. These include cognitive fluctuations, well-formed visual hallucinations, REM sleep behavior disorder, and/or slow or stiff movements (parkinsonism). Other DLB symptoms can support the diagnosis, such as autonomic dysfunction (e.g. episodes of severely low blood pressure, increased salivation).

Three ‘indicative biomarkers’ of DLB are also proposed for MCI-LB. Autopsy studies confirm these tests reflect underlying Lewy body disease pathology. The biomarkers are dopamine transporter (DAT) imaging, polysomnogram to confirm REM sleep behavior disorder, and a cardiac scan to assess nerve function called MIBG scintigraphy. The authors note that these tests may not be as sensitive at detecting the MCI stage of DLB as they are at detecting the dementia stage. As such, a normal biomarker test result does not exclude MCI-LB from consideration.

The authors also suggest new, promising biomarkers with potential to improve MCI-LB diagnosis. Such tests include sophisticated measures of alpha-synuclein and other related proteins in body fluids like saliva, plasma and cerebrospinal fluid. Peripheral nervous tissue from skin biopsy, analysis of gait (walking) pattern, or changes in color vision may also be helpful. These tests can now be investigated further, as the MCI-LB criteria enable research participants to be recruited in a standardized way.

Differentiating MCI-LB from MCI in Parkinson’s disease

Cognitive profiles in Parkinson’s disease and DLB have considerable similarity, given their shared underlying disease biology. As such, separating MCI-LB from in Parkinson’s disease requires special consideration. The authors suggest a 1-year rule may be useful, similar to how Parkinson’s disease and DLB are separated. If MCI starts a year or more before the onset of changes in movement result in a Parkinson’s disease diagnosis, for research studies this will be labeled MCI-LB. If Parkinson’s disease is present for more than 1 year prior to the development of MCI, then Parkinson’s disease MCI would be the appropriate diagnosis.

The underlying biological change in both DLB and Parkinson’s disease is called Lewy body disease. These changes are thought to develop a decade or more before symptoms begin. When early symptoms later suggest the person will develop DLB in the future, this is called the prodromal stage. It is not yet clear why some people with Lewy body disease develop DLB while others develop PD. The authors recommend the term ‘prodromal Lewy body disease’ be used in research studies for individuals who have both changes in movement (parkinsonism) and mild cognitive impairment, but do not meet the criteria for Parkinson’s disease. Further research is needed to understand why and how prodromal Lewy body disease later evolves into different clinical entities.

Delirium-onset DLB

Studies suggest delirium is a possible warning sign of impending DLB, as it occurs more frequently before the onset of dementia in DLB than in Alzheimer’s disease. After diagnosis, people with DLB are hospitalized more frequently for delirium than those with AD. One study of people experiencing prolonged delirium revealed 32% had a DLB-like pattern on FDG-PET imaging. The researchers propose that delirium prior to dementia be explored as possible prodromal DLB; this is especially important in cases where there are no other identifiable medical factors provoking the delirium, or if delirium is prolonged or reoccurs.

Psychiatric-onset DLB

A significant psychiatric disorder may precede cognitive changes in a subset of people with DLB, including late-onset major depressive disorder or late-onset psychosis. Symptoms experienced may include visual hallucinations (and/or hallucinations in other senses), delusions (including Capgras syndrome), apathy, anxiety and depression. Other symptoms that may occur include cognitive changes, slowed speech, resting tremor or muscle rigidity. Japanese researchers have shown that a heart imaging study technique, called MIBG scintigraphy, may be especially useful in the study of psychiatric-onset DLB. Previous research revealed 18 out of 35 subjects with late-onset depression, slowed movements and an abnormal scan developed DLB within 6 years. Further research is needed to confirm and better understand these findings.

Conclusion

The new research criteria for MCI-LB, along with the description of two new possible patterns of how DLB may develop early in the disease course, now allows for a unified global approach to the study of DLB before dementia develops. By assessing study participants with MCI-LB over time, research will provide greater insights on ways to identify the disease at its very earliest stages. This may help identify different subtypes in how the disease presents and progresses. Ultimately, the study of MCI-LB will contribute data and biological samples needed for the study of disease-modifying treatments for Lewy body dementias.

Reference: McKeith IG, Ferman TJ, Thomas AJ, et al. Research criteria for the diagnosis of prodromal dementia with Lewy bodies. Neurology. 2020:94(7);1-13

Alzheimer’s and Lewy bodies: When Two Pathologies Collide

DLB is one of two clinical diagnoses under the Lewy body dementia umbrella. When DLB co-occurs with Alzheimer’s disease, a clinical diagnosis is even more difficult to make as symptoms of both disorders may be present. Autopsy studies reveal that only 30% of people with DLB are diagnosed during life. The most frequent misdiagnosis is Alzheimer’s disease.

In a recent study of autopsy data in the National Alzheimer’s Coordinating Center (NACC) database, Lewy body pathology was the most common co-existing pathology in people with Alzheimer’s disease up to 80 years of age. Imaging tests can reveal Alzheimer’s disease in the brain, but no similar imaging tests can confirm the presence of Lewy bodies. While tests used in DLB diagnosis confirm the damage from the disease, no test shows the disease itself. One test used to aid in DLB diagnosis, MIBG scintigraphy, reveals a decline in cardiac nerves; this may be why people with Lewy body disorders have problems with blood pressure control.

While MIBG scintigraphy has been extensively studied in DLB in Japan, it hasn’t received the same amount of research or clinical interest in the U.S. People with diabetes and heart disease can have abnormal results with this scan, potentially limiting its use for diagnosis of DLB in the U.S.

Researchers at Banner Sun Health Research Institute analyzed data and samples from whole body autopsies of deceased participants of the Arizona Study of Aging and Neurodegenerative Disorders. Study subjects included people with autopsy-confirmed pure Alzheimer’s disease (AD), AD+DLB, Alzheimer’s disease with lesser amounts of Lewy bodies (ADLB), incidental (minimal) Lewy body disease (iLBD), Parkinson’s disease (PD), and people with no cognitive or movement disorders (healthy controls).

Tissue samples from the heart were studied to compare the number of cardiac nerve fibers. These fibers are very thin thread-like lines that transmit nerve signals. The subjects with PD and AD/DLB had fewer nerve fibers than the healthy controls. There was no significant difference in nerve fibers between healthy controls and subjects with AD, ADLB or ILBD.

In this study, nearly 50% of the AD+DLB cases had been diagnosed with AD during life. These mixed dementia cases are of considerable concern in clinical trials; individuals with AD+DLB can have a blended clinical picture and even different responses to medications than those with AD alone.

Further research is needed to determine the role MIBG scintigraphy might play in clinical trials for AD and DLB.

Reference: Geidy E Serrano, David Shprecher, Michael Callan, Brett Cutler, Michael Glass, Nan Zhang, Jessica Walker, Anthony Intorcia, Charles H Adler, Holly A Shill, Erika Driver-Dunckley, Shyamal H Mehta, Christine M Belden, Edward Zamrini, Lucia I Sue, Daisy Vargas, Thomas G Beach, Cardiac sympathetic denervation and synucleinopathy in Alzheimer’s disease with brain Lewy body disease, Brain Communications, Volume 2, Issue 1, 2020, fcaa004, https://doi.org/10.1093/braincomms/fcaa004

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.

Vehicle, Real Estate and In-Kind Donations

LBDA is honored you are considering donating in-kind, vehicle or real estate. Your support helps to continue our mission while advancing our efforts in the LBD and medical communities. Thank you for choosing LBDA.

Vehicle Donations

Do you have a car, boat or motorcycle that you no longer want? We’ll have it picked up from you free of charge—whether it’s running or not. It will be sold at auction with the proceeds benefiting the Lewy Body Dementia Association. After you submit the online form you will hear from our friends at Donate For Charity. They will make arrangements to pick up your vehicle

Click here to donate your vehicle to Lewy Body Dementia Association and take a stand against LBD!

Real Estate Donations

LBDA has been very fortunate to receive real estate donations in the past, and such special contributions have had significant impact on our organization and the LBD community. We are very gracious to those that give real estate, and any other form of donation, in advancing out mission.

If you are considering donating your property or land to LBDA, please contact Mark Wall, Executive Director, at mwall@lbda.org or (404) 549.4255.

Again, we thank you for your generous contribution and support of LBDA and joining the fight against Lewy body dementias.

In-Kind Donations

LBDA accepts limited donations due to the fact that we’re unable to properly accommodate in-kind donations at our offices. Generally, in-kind donations are used for auction items during special events and galas. We’re currently preparing for a major event in October 2020, and would greatly appreciate your in-kind donations of high art, unused gift cards, unopened electronics, etc.

Unfortunately, we’re unable to accept clothing, food items, medical equipment or prescriptions, or damaged/used items. We appreciate your understanding and thank you for choosing to support the LBD community.

To make an in-kind donation, please contact lbda@lbda.org.

Updated LBD Research Recommendations Published

Every 3 years, a national research summit is held to update research strategies for non-Alzheimer’s dementias. This 2-day national event is one of 3 rotating summits held in response to the National Alzheimer’s Plan, which also includes the related dementias.

The newly-published report from the Alzheimer’s Disease‐Related Dementias (ADRD) Summit 2019 provides recommendations to advance the study of LBD, frontotemporal, vascular and mixed dementias. Each session included three main topics: updates on research progress since the last summit, new draft research recommendations, and time for public comment from summit attendees.

The LBD session was co-chaired by two long-time members of LBDA’s Scientific Advisory Council, Bradley Boeve, MD of Mayo Clinic and Carol Lippa, MD of Thomas Jefferson University. Numerous members of LBDA’s Scientific Advisory Council and Angela Taylor, LBDA’s Senior Director of Research and Advocacy, served on the committee.
Other sessions included a focus on improving dementia nomenclature, research in communities affected by health disparities, and evolving science in the link between traumatic brain injury and dementia, and a brain pathology called TDP-43.

The Dementia Nomenclature session was co-chaired by LBDA’s Angela Taylor and Ronald Petersen, MD, PhD of Mayo Clinic. The committee included a diverse group of researchers, clinicians, people with dementia and family caregivers, as well as representatives from nonprofits, federal agencies and pharmaceutical companies.

This report will be presented to the National Institute of Neurological Disorders and Stroke for approval, and then proceed to the Department of Health and Human Services (DHHS) National Alzheimer’s Project Act (NAPA) Council. Ultimately, approved recommendations help guide the funding of research by the National Institutes of Health.

LBD is the Most Expensive Dementia in America

Dementia is one of the most expensive diseases in the United States, increasing healthcare costs 3 times over those without dementia. Until now, studies on the costs of different dementia sub-types were limited by small sample sizes. In the first population-based study estimating healthcare costs by type of dementia, Lewy body dementia (LBD) was identified as the costliest form of dementia.

A recent study led by Katherine Possin, PhD at the University of San Francisco, breaks down costs for the most common forms of dementia. Researchers analyzed 100% of the 2015 California Medicare fee-for-service data to identify the direct health care costs and utilization by people diagnosed with dementia.

Of the original 3+ million beneficiaries, 8.2% had a dementia diagnosis. Most people (59.6%) had an unspecified dementia diagnosis, followed by Alzheimer’s disease (23.2%), Lewy body dementias (4.2%), vascular dementia (4.0%) and frontotemporal dementia (FTD) (0.3%).

Healthcare Costs

Claims data were used to estimate total cost of care, and to break down costs by specific services, including hospitalization, physician visits, emergency room visits, and ambulance services.

The analysis compared Medicare costs of those individuals with specific dementia diagnosis, e.g. Alzheimer’s disease, LBD, vascular or frontotemporal dementia. The cost of care was highest for those with LBD ($22,514 per beneficiary), followed by vascular dementia ($21,002) and FTD ($14,853). People diagnosed with Alzheimer’s disease had the lowest healthcare cost per person ($13,935).

Cost and duration of hospital visits were highest for LBD and vascular dementia, almost double the cost of AD. These higher costs were driven by more frequent visits to the emergency department and the use of ambulances. Those with LBD also had higher Medicare-funded home health costs.

Researchers then controlled for demographic, comorbid conditions and length of Medicare coverage in 2015. Those with LBD had 31% higher healthcare costs over those with Alzheimer’s disease. Vascular dementia care cost 10% more than Alzheimer’s disease.

Drivers of Cost

Symptoms or features of the disorder that might drive healthcare costs were also identified. Those included injury-causing falls, delirium, depression, anxiety, delusions, hallucinations, dehydration, urinary incontinence or infection, orthostasis, insomnia or REM sleep behavior disorder.

Of the dementia sub-types studied, people with LBD were more likely to have a history of falls (72.4%), urinary incontinence or infection (27.7%), dehydration (15.6%), depression (15.5%) and anxiety (9.5%). LBD also had the second highest history of delirium (17.4%).

The higher cost of LBD care over Alzheimer’s disease was driven by falls (21.3%), urinary incontinence or infection (15.2%), and psychiatric symptoms (depression 4.9%, anxiety 3.4%, hallucinations 1.25% and delusions <1%), dehydration (4.2%), delirium (3.3%), blood pressure regulation issues (2.7%) and sleep disorders (1.9%).

Breaking LBD into the two distinct diagnoses of dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD), the total costs per person were similar ($23,527) for DLB and ($21,639) for PDD. The similar cost of care echoes the overlapping and similar features of DLB and PDD, however differences were also noted. Higher inpatient costs in people with DLB were responsible for the higher healthcare cost. Those with PDD had slightly more falls and those with DLB had more delirium, depression, hallucinations, dehydration, urinary incontinence and infection, and blood pressure regulation problems.

This study has some limitations, as it did not assess costs that are paid privately. For example, the Medicare data studied only included a fraction of the cost of long-term care, which is often privately paid. More research is needed to assess if the long-term care varies by sub-type of dementia. Further, claims-based data limits the true prevalence and thus cost of dementia care. And as this study focused on a single year of claims, it cannot capture changing costs of healthcare as these disorders progress. Medical costs for individuals with younger-onset dementias such as FTD would not be captured in this study. Lastly, the study included data only for the state of California, where most of the population lives in metropolitan areas.

The study highlights an ongoing diagnostic challenge; most cases of dementia were “unspecified” meaning no specific sub-type was identified. This underscores an important gap that can negatively impact clinical management and poses a barrier to adequate education and support of the person with dementia, their primary caregiver and family. Better diagnostic tools and professional education are urgently needed to improve differential dementia diagnosis.

Understanding what drives the higher cost of LBD opens opportunities to develop and proactively deliver interventions in a home or outpatient setting. Opportunities to contain costs and improve care quality include dementia care management, care navigation and clinical management. The authors suggest programs include a focus on those items that drive up the cost of LBD healthcare. This includes fall prevention, early identification and treatment of medical issues including urinary tract infections and dehydration, and attention to any sudden change in health status such as delirium, worsening psychiatric symptoms and sleep problems.

Source: Chen Y, Wilson L, Kornak J, et al. The costs of dementia subtypes to California Medicare fee-for-service, 2015. Alzheimers Dement. 2019;15:899–906.

Increased Hospitalization in DLB Compared to AD

A study out of the U.K. revealed that people with one form of LBD, specifically, dementia with Lewy bodies and more frequently admitted to general hospitals that people with Alzheimer’s disease or the general elderly population.

Researchers used a sampling of AD and DLB cases from a databases of one of Europe’s largest mental health and dementia care providers. Comparing 194 DLB cases to 776 AD cases, researchers studied the different rates of hospitalizations and length of hospital stays between the two groups. This included planned and unplanned admissions and the cost of hospitalizations.

Compared to those with AD, the DLB cohort had worse physical and mental health at the time of diagnosis. This included more neuropsychiatric features (e.g. hallucinations and delusions), more aggression, self-injury, and depressed mood. Those with DLB also had greater problems with activities of daily living both job performance and recreational activities, and social relationships.

The DLB cohort were more likely to be hospitalized within a year of diagnosis and their overall risk of hospitalization was 46% higher than those with AD. The DLB cohort also had an average of almost 4 additional days in the hospital per year than the AD group. The presence of hallucinations and/or delusions were linked to longer hospital stays in those with DLB.

In both the AD and DLB cohorts, infection and falls/fractures were the most common cause for hospitalization, but those with DLB were more likely to be hospitalized for infection than those with AD.

Infections often causes a sudden worsening of confusion and behavioral symptoms in people with dementia. They require prompt treatment to increase the chance that people with dementia return to the baseline functioning they had prior to the infection.

More research is needed to determine how to reduce hospitalizations and to minimize the duration of hospital stays (and cost) for those with DLB. This could include efforts to recognize DLB earlier, novel ways to address hallucinations, either through medications or psychological treatments, or more holistic care for people with DLB.

Preparing LBD Families about End of Life

End of life factors are known to be different in LBD compared to Alzheimer’s disease. The progression of LBD averages 5-7 years from onset to end of life. This is considerably shorter than the 8-10 years in Alzheimer’s disease. Adding typically-delayed diagnosis, this results in a compressed time to address LBD’s complex diagnostic, clinical and caregiving issues.

A new study highlights that Lewy body dementia (LBD) families need better guidance from their healthcare professionals on end of life issues. This includes likely causes of death, timing of engaging hospice services, and what to expect at end of life.

Led by Melissa Armstrong, MD, MSc of the University of FL, Gainesville, researchers explored the end of life experiences in people with one form of LBD: dementia with Lewy bodies (DLB). The study, a collaboration with the Lewy Body Dementia Association, used an online survey about end of life experiences.

The study included caregivers, family members and friends of people who died within the previous 5 years with a DLB diagnosis. Of the 658 respondents, most (89%) were female with a median age of 50-69. The study revealed most care recipients died within 5 years of their diagnosis.

Less than half of the full cohort reported early advanced care planning with their physician (within the first 1-2 years). This underscores a missed opportunity for the patient to discuss preferences and priorities for care with their physician before the disease progresses.  Seventy percent (70%) indicated having advanced directives completed prior to diagnosis. Only 10% indicated advanced directives were revised after diagnosis.

Caregivers indicated providers rarely addressed what to expect at end of life (40% total, but only 22% to a helpful degree). Most conversations on end of life issues were first broached by the caregiver.

Hospice services were used by 78% of respondents, but with widely varying lengths of time. The median time for hospice service use was 1-2 months.  Two thirds of respondents felt hospice was started at the right time. However, that left a substantial minority (25%) feeling hospice was started too late, often within weeks of death. Only 3% felt hospice was started too early.

Care recipients commonly died in skilled nursing or memory care (43%) or at home (36%). Most caregivers (74%) reported they expected the care recipient’s death. Respondents reported the most common causes of death were failure to thrive, such as not eating or drinking (65%), pneumonia and swallowing difficulties (23%). Less common causes included other medical conditions (19%) and complications from falling (10%).  Suicide was reported as very rare (less than 1%).

This study underscores important opportunities for physician-initiated discussions on advanced care planning with persons in the early stage of LBD, counselling patients and their families on the use of palliative care and hospice and preparing patients and LBD families on what to expect at end of life.

This study was supported by the University of Florida Dorothy Mangurian Headquarters for Lewy Body Dementia, the Raymond E. Kassar Research Fund for Lewy Body Dementia, and the Lewy Body Dementia Association. Dr. Armstrong is the primary investigator at University of Florida’s LBDA Research Center of Excellence.

LBD Diagnostic Symptoms Checklist

Because Lewy body dementia is the most misdiagnosed form of dementia, LBDA developed a useful checklist to help physicians and their patients identify key LBD symptoms used to make a diagnosis.

This publication features a patient-friendly symptom checklist on the first page and the physician-oriented diagnostic criteria on the second.

This resource can be completed in advance by those who may have symptoms of LBD and provided to their doctors at their next office visit. It can also be handed out by healthcare professionals for their patients to complete at an office visit.

This free patient checklist can be downloaded and printed for unlimited use by both medical practices and individuals who want to discuss LBD with their doctor.

Download the LBD Diagnostic Symptoms Checklist

Lewy and Lumbar Punctures

Did you know that spinal fluid is extremely valuable in LBD research? It allows scientists to study changes in the levels of proteins that might be associated with LBD, Alzheimer’s disease, or other disorders that can only be found in spinal fluid. By studying spinal fluid from people with LBD, researchers hope to answer important questions about LBD, like:

  • How to diagnose LBD earlier and more accurately.
  • How to measure the effectiveness of an experimental treatment.
  • How levels of different proteins relate to the symptoms people with LBD experience.

Download “What You Need to Know About LBD and Lumbar Punctures ”today!

And consider participating in an LBD research study!

Double Your Donation

Many companies offer matching gift programs to encourage employees to contribute to charitable organizations. Some provide matching funds to support employee volunteer hours. Most of these programs match contributions dollar for dollar, and some will even double or triple the amount of your gift!

To find out if your company will match gifts to the Lewy Body Dementia Association click here.

If you do not find your employer through this search, please check with your company to see if it offers a matching gift program that will match your gift or volunteer hours to LBDA.

You may mail or email your completed matching gift form to:

Lewy Body Dementia Association
912 Killian Hill Road, SW
Lilburn, GA 30047

lbda@lbda.org

Biomarkers: The Pathway to Earlier LBD Diagnosis and Better Treatments

In LBD clinical research, scientists use tests that measure both the symptoms of a disease and also what biological changes are underway. Those tests that detect the presence or progression of a biological disease process are called biomarkers.

Finding LBD biomarkers is one of the top research recommendations for LBD in the National Plan to Address Alzheimer’s Disease (and related dementias). Thanks to increases in dementia research funding, the National Institutes of Health recently funded four new LBD biomarker research studies.

While the studies all have different aims, they include a core set of physical and neurological examinations and interviews, and collection of certain biological fluid samples. Each of these studies will carefully assess people with LBD for up to five years, with the goal of reaching a better understanding of how biological changes result in the symptoms of the disease. This can ultimately lead to better diagnostic tools and treatments. These studies will also establish a new and rich resource for the LBD scientific community – a national, centralized collection of LBD clinical and biological data.

This represents a major step forward and the participation of the LBD community in these studies will be vital. This article will help you understand what clinical assessments and biomarkers are involved and how they will help advance our understanding of LBD.

LBD Biomarker Studies: What to Expect

Those who are interested in participating in LBD research can be confident that they will learn right up front exactly what tests the study includes. All research studies include a process called “informed consent” in which the person volunteering formally agrees to participate in the study. Part of the informed consent process involves a member of the study team explaining the study, any treatments or tests involved, any benefits from participating in the study, and any risks involved.

To provide the researchers with a thorough understanding of a person’s health, participants will be asked questions to set a baseline at the start of the study. This starts with their personal and family’s medical history. A simple cognitive assessment will be done, and participants will be asked basic questions about mood or behavioral changes. Blood pressure, height and weight will be taken and a neurological exam will be done to identify any changes in movement including tremor, stiffness and slowness.

The study team will then look more deeply at LBD symptoms. These assessments may take several hours, and may be administered over two sessions. Extensive cognitive testing will help measure what skills have been affected, such as memory, language, or executive function. Questionnaires will help identify the range of mood changes, like depression or anxiety, as well as psychiatric symptoms like hallucinations or delusions. A careful assessment will be done to identify if the participant has any sleep disorders. A smell test will be given to detect any loss of the ability to smell. And other tests will identify changes in the body’s ability to regulate autonomic systems like blood pressure and pulse.

Biofluids (blood, urine and cerebrospinal fluid) provide information about the presence of other medical conditions, but are also studied to find changes that are linked to LBD and related disorders. This may include changes in genetic factors or levels of certain proteins associated with neurological disorders. The presence of these biomarkers may predict future symptoms and rate of progression.

One of the most important tests in these studies is called a lumbar puncture (or spinal tap). A lumbar puncture is the only way to get direct access to spinal fluid, the clear liquid that circulates through the brain and spinal cord. This sample of fluid gives researchers the ability to measure levels of proteins produced by the brain. Examining levels of key proteins that are associated with dementia is absolutely vital to the development of new LBD diagnostic tools and treatment options, and has revolutionized the study of Alzheimer’s disease. Because it is so essential, a lumbar puncture is considered mandatory to participate in all four LBD biomarker studies.

Advances in lumbar puncture techniques have significantly reduced the risks and side effects, making an increasingly common part of cutting-edge dementia research studies. To learn more, view this 5-minute video on lumbar puncture.

Tests Unique to Certain Studies

Depending on which of the 4 studies you choose to participate in, additional assessments may be administered to answer the aims of the study. Participants may have brain scans to help detect changes in brain structure and function. A magnetic resonance imaging (MRI) scan allows researchers to see physical changes in the brain. (Examples include the brain shrinkage seen in Alzheimer’s disease or the presence of a tumor.) A second type of scan, called single photon emission computerized tomography or SPECT, is used to look at a functional change associated with LBD. A nuclear medicine compound called 123I-FP-CIT (also called DAT scan) is used with SPECT to find changes in the brain’s abilities to use a neurotransmitter called dopamine. Dopamine is important in movement and mood.

If any of the participants should happen to pass away during certain studies, their brains can be carefully examined by a highly-trained neuropathologist. At the present time, this is the only way to currently confirm the LBD diagnosis. Because these research participants will be so carefully studied for several years, researchers can combine the research data collected during life with what is seen in the brain after death. This is the most powerful information scientists can use to advance our understanding of LBD. The donation of a study participant’s brain is the “ultimate gift” a person can make to research. Learn more about brain donations and brain autopsies in this helpful article from LBDA.

Participate in Research

These studies are funded by the National Institute of Health through a program called the Parkinson’s Disease Biomarker Program (PDBP). To learn more about these studies, visit the PDBP’s website. To find research studies and clinical trials now enrolling people with LBD, visit LBDA’s Participate in Research page.

The Importance of LBD-Specific Support Groups

A recent poster presented at the 2016 Alzheimer’s Association International Conference suggests that LBD caregivers experience unique benefits from attending an LBD-specific support group compared to a general dementia support group.

Christopher Zalewski of the Cleveland Clinic Lou Ruvo Center for Brain Health, in collaboration with the Lewy Body Dementia Association and Taylor Young of the Cleveland Area Chapter of the Alzheimer’s Association recently launched a support group for LBD caregivers in response to feedback from LBD patients and families.

LBD families reported difficulty relating to Alzheimer’s caregivers whose challenges often centered around memory loss, which is not always a concern for LBD caregivers. The lack of familiarity with LBD symptoms also resulted in LBD caregivers receiving misguided or ineffective advice.

A number of common LBD caregiver needs emerged from group discussion. On the movement side, families need assistance managing movement changes such as ‘freezing’ or slowed movement. Emotionally, family caregivers feel a lack of understanding and awareness from their peers regarding LBD. They also need help responding to hallucinations, delusions and fluctuations in LBD symptoms. Challenges in obtaining a correct diagnosis and avoiding medications potentially harmful in LBD were common clinical concerns. In addition, creating a safe environment at home in response to fluctuations is a consistent issue.

Quotes from LBD caregivers participating in the discussion underscore the importance of LBD-specific support groups. “This group is so necessary for early stage Lewy body dementia caregivers. I had no idea about how different the journey would be compared to Alzheimer’s.”

A general satisfaction survey of 10 members from the new support group confirms the participants find the group of significant value.  All respondents agreed or strongly agreed that they now know more about LBD resources, would recommend the group to other LBD caregivers, and found the group to be helpful overall. Nearly all (90%) respondents agreed or strongly agreed that the group helped them prepare for the future.

The Lewy Body Dementia Association offers training and resources to help both laypersons and professionals launch new groups across the country. For more information, contact Pamela Corsentino at pcorsentino@lbda.org.

Resources for Healthcare Professionals

LBDA Publications for Healthcare Professionals

NEW :  Diagnosing and Managing Lewy Body Dementia  – An expansive look at clinical managment strategies for LBD, covering the Lewy body spectrum, symptoms, treatments, what medications to avoid, guidance for discussing the diagnosis, prognosis and progression, and the impact of LBD on the family caregiver.

Professional Brief: New DLB Diagnostic Criteria – This at-a-glance resource provides an update to healthcare professionals on the new 2017 diagnostic criteria for dementia with Lewy bodies (DLB).

Diagnostic Symptoms ChecklistA simple tool to help patients, caregivers and healthcare providers quickly and easily identify symptoms that are required for diagnosis of dementia with Lewy bodies (DLB).

Comprehensive Symptoms Checklist – A useful checklist to help people diagnosed with LBD or their caregivers report new or concerning LBD symptoms to their physician.

Caregiver Burden White Paper – This white paper examines the experience of hundreds of LBD caregivers seeking medical care for LBD and the psychosocial impact of being an LBD caregiver.

Understanding Behavioral Challenges in Dementia – Anticipating behavioral changes in dementia and understanding the causes helps caregivers deal with them more effectively.  This is a must-read for family caregivers. 

Emergency Room Treatment of Psychosis – Guidance from LBD experts on the treatment of psychosis in the E.R., including key considerations to take BEFORE treating behavioral disturbances in LBD.

Caregiver Impact

The combination of cognitive, motor and behavioral symptoms imposes significant challenges and stressors on caregivers. Education of and support for the primary caregiver is essential, and building a care team, when possible, can lessen the burden on any one individual.

Caregiver Burden

Early symptoms that are characteristic of LBD are associated with higher levels of caregiver burden, above and beyond impact of stress associated with early dementia in general.1 Key factors in LBD caregiver burden include behavioral problems (e.g., psychosis, apathy and agitation), an impaired ability to perform activities of daily living (due to both cognitive impairment and parkinsonism), the caregiver’s sense of isolation, and challenges with the diagnostic and treatment experience.
Research suggests that people with LBD may be more functionally impaired than individuals with AD with the same level of global cognitive impairment.2 Loss of independence in ability to perform instrumental activities of daily living typically occurs early in LBD, including the inability to manage one’s own medications and finances. Driving may also need to be curtailed early due to changes associated with LBD, i.e. variable levels of attention and alertness, visual hallucinations, slowed reaction time, and decreased spatial awareness.
LBD caregivers need to increasingly supervise and monitor LBD patients as particular symptoms manifest themselves or worsen, including executive impairment (i.e., difficulty planning and completing tasks), fluctuations in alertness, incontinence, intrusive hallucinations, and falls.

Diagnostic Delays

DLB caregivers often encounter significant barriers in obtaining an accurate diagnosis for their loved ones. Most see multiple physicians over more than a year before their relative is diagnosed with DLB, and more than three-quarters of persons with DLB are given a different diagnosis initially.3

Community-Based Services for Patients and Caregivers

The range and intensity of care required for LBD patients means that greater attention to and allocation of resources to assist LBD families are needed. One study compared resource use, cost of care, and determinants of cost of care in patients with DLB and AD. DLB patients utilized more than twice the amount of resources compared with AD patients. Specifically, DLB patients used greater resources in accommodations (long-term residential care), and required more outpatient care, informal care (measured by caregivers’ lost production and lost leisure time), community services and pharmacological therapy.4
Among neuropsychiatric features, apathy (i.e., loss of motivation to participate in routine activities) was found to be higher in DLB patients than AD patients. In addition, the cost of care for DLB patients with apathy was almost three times as high compared with AD patients with apathy. Thus, apathy is an important behavioral feature in LBD.

Low Public Awareness

The lack of LBD awareness in the general public increases the subjective burden of LBD on families, which echoes the experience of dementia caregivers in the days before extensive public education had been provided regarding AD.1

Performance Worry of Caregivers

Also problematic for LBD caregivers are concerns about their own capabilities as caregivers, which is amplified due to fewer informational resources on LBD caregiving compared with those available for AD, LBD caregivers’ sense of social isolation, and the challenges in finding supportive medical professionals or community services. Thus, LBD caregivers may be more concerned than other dementia caregivers about the quality of care they are providing.1

Monitoring for Depression and Burnout in Caregivers

Family caregivers often experience sleep deprivation, have poor eating habits, and fail to exercise enough. When it comes to their own medical care, their caregiving responsibilities may prevent them from convalescing when ill, and they often postpone or neglect to make medical appointments for themselves. The caregiver should also be considered a patient in some respects, as the stress of being in an intense, long-term caregiver role can lead to depression, poor health and burnout, which can increase the likelihood of institutionalization of the LBD patient. Healthcare providers should urge caregivers to prioritize their own health as highly as they do that of their loved one with LBD.
1. Legget, A., Zarit, S., Taylor, A. & Galvin, J. Stress and burden among caregivers of patients with Lewy body dementia. The Gerontologist 51, 76–85 (2011).
2. McKeith, I. G. et al. More severe functional impairment in dementia with Lewy bodies than Alzheimer disease is related to extrapyramidal motor dysfunction. Am. J. Geriatr. Psychiatry Off. J. Am. Assoc. Geriatr. Psychiatry 14, 582–588 (2006).
3. Galvin, J. E. et al. Lewy body dementia: the caregiver experience of clinical care. Parkinsonism Relat. Disord. 16, 388–92 (2010).
4. Boström, F., Jönsson, L., Minthon, L. & Londos, E. Patients with Lewy body dementia use more resources than those with Alzheimer’s disease. Int. J. Geriatr. Psychiatry 22, 713–719 (2007).

Referrals

Specialists

A team approach will result in the best outcomes for patients and their families. Referral to an informed neurologist is recommended for diagnosis and management of LBD symptoms; neuropsychologists may also be helpful in making a differential diagnosis. Geriatric psychiatrists may be needed to manage refractory behavioral problems.

LBDA

People with LBD and family caregivers need to be educated about the symptoms of LBD, standard treatment options, and how to find supportive services that may be needed over the disease course. A referral to the Lewy Body Dementia Association is recommended upon diagnosis for educational and support resources.

Legal counsel

Early in the course of dementia, physicians can help the patient identify and share their personal goals of care and discuss advanced care planning. Health care providers should also encourage families to consult an attorney to ensure their legal affairs are in order, such as a will, durable power of attorney and advanced directives.

Other referrals

A brief assessment may reveal the need for pastoral counseling or hospice care, as LBD is often life-shortening. Caregivers may also require referral for counseling due to depression or burnout.

Treatment

Download this article as a PDF

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 caregiver 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

Parkinsonism

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 http://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 http://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).
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