In mid-October 2023, Stanford’s Lewy Body Dementia Research Center of Excellence and Brain Support Network co-hosted a hybrid symposium on Lewy body dementia (LBD) caregiving. The first talk was an overview of LBD by Stanford Movement Disorders Division Chief Katherine Poston, MD. Dr. Poston shared how the diagnosis of LBD is made, the similarities and differences between LBD and Parkinson’s disease (PD), and LBD symptoms.
Below are my paraphrased notes on Dr. Poston’s talk during the symposium, as well as the question and answer session afterward.
-- By Jordan Dagan, Stanford Parkinson’s Community Outreach
DEFINING LEWY BODY DEMENTIA (LBD)
Lewy Body Dementia (LBD) is a neurodegenerative disorder caused by the buildup of Lewy bodies in nerve cells, which leads to those neurons dying. Lewy bodies are deposits of alpha-synuclein protein which have mis-folded. Alpha synuclein protein is very important for communication between neurons, and researchers don’t currently know what causes them to mis-fold and clump together, or why this mis-folding causes neurons to die. Parkinson’s disease dementia (PDD) and Dementia with Lewy bodies (DLB) are types of Lewy Body Dementia. Autopsies have shown that other neurodegenerative diseases, including Parkinson’s disease (PD) and multiple system atrophy (MSA) are caused by mis-folding proteins.
While both PD and LBD are caused by Lewy bodies, and both are associated with motor dysfunction, the timing of symptoms is what movement disorder specialists use to distinguish between them. Researchers don’t yet know why the progression of symptoms varies so broadly between PD and LBD, or between people with the same diagnosis.
A person with PDD most often develops motor issues years before they have cognitive impairment, while a person with DLB has cognitive impairment first, and motor symptoms later.
WHAT PEOPLE WITH LBD EXPERIENCE
The following lists are non-cognitive symptoms people with PD and LBD might both experience:
Parkinsonism: motor symptoms –
Bradykinesia: slow movement
Rigidity, stiffness in the muscles
Tremor, mainly in resting position
Abnormal gait and posture, often shuffling gait and hunched forward posture
Non-motor symptoms in those with LBD or PD –
Soft, low speech (hypophonia), slurred speech
Depression, apathy, anxiety
Excessive sweating, salivation
Loss of smell
Neurogenic orthostatic hypotension (nOH)
Dementia-related psychosis and hallucinations
TREATMENT FOR SYMPTOMS
When people with LBD experience Parkinsonism, levodopa sometimes helps. However levodopa can worsen non-motor symptoms of LBD such as low blood pressure and hallucinations.
People with LBD often develop REM sleep behavior disorder (RBD). They tend to be very mobile during REM sleep, acting out their dreams with erratic movements. This is often disruptive to anyone they share a bed or room with while they sleep, and they might hurt their sleeping partners accidentally. This sleep pattern can be diagnosed with a sleep study. High doses of melatonin can treat disordered sleep, and it may be safer to put a bed on the floor. Clonazepam is sometimes prescribed to treat RBD, but this is a sedative and may make cognition worse for people with LBD.
Most people with LBD experience visual hallucinations, which is not usual among those with other neurodegenerative diseases. In the early stages of LBD, people usually see visual illusions, such as patterns popping out at them, or thinking an object is in the room when it is not. Hallucinations tend to be more frequent in low light, and they get more intense as the disease progresses. People often see animals, or “small people” or children, which aren’t there. Earlier in LBD, people tend to be aware that what they’re seeing is not real, and may not mention their hallucinations to family or friends because they can distinguish between hallucinations and reality. Later on, they may lose track of what’s real and what’s not, which can be distressing. Hallucinations usually develop gradually in LBD, and if they begin or get worse suddenly, this may be a sign of a urinary tract infection or a medication change.
Treating hallucinations using medication should be very carefully done for someone with LBD, and antipsychotics should be avoided! The process of treating hallucinations with medication is trial-and-error, and the first treatment is usually to reduce the dose of dopa medication. One drug has been approved to treat hallucinations in those with LBD, called pimavanserin/Nuplazid. This is a specialty medication and takes 2-4 weeks to start working. Low-dose quetiapine may be used as well, though this is considered off-label usage. Cholinesterase inhibitors may also be used.
DIAGNOSING LEWY BODY DEMENTIA
It is difficult to diagnose LBD in one session with a neurologist or behavioral neurologist, because every person with cognitive changes is unique, and not everyone has symptoms that directly match the diagnostic criteria. When making a diagnosis, doctors should consider medication interactions, thyroid function, independent treatment for depression/other mental health concerns, and they should check on the person’s sleep to see if they’ve developed parasomnia.
Diagnosing someone with dementia can be tricky, since the transition from “mild” cognitive impairment to a stage where daily activities are impaired is often non-linear. The diagnosing neurologist must examine the person’s medical history, looking for instances of daytime drowsiness, lethargy, staring into space, episodes of disorganized speech, and other cognitive symptoms which may have become worse over time.
When evaluating a person for a diagnosis of dementia with Lewy bodies (DLB), neurologists look for cognitive impairment first. If the person or their family tells the doctor of a cognitive change, such as memory loss or trouble remembering words, the neurologist will offer cognitive testing. These tests are consistent among people of multiple ages and education backgrounds, but how the person performs on the test will tell the neurologist whether the cognitive change is in the expected range or not. If the test results are outside of what would be expected for the individual, they’re likely experiencing cognitive impairment. The next criteria for dementia is whether the person’s symptoms are preventing engagement with daily life. If the person is unable to complete daily functions such as cleaning, cooking, or paying bills, even with some help, dementia is included in the diagnosis.
LBD is the second most common cause of neurodegenerative dementia, after Alzheimer’s disease, and may be misdiagnosed as Alzheimer’s disease. Dementia might be caused by both Lewy bodies and the misfolded proteins amyloid and tau which cause Alzheimer’s, or it might be caused by a combination of Lewy bodies and small strokes.
The cognitive impairments in LBD tend to affect executive functions, visuospatial function, attention and working memory. Alzheimer’s disease, in contrast, tends to produce changes in memory and language processing.
TOOLKITS FOR NEUROLOGISTS
There are some toolkits available for helping neurologists assess someone for LBD diagnosis. These are the “Diagnosis and Management of Neurodegenerative Dementia of Lewy Body Type” (DIAMOND-Lewy) assessment toolkit, and the LBDA diagnostic symptoms checklist.
LUMBAR PUNCTURE AND BRAIN SCANS
There is not a specific way to diagnose that’s based on a biological marker for the disease. Doctors can assess alpha-synuclein protein for the formation of Lewy bodies by collecting spinal fluid via a lumbar puncture or performing a skin biopsy. The lumbar puncture test can also check for amyloid and tau protein clumps, which are associated with Alzheimer’s disease. These tests are not paid for by insurance, and are not generally recommended unless a neurologist is very unsure which type of neurodegenerative disease is causing cognitive impairment. There are brain scans which allow doctors to see the system of dopamine in the brain, which can aid in diagnosis. These are called SPECT or PET scans.
Finally, it’s important for those with cognitive impairment, hallucinations, sleep disturbances, and/or Parkinsonism to be a part of research. Further research will help clarify the differences in presentation and biology between LBD, PD, and Alzheimer's!
QUESTIONS AND ANSWERS
Question: My loved one’s physician is dismissing my concerns, because my loved one compensates very well while at their doctor visits.
Answer: Give direct examples of how it’s impacting your daily life, and your loved one’s daily life. For example, your loved one’s tremor impacts holding a spoon and reaching for objects.
Question: What is the importance of an early diagnosis?
Answer: Early diagnosis is valuable on an emotional level, because the patient and family are validated in their troubles and concerns. Early diagnosis also allows the person with LBD and their loved ones to anticipate and prepare for disease-specific issues that may happen, especially blood pressure drops and hallucinations.
Question: Is LBD hereditary?
Answer: Generally, no. There’s no certain causal gene. There are a couple of genes known to increase risk over lifetime, but very few people diagnosed with LBD have those genes.
Question: Please share more about the skin biopsy for diagnosis.
Answer: The skin biopsy test doesn’t work well for people with LBD. In people with PD, tissue staining for alpha-synuclein can be seen on the skin. The test requires three biopsies, and is time consuming and labor intensive. The test may not detect the Lewy bodies, producing a false negative result. If the laboratory does find Lewy bodies in the skin biopsy, it’s a very sure sign that you’ve got PD.
Question: What meds can worsen cognition in LBD? Is it best to reduce the dosage or amount of my loved one’s medications, and try to keep their medication routine simple?
Answer: Any medication has the potential to make cognition worse. Anything that crosses the blood-brain barrier is particularly concerning, especially medicines with a sedating effect. Certain pain medication is also of concern.
Question: When diagnosing LBD, is diagnosing REM sleep disorder important?
Answer: There are formal criteria for diagnosing LBD, but these are not aligned with recent and quick developments in research. To diagnose LBD, a neurologist will look for two of four things: REM sleep disorder, hallucinations, fluctuating cognition, and Parkinsonism. However, LBD and Alzheimer’s, or LBD and mini strokes, can co-exist, which we know from autopsies and spinal fluid tests of those with both diseases.
Two Resources (for Neurologists) Mentioned by Dr. Poston