Lewy Body Dementia - Hidden in Plain Sight

By Robin Shepherd

Executive Director and Co-Founder, The Sue’s Story Project

Lewy Body Dementia

Hidden in Plain Sight

What is LBD?

Lewy body dementia (LBD) is a complex and challenging brain disorder that affects thinking, movement, behavior and mood. It has been “hidden in plain sight” for decades despite the fact that it is a leading cause of dementia, along with Alzheimer’s and vascular diseases.

This historic lack of awareness, education, training and research focused on Lewy body dementia created a domino effect that has hindered progress toward a cure and thwarted efforts to care for people living with LBD today.

More attention and resources must be focused on LBD to fully understand the cause, develop tests for a definitive diagnosis, and pursue clinical trials to find a cure. Until there’s a cure, improvements are needed in healthcare approaches and options for people with LBD and their caregivers.

How does LBD fit into the dementia syndrome?

Lewy body disease is associated with two possible outcomes of progressive dementia: dementia with Lewy bodies (DLB) or Parkinson's disease dementia (PDD).

Because DLB shares some symptoms with Parkinson’s, Alzheimer’s, and psychiatric disorders, it can be difficult to diagnose or be misdiagnosed. It is not unusual for patients to consult with multiple physicians over a period of three or more years before receiving an LBD or DLB diagnosis.

Today, the term Alzheimer’s Disease and Related Dementias (ADRD) is used by the National Institutes of Health (NIH) and other organizations to collectively refer to neurodegenerative causes of dementia. To further clarify, ADRD is defined to include Lewy body dementia (LBD) as well as frontotemporal degeneration (FTD), vascular contributions to cognitive impairment/dementia (VCID), and mixed etiology dementias (MED).

Lewy body dementia (LBD)

is characterized by abnormal deposits of the protein alpha-synuclein in the brain.

The pathology was first described by a German neurologist named Dr. Friedrich H. Lewy in his studies of Parkinson’s disease (1912-13). His findings were confirmed by Dr. Konstantin Tretiakoff, a Russian neuropathologist, who coined the term “Lewy bodies” (1919, 1921).

A half-century later, dementia with Lewy bodies (DLB) was first described by Dr. Kenji Kosaka, a Japanese psychiatrist (1976).

The build-up of Lewy bodies interferes with neurotransmitters (chemical messengers) in the brain, and causes neurons to die.

What symptoms are associated with LBD?

All LBD patients present with dementia: progressive cognitive decline to the extent that it interferes with normal activities of daily living. Not all patients present with the same set of symptoms, and these may change with disease progression.

• Fluctuating cognition, periods of confusion, lack of focus or attention • Trouble with executive function: thinking, judgment and decision-making • Recurrent visual hallucinations • Parkinsonism (bradykinesia, rest tremor, rigidity, balance issues) • REM sleep behavior disorder, hypersomnia, hyposomnia • Visuo-spatial deficits • Memory impairment • Difficulty with language, word-finding, conversation • Postural instability, repeated falls, syncope • Anxiety, apathy, agitation, depression • Autonomic dysfunction (for example, incontinence, constipation) • Severe sensitivity to certain medications (anti-psychotics, opioids)

LBD patients need an advocate.

Even in early stages of the disease, people may have difficulty organizing and expressing thoughts, needs and feelings.

They may exhibit “showtime” behavior, masking the fact that they are confused by test results or discharge instructions. They may be unable to say if a medication is working or describe pain or other problems.

Healthcare professionals need to bring the family caregiver into the conversation in healthcare settings from clinic to hospital.

What steps are taken to form a diagnosis?

Depending upon the health system, the physician(s) and the patient, evaluation and testing may include a combination of the following:

• Evaluation of patient’s medical history/physical examination • Neurological examination for Parkinsonism • Cognitive Screening (MoCA/MMSE/Mini-Cog),

Neuropsychological Testing • Brain Imaging—MRI, CT, PET, EEG • Bloodwork, cerebrospinal fluid testing • Functional Activities/ADLs (Activities of Daily Living) • Sleep Study

When LBD is suspected, researchers and physicians often use the “one-year rule” for diagnosis: onset of dementia within one year of parkinsonism qualifies as dementia with Lewy bodies (DLB), and onset of dementia more than one year after parkinsonism qualifies as Parkinson's disease dementia (PDD).

Diagnosis can be challenging for a number of reasons beyond the current lack of a definitive test for LBD. People may not recognize, understand or accept symptoms they are experiencing, or they may rationalize their symptoms as part of normal aging. People in these cases are less likely to discuss symptoms with their doctor or family members. Doctors with no training or experience with DLB patients may not recognize symptoms in their patients, particularly during medical visits of short duration.

A physician may refer a patient presenting with LBD symptoms to a specialist for a second opinion. For example, a neurologist specializing in movement disorders may refer a patient to a geriatric psychiatrist for additional evaluation and testing. Given that LBD involves a combination of cognitive, motor and behavioral symptoms, a second opinion can provide important insights in forming a differential diagnosis.

What are the stages of LBD progression, the prognosis?

The stages of progression are often described as early, middle and late stage dementia. While symptoms and progression vary among people with any type of dementia, during the early stage people may still be able to function independently but may experience problems with planning, decision making and other activities. In the middle stage, cognitive decline continues while behavior changes and physical symptoms may become more pronounced and the need for caregiver support increases. In late-stage dementia people typically require full-time care and support that may involve transition to a memory care facility.

LBD typically occurs in people aged 50 or older, with 67 being the average age of symptom onset and 76.3 the average age of formal diagnosis. Life expectancy for people with LBD is about 5 to 8 years from time of diagnosis, but survival can vary on both sides of this range.

How is LBD treated, and what are key challenges to treatment?

Currently there is no cure for Lewy body dementia, and as yet, no drug has been approved by the FDA for treatment of the disease.

Drugs such as donepezil or rivastigmine (acetylcholinesterase inhibitors) are used primarily to treat a patient’s cognitive symptoms. People with LBD tend to be highly sensitive to certain medications including antipsychotics or sedatives used to treat behavioral symptoms. Thus, physicians may avoid or exercise caution in prescribing them to avoid risk of worsening some LBD symptoms or other potential harms.

Advances in healthcare include increased use of palliative care and management of behavioral symptoms with non-medication alternatives such as improved caregiver training and support, creative activities involving music and art, and innovative solutions for lighting, housing design and other environmental elements of daily living.

What types of research studies/trials are underway?

As of this writing, the clinicaltrials.gov database lists a small number of clinical trials related to LBD. Among these, 41 are recruiting, 12 are not yet recruiting, 7 are recruiting by invitation, 6 are active, 52 are completed and 5 were terminated.

In November 2021, phase 2 clinical trial results were published for an investigational drug, neflamapimod, demonstrating disease-modifying potential for dementia with Lewy bodies (EIP Pharmaceutical). This type of news is encouraging given the many challenges to LBD research, from trial design and patient recruitment to diagnostic criteria, use of biomarkers, and demands on patients participating in clinical trials.

What are the key risk factors – keys to prevention?

With more research, scientists will continue to learn more about risk factors for LBD. Some of the known risk factors for LBD include:

• Age • REM sleep behavior disorder • Parkinson’s disease • Family history of LBD (variants in APOE, SNCA and GBA genes may indicate risk) Science tells us that diseases associated with dementia may begin to impact the brain long before symptoms appear. Increasingly, physicians are encouraging patients to adopt brain healthy lifestyle choices—good nutrition, regular exercise, lifelong learning, social engagement, sufficient sleep of good quality, avoidance of substance abuse, treatment for depression—early in life, to help reduce or avoid risk of dementia in our later years.

Disclaimer

The information in this article is for informational purposes only and is not intended or implied to be a substitute for professional medical advice, diagnosis or treatment. Mention of drugs or medications or their manufacturers does not constitute an endorsement, recommendation, prescription or directive of any kind.

About the Author

Robin Shepherd is the Executive Director and co-founder of The Sue’s Story Project (thesuesstoryproject.com), an initiative that seeks to increase awareness, caregiver resources, and research funding to find a cure for Lewy body dementia, a fatal neurodegenerative disease. Robin can be reached at shepherdrobin7@gmail.com or (408) 458-6102.

RESOURCES

https://www.ninds.nih.gov/Disorders/All-Disorders/Dementia-Lewy-Bodies-Information-Page https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496518/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782269/ https://pubmed.ncbi.nlm.nih.gov/28592453/ https://www.nia.nih.gov/health/diagnosing-lewy-body-dementia-professionals https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181810/ https://medlineplus.gov/genetics/condition/dementia-with-lewy-bodies/#causes