Lewy body dementia (LBD) is the second most common form of dementia after Alzheimer’s disease, but most people have never heard about it. Here, we overview the origin, types, symptoms, diagnosis and clinical management of Lewy Body dementia to better understand the disease and avoid misdiagnose. 

What causes Lewy body dementia?

Dementia is a condition that impairs the execution of daily activities, such as memory, decision-making and abstract thinking, caused by a progressive degeneration of the brain. In Lewy body dementia, a protein (α-synuclein) accumulates and forms aggregates (known as Lewy bodies and Lewy neurites) inside the neurons of the brain, leading to the misfunction and subsequent death of these cells.¹ 

Multiple, and yet not fully understood, factors can cause this protein accumulation. In some cases, Lewy body dementia is a genetic disease (caused by a mutation in a gene) and can be inherited.²

Types of Lewy body dementia

Clinicians distinguish two types of Lewy body dementias, following the 1-year rule of the onset of dementia:³

• Parkinson’s disease dementia (PDD): patients with a well-establish Parkinson’s disease develop dementia at least one year after the appearance of movement difficulties
• Dementia with Lewy bodies (DLB): dementia develops before or within one year of the motor symptoms

The main difference between DLB and PDD is the temporal onset of the symptoms, and these diseases share associated changes in the nervous system. Thus, some researchers suggest it is the same disease, which has a spectrum of expression.⁴

Epidemiology of Lewy body dementias

Lewy body dementias are age-related diseases. Older people are at the highest risk, especially between 70 and 85, but some cases before 65 have also been reported.^1,10 Moreover, the disease is more common in persons assigned male at birth (AMAB). Time is another risk factor for patients with Parkinson's disease, as the longer they live with it, the higher the risk of developing dementia.²

In the UK, a 2018 study based on data from secondary care services concluded that 4.2% of dementia cases were DLB and 9.7% of patients with PDD.¹¹ However, population studies are challenged because patients with DLB are usually misdiagnosed with Alzheimer’s disease. 

What are the symptoms of Lewy body dementias?

Clinical manifestations of DLB and PDD are almost undistinguishable. Among the symptoms associated with these diseases, there are some more frequent (core) than others (supportive). As these are neurodegenerative disorders, symptoms get worse over time and their intensity varies between patients, who may not develop all.⁵

Core symptoms

• Cognitive fluctuations: patients experience deficit of attention and alterations in the levels of alertness and clarity of mind. They seem moody and unable to multitask. Relatives and caregivers may find them staring or absent
• Visual hallucinations: patients see well-formed and complex situations involving people and animals. They are conscious when these realistic visions appear and can often explain them to others. Patient reactions to hallucinations are diverse. This symptom is more frequent in DLB than PDD and other modalities, such as auditory, are less common in both⁶
• Parkinsonism: DLB patients suffer Parkinsonian motor symptoms such as slowness of movement (bradykinesia), walking alterations, rest tremor while sitting or lying and rigidity
• Rapid eye movement (REM) sleep behaviour disorder (RBD): patients experience vivid dreams and start kicking, punching, and yelling while sleeping, leading to injuries in their bed’s partner. This symptom usually appears years before the others. Other sleep disorders, like insomnia or excessive somnolence, may also appear less frequently in DLB¹

Supportive symptoms

• High sensitivity to antipsychotics
• Delusions, especially paranoid behaviour, develop at later stages and are less common in PDD³
• Autonomic dysfunction, meaning that the part of the nervous system in charge of maintaining functional balance does not work correctly. Patients may suffer urinary incontinence, constipation or feel dizzy after standing up because blood pressure drops (orthostatic hypotension)
• Depression, anxiety and lack of motivation, usually appear at early stages
• Hyposmia
• Frequent falls

In addition to the symptoms, researchers have identified several biomarkers, which are also subdivided based on their frequency. For example, reduced reabsorption of dopamine in the basal ganglia is an indicative biomarker and slower electrical rhythms in the back of the brain is a supportive biomarker. For more information about the biomarkers of Lewy body dementia, see the review of the DLB Consortium.⁵

Diagnosis of Lewy bodies dementia

A well-established Parkinson’s disease makes it easier to diagnose PDD. As for DLB, clinicians distinguish between a probable and a possible diagnosis of DLB based on the presence of the characteristic symptoms and biomarkers:⁵ 

• Probable DLB: patients have two core symptoms or one core symptom and an indicative biomarker
• Possible DLB: patients have one core symptom or one indicative biomarker, but not both

Diagnosis criterion is highly specific, which prevents false positive patients. However, its low sensitivity leads to missing many true cases.³ More research is needed on DLB to better delineate its clinical symptoms and temporal onset. Moreover, family members and caregivers of the elderly should be aware to recognize early symptoms. Early detection is crucial in providing timely care and support.  

What differentiates dementia with Lewy bodies from other diseases?

Early diagnosis of DLB is a challenge for clinicians, as its symptoms are very similar to other types of dementia. Thus, it is important that caregivers pay attention to the temporal onset of the symptoms: 

• Cognitive fluctuations may appear in dementias from different origin, but their early onset is characteristic of DLB⁵
• Hallucinations and parkinsonism are uncommon in other dementias but DLB and PDD. When present, they occur at advanced stages³
• Memory dysfunction may develop in patients with Lewy body dementias, but it is not a symptom as usual as in Alzheimer’s disease¹
• Evidence of a severe insult is key to differentiate DLB from delirium⁷

Clinical management of Lewy body dementias

An accurate diagnosis is essential to recommend the right treatment, as treatments for other types of dementia could even worsen the symptoms of Lewy body dementias. The best approach involves a combination of pharmacological and non-pharmacological treatments.⁷ 

Non-pharmacological treatments

Non-pharmacological treatments should be the first line to address these diseases and include:

• Intellectually demanding activities, such as playing chess, doing crosswords, paring words, etc
• Physical exercise
• Social stimulation
• Caregivers’ education, including diagnosis, explanation of situation to give better understanding of patient, preparing for emergencies and adjusting expectations. This is especially important because of the elevated levels of stress they experience⁸

Pharmacological treatments

The following treatments improve the quality of life of patients with Lewy body dementias but there is no medication that can reverse one or more of their symptoms.

• Avoid antipsychotic medications as much as possible
• Cholinesterase inhibitors (CHEIs), such as rivastigmine and donepezil. Cognitive fluctuations, hallucinations, and delusions may improve with donepezil in DLB but not PDD. On the other hand, rivastigmine may be beneficial for PDD⁹
• Memantine has shown mixed effects in several studies¹
• Levodopa is a common treatment for Parkinson’s disease and has been shown to be effective for motor symptoms in DLB, though to a lesser extent
• Antidepressants, such as escitalopram or sertraline should be taken with caution, as there is a risk for increasing the tremor³
• Melatonin for the sleeping disorders

Sources of support in the UK

• Lewy Body Society 
• Parkinson's UK 
• Dementia UK 

Summary

Lewy body dementia is the second most common type of dementia in the world, yet it remains largely unknown. They appear because of the abnormal aggregation of a protein inside brain cells, which start to malfunction and eventually die. 

Depending on the temporal onset of dementia, clinicians differentiate between dementia with Lewy bodies (DLB) and Parkinson’s disease dementia. Both are age-related diseases and are more frequent in people AMAB. Their main symptoms are cognitive fluctuations, visual hallucinations, motor difficulties, and vigorous sleeping disorder (RBD), although less frequent indicators have also been described. 

The diagnosis of these diseases is challenging because of the importance of the temporal window and lack of awareness; DLB is usually misdiagnosed as Alzheimer’s disease. The best treatment is a combination of non-pharmacological and pharmacological approaches.