Lewy body dementia

Dementia with Lewy body is a common form of dementia characterised by the finding of Lewy bodies on pathology.

Dementia with Lewy body (DLB), also known as Lewy body dementia, is a common subtype of dementia that is characterised by the histopathological findings of intracytoplasmic inclusions known as Lewy bodies that contain alpha-synuclein. It is a distinctive form of dementia due to its clinical features. Typical features of DLB include visual hallucinations, parkinsonism, cognitive fluctuations, dysautonomia (abnormalities in the autonomic nervous system), sleep disorders, and sensitivity to antipsychotic medications (i.e. neuroleptics).

Dementia

Dementia describes a clinical syndrome that is characterised by a significant deterioration in mental function that leads impairment of normal function.

In healthcare, we measure ‘normal function’ by activities of daily living (ADLs). These are a series of routine activities that people should be able to do without assistance. They can be broadly divided into personal tasks and domestic tasks.

• Personal: washing, dressing, toileting, continence, transferring (e.g. bed to chair)
• Domestic: cooking, cleaning, shopping, managing finances, taking medication

Types of dementia

Dementia can be caused by several conditions, which all manifest with poor mental performance and impaired normal functioning. The clinical manifestations of dementia can reflect the underlying aetiology.

• Alzheimer’s disease (AD): 50-75%
• Vascular dementia (VD): 20%
• Dementia with Lewy-body (DLB): 15-20%
• Frontotemporal dementia (FTD): 2%
• Rare causes: Parkinson’s disease dementia (PDD), Huntington’s disease (HD), Prion disease, others.

DLB accounts for up to 20% of cases of dementia.

DLB is the third most common cause of dementia and the prevalence of the condition increases with age. The average age of presentation is 75 years old and it is more frequently observed in males with a 4:1 male-to-female ratio.

It is important to understand the distinction between Parkinson’s disease with dementia and DLB.

Parkinson’s disease dementia (PDD) and DLB are two similar conditions that each present with deterioration in mental functioning and features of Parkinsonism (e.g. bradykinesia, tremor, postural instability, rigidity).

There is an arbitrary distinction between them based on a one year timeframe:

• Parkinson’s disease dementia: dementia occurring in the setting of established Parkinson’s disease. This is defined as having Parkinson’s disease for more than one year before the onset of dementia.
• Dementia with Lewy body: development of dementia and Parkinsonism concurrently. This is defined as developing dementia within one year of Parkinsonism features

Patients with DLB usually have an older age of onset, faster cognitive decline, and reduced responsiveness to antiparkinson medications (e.g. levodopa).

The exact aetiology of DLB remains unknown.

The exact cause of DLB remains unknown but it is characterised by the presence of Lewy bodies. These are intracytoplasmic inclusions of alpha-synuclein that may be found throughout the cerebral cortex and brainstem. Alpha-synuclein is found throughout the brain and expressed in presynaptic membranes. It is suspected to play a role in neurotransmitter release and vesicle turnover. Interestingly, dopaminergic neurones (those that involve the release of dopamine) are found to be more susceptible to dysfunction of alpha-synuclein.

How Lewy bodies link to the development of clinical features of DLB is unclear. Some studies have shown that the specific location and density of Lewy bodies correlate with specific features (e.g. visual hallucinations associated with Lewy bodies in areas of the temporal lobes).

Both genetic and acquired factors are suspected to be important in predisposing an individual to develop DLB. Several genetic mutations have been identified that are associated with the development of DLB, which include SNCA, PSEN1/PSEN2, APOE, and APP. Confusingly, these mutations may be associated with other neurodegenerative disorders (e.g. Alzheimer’s disease).

DLB is characterised by fluctuating cognition, visual hallucinations, Parkinsonism, and sleep disorders.

Dementia can be difficult to identify due to insidious and non-specific symptoms. Many clinical features are attributable to dementia. Some are characteristic of all dementias whereas others are typical of a particular type, like AD or DLB.

The clinical features of dementia can be considered in the following domains:

• Cognitive impairment: poor memory, disorientation, language problems
• Behavioural and psychological symptoms of dementia (BPSD): agitation, depression, sleep cycle disturbance, motor disturbance
• Disease-specific features: DLB is characterised by Parkinsonism (tremor, rigidity, bradykinesia, postural instability), visual hallucinations, and REM sleep disorders
• Activities of daily living: an increasing reliance on others for assistance, problems with high-level functioning (e.g. work, finance), problems with basic personal care

Core features of DLB

There are several core clinical features that are specific to DLB. These include:

• Fluctuating cognition with pronounced variations in attention and alertness
• Recurrent visual hallucinations that are typically well formed and detailed
• REM sleep behaviour disorder, which may precede cognitive decline
• One or more spontaneous cardinal features of parkinsonism (e.g. bradykinesia, rest tremor, rigidity)

Supportive clinical features

Several clinical features are supportive of a diagnosis of DLB. These combined with general features of dementia help to make the diagnosis. These supporting clinical features can include:

• Severe sensitivity to antipsychotic agents
• Postural instability and repeated falls
• Syncope or other transient episodes of unresponsiveness
• Severe autonomic dysfunction (eg, constipation, orthostatic hypotension, urinary incontinence)
• Hypersomnia (i.e. excessive daytime sleepiness)
• Hyposmia (i.e. decreased sense of smell)

A formal mental status examination should be completed using a recognised cognitive assessment tool.

When assessing patients with suspected DLB it is first important to establish a diagnosis of dementia through well-validated cognitive assessment tools (e.g. Montreal Cognitive Assessment). These cognitive assessment tools are designed to test different areas of higher cortical functioning. Cognitive domains assessed include:

• Attention and concentration
• Recent and remote memory
• Language
• Praxis: planned motor movement (e.g. perform a task)
• Executive function
• Visuospatial function

There are a variety of different cognitive assessment tools that range from basic screening tools to in-depth assessments of each cognitive domain.

A comprehensive summary of cognitive assessment tools can be found in our Dementia note.

The diagnosis of DLB is largely based on the history and examination.

The diagnostic criteria for DLB are predominantly based on the finding of core clinical features of DLB. Using these, the likelihood of the diagnosis can be divided into probable, possible, and less likely.

• Probable DLB: ≥2 core clinical features OR one core clinical feature with ≥1 biomarker
• Possible DLB: only one core clinical feature and no biomarker OR ≥1 biomarker and no core clinical features
• Less likely DLB: the presence of another that could account for symptoms OR parkinsonian features are the only core clinical feature and appear for the first time at a stage of severe dementia

Biomarkers represent the results of more invasive testing to provide evidence for the diagnosis of DLB based on specialist neuroimaging (e.g. SPECT - looks at dopamine uptake within the brain), polysomnography (assesses for REM sleep disorders), or other modalities (e.g. EEG, MRI)

Other investigations may be completed as part of the work-up for dementia to exclude an alternative cause of confusion. This is usually part of a ‘confusion screen’ and is discussed more in our Dementia note.

The management of DLB is complex.

There are many drug therapies that may be used to help with managing different aspects of DLB. However, it is important to treat the patient holistically using a biopsychosocial model. For a broad overview of the non-pharmacological aspects to the management of all types of dementia check out our Dementia note.

Pharmacological interventions

Several drug therapies may be tried in patients with DLB.

• Cholinesterase inhibitors (e.g. Rivastigmine, Donepezil): generally offered as first-line treatments for patients with DLB and troublesome cognitive/behavioural symptoms
• Memantine: often used in severe AD or VD but limited efficacy in DLB
• Anti-psychotics (e.g. Quetiapine): due to their anti-dopaminergic effects these may worsen symptoms in patients with DLB. These patients are particularly sensitive to their effects and some adverse events may be severe (e.g. confusion, autonomic dysfunction). They are generally reserved for severe, refractory behavioural symptoms
• Melatonin: may be used in refractory REM sleep disorders
• Levodopa: this is an antiparkinson medication that may be used for severe, disabling Parkinsonism features

Other drug therapies may be used depending on co-existent symptoms (e.g. urinary symptoms, orthostatic hypotension).

The estimated mean survival in patients with DLB is 6.1 years.

Factors associated with a worse prognosis include cognitive fluctuations, early hallucinations, and gait abnormalities. The majority of patients with DLB have features of Parkinsonism and these will worsen over time. Finally, it is estimated that the cognitive decline in DLB occurs faster than in patients with AD.

Last updated: May 2022