11th August 2024

Lewy body dementia

Overview of Lewy body dementia

Lewy body dementia (LBD) is conventionally understood to be on the same spectrum as Parkinson’s disease dementia (PDD), but nomenclature is dependent on whether cognitive impairment precedes motor symptoms of Parkinsonism (defined as LBD) or vice versa, i.e. PDD. It often co-exists with Alzheimer’s and vascular dementia.

The microscopic histopathological hallmark of LBD is intracellular neural Lewy bodies (formed of α-synuclein) distributed in three typical sites (cortex, brainstem and limbic areas). These stain with haematoxylin-eosin and α-synuclein histochemistry. Macroscopically, there is pallor of the substantia nigra and locus coeruleus and diffuse cerebral atrophy.

The cognitive presentation is similar to Alzheimer’s, however there is predominance of problems affecting executive, visuospatial and attentional functions with relatively less involvement of memory.

The key distinguishing features are:

• Fluctuations in cognition (attention and alertness)
• Visual hallucinations in up to 60% of patients – typically formed people or animals and usually not distressing (compared to psychiatric hallucinations); alternatively a sense of a ‘presence’
• Parkinsonism – eventually seen in most cases, depending on LBD/PDD, may predate or follow cognitive symptoms. Bradykinesia, rigidity, gait impairment and autonomic dysfunction

Other common features include:

• Rapid eye movement (REM) sleep behavioural disturbance
• Daytime somnolence
• Autonomic dysfunction (falls, syncope, postural hypotension, constipation, urinary urge, frequency and incontinence)
• Mood disturbance, including anxiety and depression

Diagnosis of Lewy body dementia

Although brain imaging is recommended at least once in dementia work up, there are no specific structural imaging features of LBD. Single-photon emission CT (SPECT) or PET can help differentiate between LBD and Alzheimer’s and will show reduced uptake of dopamine transporter uptake in the basal ganglia.

CSF examination is usually carried out in atypical presentations to exclude infection.

Referral to a sleep specialist and for polysomnography is advised as REM sleep without atonia is a suggestive feature of LBD.

Management of Lewy body dementia

Management is targeted at symptoms and supportive measures. Given the underlying deficits are of choline and dopamine neurotransmission, priority review of medications is important to avoid anticholinergics and dopamine agonists to reduce exacerbation of autonomic, motor and psychiatric symptoms. First-generation antipsychotics (haloperidol) should be avoided and patients tend to be very sensitive to atypical antipsychotics.

First-line treatments are anticholinesterase treatments such as donepezil and rivastigmine, which act to improve cognition and behavioural symptoms without significant worsening of motor symptoms, however side effects may include nausea and vomiting, runny nose, muscle cramps, hypersalivation, vivid dreams and postural hypotension.

Clonazepam in low doses is effective for REM sleep behaviour disturbance.

SSRIs are choice antidepressants, avoiding tricyclics that have anticholinergic effects.

Levodopa can be considered in specialist use if motor symptoms are significantly problematic.