What is Lewy body dementia?

Lewy Body Dementia: Definition, Diagnosis, and Management

Lewy body dementia (LBD) is the second most common form of neurodegenerative dementia characterized by abnormal deposits of alpha-synuclein protein (Lewy bodies) in the brain, particularly affecting the cortex and subcortical regions, causing cognitive impairment, visual hallucinations, parkinsonism, and sleep disturbances. 1, 2

Core Clinical Features

• Fluctuating cognition with pronounced variations in attention, alertness, and cognitive function that can occur over minutes, hours, or days 1
• Recurrent visual hallucinations that are typically well-formed and detailed, often involving people, animals, or objects 1, 3
• Parkinsonism characterized by bradykinesia, rigidity, tremor, and postural instability 1
• REM sleep behavior disorder (RBD) where patients act out dreams due to lack of normal muscle paralysis during REM sleep, which may precede cognitive symptoms by years 1, 4

Pathophysiology

• LBD is characterized by abnormal accumulation of α-synuclein within inclusions called Lewy bodies (LBs), as well as α-synuclein-immunoreactive neurites and diffuse cytoplasmic immunoreactivity 5, 1
• Disease progression typically follows a pattern where Lewy body deposition begins in the medulla oblongata, pontine tegmentum, and olfactory system, followed by involvement of the substantia nigra and other deep gray nuclei, and finally deposition in the cortex 1
• LBD can be classified into five categories based on distribution: none, brainstem-predominant, limbic (transitional), neocortical (diffuse), or amygdala-predominant 5
• LBD frequently coexists with Alzheimer's disease pathology, particularly in older individuals 5

Diagnostic Classification

• Neocortical LBD is considered an adequate explanation for cognitive impairment or dementia 5
• Brainstem-predominant LBD in the setting of cognitive impairment should prompt consideration of other diseases 5
• Amygdala-predominant LBD typically occurs in the context of advanced Alzheimer's disease neuropathologic changes 5
• Immunohistochemistry for α-synuclein is strongly preferred over H&E staining for detecting Lewy bodies due to greater sensitivity 5

Supportive Features and Associated Symptoms

• Transient episodes of unresponsiveness related to fluctuations in attention and consciousness 1
• Autonomic dysfunction including orthostatic hypotension, urinary incontinence, and constipation 1
• Sleep disturbances may be present in as many as 90% of people with LBD 4
• Neuropsychiatric symptoms are common and can significantly impact quality of life 2, 6

Diagnostic Approaches

• Clinical diagnosis relies on identifying core features: fluctuating cognition, visual hallucinations, parkinsonism, and REM sleep behavior disorder 1, 3
• Diagnostic biomarkers include:
  • Dopamine transporter imaging to detect nigrostriatal dopaminergic degeneration 7
  • Meta-iodobenzylguanidine (MIBG) myocardial scintigraphy to assess cardiac sympathetic denervation 7
  • Polysomnography to confirm REM sleep behavior disorder 7
  • Quantitative EEG showing specific patterns that may help differentiate LBD from other dementias 8

Management Strategies

Non-pharmacological Approaches

• Patient and caregiver education about the nature of hallucinations can significantly reduce anxiety and fear 3
• Simple coping strategies like eye movements, changing lighting, or distraction techniques can be effective in managing hallucinations 3
• Structured activities, calming measures, and support for family and caregivers should be implemented to help manage psychotic symptoms 9

Pharmacological Management

• Cholinesterase inhibitors are the Level-A recommendation for treating cognitive symptoms, visual hallucinations, and psychotic symptoms in LBD patients 7, 9
• Patients who experience clinically meaningful reduction in neuropsychiatric symptoms with cholinesterase inhibitors should continue treatment even if there is evidence of cognitive and functional decline 9
• Traditional antipsychotics should be avoided due to severe neuroleptic sensitivity, which can increase morbidity and mortality 1
• For motor symptoms, levodopa should be used carefully as dopamine agonists have the risk of inducing psychotic symptoms 7
• Melatonin and clonazepam are effective in controlling REM sleep behavior disorder 7

Clinical Challenges and Pitfalls

• LBD is often under-recognized and misdiagnosed, particularly in early stages 2
• Mixed neuropathology (LBD with Alzheimer's disease pathology) occurs in over 50% of people with LBD, complicating diagnosis 2
• Treatments may address one symptom but worsen another, making disease management difficult 6
• Symptoms are often managed in isolation and by different specialists, which makes high-quality care difficult to accomplish 6
• Regular monitoring using appropriate scales such as the Neuropsychiatric Inventory (NPI) is essential to assess symptom progression and treatment effectiveness 9, 3