What is Lewy body dementia?

What is Lewy Body Dementia?

Lewy body dementia (LBD) is a neurodegenerative disorder characterized by abnormal accumulation of alpha-synuclein protein forming Lewy bodies in the brain, presenting with a distinctive clinical triad of fluctuating cognition, recurrent visual hallucinations, and parkinsonism. 1, 2

Definition and Epidemiology

• LBD is an umbrella term encompassing two closely related conditions: dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD), distinguished primarily by the timing of cognitive symptoms relative to motor symptoms 3
• It represents the second most common cause of neurodegenerative dementia in older adults, accounting for up to 15% of dementia cases 4, 5
• The disease is characterized by abnormal deposits of alpha-synuclein protein that aggregate to form Lewy bodies and Lewy neurites throughout the brain 4, 6

Core Clinical Features

The diagnosis relies on recognizing a constellation of hallmark symptoms that distinguish LBD from other dementias:

Fluctuating Cognition

• Pronounced variations in attention, alertness, and cognitive function that can occur over minutes, hours, or days 1, 6
• These fluctuations manifest as cognitive changes secondary to impairments in attention or somnolence, and can be assessed using scales such as the Mayo Fluctuations Scale or Clinician Assessment of Fluctuation 6

Recurrent Visual Hallucinations

• Typically well-formed, detailed visual hallucinations that often involve people, animals, or objects 1, 6
• This feature is not characteristic of Alzheimer's disease and strongly suggests alternative pathology 2

Parkinsonism

• Spontaneous extrapyramidal motor symptoms including bradykinesia, rigidity, tremor, and postural instability 1, 6
• These motor features are common but not essential for diagnosis 7

REM Sleep Behavior Disorder (RBD)

• Acting out dreams during sleep due to lack of normal muscle paralysis during REM sleep 1, 6
• This symptom may precede cognitive symptoms by years and is highly characteristic of LBD 1

Pathophysiology and Disease Progression

• The disease is characterized by abnormal accumulation of α-synuclein within inclusions called Lewy bodies, as well as α-synuclein-immunoreactive neurites and diffuse cytoplasmic immunoreactivity 4, 6
• Disease progression typically follows a stereotyped pattern: initial Lewy body deposition 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, 6
• LBD can be classified into five categories based on distribution: none, brainstem-predominant, limbic (transitional), neocortical (diffuse), or amygdala-predominant 4, 6
• Neocortical Lewy body disease is considered adequate explanation for cognitive impairment or dementia 4, 6

Coexisting Pathology

• LBD frequently coexists with Alzheimer's disease pathology, particularly in older individuals, with Lewy bodies being frequent in the setting of moderate-to-severe Alzheimer's disease neuropathologic changes 4, 6
• Up to 50% of LBD cases have coexistent AD pathology, and most patients over 80 have mixed etiology dementia 1, 2
• Mixed pathology (LBD + Alzheimer's) occurs in over 50% of LBD cases, highlighting the complexity of diagnosis and treatment 1

Diagnostic Approach

• The clinical phenotype trumps biomarkers in diagnosing LBD, with diagnosis relying on the presence of core clinical features rather than biomarker results alone 2
• The presence of core features such as fluctuating cognition, visual hallucinations, parkinsonism, or RBD indicates LBD as the primary diagnosis, even if amyloid biomarkers are positive 2
• Decreased striatal dopamine transporter uptake on DaTscan (I-123 ioflupane SPECT) is a suggestive diagnostic feature for LBD and is abnormal in LBD but normal in Alzheimer's disease 4, 1
• MRI of the brain without IV contrast serves as first-line imaging to exclude secondary causes and assess for relative preservation of medial temporal lobe structures, which supports LBD over Alzheimer's disease 4, 1
• FDG-PET may show a LBD pattern with generalized low uptake, occipital hypometabolism, and the "cingulate island sign" 4, 1

Clinical Implications and Management Priorities

Critical Treatment Considerations

• Traditional antipsychotics must be absolutely avoided due to severe neuroleptic sensitivity that significantly increases morbidity and mortality 1, 2, 5
• Cholinesterase inhibitors (particularly rivastigmine or donepezil) are first-line treatment for both cognitive symptoms and visual hallucinations in LBD 1, 6, 5
• Levodopa should be used cautiously for motor symptoms, as dopaminergic agents carry risk of inducing or worsening psychotic symptoms 1
• Memantine may also be considered as an alternative or adjunctive treatment for cognitive symptoms 6, 8

Cognitive Assessment

• The Montreal Cognitive Assessment (MoCA) is more valid than the MMSE for LBD because it includes items assessing attention and executive functions like working memory, making it more sensitive for detecting cognitive impairment in LBD 6
• Neuropsychological testing should focus on attention, executive function, and visuospatial abilities as these domains are characteristically impaired in LBD 6

Non-Pharmacological Management

• Patient and caregiver education about the nature of hallucinations can significantly reduce anxiety and fear 6
• Simple coping strategies like eye movements, changing lighting, or distraction techniques can be effective in managing hallucinations 6
• Structured activities, calming measures, and support for family and caregivers should be implemented to help manage psychotic symptoms 6

Prognosis and Impact

• LBD is associated with a poorer prognosis, higher healthcare costs, and greater impact on quality of life compared to Alzheimer's disease 1
• The disease is often subject to significant delays in diagnosis and treatment, increasing the burden on patients and family care partners 3
• Recognition of hallmark symptoms is crucial for appropriate management, as patients with LBD have unique treatment considerations 1