dementia with Lewy bodies

dementia with Lewy bodies
Name	Dementia with Lewy bodies
Synonyms	Lewy body dementia, dementia due to Lewy body disease
Caption	A Lewy body (brown) in a neuron of the substantia nigra in Parkinson's disease, composed primarily of misfolded alpha-synuclein.
Field	Neurology, Psychiatry
Symptoms	Fluctuating cognition, visual hallucinations, parkinsonism, REM sleep behavior disorder
Complications	Falls, severe neuroleptic sensitivity, delirium
Onset	Typically after age 50
Duration	Progressive
Causes	Accumulation of alpha-synuclein protein into Lewy bodies in the brain
Risks	Advanced age, Parkinson's disease, REM sleep behavior disorder
Diagnosis	Clinical, based on consensus criteria (e.g., McKeith criteria)
Differential	Alzheimer's disease, Parkinson's disease dementia, vascular dementia, progressive supranuclear palsy
Prevention	Unknown
Treatment	Supportive care, cholinesterase inhibitors, cautious management of parkinsonism
Medication	Rivastigmine, donepezil, memantine; avoidance of typical antipsychotics
Prognosis	Progressive decline; average survival ~5–8 years after diagnosis
Frequency	~4% of dementia in older adults; second most common neurodegenerative dementia after Alzheimer's disease

dementia with Lewy bodies is a common type of progressive dementia characterized by the abnormal aggregation of the protein alpha-synuclein into intracellular inclusions known as Lewy bodies within the cerebral cortex. The core clinical features include pronounced fluctuations in attention and alertness, recurrent well-formed visual hallucinations, and spontaneous motor features of parkinsonism. It is recognized as the second most prevalent neurodegenerative dementia after Alzheimer's disease and shares significant pathological and clinical overlap with both Alzheimer's disease and Parkinson's disease dementia.

Signs and symptoms

The presentation is dominated by a triad of core features: fluctuating cognition with pronounced variations in attention and alertness, recurrent complex visual hallucinations, and spontaneous parkinsonism. Supportive clinical features include rapid eye movement sleep behavior disorder, severe sensitivity to antipsychotic medications, and low dopamine transporter uptake in the basal ganglia on functional imaging. Autonomic dysfunction, such as orthostatic hypotension and urinary incontinence, is also common. Neuropsychiatric symptoms like apathy, anxiety, and delusions frequently occur, while memory impairment may be less prominent early on compared to Alzheimer's disease.

Causes and pathophysiology

The primary cause is the abnormal accumulation of the presynaptic protein alpha-synuclein, which misfolds and aggregates to form Lewy bodies and Lewy neurites within neurons. This pathology, known as alpha-synucleinopathy, begins in the brainstem and olfactory bulb before spreading to the limbic system and neocortex. The exact trigger for this aggregation is unknown but is thought to involve genetic, environmental, and cellular factors. Neurochemically, there is a profound deficit of acetylcholine in the cerebral cortex and a loss of dopaminegic neurons in the substantia nigra, similar to that seen in Parkinson's disease. Co-existing Alzheimer's disease pathology, including amyloid plaques and neurofibrillary tangles, is frequently present.

Diagnosis

Diagnosis is clinical, based on established consensus criteria such as the McKeith criteria. There is no single definitive test; diagnosis relies on identifying the core and supportive clinical features. Magnetic resonance imaging may show relative preservation of the hippocampus compared to Alzheimer's disease. Functional neuroimaging like DaTscan (dopamine transporter scan) can demonstrate reduced dopaminergic activity in the basal ganglia. Electroencephalography may show background slowing with transient temporal slow waves. Differential diagnosis primarily includes Alzheimer's disease, Parkinson's disease dementia, vascular dementia, and other parkinsonian syndromes like progressive supranuclear palsy.

Management

Management is multidisciplinary and symptomatic, focusing on improving cognitive, psychiatric, and motor symptoms while minimizing adverse effects. Cholinesterase inhibitors such as rivastigmine and donepezil are first-line for cognitive and neuropsychiatric symptoms. The N-methyl-D-aspartate receptor antagonist memantine may also provide benefit. Parkinsonism is treated cautiously with low doses of levodopa, but response is often limited and can exacerbate hallucinations. Clonazepam or melatonin may be used for rapid eye movement sleep behavior disorder. Crucially, typical antipsychotics (e.g., haloperidol) must be avoided due to high risk of severe sensitivity reactions; atypical agents like quetiapine are used with extreme caution. Non-pharmacological approaches include physiotherapy, occupational therapy, and caregiver education.

Prognosis and epidemiology

The disease is progressive, with a median survival of approximately 5 to 8 years from diagnosis, though this varies widely. The course is often marked by frequent hospitalizations due to falls, infections, and delirium. It is estimated to account for about 4% of dementia cases in the community and 15-25% of dementia cases in autopsy series, making it the second most common neurodegenerative dementia. Incidence increases significantly with age, with most cases diagnosed after age 50. Major risk factors include advanced age, a history of REM sleep behavior disorder, and possibly Parkinson's disease in a first-degree relative.

History and nomenclature

The condition was first described in the early 20th century following the discovery of Lewy bodies by Dr. Friedrich H. Lewy while working in the laboratory of Alois Alzheimer. For decades, it was often misdiagnosed or considered a variant of Alzheimer's disease or Parkinson's disease. The distinct clinical and pathological entity gained formal recognition in the 1990s, culminating in the first consensus diagnostic criteria published by an international consortium led by Professor Ian G. McKeith in 1996. The nomenclature has evolved, with terms like "Lewy body dementia" serving as an umbrella category that includes both dementia with Lewy bodies and Parkinson's disease dementia, distinguished primarily by the temporal sequence of cognitive versus motor symptom onset.

Category:Dementia Category:Neurodegenerative disorders Category:Alpha-synucleinopathies