Dementia with Lewy bodies

DLB is diagnosed on the basis of core clinical features: fluctuating cognition with pronounced variations in attention and alertness, recurrent visual hallucinations that are typically well-formed and detailed, and spontaneous features of parkinsonism such as bradykinesia, rigidity, and gait disturbance.¹ Supportive features include REM sleep behavior disorder, severe neuroleptic sensitivity, and low dopamine transporter uptake in the basal ganglia on imaging. Diagnosis is often delayed because early symptoms overlap with Alzheimer's disease and Parkinson's disease, and definitive diagnosis requires neuropathological examination.²

The hallmark of DLB is the presence of Lewy bodies, intraneuronal inclusions composed primarily of misfolded alpha-synuclein, distributed throughout cortical and brainstem regions.³ These aggregates disrupt synaptic function and lead to neuronal death, particularly in cholinergic and dopaminergic pathways. The overlap with Alzheimer's pathology—amyloid plaques and neurofibrillary tangles—is common, and the degree of concurrent Alzheimer's changes influences the clinical phenotype and rate of decline.⁴ Genetic factors, including mutations in the SNCA gene and variations in APOE, contribute to risk, but most cases are sporadic.

There is no cure for DLB; management focuses on symptom relief and improving quality of life. Cholinesterase inhibitors, such as rivastigmine, are used to address cognitive and psychiatric symptoms, and may also reduce hallucinations.⁵ Levodopa can be used cautiously for parkinsonism, but it often exacerbates hallucinations and confusion. A critical aspect of care is avoiding typical antipsychotics, as DLB patients can experience severe, sometimes fatal, neuroleptic sensitivity reactions.¹ Non-pharmacological approaches, including caregiver education and environmental modifications, are essential.

Beyond the core features, DLB is associated with a range of lesser-known manifestations. Autonomic dysfunction is common, leading to orthostatic hypotension, urinary incontinence, and constipation, which can precede cognitive symptoms by years.⁶ Severe hyposmia (loss of smell) is an early indicator, and sleep studies often reveal REM sleep behavior disorder as a prodromal marker. DLB also shows a striking sensitivity to anticholinergic medications, which can precipitate delirium. The condition was historically underdiagnosed, and many patients were misclassified as having Alzheimer's disease; improved diagnostic criteria have increased recognition. Additionally, DLB is associated with a higher risk of falls and fractures, and patients may exhibit a characteristic 'sensitivity' to certain anesthetics, complicating surgical care.

Alpha-synuclein

A protein that aggregates to form Lewy bodies in DLB and other synucleinopathies.

REM sleep behavior disorder

A parasomnia in which patients act out vivid dreams, often a prodromal feature of DLB.

Neuroleptic sensitivity

A severe adverse reaction to antipsychotic medications, characterized by worsened parkinsonism and confusion, common in DLB.