Lewy Body Dementia

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia after Alzheimer disease, accounting for 15-25% of all dementias. It is characterized by the abnormal accumulation of alpha-synuclein protein aggregates (Lewy bodies) within cortical and subcortical neurons. Alpha-synuclein is a presynaptic protein involved in neurotransmitter vesicle trafficking; in DLB, it misfolds and aggregates into insoluble intracytoplasmic inclusion bodies that disrupt neuronal function and eventually cause cell death. Lewy bodies are distributed throughout the neocortex, limbic system, brainstem, and substantia nigra, producing the characteristic combination of cognitive, psychiatric, motor, and autonomic symptoms. Cortical Lewy bodies cause progressive cognitive decline with prominent deficits in attention, executive function, and visuospatial processing (unlike Alzheimer disease, where memory loss is the earliest and most prominent feature). Brainstem and substantia nigra Lewy bodies cause parkinsonian motor features (rigidity, bradykinesia, postural instability) through dopaminergic neuron loss. Limbic system involvement produces the hallmark visual hallucinations and fluctuating cognition. The four core clinical features of DLB are: (1) Fluctuating cognition with pronounced variations in attention and alertness (the patient may appear lucid one hour and severely confused...