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Dementia with Lewy bodies co-occurs with 2 specific syndromes, one beginning with dementia complicated by visual hallucinations and parkinsonism; the other beginning with Parkinson\u2019s disease and progressing to a parkinsonian-dementia syndrome. Clinical syndromes associated with these 2 pathways to dementia share many clinical features including the type of cognitive impairment, fluctuating attentional disturbances, prominent visual hallucinations and psychosis, depression, and rapid eye movement sleep behavior disorder. Lewy pathology results from protein misfolding and the accumulation of alpha-synuclein in the cell cytoplasm. Dementia with Lewy bodies is one of many neurodegenerative disorders linked to protein misfolding. Identification of clinical symptoms indicative of the presence of a specific protein disturbance will assist in choosing therapies when protein-specific disease-modifying treatments are available. Classification systems based on symptom complexes related to the presence of protein misfolding will assist therapeutic decisions. 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