The main purpose of this study is to evaluate whether treatment with donanemab slows the progression of cognitive (how we think, learn, remember, pay attention, and make decisions) and functional (how we are able to perform daily activities) decline. For each participant, the study will last one and a half years.

Inclusion Criteria:

• Have gradual and progressive cognitive decline for greater than or equal to ( ≥) 6 months.
• Have least 1 core clinical feature of dementia with Lewy bodies (DLB).
• Have a score ≥20 on Montreal Cognitive Assessment (MoCA).
• Meet plasma P-tau217 criteria.
• Have a cerebrospinal fluid (CSF) result consistent with the presence of brain amyloid pathology.
• Have a CSF result consistent with the presence of alpha-synuclein pathology.
• Have at least 1 reliable study partner who will provide written informed consent to participate, is in frequent contact with the participant, and is familiar with overall function and behavior, such as day-to-day activities and cognitive abilities.

Exclusion Criteria:

• Have a disease or condition that could interfere with this study or is a current serious or unstable illness.
• Have, or is suspected to have, a significant neurological disease (other than the studied condition) that affects the central nervous system and may affect the individual's cognition or ability to complete the study.
• Have a history of cancer that, in the investigator's opinion, has a high risk of recurrence and preventing the completion of the study.
• Have clinically significant multiple or severe drug allergies, significant atopy, or severe posttreatment hypersensitivity reactions.
• Have previously received amyloid-targeting therapy.
• Active immunization against amyloid-beta.
• Have a centrally read MRI that does not meet study entry criteria.
• Have contraindication to MRI or PET scans.
• Have any contraindication to lumbar puncture.

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Data are available 6 months after the primary publication or approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.

A research proposal should be approved by an independent review panel and researchers should sign a data sharing agreement.