This is a randomized, cross-over study to measure global and clinical impact and level of arousal in subjects suffering from moderate to severe Alzheimer's disease when exposed to emotionally impactful music compared to control intervention.

In partnership with the study partner (a person who spends 10 hours or more a week with the subject and can reliably report on the subject's condition), three tunes will be chosen for the purposes of the study. The tunes chosen will need to be related to a past meaningful, positive experience of the subject, as determined by the subject and the subject's study partner. The pieces will be restricted in duration to between 1.5 and 2 minutes each. A piece will be chosen at random and will be saved on a portable device, and subjects will be asked to listen to the melody using high quality, over-ear headphones. The total exposure time will be 10 minutes each hour over a three-hour period. The melody will be repeated as many times as necessary to complete the 10-minute period. The control intervention will involve listening to nature sounds at the same duration and administration scheme. Functional magnetic resonance imaging will be used to identify how brain networks are modulated via exposure to this music and how they associate with the clinical findings.

Inclusion Criteria:

• Provision of signed and dated informed consent form
• Person of any sex/gender aged between 55 and 90
• Stated willingness to comply with all study procedures and availability for the duration of the study
• In the opinion of the investigator, has an informant able and willing to provide accurate information about the participant (may be paid or unpaid caregiver)
• Suffer from moderate to severe Alzheimer's disease as established by the study team using the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) Alzheimer's Criteria for possible and probable Alzheimer's Disease
• Diagnosis of Alzheimer's disease or other type of dementia as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V)
• Mini Mental State Examination (MMSE) score of 5-20
• Subject is reported by the study partner to be able to listen to a minimum of 10 minutes of music and a sound in an uninterrupted manner.

Exclusion Criteria:

• Suffer from severe hearing impairment as reported by the informant
• Presence of neuropsychiatric symptoms of dementia as determined by clinical observation by the Principal Investigator, including history of agitation and/or combative behavior.
• Individuals who score ≥ 12 seconds on the Timed Up and Go (TUG) Test.

This study will be part of the Alzheimer's Clinical Trials Consortium (ACTC). The study abides by the principles for sharing of research data as described in the NIH Public Access Policy on data sharing. The researchers endorse the sharing of final de-identified research data to serve important scientific goals. This project will facilitate sharing of software, archived study datasets (including images), assessment instruments, forms, and procedures through the web-based tools of the ACTC. The ACTC web portal will include access to inventories of resources and request procedures. All ACTC archival datasets will be included on the Global Alzheimer's Association Interactive Network (GAAIN); ACTC data can be accessed via the GAAIN platform; full or partial archived datasets can be shared via the dedicated ACTC Dataset- Sharing Portal.

It will become available one year after study recruitment it completed.

5 weeks

Adverse events were not separated by intervention because no events occurred during the administration of either the experimental or control conditions. All adverse events reported occurred outside of the study visits and were determined to be unrelated to the study interventions. These events were monitored and documented in accordance with protocol guidelines and were not associated with the auditory exposures.