Effects of Binaural Beats and Spatialized Music on Behavioural and Psychological Symptoms of Dementia in Assisted Living Facility Residents

This study will recruit a total of 120 older adults who are permanent residents of the Woodlake Legacy Senior Living (Lakewood, CO) and Woodland Estates Senior Living (Denver, CO) facilities near Denver, Colorado, USA. Recruitment will take place among assisted living and memory care communities at the designated sites. Subjects and/or their legal guardian are required to provide written and informed consent prior to inclusion in the study, in accordance with the Declaration of Helsinki.

Before allocation in the study groups, subjects are screened on demographic and medical factors pertaining to the inclusion and exclusion criteria of the study. Severity of cognitive impairment will be tested using the Standardized Mini-Mental State Examination (S-MMSE). Each task is scored based on the individual's performance, with a maximum score of 30 points indicating normal cognitive function. The S-MMSE questions are asked orally and the particular questions involving writing, reading, and drawing are carried out on paper, with the total duration for each patient ranging from 30 to 40 min. S-MMSE is categorized into different levels of cognitive impairment. The scores 19-25 represent mild impairment, 10-18 indicate moderate impairment and scores below 10 signify severe impairment. Subjects will be asked to complete a customized music inventory questionnaire scoring their preference from the list of available music styles/genres. Based on the indicated preference, music playlist selection will be personalized for each subject.

Subjects are allocated to one of four groups that will receive the following interventions: (1) group B0S0: music playlist (control group); (2) group B1S0: BBM, music playlist; (3) group B0S1, SM, music playlist; (4) group B1S1: BBM + SM, music playlist.

At each of the two designated sites, a quiet room with comfortable seating is prepared to host up to 10 subjects at a time. Subjects in assisted living and memory care communities will be tested in separate rooms, located within a familiar area of their living facility, to avoid disruption of routine. Subjects are picked up at the scheduled time of their sessions, escorted to the test environment by the designated staff member, and returned after completing the music session.

After a group of subjects is seated, a tablet (Samsung A9 Android 15 11-inch Tablet, Gumi, South-Korea) and wireless noise-cancelling headphones (Sony WH-1000XM6, Minato, Tokyo, Japan) connected through Bluetooth (v5.4) are distributed to each subject. The subjects are assisted by the on-site investigators with starting the music playlist in their preferred style/genre from the tablet and adjusting the headphones to a prescribed standard playback volume, i.e., a sound pressure level of \< 75 dB. It is suggested that subjects close their eyes while enjoying the music sessions. All subjects will listen to a ±20-minute session once a day for a total period of 14 consecutive days. AM sessions take place between 9-11 a.m. and PM sessions between 2-4 p.m. Groups are equally distributed between the AM and PM sessions to control for confounding effects across groups. In this way, bias of the time of day is avoided to interfere with the type of condition, e.g., BPSD in older adults with moderate to severe dementia in an assisted living facility was found to decrease more in the AM compared to the PM in response to a music intervention. Increased agitation behaviors during the late afternoon and evening is commonly referred to as 'sundowning'.

Demographic and medical information of each subject will be collected from the web-based patient administration system (augusthealth.com) used at the designated sites, prior to allocation of the subject to the study groups. Outcome measures pre- and post-sessions will be collected using tablets operated by the on-site investigators and administered via a web-based patient administration system that includes the designated assessment instruments (sagelyweb.com). The accessible population at the designated sites is familiar with the data-collection procedure for this system. This provides for consistency across collection, analysis and reporting of the data at study completion.

Compliance with the testing and treatment protocols is warranted by the on-site investigators who schedule and guide the music sessions with the subjects. The designated staff members will follow up with reminders about the scheduled sessions and physically assist the subjects to and from the test environment at the appointed times. Progress of the enrollment, allocation of the interventions and testing will be monitored throughout the duration of the study according to the Consolidated Standards of Reporting Trials (CONSORT).

If one of the conditions occurs as following, the follow-up will be discontinued: (1) serious adverse reactions during the trial; (2) the subject and/or designated staff member and/or his/her family members request to terminate or withdrawal; (3) the subject's condition changes, and the physician in charge judges that treatment should be terminated; (4) behaviour that violates legitimacy of the trial.

The choice of measurement instruments and administration frequency was guided by two principles: (1) To assess as broad a spectrum as possible of behavioral and emotional disturbances that are considered to be of greatest concern among assisted living facility administrators and staff; and (2) to collect samples sufficiently often to allow detection of any time-varying changes.

Daily dependent measures include Emoji Mood Scales (EMS) are administered before and immediately after each music session (pre and post-session). Baseline \& Post-Intervention measures include the Neuropsychiatric Inventory Questionnaire (NPI-Q) and the WHO-5 Well-Being Index, and are administered ±3 days before the intervention period (baseline) and ±3 days after completion of the intervention period (post-intervention).

Adverse events of the interventions will be focused on, including registering side effects currently unknown. Although no adverse effects of BBM and SM have been previously reported, if there are new side effects associated with BBM and/or SM in this trial, they will be recorded. In the event of a serious adverse event, the study will be discontinued to break the blind, corresponding treatment measures will be taken to protect the safety of the subjects, and the event will be reported to the IRB.

Demographic information and outcome measures pertaining to the subjects as recorded by the investigators in the patient registration system will be anonymized before data processing and statistical analysis. The investigators responsible for data analysis will perform an intention-to-treat (ITT) analysis of the collected data using IBM SPSS (version 31). Data will be presented according to their statistical features and distribution. All continuous variables are expressed as mean and standard deviation, and categorical variables are expressed as counts and percentages. Between-group Chi-square tests, Fisher's exact tests, or nonparametric tests will be used to analyze categorical data. Analysis of variance or nonparametric tests will be used for analyzing continuous data.

The summed scores for each instrument for each participant will be assessed pre against post-session and post-intervention against baseline to model and analyze variance. Outcomes shall be evaluated using between-group comparisons of post-intervention scores against baseline. Stratification of between-groups differences will be explored by (1) diagnostic groups, i.e., assisted living or memory care; (2) time of day, i.e., AM or PM; and (3) gender. Two-tailed p-values less than 0.05 will be considered statistically significant. Effect sizes will be calculated using standardized mean differences (SMD), i.e., the difference in mean change between groups divided by the pooled standard deviation using Hedge's g with a correction factor for small study sample (n \< 50 per group).

We will perform additional multivariable regression analyses to identify potential trends and correlations and adjust for potential confounders, including (1) baseline dependent measure; (2) music preference score; (3) cognitive function; (4) ethnicity; and (5) medication (yes/no) as covariates. For secondary analyses, a Bonferroni correction will be applied to adjust for multiple comparisons with adjusted p-values.

We expect to find a statistically meaningful improvement from baseline in BPSD severity in at least one intervention group (B1S0, B0S1, and/or B1S1) compared to the control group (B0S0) or a moderate effect size in at least one intervention group compared to control. Similar findings are expected in terms of the secondary outcomes, i.e., caregiver distress, subjective well-being, and mood. If the expected results are confirmed, BBM and/or SM may be seen as a viable, non-invasive treatment for decreasing BPSD symptoms in dementia patients, as well as for reducing the onset of symptoms of MCI in older adults who are experiencing typical age-related changes. The associated benefits of the intervention may increase caregiver relief and subjective experience of well-being and mood in older adults in senior living communities.

• Caregiver Distress - assessed by the Neuropsychiatric Inventory Questionnaire (NPI-Q) [Time frame: Before the start and after completion of a 2 week treatment]
• Subjective Well-being - assessed by the WHO-5 [Time frame: Before the start and after completion of a 2 week treatment]
• Subjective Mood - assessed by Emoji Mood Scales (EMS) [Time frame: Before and after each 20 minute music sessions, for 14 days consecutively.]