P3‐004: MUSIC INTERVENTION FOR PEOPLE WITH DEMENTIA USING A DYADIC APPROACH: CLINICAL EXPERIENCE TO SHAPE A CLINICAL TRIAL

Alzheimer’s disease can be used to identify a group of patients with mild to moderate AD with more significant and consistent decline on placebo treatment over 6 months. Methods: Data were pooled from three 24-week, randomized, double-blind, placebo-controlled studies in mild to moderate AD (Atri et al 2018). The studies included men and women aged 50 years with probable AD and a Mini–Mental State Examination (MMSE) score of 12–22, who had received a Cholinesterase inhibitor for 4 months prior to screening. Key outcome measures were (1) The Alzheimer’s Disease Assessment Scale – Cognitive subscale (ADAS-Cog; a measure of cognition). (2) Alzheimer’s Disease Cooperative Study – Activities of Daily Living, 23-item version (ADCS-ADL). (3) The Alzheimer’s Disease Cooperative Study – Clinical Global Impression of Change (ADCS-CGIC). (4) Neuropsychiatric Inventory (NPI) was a secondary outcome to assess behavioral disturbances. Results:A total of 963 patients were randomized to placebo Patients with amyloid positivity had a greater decline on ADAS-Cog (mean difference: 1.51; 95% confidence interval 0.13, 2.90; p1⁄40.032) and ADCS-CGIC (0.33; 0.08, 0.57; p1⁄40.0086). ApoE-ε4 homozygotes had a greater decline on ADCS-ADL23 (-1.88; -3.60, -0.15; p1⁄40.033), ADCS-CGIC (0.24; 0.00, 0.47; p1⁄40.049), and NPI (3.68; 1.59, 5.77; p1⁄40.0006). Patients with a first-degree relative with AD had a greater decline on ADAS-Cog (1.12; 0.25, 1.99; p1⁄40.012). A merged enrichment group was identified by pooling individuals fulfilling at least one of the individual enrichment criteria. This broader enrichment group continued to identify individuals with greater decline/worsening on ADAS-Cog (1.46; 0.63, 2.30; p1⁄40.0006) and NPI (2.12; 0.77, 3.47; p1⁄40.0021). This approach substantially increased power to identify a difference of 25% between treatment groups, for example achieving a power of 75% to p<0.05 with less than 100 participants per group for individuals who were amyloid positive. Conclusions: Even in symptomatic treatment trials over 6 months enrichment is critical and can play a crucial role in designing studies with a substantially better chance of identifying any positive treatment effects.