Methylphenidate for Apathy in Alzheimer's Disease: Addressing Heterogeneity of Response, Safety Outcomes and Future Directions

Abstract

Apathy is found in 24-85% patients with Alzheimer's disease (AD), making it the most common neuropsychiatric symptom (NPS) of AD. Apathy in AD is associated with faster disease progression, greater cognitive decline, increased caregiver distress and decreased quality of life, and hence is an important interventional target with no current approved treatments. The recent Apathy in Dementia Methylphenidate Trial 2 (ADMET 2), the largest randomized, double-blind, placebo-controlled, multi-center, phase III clinical trial that investigated the efficacy of methylphenidate for apathy in patients with mild to moderate AD, found that methylphenidate showed some improvement in apathy. As a dopamine and norepinephrine reuptake inhibitor, methylphenidate increases dopamine and norepinephrine levels, dysfunction of which have been linked to apathy in dementia previously.In this symposium, Dr. Rosenberg will present the safety and efficacy results of the ADMET2 trial with methylphenidate presenting a safe profile with a small to medium effect on apathy. Additional data on cardiovascular safety will be presented and discussed. Dr. Lanctot will speak about the heterogeneity of response in methylphenidate in the trial participants, touching upon clinical characteristics and blood-based biomarkers as predictors of response. Dr. Mintzer will present the rationale and the study design for future trials. Findings from the methylphenidate trial for treatment for apathy in dementia not only shine a light on the pathophysiology of the disease but can also improve knowledge and understanding of potential treatment and research pathways.