Alzheimer's disease Brain Research

Behind the research: managing apathy in patients with Alzheimer’s disease

One of the most prevalent yet under-recognized symptoms experienced by patients with Alzheimer’s disease is apathy, characterized by a loss of motivation or diminished interest. “Research has shown that apathy is associated with decreased function, lower quality of life and increased burden to caregivers,” says Dr. Krista Lanctôt, a senior scientist and director of neuropsychopharmacology at Sunnybrook Research Institute.

“There are currently no proven therapies to treat apathy, but certain medications hold considerable promise in decreasing its severity,” says Dr. Lanctôt.

Methylphenidate, a medication commonly prescribed to treat attention deficit hyperactivity disorder (ADHD), has shown preliminary efficacy in treating apathy. Dr. Lanctôt and her collaborators at Sunnybrook and nine U.S. sites set out to investigate the drug as a potential treatment for apathy in Alzheimer’s disease.

The findings of the study were recently published in JAMA Neurology.

What are some of the signs and symptoms of apathy in Alzheimer’s disease?

People experiencing apathy may have little interest or initiative, find it difficult to complete tasks and may lack an emotional response to good or bad events. “These symptoms can greatly influence quality of life, worsen cognitive performance and be particularly worrying for caregivers,” says Dr. Lanctôt.

What did the research study look at?

The research team studied 200 participants with Alzheimer’s disease, with mild to moderate cognitive impairment and moderate to severe apathy. Participants were randomized to receive the treatment — methylphenidate, or a placebo and evaluated with standardized testing at two, four and six months from baseline.

“This pivotal trial investigated apathy in patients with Alzheimer’s disease in the absence of major depressive episodes,” says Dr. Lanctôt, a lead author of the study. “The goal was to confirm our findings from a smaller pilot study.”

What has the current study demonstrated?

The researchers found a significant decrease in apathy in patients receiving methylphenidate in comparison to the placebo, during the six-month study duration, with the largest reduction in apathy seen after two months. At six months, 43.8% of patients in the treatment group improved.

What do these results mean for patients and care providers?

Methylphenidate is a safe and well-tolerated medication, which may offer an approach for treating apathy in patients with Alzheimer’s disease, by reducing its severity. Decreasing apathy can increase a person’s interest and initiation in activities and their emotional responsiveness, improving quality of life for both patients and caregivers.

“Methylphenidate has shown to be a promising potential medication in the management of apathy in Alzheimer’s disease,” Dr. Lanctôt says. “As with other psychiatric medications, the degree of response can vary. Future research will be targeted to understanding predictors of response to help inform patients and physicians.”

This study was supported by the National Institute on Aging (R01 AG046543) and made possible thanks to the dedication of study participants, caregivers and members of the ADMET 2 Research Group.