May 17, 2024

Key characteristics could guide treatment for Alzheimer's Disease

A woman and an older woman sit at a desk. The woman is helping the older woman write in a notebook.
By Ben Gane

Apathy is among the most common symptoms of Alzheimer's disease (AD). Characterized by a loss of motivation to perform even everyday tasks, apathy can have drastic impacts on quality of life and the rate at which Alzheimer's progresses. Despite these impacts, there are no widely-used, reliable treatments for apathy. Dr. Krista Lanctôt and her team are investigating a medication called methylphenidate which is effective for treating apathy for some patients, but not all. They identified a set of characteristics that indicate whether methylphenidate is likely to be an effective treatment, providing a powerful tool to guide treatment choices for individual patients and shape our understanding of the biological mechanisms underlying AD.

Dr. Krista Lanctot
Dr. Krista Lanctot

Why is dementia-related apathy important?

KL: Apathy is the most common behavioural symptom experienced by people with AD. Apathy in AD can cause decreased quality of life, increases in disease progression and cognitive decline, and greater mortality rates. Apathy also increases the likelihood of long-term care placement for the person with dementia and makes the lives of their caregivers more stressful. Despite recognition of this, there are no approved treatments.

What motivated this research?

KL: This research followed directly from our 2021 ADMET 2 study, which showed that methylphenidate is a safe and effective medication to use in the treatment of apathy in AD, but only 44% responded to medication. We wanted to dive further into the results of the ADMET 2 study to find out more about which patients were most likely to benefit from taking methylphenidate for apathy. We examined data from 200 ADMET 2 participants who had AD plus clinically significant apathy, and who did not have major depression, clinically significant agitation/aggression, delusions, or hallucinations. These participants were followed for 6 months in the ADMET 2 study.

What was the most important finding of this study, in your opinion?

KL: Of 22 patient variables from ADMET 2 we found a constellation of 6 characteristics that predicted better response to methylphenidate over placebo for the treatment of apathy in AD. 

Methylphenidate produced the best results in patients who:

  • were not anxious or agitated
  • were younger
  • were taking a cholinesterase inhibitor to treat their AD
  • had optimal diastolic blood pressure
  • had lower levels of functional abilities in day-to-day tasks

Patients with this profile showed the most improvement in apathy with methylphenidate.

How does this change treatment in the future?

KL: Identifying these 6 patient characteristics helps clinicians determine which patients are more likely to experience improvement when their apathy is treated with methylphenidate. With this knowledge, clinicians can provide personalized medicine which can lead to better outcomes for persons with dementia and their caregivers.

Any next steps?

KL: In future studies, we hope to confirm these predictors and examine imaging and blood-based biomarkers that will help us understand the brain mechanisms underlying apathy and link these mechanisms to the characteristics of patients who experience improved apathy with treatment.

What is the major take home message for the public?

KL: Many individuals with apathy in AD can be effectively treated with methylphenidate, and we are gaining a better understanding of who is most likely to respond favourably to this treatment. This progress may lead not only to improvement in apathy symptoms, but possibly improved quality of life for both persons with AD and their caregivers.


In addition to Dr. Lanctot, contributors on this paper include Dr. Shankar Tumati (Post-doctoral Fellow at the Sunnybrook Research Institute), Krushnaa Sankhe (PhD candidate in Pharmacology at the University of Toronto), Luc Rivet (MSc in Pharmacology/ Toxicology at the University of Toronto) and Dr. Nathan Herrmann from the University of Toronto Department of Psychiatry.

ImPACT logo: Psychiatry articles that change treatment

Lanctôt KL, Rivet L, Tumati S, Perin J, Sankhe K, Vieira D, Mintzer J, Rosenberg PB, Shade D, Lerner AJ, Padala PR, Brawman-Mintzer O, van Dyck CH, Porsteinsson AP, Craft S, Levey AI, Padala KP, Herrmann N. Heterogeneity of Response to Methylphenidate in Apathetic Patients in the ADMET 2 Trial. Am J Geriatr Psychiatry. 2023 Dec;31(12):1077-1087. doi: 10.1016/j.jagp.2023.06.002. Epub 2023 Jun 15. PMID: 37385898; PMCID: PMC10765607