Pearls of Wisdom: Apathy in Alzheimer Disease

Jonathan, a 78-year-old man with Alzheimer disease of 5 years' duration, has progressively become more apathetic. He is not depressed and has no comorbidities or medications that might explain his apathy.

Which treatment might improve his apathy?

A. Droxidopa (Northera)
B. Methylphenidate (Ritalin)
C. Tea tree oil
D. High-dose vitamin D

What is the correct answer?
(Answer and discussion on next page)

Louis Kuritzky, MD, has been involved in medical education since the 1970s. Drawing upon years of clinical experience, he has crafted each year for almost 3 decades a collection of items that are often underappreciated by clinicians, yet important for patients. These “Pearls of Wisdom” often highlight studies that may not have gotten traction within the clinical community and/or may have been overlooked since their time of publishing, but warrant a second look.

Now, for the first time, Dr Kuritzky is sharing with the Consultant360 audience. Sign up today to receive new advice each week.

Answer: Methylphenidate

Apathy in Alzheimer disease (ALZ-AP) is the loss of interest and motivation in daily activities not attributable to another cause or comorbidity, such as depression, medications, heart failure, etc. Although I recall seeing little about this specific topic in the literature, apparently, ALZ-AP is a distinct and specific entity. That is, we are not talking about people with AD who also have depression.

It may surprise you to learn that, according to a 2013 study published in the Journal of Clinical Psychiatry, apathy is one of the most common syndromes faced by patients with AD, with a 5-year incidence rate as high as 71%.
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The premises for consideration of methylphenidate as a remedy for ALZ-AP are 2-fold: First, there is the decrease in dopaminergic neurotransmission present in AD. Second, other stimulants, like dextroamphetamine, have not been shown to have favorable effects in patients with AD.  In fact, there is a blunted response to dextroamphetamine, and no effect associated with modafinil, a stimulant often used in the treatment of sleep deprivation syndrome. It appears that what we may derive from these observations is that the mechanism of action of the stimulant may be critical to symptomatic improvement; that is, it’s not just that “any stimulant will do” to help ALZ-AP.

On the other hand, a pilot trial of methylphenidate showed some positive effect, perhaps related to dopaminergic effects of methylphenidate.

The Research

The researchers conducted a double-blind, randomized, placebo-controlled trial of 60 patients who were diagnosed with ALZ-AP treated with either 20 mg/d of methylphenidate or placebo for 6 weeks.¹

Participants’ results were measured using their Apathy Evaluation Scale score, a modified Alzheimer Disease Cooperative Study-Clinical Global Impression of Change score. Overall, everything on the scale was favorably affected in patients taking methylphenidate (although the Apathy Evaluation Scale score did not achieve statistical significance).

Methylphenidate for Alzheimer Apathy Outcomes

The researchers concluded that the study results suggest that methylphenidate may be a safe and effective treatment for ALZ-AP and also may be associated with cognitive improvements.

What’s the “Take-Home”?

Because the study was so small and preliminary, of course it would enhance our confidence if a larger, longer-term trial were performed. On the other hand, for a disorder about which we do not have many prominent success stories, methylphenidate may be worth a try.

Reference:

Rosenberg PB, Lanctôt KL, Drye LT, et al; ADMET Investigators. Safety and efficacy of methylphenidate for apathy in Alzheimer’s disease: a randomized, placebo-controlled trial. J Clin Psychiatry. 2013;74(8):810-816.