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Methylphenidate improves apathy in mild Alzheimer’s disease

Methylphenidate significantly improved apathy, cognition, functional status, caregiver burden and depression among community-dwelling veterans with mild Alzheimer’s disease.

“Apathy, a profound loss of motivation, is the most common behavioral problem in Alzheimer’s disease,” Prasad R. Padala, MD, MS, of Central Arkansas Veterans Healthcare System, Little Rock, and colleagues wrote, later noting that apathy has profound consequences for both patients and caregivers. “The presence of apathy with Alzheimer’s disease is associated with functional impairment. Even after controlling for age, education, cognition and depression, those with apathy are 1.9 to 2.8 times as likely to have deficits in activities of daily living compared with those without apathy.”

To assess effects of methylphenidate on apathy in Alzheimer’s disease, researchers conducted a 12-week, double-blind, randomized, placebo-controlled trial among 60 community-dwelling veterans with mild Alzheimer’s disease. Participants (mean age, 77 years) were randomly assigned to receive 5 mg of methylphenidate or placebo twice daily; those in the methylphenidate group were titrated to 10 mg twice daily at 2 weeks. The first dose was taken in early morning and the second dose no later than 3 p.m.

Apathy was determined via Apathy Evaluation Scale-Clinician (AES-C) score. Secondary outcomes included cognition, functional status, improvement and severity on the Clinical Global Impressions Scale (CGI), caregiver burden, and depression, which were assessed at baseline and 4, 8 and 12 weeks.

After adjusting for baseline AES-C scores, participants who received methylphenidate exhibited significantly greater improvement in AES-C scores at 4 weeks (–5.2; 95% CI, –9 to –1.5); 8 weeks (–7.2; 95% CI, –10.9 to –3.5); and 12 weeks (–9.9; 95% CI, –13.6 to –6.2) compared with placebo.

Improvement in AES-C scores was driven by improvements in behavioral, cognitive and emotional apathy domains, according to researchers.

At 12 weeks, participants who received methylphenidate exhibited significantly greater improvement in cognition based on Mini-Mental State Examination (6.1; 95% CI, 2.7-9.6) and Modified Mini-Mental State Examination scores (2.6; 95% CI, 1.1-4).

Further, participants who received methylphenidate exhibited significantly greater improvements in daily living functionality (2.3; 95% CI, 0.7-3.9), caregiver burden (–5.8; 95% CI, –10.1 to –1.4), CGI–Improvement (–1.3; 95% CI, –1.9 to –0.6), CGI–Severity (–1.1; 95% CI, –1.6 to –0.6), and on the dementia depression scale (–2.5; 95% CI, –4.2 to –0.8) at 12 weeks.

CGI-I scores were significantly better in the methylphenidate group at 4 weeks.

“There was significantly greater improvement in apathy with methylphenidate compared with placebo after 4 weeks of treatment, and apathy continued to improve with methylphenidate at 8 and 12 weeks, with the highest between-group difference at 12 weeks,” the researchers wrote.

“Twelve-week methylphenidate treatment improved apathy in community-dwelling older veterans with mild Alzheimer’s disease,” they concluded. “Methylphenidate also improved cognition, functional status, caregiver burden, CGI scores (improvement and severity), and depression.” – by Amanda Oldt

Disclosures: Padala reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.