Treating Apathy in Alzheimer Disease

Summary and Comment |
September 29, 2017

Treating Apathy in Alzheimer Disease

  1. Joel Yager, MD

Methylphenidate improved motivation, cognition, mood, functioning, and caregiver burden in community-dwelling men with mild disease.

  1. Joel Yager, MD

Apathy, a prominent feature of Alzheimer disease, impairs motivation, reduces spontaneous behavior, and has been associated with a heavier caregiver burden. In a 12-week trial, investigators randomized 60 community-dwelling male veterans with mild Alzheimer disease and apathy to methylphenidate (target dose, 10 mg twice daily) or placebo (mean age, 77; mean Mini-Mental State Exam [MMSE] score, 24; >90% white).

Participants did not have active psychosis, frontotemporal dementia, or current major depression, although 58% had depressive symptoms. About 85% had hypertension, and 47% had coronary artery disease. Polypharmacy was common (cholinesterase inhibitors, 63%; antidepressants, 55%; memantine, 30%).

Significant improvements for methylphenidate vs. placebo were first seen at 4 weeks for overall apathy scores; at 8 weeks for the behavior, cognition, and motivation domains of apathy; and at 12 weeks for depression and emotion scores, MMSE scores, activities of daily living, and caregiver burden. Adverse events and serious adverse events were similar in the groups, with only one serious event possibly attributable to medication.


These results bear replication in larger samples and both sexes. Still, the study suggests several clinically important points. First, treating apathy might help to reduce depressive symptoms, but apathy and depression should be distinguished from each other and warrant separate attention. Second, in these elderly patients with hypertension and cardiovascular disease, adverse effects were no more frequent for modestly dosed methylphenidate than for placebo. Third, improvements occurred within 4 weeks for apathy but more gradually in other psychological and functional areas. Fourth, cognitive improvements at 12 weeks were comparable to those reported for cholinesterase inhibitors. Overall, treating apathy with methylphenidate may benefit both patients with mild Alzheimer disease and their caregivers.

Editor Disclosures at Time of Publication

  • Disclosures for Joel Yager, MD at time of publication Editorial boards Bulletin of the Menninger Clinic; Eating Disorders Review; International Journal of Eating Disorders; UpToDate; FOCUS: The Journal of Lifelong Learning in Psychiatry


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