Neurobiologic Rationale for Treatment of Apathy in Alzheimer's Disease With Methylphenidate

•What is the primary question addressed by this study?—Methylphenidate treatment has shown encouraging results in initial trials of apathy in Alzheimer's disease; however, its neurobiologic rationale remains unclear.•What is the main finding of this study?—We propose that the degeneration of the prefrontal cortex in Alzheimer's disease produces symptoms of apathy. We further propose that methylphenidate treatment may ameliorate those symptoms by boosting norepinephrine and dopamine actions in prefrontal-striatal-thalamocortical circuits.•What is the meaning of the finding?—Understanding the neuronal circuits subserving motivated behavior and their reliance on catecholamine actions provides a rationale for methylphenidate in the treatment of apathy in patients with Alzheimer's disease.