Apathy in Alzheimer's disease: A neurocircuitry based perspective

In addition to memory deficits and other cognitive disturbances, patients with Alzheimer's disease (AD) experience neuropsychiatric symptoms, notably apathy, which is a state of impaired motivation observed by deficits in goal directed behavior. Apathy is a multifaceted neuropsychiatric condition and appears to be a prognostic indicator, correlating with the progression of AD. Strikingly, recent studies point out that the neurodegenerative pathology of AD may drive apathy independent of cognitive decline. These studies also highlight that neuropsychiatric symptoms, in particular apathy, might manifest early in AD. Here, we review the current understanding of the neurobiological underpinnings of apathy as a neuropsychiatric symptom of AD. Specifically, we highlight the neural circuits and brain regions recognized to be correlated with the apathetic symptomatology. We also discuss the current evidence that supports the notion that apathy and cognitive deficits may develop as independent but concurrent phenomena driven by AD pathology, suggesting its efficacy as an additional outcome measure in Alzheimer's disease clinical trials. The current and prospective therapeutic interventions for apathy in AD from a neurocircuitry based perspective are also reviewed.