Impaired cognition in narcolepsy: clinical and neurobiological perspectives

Abstract

In addition to well-known symptoms such as sleepiness and cataplexy, many people with narcolepsy have impaired cognition, reporting inattention, poor memory, and other concerns. Unfortunately, research on cognition in narcolepsy has been limited. Strong evidence demonstrates difficulties with sustained attention, but evidence for executive dysfunction and impaired memory is mixed. Animal research provides some insights into how loss of the orexin neurons in narcolepsy type 1 may give rise to impaired cognition via dysfunction of the prefrontal cortex, and cholinergic and monoaminergic systems. This paper reviews some of these clinical and preclinical findings, provides a neurobiological framework to understand these deficits, and highlights some of the many key unanswered questions.

Keywords: arousal; attention; cognition; executive function; hypocretin; memory; narcolepsy; orexin.

Figure 1.

Cognition relies on networks within the prefrontal cortex, which are modulated by ascending signals from noradrenergic neurons of the locus coeruleus, dopaminergic neurons of the ventral tegmental area, and cholinergic neurons of the basal forebrain. All these regions are excited by the orexin neurons, and loss of orexin signaling likely contributes to the cognitive problems of narcolepsy.