Approaches to measuring the effects of wake‐promoting drugs: a focus on cognitive function

Abstract

Objectives In clinical drug development, wakefulness and wake-promotion maybe assessed by a large number of scales and questionnaires. Objective assessment of wakefulness is most commonly made using sleep latency/maintenance of wakefulness tests, polysomnography and/or behavioral measures. The purpose of the present review is to highlight the degree of overlap in the assessment of wakefulness and cognition, with consideration of assessment techniques and the underlying neurobiology of both concepts. Design Reviews of four key areas were conducted: commonly used techniques in the assessment of wakefulness; neurobiology of sleep/wake and cognition; targets of wake promoting and/or cognition enhancing drugs; and ongoing clinical trials investigating wake promoting effects. Results There is clear overlap between the assessment of wakefulness and cognition. There are common techniques which may be used to assess both concepts; aspects of the neurobiology of both concepts may be closely related; and wake promoting drugs may have nootropic properties (and vice-versa). Clinical trials of wake promoting drugs often, though not routinely, assess aspects of cognition. Conclusions Routine and broad assessment of cognition in the development of wake promoting drugs may reveal important nootropic effects, which are not secondary to alertness/wakefulness, whilst existing cognitive enhancers may have under explored or unknown wake promoting properties.

Cholinergic receptor subtypes and their role in cognition, emotion, and vigilance control: An overview of preclinical and clinical findings

“…Chuah et al 2006;Peigneux et al 2001;Turner et al 2007;Van Dongen et al 2003). In a recent review article, Edgar et al (2009) discuss the relationship between wakefulness/vigilance and cognition. They demonstrate a clear overlap not only in the assessment of both concepts but also in the neurobiological correlates underlying them.…”

Cognitive enhancement by drugs in health and disease

“…More detailed assessment using sensitive computerized cognitive tests has revealed widespread improvements in the domains of attention, WM and episodic memory [36–38] . However, these positive effects of AChEIs might all be mediated via a common process such as elevated arousal [39,40] . In fact, the very same issue pertains to the modulatory effects of AChEIs in healthy subjects [41] .…”

Change in intraindividual variability over time as a key metric for defining performance-based cognitive fatigability

“…There are many similarities between conditions associated with heightened intraindividual variability and fatigability of cognitive performance including: (1) Associations with aging and other neurological illnesses (Eldadah, 2010; Kluger et al, 2013); (2) Neuroimaging evidence for similar neuronal resources (Boksem & Tops, 2008; Chaudhuri & Behan, 2004; MacDonald, Li, et al, 2009); and (3) Reduction by similar interventions (Edgar, Pace-Schott, & Wesnes, 2009; Spencer et al, 2009). Review of reaction time variability from other fatigue studies also supports this contention in some (van der Linden & Eling, 2006) but not all (Lorist & Jolij, 2012) studies.…”