The value of assessing cognitive function in drug development

Abstract

This paper reviews the value and utility of measuring cognitive function in the development of new medicines by reference to the most widely used automated system in clinical research. Evidence is presented from phase 1 to 3 of the nature and quality of the information that can be obtained by applying the Cognitive Drug Research computerized assessment system to ongoing clinical trials. Valuable evidence can be obtained even in the first trial in which a novel compound is administered to man. One application of such testing is to ensure that novel compounds are relatively free from cognition-impairing properties, particularly in relation to competitor products. Another is to ensure that unwanted interactions with alcohol and other medications do not occur, or, if they do, to put them in context. In many patient populations, cognitive dysfunction occurs as a result of the disease process, and newer medicines which can treat the symptoms of the disease without further impairing function can often reveal benefits as the disease-induced cognitive dysfunction is reduced. Another major application is to identify benefits for compounds designed to enhance cognitive function. Such effects can be sought in typical phase 1 trials, or a scopolamine model of the core deficits of Alzheimer's disease can be used to screen potential antidernentia drugs. Ultimately, of course, such effects can be demonstrated using properly validated and highly sensitive automated procedures in the target populations. The data presented demonstrate that the concept of independently assessing a variety of cognitive functions is crucial in helping differentiate drugs, types of dementia, and different illnesses. Such information offers a unique insight into how the alterations to various cognitive functions will manifest themselves in everyday behavior. This reveals a major limitation of scales that yield a single score, because such limited information does not permit anything but a quantitative interpretation; and the concept of "more" cognitive function or "less" is manifestly inappropriate for something as complex and diverse as the interplay between cognitive function and human behavior. Finally, the next generations of cognitive testing are described. Testing via the telephone has just been introduced and will have dramatic effects on the logistics of conducting cognitive testing in large patient trials. Testing via the Internet is not far off either, and will come fully into play as the proportion of homes connected to the Internet increases in Europe and North America. There are no sound reasons for not wishing to include cognitive function testing in the development protocol of any novel medicine.

The Relationship between Gut Microbiome and Cognition in Older Australians

“…In the present study, our primary aim was to assess the relation between the gut microbiome and cognitive domains as calculated using a validated and standardised computerised assessment system, the Cognitive Drug Research battery (CDR). The CDR system is designed to test the attention, executive function and working memory, episodic secondary memory, motor control and psychophysical thresholds [ 46 ], and the CDR system is also sensitive to age-related cognitive decline [ 40 ]. Further, we derived five factors representing five different cognitive domains including ‘Quality of Episodic Secondary Memory’, ‘Quality of Working Memory’, ‘Power of Concentration’, ‘Continuity of Attention’ and ‘Speed of Memory’.…”

Effect of alcohol coadministration on the pharmacodynamics, pharmacokinetics, and safety of lemborexant: A randomized, placebo-controlled crossover study

“…These types of psychomotor and cognitive assessments have been used in prior studies to examine drug interactions with alcohol ( Hoch et al, 2013 ; Sun et al, 2015 ; Wesnes et al, 2000 ). In particular, the power of attention test has been shown to be sensitive to the impairing effects of alcohol ( Sun et al, 2015 ; Wesnes, 2000 ).…”

“…Cognitive performance. The cognitive performance assessment battery (CPAB) was administered after each postural stability test (Wesnes, 2000). The computerized CPAB consisted of nine tasks assessing memory and attention (simple reaction time, choice reaction time, digit vigilance, immediate word recall, delayed word recall, numerical working memory, spatial working memory, word recognition, and picture recognition), and was the same battery employed in one of the Phase 3 pivotal studies (Moline et al, 2021).…”

“…As the result of the sedative effects of alcohol, individuals may also use alcohol to self-treat insomnia (Vitiello, 1997). Alcohol consumption is known to impair sustained attention, disrupt the ability to learn new information, impair coordination, increase body sway, and to lower self-rated alertness (van Harten et al, 1992;Wesnes et al, 2000). In addition, alcohol consumption is associated with falls, accidents, and accident-related injuries (Chen and Yoon, 2017;Kurzthaler et al, 2005;Taylor et al, 2010).…”

The Safety and Efficacy of Botanicals with Nootropic Effects

“…This is a set of 25 tests that measure memory, learning, working memory, executive function, attention and reaction time, decision making, response control, semantic/verbal memory and can be administered using a touch-screen computer. Another computer based automated assessment that is commonly used is the Cognitive Drug Research (CDR) battery [ 24 ]. Tests available in this system include attention (simple reaction time, choice reaction time, digit vigilance), executive function and working memory (semantic reasoning, rapid visual information processing), episodic secondary memory (word recall, word recognition, picture recognition), and motor control (joystick tracking task, tapping task).…”