Cognitive functions are critical for everyday functioning, in the workplace, academic environments, and social situations.
Problems with cognition are central to understanding psychiatric and neurological conditions across the lifespan. Examples include childhood onset conditions such as attention-deficit hyperactivity disorder (ADHD) or autism, conditions with onset in adolescence/early adulthood such as schizophrenia and depression, and disorders of older age including dementia.
In a given year, approximately one-third of the adult population will suffer from a mental disorder, but less than one-third of these individuals receive any form of treatment1, 2.
Collectively, brain disorders represent a leading cause of morbidity across the globe, and this burden of disease is likely to increase over time3.
Treatments capable of reversing cognitive dysfunction in brain disorders can help maximise quality of life and everyday functioning for affected individuals, in turn minimising suffering and the economic impact of these illnesses.
Cognitive enhancement is also relevant in our daily lives, even in people without brain disorders. Caffeine consumption is an everyday occurrence in much of the world, and is used to regulate alertness and concentration, including in high-level athletes4.
Surreptitious use of psychostimulants is increasingly reported in academic environments, while brain training products are being investigated as a means of maintaining ‘brain health’ as we age5.
Pathology and functional impact of cognitive dysfunction
Translational research using animal models, neuroimaging, and objective neuropsychological tests, indicates that multiple distinct cognitive abilities exist, which are dependent on the integrity and functioning of particular circuitry within the brain. In turn, these circuits are regulated by neuromodulators.
Of several hundred chemicals identified in the human brain, only a handful of these appear to be important regulators of cognition6. Key examples of these so-termed neuromodulators include serotonin, noradrenaline/norepinephrine, dopamine, acetyl choline, adenosine, and glutamate.
Established treatments for common brain disorders including ADHD, depression, and dementia act directly on these neural circuits and neuromodulators in order to dampen down symptoms and alter aspects of cognition.
Psychoactive substances used by a considerable proportion of the population affect some of these brain systems – for example, caffeine exerts its cognitive effects mostly by antagonising brain adenosine receptors4. Even medications that were not developed with cognition in mind can affect cognition, especially small molecules capable of crossing the blood-brain barrier7.
Research and development in neuropsychological conditions
Considering the huge economic burden and suffering attributable to brain disorders3, it is unfortunate that evidence-based treatments capable of reversing neuropsychological dysfunction are lacking for many of these conditions.
Cognitive dysfunction is common in people with schizophrenia, OCD, or multiple sclerosis, but existing first-line treatments – while helping other aspects of symptoms – do not generally reverse the underlying cognitive dysfunction.
As such, there is a considerable need to explore novel interventions and to measure effects of these interventions on cognition using sensitive and objective tests.
For other conditions, evidence-based treatments exist and partly reverse underlying cognitive dysfunction – psychostimulants and the noradrenaline/norepinephrine reuptake inhibitor, atomoxetine, ameliorates cognitive problems in ADHD with a medium-large effect size8, 9.
However, these treatments are not universally effective, and some individuals cannot tolerate the medications, or cannot use them due to contraindications (e.g. comorbid physical health problems). Hence, new interventions are needed. Cognitive training holds promise, in brain diseases and in healthy people, but much research into its usefulness has used cognitive tests without sound psychometric properties.
- Kessler RC, Aguilar-Gaxiola S, Alonso J, Chatterji S, Lee S, Ustün TB. The WHO World Mental Health (WMH) Surveys. Psychiatrie (Stuttg). 2009 Jan 1; 6(1):5-9
- Wittchen HU, Jacobi F, Rehm J, Gustavsson A, Svensson M, Jönsson B, Olesen J, Allgulander C, Alonso J, Faravelli C, Fratiglioni L, Jennum P, Lieb R, Maercker A, van Os J, Preisig M, Salvador-Carulla L, Simon R, Steinhausen HC. The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol. 2011 Sep; 21(9):655-79.
- Gustavsson A, Svensson M, Jacobi F, Allgulander C, Alonso J, Beghi E, Dodel R, Ekman M, Faravelli C, Fratiglioni L, Gannon B, Jones DH, Jennum P, Jordanova A, Jönsson L, Karampampa K, Knapp M, Kobelt G, Kurth T, Lieb R, Linde M, Ljungcrantz C, Maercker A, Melin B, Moscarelli M, Musayev A, Norwood F, Preisig M, Pugliatti M, Rehm J, Salvador-Carulla L, Schlehofer B, Simon R, Steinhausen HC, Stovner LJ, Vallat JM, Van den Bergh P, van Os J, Vos P, Xu W, Wittchen HU, Jönsson B, Olesen J, CDBE2010 Study Group. Eur Neuropsychopharmacol. 2011 Oct; 21(10):718-79.
- Ioannidis K, Chamberlain SR, Müller U. Ostracising caffeine from the pharmacological arsenal for attention-deficit hyperactivity disorder--was this a correct decision? A literature review. J Psychopharmacol. 2014 Sep;28(9):830-6. Review.
- Sahakian B, Bruhl AB, Cook J, Killikelly C, Savulich G, Piercy T, Hafizi S, Perez J, Fernandez-Egea E, Suckling J, Jones PB. The impact of neuroscience on society: cognitive enhancement in neuropsychiatric disorders and in healthy people. Philos Trans R Soc Lond B Biol Sci. 2015 Sep 19;370(1677):20140214.
- Chamberlain SR, Robbins TW. Noradrenergic modulation of cognition: therapeutic implications. J Psychopharmacol. 2013 Aug;27(8):694-718.
- Blackwell AD. Measuring cognitive effects: cognition in drug development and repositioning. Drug Discov Today. 2015 Apr;20(4):391-2.
- Bushe C, Day K, Reed V, Karlsdotter K, Berggren L, Pitcher A, Televantou F, Haynes V. A network meta-analysis of atomoxetine and osmotic release oral system methylphenidate in the treatment of attention-deficit/hyperactivity disorder in adult patients. J Psychopharmacol. 2016 May;30(5):444-58.
- Chamberlain SR, Robbins TW, Winder-Rhodes S, Müller U, Sahakian BJ, Blackwell AD, Barnett JH. Translational approaches to frontostriatal dysfunction in attention-deficit/hyperactivity disorder using a computerized neuropsychological battery. Biol Psychiatry. 2011 Jun 15;69(12):1192-203.