Major psychiatric disorders are extremely common and their effects on behaviour, perception, emotion and cognition constitute an enormous contribution to worldwide disability.

Numerous disorders, such as attention deficit hyperactivity disorder (ADHD), schizophrenia, frontal dementia, Alzheimer’s, Huntington’s and Parkinson’s diseases are characterized by cognitive impairments. Patients frequently struggle with many everyday activities requiring concentration, memory, problem-solving and planning. The potential public health benefit of improving current treatments for cognitive disabilities in patients is undisputed.

The disorder of schizophrenia provides a particularly good illustration of the potential benefits to be had from exploring new options for the treatment of cognitive dysfunction. It is estimated that 24 million people worldwide suffer from schizophrenia, with the condition ranking third in terms of the global burden of neuropsychiatric conditions, following depression and alcohol dependence.

The economic impact alone of the disorder is enormous: in the United States the direct and indirect costs of schizophrenia were estimated to have been as much as $40 billion in the year 2000. In many patients with schizophrenia, cognitive difficulties are the main factor limiting full rehabilitation – such as returning to work – and quality of life, particularly after the clinical symptoms have remitted.

Indeed, it has been proposed that in certain patients with schizophrenia even small improvements in cognitive functions, such as enhancing the ability to adapt efficiently to new situations and to plan effectively, could help patients make the transition to independent living outside a psychiatric institution. The relatively recent shift in clinical emphasis, away from a restricted targeting of the more overt psychotic symptoms of this disorder, serves to emphasize the debilitating long-term effects that cognitive impairments can have, and the need to identify effective treatments.

Research on cognitive enhancement

A major problem in patients with schizophrenia, including those with first episode psychosis is the lack of cognitive flexibility in problem solving, which impacts on their ability to adapt effectively in daily life. Evidence suggests that impaired cognitive flexibility may be a marker of disease progression since it may deteriorate over time despite antipsychotic medication, and relates to duration of untreated psychosis. Recent research shows that patients with schizophrenia given the cognitive enhancer modafinil significantly improve in terms of their cognitive flexibility so that their performance is similar to that of healthy volunteers.

In addition, it has been demonstrated that modafinil is able to improve impulsive behaviour in adults with attention deficit hyperactivity disorder and even improves aspects of memory and executive functions such as planning in healthy volunteers. Similar results have also been demonstrated in patients with ADHD and frontotemporal dementia and healthy volunteers using methylphenidate. PET neuroimaging has shown that the improvement demonstrated with methylphenidate on executive tasks such as strategic working memory are associated with increased efficiency in the frontal and parietal neural network activated during strategic working memory performance.

Professor Barbara Sahakian’s laboratory has had extensive experience with proof-of-concept studies in cognition enhancement. Indeed, her early research demonstrated the feasibility of treating the problems in attention and concentration in patients with mild and moderate Alzheimer’s disease with cholinesterase inhibitors which have formed the basis for current treatments. More recently the laboratory has turned its focus on early detection of mild cognitive impairment (MCI) and Alzheimer’s disease with a view to assessing novel cognitive enhancers and neuroprotective agents.

This work will utilise clinical neuropsychology, cognitive psychopharmacology and neuroimaging to devise early outcome measures to short-cut the drug development process for the pharmaceutical industry. Hopefully this will allow for novel effective symptomatic treatments and neuroprotective agents to become available to patients much faster. Currently there are ongoing studies using modafinil to enhance cognition in neurosurgical patients, Huntington’s disease and depression. Studies about to begin include first episode psychosis, mild cognitive impairment and mild Alzheimer’s disease.

A paper published in Science examines research to determine the effects on cognition of novel treatments for ADHD, such as Atomoxetine. This is currently an ongoing focus of PET neuroimaging studies at the Wolfson Brain Imaging Lab alongside investigating non-pharmacological means of enhancing cognition, such as neurocognitive activation.

This work is licensed under a Creative Commons Licence. If you use this content on your site please link back to this page.