Patients with bipolar disorder often manifest cognitive disturbances during acute manic, depressive, and mixed states which include difficulties with attention, concentration, planning and memory. It may come as a surprise, though, to learn that cognitive deficits can persist into euthymia – a state of relative mood stability. Indeed, approximately 40 % of euthymic bipolar patients show evidence of cognitive impairment (1,2) involving attention, executive function (i.e. planning and organization, cognitive flexibility and set-shifting, and working memory), verbal memory, processing speed and visual memory (3,4). Patients with bipolar I and bipolar II disorder appear to have a similar pattern of deficits (4). The purpose of this brief review is to identify cognitive deficits that help distinguish bipolar disorder from other disorders of mood, memory, and executive functioning. An improved understanding of these deficits will help clinicians tailor their treatment interventions to address the individual needs of patients.
How do such deficits affect the day-to-day functioning of a patient with euthymic bipolar disorder? One example would be a college student who is struggling to perform well in school despite having fully recovered from a manic episode several months before. Areas of difficulty include maintaining focus on class lectures, learning new material, and completing coursework on time. Another scenario involves a manager, back at work following a prolonged depressed period, who feels completely overwhelmed in the course of a seemingly normal day. Routine tasks take much longer and lead to an overall feeling of being ‘stuck,’ unable to move on to other projects or work on multiple projects simultaneously.
This constellation of symptoms described above resembles another disorder of executive functioning, Attention Deficit Hyperactivity Disorder (ADHD). Research on cognitive findings in bipolar disorder has had to address the question of which psychological test (s) can most effectively differentiate between bipolar disorder and ADHD. In a 2014 study, conducted by Silva et. al. (5), patients were divided into three groups: ADHD with bipolar disorder (n=51), ADHD without bipolar disorder (n=278) and healthy subjects (n=91). The Wisconsin Card Sort (WCST) was administered to all of the patients. In the WCST, patients are asked to organize cards displaying various colors and shapes in the face of changing rules. The test is a measure of the patient’s ability to ‘set-shift,’ or adapt to shifting contingencies. Patients with both ADHD and bipolar disorder had lower scores than patients with ADHD without bipolar disorder and healthy controls (the latter two groups did not differ from each other). The authors concluded that impairments in ‘set-shifting’ are strongly related to bipolar disorder but not ADHD (5).
Several years later, Gruber et. al. administered the Multi-Source Interference Task (MSIT) to 29 patients with euthymic bipolar disorder and 21 healthy controls with concurrent functional magnetic resonance imaging (fMRI) (6). The MSIT consists of three-digit stimuli sets (using numbers 0, 1, 2, or 3) that are presented briefly on a screen. Each set contains two identical distractor numbers and a target number that differs from the two distractors. Participants are asked to press a button corresponding to the identity of the target number that differs from the two distractor numbers. There are two scenarios presented: a ‘control’ condition in which the target number corresponds to position on keypad, and an ‘interference’ condition in which the target number does not correspond to position on the keypad. Overall, the patients with bipolar disorder exhibited slower response time and lower accuracy in the interference condition, which required adaptation to a new and more challenging situation. In addition, neuroimaging revealed decreased activation of the anterior and middle cingulate cortex and increased activation of the dorsolateral prefrontal cortex, which are regions of the brain associated with cognitive control processing (6).
Taken together, these studies help us piece together a pattern of neurocognition that is potentially specific to bipolar disorder: deficits in planning and set-shifting as a result of impairment in cognitive control. Cognitive control is a form of executive functioning that allows patients to adapt their thoughts and actions appropriately in the face of changing environmental scenarios (6). More specifically, it is ‘an executive control system… whose central purpose is to overcome (i.e. to resolve) interference or conflict in cognitive control processing’ so that one can ‘maintain adequate performance in the face of significant distraction.’ Interference comes in the form of ‘task-irrelevant information’ that results in slower processing speeds and increased errors (7). The cognitive control system is what allows us to ‘switch gears’ and move on in a more efficient way when environmental changes occur.
Clinically, these findings point to a difference in how patients with bipolar disorder process new information, including environmental changes, differently from unaffected controls due to alterations in brain connectivity. Research on neurocognitive aspects of bipolar disorder, while still in its early stages, can assist clinicians in targeting their therapeutic interventions. In recent years, several cognitive rehabilitation-based therapies have emerged that show promise.
In cognitive remediation (CR), attention, memory and executive functioning are targeted primarily with computerized exercises. CR is said to work by enhancing the neuronal plasticity of the brain by ‘restitution’ (stimulation of cognition by repetitive exercises) and ‘compensation’ (such as memorization skills and use of environmental aids) (8). In study of 39 bipolar patients showing cognitive impairment, improvement after CR was observed in working memory (p=0.043), problem solving (p=0.031) and divided attention (p=0.065) (8). In another recent study, 75 patients with bipolar disorder were randomized to a 70-hour computerized cognitive remediation(CR) program or a computer control. Post-treatment results showed medium to large positive effects of CR on processing speed and visual memory (9).
Critics of CR argue that while patients may do well on computer-based tests following the intervention, there is no significant improvement in overall functioning or quality of life. Functional remediation has thus been developed, in order to allow the use of ‘ecological neurocognitive techniques’ that improve outcome in daily life (10). When tested in a multicenter controlled study involving 77 patients with bipolar disorder, there was an improvement in functional outcome after 21 weeks of treatment, especially in the areas of enhanced occupational and interpersonal functioning. However, performance on cognitive testing did not significantly improve. The authors suggest that ‘even though cognitive deficits may persist, patients exhibit greater ability and more strategies to cope with those deficits in daily life’ (11).
More recently, cognitive behavioral rehabilitation (CBR) has been developed and is still under study. This new approach combines cognitive remediation (CR) with cognitive behavioral therapy (CBT). This method includes using CBT to identify ‘automatic thoughts’ and ‘thought distortions’ and to restructure these thoughts. ‘Mental flexibility’ is also addressed (12). While results are pending, this study is of interest in that it suggests that it may take on some of the core neurocognitive challenges previously mentioned in this article, specifically, problems with ‘set-shifting.’
To summarize, patients with bipolar disorder often experience difficulties with attention, memory, and executive function that persist even in the absence of a mood episode. These cognitive deficits can cause disruptions in many areas of daily functioning including home, work and school. A clear pattern of deficits has not yet been identified, but evidence thus far converges on attention, memory, and executive function as being affected. One finding of interest across several studies is that patients with bipolar disorder struggle with ‘set-shifting’ due to deficits in cognitive control. These deficits can be localized to the anterior/middle cingulate cortex and its connections to the prefrontal cortex. Rehabilitation strategies currently being studied consist of computer-based cognitive remediation, functional remediation, and/or cognitive-behavioral rehabilitation. As we increase our understanding of the cognitive manifestations of bipolar disorder, we will have more choices available to help patients achieve optimal functioning in many areas of their lives.
Susan Stern, M.D.