Cognition and clinical outcome
As additional studies are published, it is becoming increasingly evident that some level of neuropsychological dysfunction often occurs in individuals with bipolar disorder, which raises questions about the functional consequences of these cognitive deficits. In schizophrenia, where far more is known about the nature and extent of neu- ropsychological dysfunction, verbal memory and vigilance appear to be necessary for adequate functional outcomes.8 Furthermore, cognitive impairment with schizophrenia prevents optimal psychosocial functioning and acts as a neurocognitive "rate-limiting" factor.8 Currently, there are not enough data to make similar claims with bipolar disorder.
Several investigators have demonstrated that verbal memory impairments or executive dysfunction are associated with reduced social and vocational functioning in patients with bipolar disorder, even in the absence of manic or depressive symptoms.9,10 Interestingly, even though the magnitude of neuropsychological impairment in bipolar disorder is typically less than that reported in schizophrenia, the strength of the association between cognitive functioning and functional outcome measures is comparable between the groups.8,9 This suggests that patients with bipolar disorder could potentially benefit from cognitive remediation or rehabilitation therapies.
Cognition as a treatment target
The evidence for cognitive impairment and its functional consequences in bipolar disorder raises the issue of cognition as a target for treatment for individuals with this illness. In the literature on schizophrenia, there is substantial support for pursuing cognition as a treatment target.11,12 The first goal in targeting cognition for either illness is to select medication treatments that do not further impair cognitive functions. A number of atypical antipsychotic medications have indications for the treatment of bipolar disorder in various phases, including aripiprazole(Drug information on aripiprazole), olanzapine(Drug information on olanzapine), quetiapine, risperidone(Drug information on risperidone), and ziprasidone(Drug information on ziprasidone). Data for schizophrenia suggest relatively minor differences in efficacy among these medications but major differences in the side-effect profiles.13
To maximize cognitive function with atypical antipsychotics, it is important to use doses that adequately control target symptoms without producing extrapyramidal symptoms (EPSs) or necessitating the use of concomitant anticholinergic medications. EPSs decrease speed of response and impair performance on a range of neuropsychological tests. Anticholinergic medications have been found to cause impairments in memory function. In addition, researchers are pursuing a variety of cognitive enhancing medications that could be added to atypical antipsychotic medications in an effort to improve cognitive functioning. Indeed, preliminary data suggest that moderate doses of galantamine(Drug information on galantamine) could help minimize cognitive dysfunction in bipolar disorder.14 Although these findings are limited, they demonstrate the potential of galantamine or other similar agents to improve the cognitive deficits in bipolar disorder.
In addition to tailoring medication treatments to maximize cognitive functioning, it is important to pursue psychosocial treatments for targeting cognitive deficits in bipolar disorder. In the schizophrenia literature, some of these approaches seek to directly improve or restore cognitive abilities. Others are considered compensatory in nature and attempt to bypass impairments in cognitive functioning to improve community outcomes.15
Cognitive remediation (CR) seeks to directly improve and/or restore cognitive functions using a variety of pen and paper or computerized tests or games requiring cognitive skills such as attention, planning, problem solving, and/or memory.16 A basic notion of CR is that the brain's neuroplasticity reserve can be enriched by cognitive experiences provided through training. Reviews of the CR literature have generally been positive and have concluded that CR improves multiple domains of cognitive functioning. These improvements are not limited to cognitive progress but encompass a range of outcomes, including improved independent living skills, increased hours worked and money earned in vocational rehabilitation, and improved social adjustment.15,17 Effect sizes for improvements in specific training exercises have generally been large, with more moderate effect sizes for other cognitive outcomes and improvements in community functioning.16,18,19
Rather than attempting to alter neurocognitive function per se, compensatory strategies attempt to bypass cognitive deficits by establishing supports or prosthetic devices in the environment to improve functioning. One example of such a treatment is Cognitive Adaptation Training (CAT).18 CAT uses environmental supports, including alarms, signs, checklists, and the reorganization of belongings to cue and sequence adaptive behavior in the home. Treatment strategies are based on a comprehensive assessment of cognitive functioning, behavior, and environment. CAT is based on the idea that impairments in executive functioning lead to problems in initiating and/or inhibiting appropriate behaviors. Using behavioral principles such as antecedent control, environmental adaptations are set up to cue appropriate behaviors, discourage distraction, and maintain goal-directed activity.
CAT has been shown to improve adherence to medication, community functioning, and rates of relapse for individuals with schizophrenia.16,18,19 Effect sizes for improvements in functional outcome and medication adherence have been large for CAT relative to control conditions. The literature for schizophrenia suggests that targeting cognitive deficits can significantly improve a broad range of outcomes. Pursuing cognition as a treatment target in bipolar disorder is a logical extension of this work.
In the next few years, we will undoubtedly learn more about the scope and consequences of cognitive impairments in bipolar disorder. Even now, it is clear that a significant portion of patients have neuropsychological deficits that influence their social and vocational functioning and potentially limit their social problem-solving abilities. Although the cognitive impairments found in persons with bipolar disorder are often subtle, improving neuropsychological processing may dramatically improve psychosocial functioning in these patients. It would seem beneficial to consider neuropsychological functioning when developing long-term care plans for individuals with bipolar disorder. However, at present there are no standards for assessing the changes in cognitive functioning caused by behavioral or pharmacological intervention specifically designed for bipolar disorder.
Recently, the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS)20 initiative developed a battery of neuropsychological tests for schizophrenia, and a number of pharmacological agents designed to improve cognitive functioning are currently being studied. While the MATRICS battery represents a significant advance for cognitive-pharmacological research, it is necessarily specific for schizophrenia and may need to be adjusted for use in bipolar disorder. Indeed, the development of an easily administered and psychometrically valid neuropsychological battery for use in bipolar disorder is a necessary prerequisite for the widespread use of cognitive measures when treating patients with bipolar disorder.