Cognitive Impairment in Patients With Bipolar Disorder: Effect on Psychosocial Functioning: Page 2 of 2
Cognitive Impairment in Patients With Bipolar Disorder: Effect on Psychosocial Functioning: Page 2 of 2
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 neuropsychological 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, olanzapine, quetiapine, risperidone, and 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 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.
1. Burdick KE, Endick CJ, Goldberg JF. Assessing cognitive deficits in bipolar disorder: are self-reports valid? Psychiatry Res. 2005;136:43-50.
2. Glahn DC, Bearden CE, Barguil M, et al. The neurocognitive signature of psychotic bipolar disorder. Biological Psych. In press.
3. Quraishi S, Frangou S. Neuropsychology of bipolar disorder: a review. J Affect Disord. 2002;72:209-226.
4. Honig A, Arts BM, Ponds RW, Riedel WJ. Lithium induced cognitive side-effects in bipolar disorder: a qualitative analysis and implications for daily practice. Int Clin Psychopharmacol. 1999:14:167-171.
5. Engelsmann F, Ghadirian AM, Grof P. Lithium treatment and memory assessment: methodology. Neuropsychobiology. 1992;26:113-119.
6. Amado-Boccara I, Gougoulis N, Poirier Littré MF, et al. Effects of antidepressants on cognitive functions: a review. Neurosci Biobehav Rev. 1995;19:479-493.
7. Bearden CE, Glahn DC, Monkul ES, et al. Sources of declarative memory impairment in bipolar disorder: mnemonic processes and clinical features. J Psychiatr Res. 2006;40:47-58.
8. Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry. 1996;153:321-330.
9. Martínez-Arán A, Vieta E, Colom F, et al. Cognitive impairment in euthymic bipolar patients: implications for clinical and functional outcome. Bipolar Disord. 2004; 6:224-232.
10. Dickerson FB, Boronow JJ, Stallings CR, et al. Association between cognitive functioning and employment status of persons with bipolar disorder. Psychiatr Serv. 2004;55:54-58.
11. Green MF, Olivier B, Crawley JN, et al. Social cognition in schizophrenia: recommendations from the measurement and treatment research to improve cognition in schizophrenia new approaches conference. Schizophr Bull. 2005;31:882-887.
12. Marder SR, Fenton W, Youens K. Schizophrenia, IX: cognition in schizophrenia—the MATRICS initiative. Am J Psychiatry. 2004;161:25.
13. Simpson GM, Pi EH. The efficacy and tolerability of atypical compared with typical neuroleptics in schizophrenia. Direct Psychiatry. 2006;26:207-219.
14. Schrauwen E, Gaemi SN. Galantamine treatment of cognitive impairment in bipolar disorder: four cases. Bipolar Disord. 2006;8:196-199.
15. Velligan DI, Kern RS, Gold JM. Cognitive rehabilitation for schizophrenia and the putative role of motivation and expectancies. Schizophr Bull. 2006;32:474-485.
16. Velligan DI, Prihoda TJ, Ritch JL, et al. A randomized single-blind pilot study of compensatory strategies in schizophrenia outpatients. Schizophr Bull. 2002;28:283-292.
17. Medalia A, Richardson R. What predicts a good response to cognitive remediation interventions? Schizophr Bull. 2005;31:942-953.
18. Velligan DI, Bow-Thomas CC, Huntzinger CD, et al. A randomized controlled trial of the use of compensatory strategies to enhance adaptive functioning in outpatients with schizophrenia. Am J Psychiatry. 2000;157:1317-1323.
19. Velligan DI, Diamond PM, Zeber J, et al. Cognition adaptation training improves adherence to medication and functional outcome in schizophrenia. Schizophr Bull. 2007;3:609.
20. Green MF, Nuechterlein KH, Gold JM, et al. Approaching a consensus cognitive battery for clinical trials in schizophrenia: the NIMH-MATRICS conference to select cognitive domains and test criteria. Biol Psychiatry.2004;56:301-307.