To our knowledge, this is the first comprehensive study of neuropsychological functioning in middle-aged and older outpatients with BD. As hypothesized, the group with BD performed worse than NCs (with medium effect sizes) on nearly all neuropsychological tests. However, in contrast to our hypothesis, impairment was distributed across nearly all ability areas assessed, and were unrelated to psychiatric symptom severity or duration of illness. As hypothesized, neurocognitive ability among BD patients predicted a significant proportion of variance in quality of life. The BD patients performed similarly to those with SC in half of the cognitive domains, and performed better on the remaining tests with small effect sizes. These results highlight cognitive impairment as a common and disabling aspect of late-life BD, but also suggest some differences in neurocognitive abilities between BD and SC in later life.
Our data suggested that over half (56%) of the BD patients had clinically significant overall cognitive impairment (defined as a Deficit Score≥0.5). Given the heterogeneity of BD and variance in methods used to assess cognitive abilities, comparisons across studies are somewhat difficult. Nevertheless, this finding is consistent with previous studies of late-life BD employing cognitive screening measures. Gildengers et al. (2004)
found impairment in about half of a sample of 18 older BD inpatients and outpatients and Burt et al. (2000)
(n=13) and Savard, Rey and Post (1980)
(n=7) found significant (although not age-corrected) differences between younger and older inpatients with BD in verbal memory and problem solving.
Relative to previous studies directly comparing younger adults with BD, NCs, or SC (Altshuler et al., 2004
, Krabbendam et al., 2005
, Dickerson et al., 2004
), our findings suggest broader impairment among older BD patients compared to NCs. Moreover, these differences between BD and NC groups were unrelated to educational and occupational attainments, which were both slightly higher in the BD group. It is further notable that occupational level had no association with cognitive performance in the BP patients, although this finding requires replication. Among younger adults, deficits in verbal memory and executive functioning have been identified in euthymic states, and are perhaps the most robust domains of impairment (Bearden et al., 2001
, Krabbendam et al., 2005
). In our outpatient sample, depressive or psychotic symptoms did not correlate with verbal memory or reasoning/problem solving scores, further suggesting that these deficits are not simply a byproduct of these symptoms. We also found evidence for speed of information processing deficits, with the largest effect sizes between BD and NC groups among all measures seen on the Trailmaking Test (Parts A and B), WAIS-R Digit Symbol, and Grooved Pegboard, and performance on these measures related to health-related quality of life. Cognitive slowing has been identified as a central and persistent component of late-life depression (Butters et al., 2004
), which raises the question of whether late-life BD may involve similar neurocognitive underpinnings.
The neurocognitive distinctions between the BD and SC samples were more subtle than between the BD and NC groups, with smaller effect sizes than those observed in studies of younger adults. In a meta-analysis of 31 studies, Krabbendam et al. (2005)
reported a mean effect size difference across cognitive measures of 0.49, which is approximately twice as large as that found in our sample. This relatively small level of distinction between older patients with BD and SC was also evident in a study of chronically institutionalized patients (Harvey et al., 1997
). As predicted, our BD group performed better than patients with SC on measures of verbal skills/crystallized knowledge, information processing speed, and verbal memory. Therefore, our findings support the notion that BD patients are less cognitively impaired than patients with SC in later life. However, the overall gap in neurocognitive abilities between these disorders may be narrower in later life. There is evidence for stability in cognitive functioning among community-dwelling middle-aged and older adults with SC (Heaton et al., 2001
), and longitudinal studies comparing these two disorders will be useful to determine if there are actual disease-related declines in BD. Possible cohort differences between younger and older persons with BD cannot be ruled out in cross-sectional comparisons.
Although we did not group BD patients into euthymic, depressed, and manic subgroups as in some previous reports (Martinez-Aran et al., 2004
, Altshuler et al., 2004
), it is doubtful that their neurocognitive deficits are solely attributable to concurrent depression or mania for two main reasons: 1) Our sample was comprised of outpatients who had, in general, mild levels of depressive, manic, and psychotic symptoms, and 2) None of the symptom measures showed any significant relationships with any domains of cognitive performance in the BD group, similar to the lack of association between manic symptoms and cognitive functioning reported among older adults with BD (Young et al., 2006
). Thus, from a clinical standpoint, neuropsychological impairment should be considered an important part of the presentation of older adults with BD, and are at least somewhat independent from symptom severity.
Patients with BD taking lithium or antipsychotic medications (typical or atypical) had worse cognitive functioning, which corresponds to previous literature on the incidence of cognitive side effects of these medications in elderly BD patients (Young et al., 2004
). However, we cannot determine from our data whether the relationship of these medications to cognition can be attributed to the medication itself or to other patient or provider-related factors, especially since a higher proportion of our sample was unmedicated than might be predicted. Nevertheless, these findings suggest that further research should investigate the incidence and severity of cognitive side effects of the medications commonly used to treat BD. Finally, similar to a previous study linking global cognitive functioning with community living skills among older BD patients (Martinez-Aran et al., 2004
), we found that better attention/working memory, verbal memory, and information processing speed related to better health-related quality of life. Parallel to the growing recognition of the centrality of neurocognition to treatment of SC (Heinrichs, 2005
), the extent to which these deficits in later-life BD is altered by medications should be examined.
The strengths of this study include a relatively large outpatient sample of older BD patients, use of two comparison groups that have been better characterized in previous literature, and administration of a comprehensive battery of neuropsychological tests and symptom measures to assess a range of cognitive and psychopathologic factors. However, these findings must be interpreted in light of several limitations of the study. Both patient samples were comprised of community-dwelling outpatients who were generally experiencing low levels of symptoms. Therefore, our findings may not generalize to hospitalized or acutely ill patients. In addition, the proportion of women in the sample was low and fewer patients had a history of substance abuse than is typically reported for BD samples, which may further limit the generalizability of the results. Some of our data predate the widespread usage of atypical antipsychotics, which may attenuate the differences between the SC and BD groups if atypical antipsychotics indeed enhance cognitive abilities, a point of some controversy. These data are cross-sectional; thus, future longitudinal research will be needed to examine the effects of aging on the development of cognitive deficits. We did not have available a commonly used standardized measure of mania such as the Young Mania Rating Scale (Young et al., 1978
), and therefore, the effect of manic symptoms on neuropsychological performance in older adults deserves further study. However, we did not find evidence for a significant relationship with a mania-like ‘excitement’ subscale of the PANSS nor general psychopathology (i.e., BPRS scores), and thus, it is unlikely that acute and undetected manic symptoms greatly impacted performance in the BD group. Finally, we did not have detailed information about illness history, such as the number of previous manic or depressive episodes, nor reliable information on cumulative exposure to psychiatric medications. In previous studies, cumulative illness burden appeared to have a greater negative impact on cognitive functioning than duration of illness or concurrent symptoms (Bearden et al., 2001
, Robinson and Ferrier, 2006
) Again, a longitudinal investigation of cognitive functioning would help address these shortcomings.
In conclusion, we found neurocognitive impairments in a sample of community-dwelling middle-aged and older patients with BD that were more diffuse and also more similar in severity to those in patients with SC than has been reported in studies of younger adults with these diagnoses. Therefore, clinical care of BD patients who enter later life should take into account the presence of cognitive impairment, and future longitudinal research should examine the mechanisms related to the development of cognitive deficits in BD across the life span, so that preventive and rehabilitative interventions could be designed and implemented.