Bipolar Disorders: Mixed States, Rapid-Cycling, and Atypical Forms

255 Atypical features of bipolarity in old agedied at follow-up. Shulman et al.(1992) found a significant difference in mortalityin an elderly manic group compared to an age- and sex-matched group of unipolardepressives. At the end of the 6-year mean follow-up period, 25 of the 50 manicpatients were dead compared with only 20% of the depressed patients. After 5years of follow-up, the probability of remaining alive was 90% for those withunipolar major depression and only 65% for patients with mania. At 10-yearfollow-up, the probability of remaining alive was 75% for the depressives andonly 30% for the manic group. It should be noted that the data for the study werefor hospitalized manic patients and studies of mortality outcome in outpatientsare now needed.Neurologic comorbidityRetrospective cohort studies of mania in late life have established a very clearassociation between bipolarity in old age and a heterogeneous group of neurologicaldisorders (Shulman and Post, 1980; Shulmanet al., 1992; Shulman and Singh,1999). Even when compared to age-and sex-matched cases of depression wherethe prevalence of neurologic disorders was 8%, the elderly bipolar patients had asignificantly higher rate of heterogeneous neurologic comorbidity (36%) (Shulmanet al., 1992). Within the elderly manic subgroup, a very late onset of mania was evenmore likely to be associated with neurologic disease (71%) compared to those withmultiple previous episodes (28%) (Tohen et al., 1994). Thus, very-late-onset maniais strongly associated with neurologic comorbidity as well as an increased mortalitymost likely related to the presence of cerebrovascular disease. This was true in 10 of14 patients whose first affective episode was manic in nature. Furthermore, comprehensivereviews of mixed-age populations with ‘‘secondary mania’’ show a varietyof both common and exotic neurologic conditions (Strakowski et al., 1994; Verdouxand Bourgeois, 1995). However, in both cohorts, cerebrovascular disease predominatesin terms of its association with mania, especially right-sided lesions involvingthe orbital-frontal and temporal cortices. This was most pronounced in those elderlybipolars with very-late-onset mania (Tohen et al., 1994).The evidence for localization in geriatric mania is based primarily on individualcase reports and case series (Starkstein et al., 1990). However, Braun et al. (1999)pooled all case reports involving focal unilateral cortical lesions and confirmed thetrend for right-sided lesions to produce manic syndromes while left-sided lesionswere associated with depressive symptomatology. Similar to other reports, thebrain lesions described in the literature were dominated by cerebrovascularpathology and in particular cerebral infarction.In neuroimaging studies, two areas of research have strengthened the associationbetween cerebrovascular disease and manic syndromes (McDonald et al.,1999). The first is the finding of an increase in subcortical hyperintensities on