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

256 K. I. Shulmanmagnetic resonance imaging scans. These hyperintensities are associated withhypertension, diabetes mellitus, and arteriosclerotic heart disease. The secondmajor neuroimaging finding, led by Japanese investigators (Kobayashi et al.,1991; Fujikawa et al., 1995), is the presence of silent cerebral infarctions. Theseinvestigators have shown a progressive age-related increase in silent cerebralinfarctions ranging from 6% in middle-aged individuals to greater than 20% inan elderly subgroup. Compared to late-onset depression and early-onset mooddisorder, the highest frequency of silent cerebral infarctions occurs in the lateonsetmanic subgroup (Fujikawa et al., 1995). Conceptually, these individuals fallinto the category of secondary mania with a relatively lower incidence of familyhistory in first-degree relatives and a higher prevalence of cerebrovascular riskfactors.Recent volumetric studies of bipolar patients show a trend towards diffusecerebral atrophy (Steffens and Krishnan, 1998; Young et al., 1999). These studiesneed replication and further elaboration of their significance.Cognitive impairmentOne of the unique elements of studying an elderly cohort is the expected higherprevalence of cognitive dysfunction that may affect outcome and potentiallytreatment response. In preliminary studies of manic syndromes in late life, therehas been a consistent association of cognitive dysfunction. Berrios and Bakshi(1991) found elderly manic patients to be more cognitively impaired and to havescored higher on the Hachinski Scale, reflecting cerebrovascular pathology, whencompared to a matched group of elderly depressives. Furthermore, Dhingra andRabins (1991) reported scores of less than 24 on the Mini-Mental State Examinationin almost one-third of their elderly manic patients during a 5–7-year follow-up. Anearlier suggestion that the increased incidence of first admission rates for mania atthe extremes of old age might be due to the onset of a dementing illness (Spiceret al., 1973) has not been substantiated by the few outcome studies available(Stone, 1989; Shulman et al., 1992). However this issue still requires clarificationand long-term follow-up, including documentation of cognitive function. This isespecially true since the finding by Alexopoulos et al. (1993) that patients withdepressive pseudodementia, if followed for more than 3 years, will develop anirreversible dementia.Preliminary studies have suggested that cognitive impairment will affect treatmentresponse (Wylie et al., 1999; R. C. Young, personal communication, 2002).Recent interest has focused on executive performance in elderly bipolars and initialfindings on a variety of tests of executive and frontal function show impairment inelderly manic patients compared to controls (R. C. Young, personal communication,2002).