The pathophysiology behind the link between
bipolar disorder and the subsequent development
of dementia largely remains unclear (13). Previous
work has reported that a reduction in the frontal
lobe volume may be associated with diffuse cognitive
impairments in patients with bipolar disorder
(22). In addition, a brain imaging study has suggested
that bipolar patients may have abnormal
brain structures in neural pathways (23). Several
studies have proposed that the glucocorticoid cascade
(24), vascular disease (25, 26), and even a trait
marker of genetic vulnerability (27, 28) may play
an important mechanistic role in neurodegenerative
change over time for affective disorders including
bipolar disorder. However, we found that
patients with bipolar disorder, especially elderly
patients, represented an etiologically heterogeneous
group (i.e., different age at illness onset, different
number of acute relapses, and different