Although our findings are compelling, several
potential limitations should be noted. First, based
on the use of the claims data, the reliability and
validity of the diagnoses of bipolar disorder and
dementia remain a major concern. A previous
study found that the accuracy of dementia diagnosis
was increased when the severity of cognitive
impairment increased (29). To ensure the validity
of dementia and bipolar disorder diagnoses in the
present study, we included only patients who had
had at least three consistent diagnoses (for both
bipolar disorder and dementia) identified from outpatient
and inpatient claim data, which was similar
to the criteria used in other studies using the
NHIRD source in Taiwan (30, 31). However,
because of the NHIRD data protection policy, it
was impossible to validate the subjects’ data in the
medical records to confirm the diagnosis of bipolar
disorders. In addition, subjects with a six-month
latency period between diagnoses of bipolar disorder
and dementia were identified as having the prodrome
of dementia and were excluded from
subsequent analysis. Second, detailed information
on some clinical variables, such as various clinical
subtypes of dementia, severity of bipolar disorder,
and number of acute relapses, were not available in
the NHIRD. Therefore, we could not further evaluate
whether there was a gender difference for different
clinical subtypes of dementia. Third, to
control for potential detection bias, we treated
cerebrovascular and related diseases and health
system utilization within the preceding year of the
index diagnosis as potentially important confounders,
and adjusted for them as covariates in the
analyses. We also excluded a directly etiological
factor, Down syndrome, in all analyses. However,
unadjusted confounding factors such as educational
level, family history of dementia, and socioeconomic
status may still partially affect the risk
for dementia. Lastly, patients aged < 45 years at
the time of the first dementia diagnosis were
excluded from the study, and the study period was
set from 2000 to 2009, a ten-year period. Therefore,
we could not examine the potentially differential
relationship between dementia and a diagnosis
of bipolar disorder early versus late in life. It will
be of interest to investigate this issue when data are
available in the future