| Abstract | Current evidence suggests that there is an association between benzodiazepinereceptor-agonist medications (BZRA) and subsequent dementia. Expert opinions differ
regarding whether the association indicates a causal relationship. There is sufficient
evidence that neuropsychiatric symptoms, such as anxiety and insomnia, are indicators of
prodromal dementia which may lead to treatment with benzodiazepine-receptor agonist
medications. Therefore, the association between BZRAs and subsequent dementia may be
a spurious correlation for which the prodromal onset is responsible. This study proposed
to test the postulate that the anxiety and insomnia symptom cluster (A/I) is a predictor of
dementia.
A retrospective data analysis was conducted on the Aging, Demographics, and
Memory Study (ADAMS) dataset in order to determine whether A/I symptoms or
treatment were associated with subsequent dementia or cognitive impairment (DOCI). The
study controlled for gender and comorbid depression. The study excluded BZRA usage
and medical comorbidities that were either confounding variables in assessment or
alternative explanations of cognitive decline. The study used chi-square analysis,
comparison of incidence rates, odds ratios, relative risk, and logistic regression to
investigate the idea that the A/I symptom cluster indicates developing prodromal dementia.
The study failed to find an association between A/I symptoms and subsequent
DOCI in the total sample. However, there was a significant relationship between A/I
symptoms and subsequent DOCI in the male gender that was not found in females. No
association was found for the A/I medications in any of the analyses. Further investigation
of the ADAMS dataset without removing the exclusion variables also showed that BZRA
usage was not associated with subsequent DOCI.
The gender differences identified suggest prodromal dementia phenotypes that are
differentially expressed in males and females. The lack of association between A/I
medications and subsequent DOCI in this study is validated by the lack of association
between BZRA medications and subsequent DOCI in the larger ADAMS dataset. While it
is unlikely that a single reliable predictor of subsequent dementia exists, by triangulating
the approaches between multiple disciplines—such as biomarkers and neurological
studies—with neuropsychiatric manifestations of prodromal dementia, it is possible that
reliable early prediction may be accomplished. Earlier identification would then lead to
effective treatments and ultimately prevention.
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