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S012-2

Neuroprogression, Brain Health, and Cognition In Older Adults with Bipolar
Disorder

Shou-Hung Huang1, Ariel G. Gildengers2

1Department of Psychiatry, Taipei Medical University Hospital and College of Medicine, Taipei Medical University,
Taipei, Taiwan 2University of Pittsburgh School of Medicine, USA

Background/Objective: In the past several years, there has been a paradigm shift in the
understanding of bipolar disorder (BD). BD is no longer considered an illness solely of cyclical
mood episodes interspersed with normal euthymic periods, but rather as a multi-system disease that
is chronic and progressive. Numerous studies have now shown that across the life span BD is
associated with increased medical comorbidity, cognitive dysfunction, and substantial impairment in
everyday function (instrumental activities of daily living). Additionally, while suicide contributes to
premature mortality in BD, medical comorbidity (especially cardiovascular and cerebrovascular
disease) also contributes substantially to excess mortality, ranging from 35% to 2-fold higher than
the general population and higher than major depressive disorder.

Method: We will summarize the existing literature on neuroprogression, brain health, and cognition
in BD, focusing on older adults. We will discuss the potential biological pathways related to brain
changes and cognitive function in BD subsumed in the model of allostatic load. Altered allostasis
includes, and are not limited to, mitochondrial dysfunction, oxidative stress, inflammation, and
neurotransmitter and neuropeptide dysregulation. We will balance the discussion of neuroprogression
by discussing some countervailing positions arguing against the model.

Result: While reports reveal increased gray matter and white matter abnormalities in older adults
with BD and greater than expected cognitive dysfunction, it does not appear that the brain and
cognitive changes are related to accelerated neurodegeneration or cognitive decline in old age, but
rather the cumulative effect of long-standing BD and its comorbidities that begin early in the illness.

Conclusion: The paradigm shift in understanding the impact of BD on an individual should lead to
broadening of treatment goals to encompass medical comorbidity, brain health (including cognitive
function), and everyday function.