Bipolar Disorder and Cognitive Decline

By Eric Levine Ed.D. with Becky Shipkosky

Cognitive dysfunction is a core trait of bipolar disorder. That's a short assertion bursting at the seams with nuance and caveat. For starters, what causes this core trait? The consensus had been that manic episodes progressively damage the brain, causing cognitive dysfunction, and eventually lead to dementia for some. Now we're not so sure.

In this post, we’ll follow a fictional composite named Josie whose story reflects what we see in research. She will help us sort out what’s known and reasonably hypothesized as of the late 2020s. Based on scans of her brain captured two years apart, we'll consider what she might expect as she gets older and what protective measures she might take.

Chicken or Egg?

Josie is a 25-year-old single mother and a participant in a longitudinal research study on cortical thickness changes in the brains of people with genetic risk for bipolar diagnosis. (Cortical thinning is one of several brain changes seen in bipolar disorder and is generally associated with cognitive impairment.)

Josie’s father had bipolar disorder, and while he was often supportive and loving, he also struggled with addiction and bouts of explosive anger. Genetically, she carries a baseline 5-10% risk of developing clinical bipolar disorder herself, and the trauma of her childhood may increase this risk.

Married at 20, Josie felt stable for the first time. She and her husband had two children before he was diagnosed with an aggressive terminal cancer. Widowed just before her 25th birthday, the young mother entered a new era of her life. Now a single parent, she works full-time, stresses frequently about money, and doesn’t get enough sleep.

Josie began the study and received her first scan at age 23. The second was about a year after her husband passed away. Here, we’ll need to make a small methodological leap to imagine that we have access to both Josie’s brain scans and her follow-up interview for analysis.

Cortical thickness in her first scan looks indistinguishable from that of the control group. In the second scan, however, we see excess thinning in frontal and temporal regions. And sure enough, the clinician’s notes indicate that Josie was hospitalized three months ago for her first manic episode.

So, what would you reason caused Josie’s cortical thinning? Two main frameworks have sought to answer this question.

Neuroprogressive

Neuroprogression is a theoretical neurotoxic process of brain changes thought to be caused by repeated psychiatric episodes. When we consider that Josie’s cortices looked typical before onset and began to show thinning after her first episode, it would seem this event triggered the thinning.

Therefore, it would be crucial for her long-term brain health that she access treatment to prevent or minimize mania. Failure to do so could worsen cognitive decline and increase her risk of developing dementia.

Neurodevelopmental

Now consider Josie’s scans and diagnosis alongside the following two insights:

• Many young people with genetic risk for bipolar start out with more cortical thickness than their peers with no genetic risk.
• Among people with genetic risk for bipolar, the structure of a symptomatic person’s brain cannot reliably be distinguished from that of a never-symptomatic person.

So, Josie’s cortical thickness looked typical at age 23. But if our study had been performing biannual scans since Josie was 15, we might see a thinning process that began long before diagnosis. We do in fact see this in youth with genetic risk, along with accelerated thinning around typical onset age, even in those who remain asymptomatic.

According to this framework, Josie’s cortical thinning was a result of her genetic risk and likely her childhood trauma. Her recent trauma and stress may have created additional vulnerability and tipped the scale in favor of disease onset.

If Josie experiences future cognitive impairment, it would be the result of her underlying neurobiology, not bipolar disorder itself. In fact, from a purely neurodevelopmental perspective, her pre-diagnosis cognitive function is the primary predictor of:

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• Number and frequency of future episodes
• Likelihood of psychosis
• Future cognitive impairment

Some Caveats

Recent consensus favors a hybrid model, but a shortage of longitudinal studies and the brevity of those that exist still leave the picture somewhat nebulous. What’s more, most available data is group-level, and with subgroups not well understood, the known trajectories may not translate to individual experience. For example, some researchers regard a neurodevelopmental phenotype, or a portion of all people with bipolar who have a neurodevelopmental subtype of the condition.

Furthermore, there could be any number of other drivers, both known and unknown; inflammation pathways, for example, are increasingly implicated in the etiology of bipolar disorder and may even represent a primary mediating factor in cognitive impairment.

Finally, a variety of brain changes are associated with bipolar disorder beyond cortical thinning, and no structural change’s link to cognition is entirely linear.

What is Josie’s Risk for Dementia?

Dementia risk for people with bipolar disorder is two or three times that of the general population. But how do we interpret this? Neuroprogressively speaking, preventing episodes should be the most important measure in preventing dementia.

From a neurodevelopmental standpoint, however, a person’s risk for dementia might be rooted in their underlying neurobiology, not bipolar itself. Consider the following:

• Three or more adverse childhood experiences (ACEs) translates to a 3.3-fold dementia risk; and approximately 2.5 to 3 times more people with bipolar have childhood trauma compared with the general population.
• Those with alcohol use disorder (AUD) are overrepresented in bipolar by 4-fold and are 3 times more likely to develop dementia.

It’s not a far stretch, then, to consider that dementia risk could have its roots in these and other factors that impact brain development and aging, not in bipolar itself.

The Good News

We can’t currently know how much influence Josie’s childhood or recent stress has had on her bipolar disorder onset, but her treatment outlook doesn’t change much when we factor it in. Whatever the causal direction, cognitive impairment and number of episodes are positively correlated, and many of the same efforts happen to prevent both.

• Medication: Lithium reduces dementia risk by about 23%, manic episodes by 38%, and depressive episodes by 35%.
• Trauma: Up to 75% of ACE-associated dementia risk is due to the stress response, not the event itself. A stable autonomic nervous system is positively correlated with cognitive function and may reduce Josie’s developmental load to prolong remission. Healing trauma supports mental health at any stage of life and may reduce dementia risk.
• Lifestyle: Good stress management, sufficient sleep, metabolic health, and substance moderation or abstinence offset dementia risk and support remission as well as cognitive function.
• Protective: A neurodevelopmental component raises hopes that early interventions (sleep, nutrition, substance use prevention, and stress management) for Josie’s children can reduce their risk of onset during the apparent danger zone of accelerated cortical thinning.

Returning to our original question of whether bipolar disorder causes cognitive impairment and dementia, the answer is: not straightforwardly. Josie’s future is not predetermined. Even after diagnosis, she continues to have agency in how she manages risk factors and leverages the efforts most likely to influence her cognitive health.