CGPR: How do you categorize older adults with bipolar disorder (BD) in terms of the course of their illness?

Dr. Lehmann: Older adults with BD comprise a mixed group of individuals. They include people who experience their first mood episode in older age, as well as individuals with a recurrent mood disorder like depression or mild hypomania. The individuals in the latter group have never had a full-blown manic episode until later life. And then there are older individuals with BD who have had BD their whole life—referred to as early-onset BD. Most cases of BD happen before the age of 50, although the literature is unclear about what percentage of BD cases might develop for the first time later in life. In comparing those with early onset to later onset, these seem to be different forms of BD.

CGPR: In what ways do older adult patients with new-onset BD differ from patients with earlier-onset BD?

Dr. Lehmann: Early-onset BD patients are much more likely to have a positive family history of mood disorder compared to late-onset BD patients. The late-onset patients are much more likely to have cerebrovascular disease (Azorin JM et al, CNS Neurosci Ther 2012;18(3):208–213). We think that cerebrovascular disease has more of an etiologic role in late-onset BD than in early-onset BD. But interestingly, there don’t seem to be significant differences in phenomenology between early-onset and late-onset BD.

CGPR: What do we know in terms of the epidemiology of BD in older adults? Does the US have higher rates of BD in older adults compared to other countries?

Dr. Lehmann: We don’t have good epidemiologic data comparing the US to other countries. Among adults over the age of 60, the lifetime prevalence rate of BD is around 1% (Valiengo L et al, Neuropsychiatr Dis Treat 2016;12:2105–2114). But even though the prevalence is relatively low, morbidity is pretty high. Older-age BD represents a significant proportion of patients seen on inpatient units, in partial hospitalization programs, and for outpatient treatment because there’s a high frequency of relapse and a need for good clinical care.

CGPR: What is the gender ratio in older adults with BD?

Dr. Lehmann: One of the things that distinguishes BD in later life compared to younger life is a notable difference in the gender ratio. In younger people the gender ratio is about 1:1. We know that among aging older adults with BD, there’s a predominance of women, which may have to do with the fact that women live longer than men. When we’re talking about older-age BD, in some ways we’re talking about a survival cohort. People with BD have a relatively higher mortality than the general population, with a lifespan approximately 8–15 years shorter (Chan JKN et al, Epidemiol Psychiatr Sci 2021;30:e39). Rates of suicide and cardiovascular disease are higher among people with BD, and they are more likely to smoke, use substances, and experience metabolic complications from pharmacological treatment (Kemp DE et al, Bipolar Disord 2010;12(4):404–413).

CGPR: What is secondary mania, and how do we differentiate this from late-onset BD?

Dr. Lehmann: Secondary mania is a term that was coined in 1978 (Krauthammer C and Klerman GL, Arch Gen Psychiatry 1978;35(11):1333–1339). It is mania that is due to a specific medical trigger or medical etiology. We’ve known for many years that medications can trigger manic episodes. Most prominently are corticosteroids, but there are other medications as well, including dopaminergic medications and antidepressants. Certain types of illnesses can trigger manic episodes, such as neurosyphilis, multiple sclerosis, Cushing syndrome, and brain tumors. Substances that are misused or abused, such as cocaine, may also mimic or trigger mania. Finally, certain types of dementia may look like mania or trigger a manic episode, in particular the behavioral variant type of frontotemporal dementia (bvFTD). What distinguishes secondary mania from other forms of BD is the trigger. If the trigger is removed—if the medication is withdrawn or the medical condition treated—then the episode of mania typically resolves. Sometimes an episode of secondary mania resolves completely without recurrence, although a manic episode due to a trigger may also become BD, perhaps due to vulnerability to BD that was unmasked.

CGPR: Have you seen secondary mania lead to BD?

Dr. Lehmann: I had a patient without a history of a prior mood episode who received treatment with a steroid medication, which triggered a classic manic episode. Her steroid treatment was time-limited for her medical condition, and her mood returned to normal when the steroid was discontinued. But then, a few months later, she developed a very classic major depressive disorder, and after that she seemed to develop a late-onset BD. She was treated very successfully with lithium. Initially it seemed like she had a secondary mania, but it evolved and became a BD.

CGPR: How often does secondary mania or depression occur after strokes?

Dr. Lehmann: We don’t have good epidemiologic data about the frequency of secondary mania, in part because we lack good epidemiologic and prospective data in BD. Data about strokes inducing manic episodes suggest that it is very uncommon. Less than 1% of all strokes induce manic episodes, particularly those involving the right frontal and right temporal areas (Yeh YW and Peng GS, Gen Hosp Psychiatry 2011;33(3):301.e13–e15). Strokes are much more commonly associated with causing major depression; in fact, rates of major depression after strokes are significantly higher up to five years after the stroke (Robinson RG and Jorge GE, Am J Psychiatry 2016;173(3):221–231).

CGPR: What’s the course of depressive and manic episodes over a patient’s lifespan? Do the episodes become more or less frequent as patients age?

Dr. Lehmann: This is not a condition that burns out or goes away over time. There is a tendency for more frequent episodes with aging, with more time in depressive episodes than manic episodes. Data suggest that individuals with early-onset BD may be more likely to have rapid cycling with age, with rapid cycling defined as four episodes or more a year. We know that treatment can be effective and that even individuals with late-onset BD can do well with treatment, although the evidence is sparse (Ljubic N et al, Ann Gen Psychiatry 2021;20(1):45). It can be more complicated to treat the older adult. As adults age, they develop chronic medical conditions, which can make it more difficult to manage their BD. For example, individuals may do very well with lithium but then become unable to tolerate it upon developing renal disease. It can be hard to find good substitutes to manage and maintain long-term mood stability and well-being.

CGPR: What are the effects of repeated mood episodes on the brain?

Dr. Lehmann: More frequent episodes of illness may have deleterious effects on the brain. Researchers are starting to look at the concept of neuroprogression. It’s a relatively new term that describes the harmful effects that can happen in the brain due to inflammation, cytokines, and oxidative stress. Recurrent episodes of illness take a toll on the brain itself, which may or may not be related to medications as much as the episodes of illness. Lithium may have a neuroprotective effect on the brain and may help mitigate against neuroprogression. However, the findings right now are still in the early stages.

CGPR: When a patient shows up with suspected mania, how do you evaluate them?

Dr. Lehmann: The first and most important step is taking a good history. I ask about changes happening now in terms of mood, behavior, activity, and sleep. I ask how the patient was functioning; how they did at their job. I assess for prior episodes that may not have risen to clinical attention (eg, minor mood swings). In mothers, I ask if they experienced peripartum mood changes, as the risk of BD is higher in women with peripartum affective episodes (Liu X et al, J Clin Psychiatry 2017;78(5):e469–e476). I take a thorough family psychiatric history. I often find out that other, especially older, family members likely had a mood disorder that went undiagnosed or did not receive clinical attention. I also take a comprehensive medical history, looking at all medications and substances. My usual workup in older adult patients with suspected BD includes a complete blood cell count, a comprehensive metabolic panel, thyroid function tests, vitamin B12, folate, and a urinalysis. For patients with a new-onset manic episode in later life and no prior mood illness history, I often recommend imaging of the brain such as a CT scan or MRI to look for a mass, tumor, or stroke.

CGPR: What’s at the top of your differential, and how do you systematically narrow your differential?

Dr. Lehmann: I think about whether this could be frontotemporal dementia (FTD), of which bvFTD is the most common variant. It tends to happen in individuals between the ages of 50 and 70—this is also the age group in which we’re thinking about late-onset BD. Late-onset BD is not very common, about 10% of all cases of BD. FTD has a prevalence of about 5% of all dementias, so it’s up there. Sometimes it can be hard to differentiate BD from bvFTD, as bvFTD doesn’t present with memory impairment, but rather, it presents with changes in personality and behavior. These may include impulsive behaviors, hedonic behaviors, and overengagement in risky behaviors. Usually, for individuals with bvFTD, we don’t see changes in sleep or changes in attitude like grandiosity that we see in mania. But in many cases, it warrants further investigation. Neuropsychological testing and imaging can help to differentiate between the two, particularly SPECT scans or PET scans. In general, for late-life BD, the kinds of structural brain changes we see are mild. We see gray matter volume reduction. We frequently see white matter hyperintensities, which are nonspecific, or we may see evidence of silent infarction.

CGPR: What’s the relationship between BD and cognitive impairment?

Dr. Lehmann: Older adults with BD have more cognitive impairment. We see cognitive dysfunction in 30%–50% of older-age BD patients. It presents in all mood states: depression, mania, and euthymia. There is a range of deficits in terms of attention, cognitive flexibility, processing speed, memory, and semantic fluency. BD accelerates or increases the risk for cognitive impairment (Diniz BS et al, Am J Geriatr Psychiatry 2017;25(4):357–362). One study found that the risk of developing dementia increased with each mood episode (Kessing LV and Andersen PK, J Neurol Neurosurg Psychiatry 2004;75(12):1662–1666). Another study noted that the length of illness correlated with a lower level of gray matter volume (Frey BN et al, Eur Neuropsychopharmacol 2008;18(10):717–722).

CGPR: Individuals of African ancestry have higher rates of misdiagnosis of BD than individuals of European ancestry (Akinhanmi MO et al, Bipolar Disord 2018;20(6):506–514). What steps can clinicians take to minimize disparities in diagnosis, especially as older adults often present to clinicians with an established diagnosis?

Dr. Lehmann: Every clinician should train themselves to start at the beginning. If you’re concerned about unusual aspects of a patient’s behavior, don’t assume that the correct diagnosis is there. Instead, start with a fresh approach and an open mind. There’s no substitute for taking your own history and spending the time. The challenge for making a BD diagnosis is to get another informant, someone who knows the individual well. That informant will be helpful in providing the longitudinal history to help you understand a patient’s baseline and whether they have had episodes of change in behavior that may have gone unnoticed.

CGPR: How do relationships in older age influence the trajectory of BD?

Dr. Lehmann: Sometimes it’s a change in the family member that affects the older patient. I can think of one woman whose story is very vivid to me. She had an early-onset BD and was now of older age. And she was very stable on treatment—what stabilized her was that we recruited her husband to help manage her medications and to provide reminders. With his partnership she did well for several years. And then she started to have frequent relapses, and I remember wondering whether her BD was developing into a more severe form now that she was aging. It turned out that her husband developed dementia, and because of his memory impairment, he was no longer able to remind her to take her medication. This was eye-opening for me. We must think about the health of both partners and how aging couples often become supports to each other. The illness of one partner can destabilize the other, and vice versa.

CGPR: Thank you for your time, Dr. Lehmann.