An adult >age 50 with
Early-onset bipolar disorder
=
Older age bipolar disorder
Early-onset depressive disorder with new-onset mania
New-onset mania in individual with no prior mood illness (in the absence of a specific medical trigger, but may be associated with brain injury, silent stroke or cerebrovascular risk factors)
Secondary mania (temporally and directly linked to a specific medical trigger) followed by symptoms consistent with bipolar disorder
1.3 Limitations
One of the major challenges in studying bipolar disorder in older age is that it is less common in older than in younger individuals. An important limitation to the majority of studies to date is small sample size. The largest research samples of individuals with bipolar disorder have had populations in the low thousands [9, 10], with the majority of studies looking at sample sizes in the low hundreds or less [5]. Because searching within inpatient populations is a convenient way to locate subjects with a relatively rare disorder, the majority of studies on late-life bipolar illness focus on this group. However, this approach skews samples toward those individuals with more severe illness, and thus, findings may not be relevant for individuals with milder symptoms and those who require only outpatient care [5, 11]. Additionally, there is a lack of longitudinal studies in this area, resulting in a paucity of information about the long-term course of older age bipolar disorder. Further, retrospective collection of historical details, such as an individual’s age of onset and clinical presentation, is subject to recall bias or error. Lack of prospective data may also contribute to a selection bias of individuals who survive into later life.
In general, the studies we cite are from US samples unless indicated. Different countries have varying demographic proportions between old and young, different medical and mental health systems in place, and different social services available which may affect age of onset proportions and prevalence rates in inpatient versus outpatient populations as well as health services utilization.
1.4 Prevalence in the Community
Overall, the prevalence rates of individuals living in the community with bipolar illness decrease with age [1, 12, 13]. Whereas bipolar disorder is present in 1.4 % of individuals aged 18–44, prevalence rates decrease to 0.1–0.5 % in people aged 65 and older [11, 14]. When individuals with both bipolar type 1 and bipolar type 2 disorders are considered, prevalence of OABD has been reported to be 1 % of individuals over the age of 60 [15]. It remains unclear whether this is a historic effect, related to diagnosis and identification of older patients, a cohort effect related to a lower level of disease among adults born earlier, a result of increased mortality among individuals with early-onset bipolar disorder (EOBD), or a combination of factors [16].
1.5 Prevalence in Treatment Settings
However, in contradistinction to low prevalence rates among older people living independently in the community, late-life bipolar disorder is more common in treatment settings. Since the landmark Epidemiologic Catchment Area study (ECA) in the 1980s, which found bipolar illness in 9.7 % of chronically institutionalized adults in prisons or nursing homes, researchers have recognized that the illness is overrepresented in care settings, and this discrepancy increases as people age [14, 17, 18]. For instance, a recent survey of 2600 New York City senior living facility residents found a bipolar disorder prevalence rate of 7.8 % [19]. In addition, a large study of all veterans in a national database found that fully one-quarter of those receiving either outpatient or inpatient treatment through the Veterans Administration for a bipolar diagnosis were aged 60 or older [20].
On inpatient psychiatric units, there seems to be relatively equal rates of younger and older adults with bipolar illness, close to 10 % for each, despite the declining prevalence of bipolar disorder in older age [5, 12, 15]. An early study of patients with late-onset bipolar disorder (LOBD) found that they accounted for 9.3 % of geriatric affective disorder admissions over a 2-year period [21]. One recent review article calculated the prevalence of mania in adults over the age of 50 who were being treated in a hospital for any mental illness to be 6.0 %, with one-third of those having first-time late-onset mania [11]. Rates of bipolar illness among those presenting to psychiatric emergency rooms are higher than in inpatient settings. A study of 2419 adult visitors to a Seattle psychiatric crisis unit found that 14 % of these patients had bipolar disorder [22]. Another study that focused on psychiatric emergency department visitors older than age 60 found that 17 % had bipolar disorder [23].
Therefore, although the prevalence of bipolar disorder decreases with advancing age, individuals with OABD represent a sizable proportion of the bipolar community, with a need for acute psychiatric services as well as day hospital treatment and case management that is equal to or greater than their younger cohort [2, 5, 13, 20].
1.6 Age of Onset
The clinical heterogeneity of older individuals with bipolar disorder is an ongoing area of research. As a group, older adults with bipolar illness share qualities of aging, including greater medical comorbidity, increased risk for polypharmacy, and physiologic reduction in renal function. However, research over many years has identified two distinct types of bipolar disorder among older adults, each with varying courses: EOBD and LOBD.
When this phenomenon was initially observed, there was interest in distinguishing between these two groups. However, it has been challenging to assemble large sample populations, and most studies have had modest numbers and inconsistent findings, making conclusions hard to draw. Some trends have been observed but with uncertain clinical significance. Over the past decade, researchers have placed less emphasis on distinguishing between early- and late-onset illnesses. It remains to be seen whether larger studies may reveal important clinical distinctions between these two groups. However, generalizing about the nature of bipolar disorder in later life, without taking into account these possible subtypes, runs the risk of conflating age-related versus disease-specific effects.
1.6.1 Bimodal Distribution
Defining the age at onset of bipolar disorder has posed significant challenges for researchers and there continues to be no clear consensus about how this should be done. Does one use the age at first mental health contact, the age at first psychiatric hospitalization, or the first time the patient experienced significant mood symptoms causing impairment in functioning? Does onset of bipolar disorder begin at the first depression or the first mania? If manias present first, the task of determining age of onset is relatively straightforward. However, for as many as 25 % of individuals who eventually meet DSM 5 diagnostic criteria for bipolar disorder, the first psychiatric treatment or hospitalization for any mood disorder will be for major depression, sometimes years to decades prior to the emergence of mania, delaying a correct diagnosis [7, 13, 24–27].
Despite these challenges, multiple studies of bipolar disorder have found a bimodal distribution of age of onset, with two major groups: a larger group experiencing onset of manic symptoms before age 30 and a smaller group with onset after age 40 [1, 7, 10, 24, 25, 28–32]. Some studies have defined an additional group with early onset in childhood or adolescence [33–36]. For the most part, two groups of individuals have been described: those with early-onset and late-onset disease.
1.6.2 Cutpoints and Proportionality of Early- Versus Late-Onset Bipolar Disorder in the Treatment Population
It is important to recognize that although an estimated 90 % of patients who will develop bipolar illness over their life span are diagnosed by the age of 50, first mental health contact occurs after age 60 for a significant minority of 8–9 % [24, 25, 28]. Although the findings are not unequivocal, research suggests that those who experience bipolar disease onset later in life may have different demographic profiles, risk factors, clinical presentation, and disease course. Future research may delineate whether they have distinct etiologies.
Various studies not only differ in the definition of “age of onset” for their subject population, but also use different cutpoints to distinguish early- and late-onset groups, challenging comparisons across studies. Researchers have utilized different approaches to determine which age cutpoint to use. Some studies have attempted to calculate a mathematically likely age dividing line based on the statistical distribution of their sample, while other studies have used arbitrary or convenience cutpoints. Using a cutpoint at age 40, one study found the proportion of early- and late-onset bipolar patients in a community sample in England to be 78 and 22 %, respectively [25]. Using a cutpoint at age 50, a study looking at both inpatients and outpatients diagnosed with bipolar I disorder, found that of those over 60, about one-third had experienced late onset of their illness [37]. Using a later cutpoint at age 60, a large Veterans Administration study of both inpatients and outpatients found that at least 9 % of individuals over 60 with bipolar disorder had just been diagnosed with that disorder in the prior year [20]. Using a lower cutpoint at age 45, a small study of inpatients hospitalized with mania found the proportion of patients with late versus early onset to be roughly equal [7]. Using a cutpoint at age 47 based on first psychiatric hospitalization, a midsize retrospective study of inpatients with bipolar disorder found that only 6.3 % had LOBD [29]. There remains a wide variation in the proportion of OABD that current studies ascribe to early- versus late-onset disease. The International Society for Bipolar Disorders Task Force on Older Age Bipolar Disorder noted that while age 50 may be a reasonable cutpoint to distinguish EOBD from LOBD, this is an area requiring further study, and a lower cutpoint of age 40 may be warranted if supported by future research [1].
1.7 Demographic Distinctions
Individuals who present with bipolar illness at a later age tend to be skewed demographically in three ways. One distinction is that while male to female gender ratios are fairly even among younger adults with EOBD, women predominate in many late-onset bipolar samples [9, 21, 25, 27, 35, 38]. It remains unclear whether this indicates a survival cohort, a bias in users of medical services, or a correlation between female gender and vulnerability to late-onset disease. A large study of both inpatients and outpatients in Denmark saw no statistically significant gender difference among older patients with bipolar disorder [10], similar to results from an inpatient study in Scotland that took population gender rates into account [39] and a small study of outpatients in England [30]. One finding that has been consistent across studies is that individuals presenting with bipolar illness later in life are less likely than early-onset patients to have a family history of bipolar illness [21, 24–26, 31], raising the question of alternative pathways to disease.
Finally, bipolar illness impacts close relationships [40]. Two studies found that those with later onset of illness were more likely to be married or living with someone in their older age than those with earlier onset of disease [32, 35]. One of the few prospective examinations of age of onset in bipolar illness found that 52 % of those who first became ill after age 30 were married at the time of the study compared to 27 % of those who experienced illness before age 21 and 40 % of those first ill before age 30 [33]. Another small study found that those with later onset reported more social support and perceived their social support to be more adequate compared with those who had earlier onset of bipolar disease [26]. These results suggest that social support may be a casualty of the disease striking before or during the age when people often find and consolidate partnerships and also has ramifications for prognosis and service utilization as patients age.
1.8 Heterogeneous Etiologies—Including Cerebrovascular Risk Factors and Secondary Mania
The bimodal distribution of age of onset, demographic differences, and possible distinctions in natural course of disease all beg the question, “Could LOBD be secondary to or exacerbated by cerebrovascular disease or any other focal neurobiological insult?” There seems to be clear evidence that cerebrovascular disease is frequently associated with LOBD, but not through one definitive pathway, and little characterization of predisposing factors. Furthermore, there is evidence for both new-onset mania in the setting of cerebrovascular risk and secondary mania triggered by a proximate medical cause.
The hypothesis that cerebrovascular insult may initiate onset of bipolar disorder later in life comes from rare observations of new-onset mania following brain injury. Mania-inducing strokes represent <1 % of all strokes but seem to predominate in the right frontal or temporal region [41–45]. There are no prospective studies following these patients over the long term; what evidence there is suggests that a proportion have resolution of their manic symptoms after one episode of mania and others go on to have bipolar disorder with recurring episodes of mood disturbance [44].
In addition to strokes causing mania, there is a growing literature suggesting a role for silent cerebral infarctions in late-onset bipolar illness. These are brain lesions seen on imaging but not known to be linked temporally to symptoms. An early small study found that 65 % of patients with LOBD had silent brain infarcts compared to 25 % of patients with early onset of either depression or bipolar disorder [46]. A more recent small study found that 92 % of patients with LOBD (compared to 53 % of those with EOBD) had visible brain infarctions on imaging, the majority of which, 62 %, were silent [47]. A small study of patients with their first episode of mania after age 65 found that 71 % had a comorbid neurologic disorder, twice as many compared to their age cohort with earlier onset bipolar illness [48].
More broadly, the link between LOBD and general cerebrovascular risk has been examined by many studies, with inconclusive results. An early study found that elderly patients with bipolar illness had significantly more cortical atrophy and poorer scores on cognitive tests than age-matched controls but did not find differences between those with early- versus late-onset illness [24]. However, a later study found that those with LOBD had significantly more cerebrovascular abnormalities [32]. Another small study that rigorously matched late-onset and early-onset patients by race, sex, and age found that the late-onset group had significantly more vascular risk factors and disease than those who were their same age but had disease onset earlier in life [29]. A small study in England found that among an older group of outpatients, those whose bipolar disorder occurred later had a significantly higher stroke risk compared to those who had earlier onset [30]. A large prospective Danish registry study of more than 200,000 patients found that having dementia, a disease of diverse etiologies but always related to structural brain disease, significantly increased the risk of developing mania or bipolar disorder [49].
In fact, the relationship between brain ischemia and bipolar illness may be more complex. Cerebrovascular disease may be a cause of LOBD, but early-onset bipolar illness itself, or its treatment, may predispose to conditions causing strokes such as inflammation, metabolic derangements, and obesity. The small study mentioned above found a higher incidence of silent cerebral infarcts in individuals with late-onset bipolar illness. This study also demonstrated that 47 % of patients in their 60s with early-onset bipolar illness had silent infarcts on brain imaging compared to 20 % of healthy people the same age [47], suggesting ischemia as both a trigger for and a consequence of bipolar illness.
The hypothesis that vascular injury to the brain may contribute to the onset of bipolar illness in a subset of individuals is particularly intriguing because it suggests that screening for and treating vascular risk factors could potentially delay or prevent onset of mania, and is an important question for future research. In addition, the increased risk for vascular disease in those with EOBD needs to be factored into treatment.
In addition to the possibility that symptomatic or silent cerebrovascular injury can cause new-onset mania in later life, the phenomenon of mania secondary to medication, somatic illness, delirium, or dementia is well established (Fig. 1.1) [11, 50, 51]. In some cases, when the offending agent or illness is removed or successfully treated, mania resolves and does not recur. However, other patients may recover from the inciting factor but go on to develop repeating patterns of mania and depression best characterized as bipolar disorder, that we may think of as having been unmasked or triggered by the event. Others still may have chronic illnesses which cause a manic-like syndrome best thought of as a mood disorder secondary to a medical condition. Medications implicated are numerous and include corticosteroids, isoniazid, dopaminergic agents, and antidepressants [50]. Drugs of abuse including alcohol, cocaine, stimulants, and hallucinogens can also incite mania [52]. Illnesses-causing mania are likewise numerous and include Cushing’s disease, influenza, HIV, neurosyphilis, multiple sclerosis, hyperthyroidism, brain tumors, and seizure disorders among others [52]. Delirium is an acute state of global confusion that can present with manic symptoms but should be resolved before diagnosis of ongoing mania is made. Dementias, especially frontal-temporal dementia, can present with manic-like syndromes and have cerebrovascular injury as an overlapping risk factor (Fig. 1.1).
Fig. 1.1
Possible causes of late-life mania
Clinical Vignette 1.1
Ms. S is a 70-year-old married African American woman who was diagnosed with bipolar disorder in her 60s after experiencing a steroid-induced psychosis.
Her family history was notable for dementia in her mother. Her personal history was notable for an unremarkable birth and development; she successfully completed college and worked as a nurse until retirement in her 50s, and was married with one child. Her medical history was significant for giant cell arteritis requiring treatment with steroids.
Her psychiatric history was notable for the absence of mental illness until her 60s, when Ms. S was brought to the emergency department by her husband for talking fast and not making sense. A psychiatric consult attributed her abnormal behavior to high-dose prednisone she was taking at the time. This was tapered off and she returned to baseline. Six years later, she began having increased energy, with problems falling asleep, and increased cleaning at night while again on steroid medication. She was hospitalized on a medical service, diagnosed with steroid-induced psychosis, treated with low-dose neuroleptic medication, and discharged on a lower dose of steroids. Two months later, Ms. S presented with her first episode of depression marked by low mood, low appetite with weight loss, low energy, sadness, loss of confidence, isolation, and poor concentration. She was diagnosed with major depression and started on nortriptyline and after two months had resolution of depression but then began to experience decreased sleep and increased energy. Lithium was added to her regimen and her diagnosis was changed to bipolar disorder. Eventually, nortriptyline was tapered and discontinued and her mood remained stable on lithium alone for years with no further episodes of mania or depression.
Learning Points
Steroids are an example of a medication that can trigger manic episodes which respond to antipsychotic treatment.
Some patients will go on to develop recurrent mood episodes which may be managed with usual treatments for bipolar disorder such as mood stabilizers.
1.9 Bipolar 1 Disorder Versus Bipolar 2 Disorder
The majority of studies of OABD do not distinguish between bipolar 1 and bipolar 2 disorders, and the use of mania as a convenient defining feature of bipolar disorder naturally skews samples toward those with bipolar 1 disease. Bipolar spectrum disorders are a relatively recent area of interest post-dating many studies and will not be discussed here.
There have been relatively few studies looking specifically at older age or late-onset bipolar 2 disorder. One study of 525 outpatients in Italy noted a statistically significant reduced prevalence of late-life (defined as age 50) bipolar 2 disorder similar to the reduced prevalence of bipolar 1 disorder found elsewhere [6]. An additional observation was that features of atypical depression (defined in DSM-IV as hypersomnia, increased appetite or weight gain, leaden paralysis, and rejection sensitivity), which were seen more frequently in younger patients with bipolar 2 illness, seemed to diminish as patients aged.
1.10 Natural History and Course of Illness
1.10.1 Initial Presentation
As previously discussed, mania, the hallmark of bipolar illness, can occur for the first time at any age, with elders in their 90s experiencing new-onset mania [39, 53–55]. When the first manic episode arises in the context of a lifetime of unipolar depression, the clinical diagnosis is changed to bipolar illness. However, there is disagreement about whether to define bipolar disorder onset as occurring at the time of first depression, decades prior, or whether to consider the later onset of mania as initiating bipolar disorder, representing a change or evolution in illness course.
There may be important differences in the way older and younger patients first present with mania. An older study that defined late-onset bipolar illness as occurring after age 40 found the late-onset group to present less acutely, with less violence, irritability, and psychosis, but with more visual, olfactory, and somatic hallucinations [25]. A population-wide Danish study of 1719 inpatients and outpatients found that of those diagnosed with bipolar disorder by the end of their first hospital admission, those with late-onset bipolar illness (defined as beginning after age 50) presented with more psychosis related to depressions and less psychosis related to manias when compared to other inpatients with early onset disease [10]. However, these are relative differences between those with EOBD and LOBD and should not give the impression that those with LOBD do not frequently present with manias or that these manias do not feature psychotic symptoms. Notably, the same study, one of the few looking at a large group of older outpatients, found no differences in initial presentation for outpatients with late-onset compared with early-onset bipolar illness, suggesting that differences between the two groups may be less prominent among individuals with milder disease.
Related posts:
Clinical Management of Older Age Bipolar Disorder
Neuromodulation Therapies and Ketamine in Older Age Bipolar Disorder
Lithium in Older Age Bipolar Disorder
Psychotherapy and Psychosocial Interventions, Family Psychoeducation, and Support for Older Age Bipolar Disorder
Treatment Settings for Older Age Bipolar Disorder: Inpatient, Partial Hospitalization, Outpatient, Models of Integrated Care
Neurobiology of Older Age Bipolar Disorder
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
