Bipolar Disorder in the Elderly

Abstract

Over 1200 participants from a wide array of psychogeriatric disciplines attended the 15th world congress of the International Psychogeriatric Association (IPA) in The Netherlands. In previous years, the meetings and activities of the IPA were strongly focused on research restricted to diagnosis and care of individuals with dementia. In recent years, there has been a shift of attention towards other psychiatric disorders in the elderly such as schizophrenia, substance abuse and bipolar disorder, which were for a long time nearly invisible in the scientific literature. The symposium venue was located in The Hague, a typical Dutch town not far from the coastline and home to several famous international institutions in the field of peace and justice. This successful meeting with the theme ‘Reinventing Aging through Innovation, Care, Research, Technology’ was co-chaired by Anne Margriet Pot (Professor of Geropsychology, Amsterdam, The Netherlands) and Frans Verhey (Professor of Neuropsychiatry, Maastricht, The Netherlands). A special symposium on ‘Bipolar Disorder in the Elderly’ also took place during the 4-day meeting. This symposium was organized by The Netherlands Psychiatric Association, Faculty of Old Age Psychiatry and is an example of a neglected topic in geriatric mental health and represents the important diverse mental disorders that a large proportion of older adults and their families can experience. The symposium was co-chaired by Max Stek, Professor of Old Age Psychiatry and Chair of the Dutch Faculty of Old Age from The Netherlands and Martha Sajatovic from the USA. Presenting faculty were Ralph Kupka and Annemiek Dols from The Netherlands and Lars Kessing from Denmark.

An overview of geriatric bipolar disorder

Bipolar disorders (BDs) are complex genetically and neurochemically based illnesses, which affect approximately 2.6% of the population aged 18 years and older. Martha Sajatovic, Professor of Psychiatry at Case Western Reserve University (Cleveland, OH, USA) and Director of the Neurological Outcomes Center at University Hospitals Case Medical Center (Cleveland, OH, USA) presented an overview of late-life bipolarity. By contrast to rather low rates in the community, BD is present in 6% of geriatric outpatient visits, 8–10% of geriatric inpatient admissions, 3% of nursing home residents and 17% of geriatric patients presenting to psychiatric emergency departments. Given the global increase in the elderly population it is anticipated that absolute numbers of elderly patients with BD will also increase. While the evidence base on late-life BD has been limited, the last decade has seen growth in this much-needed area of focus.

As with younger adults, BD in the elderly may be underdetected and undertreated and 10% of BD cases first occur after the age of 50 years. Comorbidities, such as anxiety, substance abuse and medical illness, complicate diagnosis and treatment. BD elders are especially vulnerable to adverse pharmacotherapy effects as a result of their multiple chronic diseases, use of multiple concomitant medications, and the pharmacokinetic and pharmacodynamic changes that accompany aging. Adverse drug reactions are a function of increase in age with the number of adverse drug reactions per 10,000 individuals relatively low before the age of 40 years; increasing sharply in the fifth decade of life and reaching 60 per 10,000 in the 80-year-olds. Factors that affect the types of adverse effects observed in older patients include age, gender, genetics, timing of medication, body habitus and pharmacokinetic drug interactions.

Lithium, anticonvulsants, atypical antipsychotics, antidepressants and electroconvulsive therapy are all established treatments for mixed-age patients with BD, and data are accumulating on the use of these modalities in geriatric BD. A growing body of evidence has identified biomarkers that are associated with disease, disease trajectory or duration, and with aspects of treatment response both in mixed-age and elderly BD populations [1,2]. Preliminary open-label trials in BD elders and secondary analyses from mixed-age populations have suggested a beneficial role for lithium and the novel anticonvulsant lamotrigine as well as the atypical antipsychotics quetiapine, olanzapine and aripiprazole [3,4]. However, larger and controlled trials are needed to validate the findings from smaller-sample analyses. While preliminary data on pharmacotherapies is encouraging, treatment nonadherence remains substantial in geriatric bipolar patients as is the case with younger BD populations. Finally, psychological therapies appear promising, but have been understudied.

BD across the lifespan

BD is a highly hereditary mood disorder that typically has its first manifestations in adolescence and early adulthood. Onset in prepubertal childhood is currently a matter of considerable controversy. New cases of BD may occur at any age. In retrospective analysis, subsyndromal symptoms of mood disorder may precede the onset of full-blown episodes for years. Ralph Kupka (Professor of BDs, GGZ inGeest, VU University Medical Center, Amsterdam, The Netherlands) discussed the characteristics of BD across the lifespan. A staging model has been proposed, including an asymptomatic at-risk period, subsyndromal or aspecific prodromes, a first full-blown mood episode (either depression, which would lead to the diagnosis of depressive disorder, or mania/hypomania, directly indicating BD), recurrent BD with or without interepisodic symptomatic or functional impairment, and chronic or treatment-resistant BD [5]. These stages can occur early or later in life, and evolve slowly or rapidly. It is unclear whether childhood-onset, adolescent/adult-onset, and late-life BD have shared or distinct etiological and pathogenetic underpinnings. In shorter-term studies, it has been estimated that approximately 10% of patients with unipolar depression convert to BD over time but some longer-term studies suggest conversion rates of up to 40–50% over a lifetime [6,7]. At every age, BD has a different impact on the emotional and psychosocial development of the patients, and treatment approaches will be adapted accordingly. Conversely, the demands of each stage in life may influence the illness course. For women, hormonal influences appear to play an important role, since both the postpartum period and perimenopause are associated with increased incidence of mood disorders in general and BDs in particular. Cumulative risk factors in the longitudinal course are diagnostic delay, comorbid substance abuse, treatment nonadherence, psychosocial and circadian disruptions, the effect of multiple episodes (i.e., episode sensitization and kindling), cognitive deficits and medical comorbidity. In contrast to what many believe or hope, there is no evidence that BD fades out with increasing age. True late-onset BD (i.e., after the age of 50 years) differs in various aspects from early-onset BD, and is associated with more somatic determinants. Data from a large longitudinal international cohort study from the Stanley Bipolar Treatment Network, including patients aged from 18 to 82 years, show fewer patients with late-onset BD had a family history of mood disorder than early-onset patients [8]. Patients over the age of 50 years had a later onset of illness than younger patients (mean age of onset 25.9 vs 19.1 years). Time spent symptomatic during the first year of prospective follow-up increased with the total duration of illness, but not with age per se, despite adequate treatment. This underscores the necessity of early and continuous intervention in patients with this chronic, evolving disorder.

Late-life mania

Mania can occur at any age, with de novo manic symptoms described in patients in their eighth and ninth decades. Late-onset mania can be caused by late-onset BD but also by a somatic condition or medication. The literature is sparse on this topic. Annemiek Dols (GGZ inGeest, Free University, Amsterdam, The Netherlands) presented a comprehensive critical review of studies reporting the prevalence of late-life mania in different patient populations.

The estimated prevalence of mania in older patients in geropsychiatric hospitals was 8%. Late-onset mania had a mean prevalence of 20% in admitted bipolar patients. Reviewing the data on older bipolar patients admitted for mania one can conclude that medical comorbidity seems frequently, and in all cases potentially, related. In addition, several studies in late-onset mania patients aged 50 years and older show increased neurological comorbidity, suggesting that vascular risk factors prime development of mania [9].

Studies in older bipolar outpatients show that, as in younger adults, (hypo)manic symptoms are not as frequent as depressive symptoms, but still approximately 5% of bipolar patients experience (hypo)mania each year. It is not possible to draw firm conclusions on prevalence rates in communities, nursing homes and other study samples because of limited data.

Estimation of the prevalence of mania in the elderly is hampered by several factors. First, mania is not a diagnosis but part of a psychiatric diagnosis such as late-onset BD or schizoaffective disorder, or due to an organic syndrome such as delirium, dementia or secondary mania. Second, there seems to be an overlap between the psychiatric diagnosis of ‘mania’ and the neurologic ‘disinhibition syndrome.’ The last condition can include distractibility, euphoria, emotional lability and impulsive behavior and is mostly seen in patients with lesions in the orbitofrontal circuit. The disinhibition syndrome appears to overlap at most with the psychiatric concept of vascular mania as was initially proposed by Steffens and Krishnan [10]. Then, the concept of secondary mania is more challenging in the elderly. The list of medications, metabolic disturbances and neurological conditions that can cause secondary mania is extensive [11]. While secondary mania can occur at any age it can be expected to occur more often in the elderly, given the higher prevalence of potentially related medical conditions and pharmacotherapy in older adults. However, one could argue that coincidental somatic findings should not be considered as a cause of manic symptoms, since the vast majority of patients with physical comorbidity do not develop manic symptoms. These factors can all account for an underestimation of the prevalence of late-life and late-onset mania. Based on the sparse published literature late-life mania is not rare, but further research is warranted to understand late-life mania and to help these patients with proper diagnostics and treatment tools/diagnostic considerations.

BD, dementia & lithium

Lars Vedel Kessing, Professor of Psychiatry at the University of Copenhagen in Denmark, discussed the role of cognition in BD and the neuroprotective effects of lithium. Cognitive disturbances in patients with BD have attracted more attention during recent decades. Cross-sectional data have shown that cognitive problems are prevalent also during remitted phases of BD across a number of cognitive domains, including sustained attention, processing speed, memory and executive function. These cognitive disturbances have an impeding effect on patients’ social and occupational function. It is estimated that overall approximately half of euthymic bipolar patients over the age of 60 years exhibit neuropsychological deficits.

Furthermore, a wealth of studies suggest that depression is a predictor of subsequent dementia although causality and pathogenesis continue to be unclear. The prevalence of dementia in patients with BD has received inadequate attention but results from a few studies suggest that patients with BD may be at increased risk of developing dementia in the long run [12,13]. It is well known that the risk of recurrence of affective episodes increases with the number of prior affective episodes and some evidence further suggests that the rate of dementia also increases with the number of affective episodes as the illness goes on [14]. The pathogenetic mechanisms are unknown but a key hypothesis has emerged in relation to glycogen synthase kinase 3B, which is a key enzyme in the metabolism of amyloid precursor protein and in the phosphorylation of the tau protein involved in the pathogenesis of Alzheimer‘s disease [15,16]. Preliminary new data suggest that glycogen synthase kinase 3B activity is increased in patients with mild cognitive impairment and in Alzheimer‘s disease [17] and also in patients with late-life depression [18]. Interestingly, among the many effects of lithium, it inhibits glycogen synthase kinase 3 [15,16]. Accordingly, findings from large register-based studies suggest that continued treatment with lithium reduces the risk of developing dementia in the long run among patients with BDs [19,20]. Other recent data suggest that lithium may prevent amnestic mild cognitive impairment from progressing to Alzheimer‘s disease [21]. Lithium has previously been suggested to have neuroprotective effects and potentially to prevent the progression of other neurodegenerative disorders such as Parkinson‘s disease, stroke and Huntington‘s chorea although data to confirm these speculations are still missing. The wide clinical and molecular effects of lithium may begin to emerge after more than 60 years of use in BD.

Conclusion

The 15th Congress of the International Psychogeriatric Association (IPA) brought together scientific and clinical experts as well as bright, promising young researchers to present data and new ideas intended to facilitate advances in care for older individuals with mental disorders including dementing illness, mood disorders and psychoses. The active discussion that followed the symposium on geriatric BD highlighted the strong interest among researchers and clinicians in better understanding how conditions that occur across the lifespan may be manifested in elderly patients. In line with the overall theme of the congress it is critical that continued effort be focused on improving the care of people with serious mood conditions such as BD across the lifespan. Research and innovation specifically focused on the older individual have the potential to improve health outcomes for geriatric patients and their families. The next international meeting of the IPA in Cairns, Australia from 8–11 September 2012 and their next world congress in 2013 in Seoul, South Korea will again bring together scientific and clinical experts in the field of care for older individuals with mental disorders.

Financial & competing interests disclosure

R Kupka has received a research grant from AstraZeneca. LV Kessing has been a consultant for Bristol-Myers Squibb, Eli Lilly, Lundbeck, AstraZeneca, Pfizer, Wyeth, Servier and Janssen-Cilag. M Sajatovic has received research grants from GlaxoSmithKline, AstraZeneca, Pfizer, Merck and Ortho-McNeil Janssen, is a consultant for the Cognition Group of United BioSource Corporation (UBC), and has received royalties from Springer Press, Johns Hopkins University Press and Oxford Press. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

R Kupka has received a research grant from AstraZeneca. LV Kessing has been a consultant for Bristol-Myers Squibb, Eli Lilly, Lundbeck, AstraZeneca, Pfizer, Wyeth, Servier and Janssen-Cilag. M Sajatovic has received research grants from GlaxoSmithKline, AstraZeneca, Pfizer, Merck and Ortho-McNeil Janssen, is a consultant for the Cognition Group of United BioSource Corporation (UBC), and has received royalties from Springer Press, Johns Hopkins University Press and Oxford Press. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.