Bipolar disorder and aging

Bipolar disorder is a chronic illness, defined by a succession of depressive and/or manic periods separated by free intervals. Its evolution with aging is marked by a high suicide mortality rate. Bipolar disorders raise the question of their evolution when the age of the subject, in particular with regard to their frequency, their clinical characteristics, their prognosis and their management. The evolution of bipolar disorder with aging poses several difficulties in clinical practice due to its underestimated frequency and its misleading presentation and in particular by the presence of sometimes significant cognitive alterations leading sometimes to dementia.

Introduction

Although much research has been done in the field of depression in the elderly [1], the literature pays little attention to bipolar disorders related to old age and it seems difficult to describe them as they develop over the course of aging and to produce an evolutionary model specific. However, it is now accepted that bipolar illness can manifest throughout life following very different evolutionary profiles according to the age at the onset of the disorders and the polarity of the episodes anterior.

The study of prognosis of bipolar disorder has been the subject of numerous short-term studies (cross-section of the cohort, mainly) and long-term studies. Short-term studies tend to report prognosis worse than long-term studies, probably because the duration of major mood episodes is extremely variable and these studies to short term took into account patients who were not yet in remission. Thus, the analysis of the literature clearly indicates that study duration is an artifact predictor of a better prognosis.

The most recent studies report that bipolar disorder affects 0.5% to 1% of people over the age of 60 and represents about 4% to 17% of psychiatric hospitalizations of the elderly subject [2]. Bipolar disorders in the elderly force us to wonder about their often marked association with cognitive impairment both during episodes acute and during the remission phases of the disease bipolar. Bipolar disease is considered by certain authors as a pathology at risk of evolution towards cognitive disorders that can be considered as predementia states, even real dementia syndromes [3].

What clinical particularities?

With advancing age, the clinical picture of the disorder bipolar disorder in the elderly becomes atypical: indeed, certain symptoms appear, which are not observed in young patients. However, these semiological specificities of aging-health bipolarity, often derived from empirical data, do not are not fully supported by the literature [4].

Studies suggest that the clinical picture of bipolar disease gets better with aging troubles. Manic attacks would be less intense. Symptoms more often include irritability, sometimes associated with a delusion of persecution, behavioral disorders such as agitation, motor instability and ambulation and cognitive disorders which are also more frequently associated with confusion and agitation. On the other, there is a risk of conversion to bipolar disorder in patients with late-onset major depression [5].

The existence of depressive symptoms would be frequent [6] and we would observe more mixed states like dysphoric mania and more recurrences in the case of late-onset of bipolar disease. Currently, it is accepted that bipolar disease continues to re-offend over time – the rate of recurrence is between 32 and 51%, depending on the studies – and that it is the seniority of the disease bipolar and, therefore, the large number of episodes anterior, which is the prognostic variable of the number future recurrences and difficulties adapting upcoming psychosocial [7].

Prevalence

According to studies, the prevalence of the bipolar disorder in geriatric psychiatry services ranges from 4% to 17%. Epidemiological studies [8] report that type 1 and type 2 bipolar disorders affect 0.5% to 1% of the elderly, while this rate is 4% in the general population.

An Australian study [9] indicates that the prevalence of people aged over 65 with bipolar disease increased from 2% in 1980 to 10% in 1998 with a higher sex ratio for women (3 women for 2 men).

The survey called ESPRIT [10] (risk, incidence and treating psychological health survey) was carried out among 1,873 people aged over 65 and found a point prevalence of 0.4%.

This lower result than those observed in other studies can be explained by several hypotheses, in particular the cohort effect due to premature excess mortality in bipolar patients, an abrasion of symptoms with age, and the diagnosis is more difficult to make. under these conditions with a relative inadequacy with the diagnostic criteria established for the young subject. Thus, bipolar disease in the elderly has a prevalence equal to approximately one-third of the younger bipolar population [11].

What evolutionary profile?

The influence of normal aging on bipolar disorder is still misassigned. Studies on bipolar disorders in the elderly have made it possible to highlight a great variability of the course evolution according to the age of onset and the polarity of successive episodes [12]. Cognitive impairment is a feature of major bipolar disorder and they are commonly observed, whether during the active phases of the disease or during periods of remission. During euthymic periods are mainly executive functions, learning and memory verbally, but also, to a lesser degree, visual memory, sustained attention and speed of information processing, are affected. Cognitive disorders are therefore encountered in bipolar disorder regardless of age, but the profile neurocognitive of bipolar disorders in the elderly seems different from that of young subjects [13]. We find, in fact, the same damage at the level of executive functions, learning and verbal memory but, with advancing age, much more marked damage to their formation processing [14]. Moreover, it is difficult to show factors influencing the onset of cognitive dysfunction in bipolar disease, even if we know that psychotic symptoms or comorbidities such as substance abuse are likely to influence the cognitive profile of patients, including verbal memory and executive functions. Currently, the links between cognitive abnormalities and the severity of bipolar disorder or its chronicity are difficult to elucidate [15]. However, a number of arguments plead in favor of the fact that the severity of the attacks and their duration are likely to affect attentional capacities and verbal memory performance.

Is bipolar disorder a dementia risk factor?

The evolution of bipolar disorder towards an array of insane seems debatable. Recent studies suggest that bipolar disorder in itself would be a risk factor for cognitive impairment due to neurodegenerative damage to the cortical and limbic regions [16]. Some authors [17] suggest that the damaged cognition of elderly bipolar patients could be different from those encountered in the subjects younger and would constitute a veritable painting of dementia specific to bipolar disease. Their clinical approach would be similar to certain frontotemporal degenerations, comprising a cognitive impairment that would be focused on attention, executive functions, verbal memory and language, as well as frequent behavioral, essentially frontal. But it walks away distinguished in particular by a lower frequency of physical neglect and emotional indifference [18].

In addition, the risk of dementia appears to increase with the number of decompensation episodes mood and the rate of dementia would increase by 6% at each hospitalization [19]. It was observed that the rate of evolution dementia in bipolar subjects is 10 times higher than the 1 to 2% incidence rate of dementia expected given the age of the patients [20]. The aging of the bipolar disease and its evolution towards a degenerative pathology or its involution from the cognitive point of view can make evoke several origins: the long-term effect of the treatments, the longitudinal history of the disorder (age of occurrence, number and accordingly, neurotoxicity depressive episodes and deleterious cognitive effects of duration of hospitalization), addictive comorbidities or the existence of a neuroanatomical substrate [21].

Thanks to the development of functional and structural neuroimaging, bipolar disease can be considered a neurodevelopmental disease. Highlighting anomalies in cerebral effects such as reduction in density or the size of certain parts of the brain seems to explain both the genesis of bipolar disorder to an early stage and the onset of cognitive and dementias at a later stage accompanied by neurodegenerative disorders [22].

In addition, the hyperactivation of the HPA axis by repeated episodes of thymic decompensation plays an important role in brain neuroplasticity [23]. Therefore, it is possible that the repetition of mood episodes decreases the death threshold cell and contributes to the appearance of disorders cognition in bipolar patients [24]. To date, the origin of the cognitive impairment of, however, bipolar disease and its pathophysiological mechanisms remain unclear.

In summary, a considerable body of data confirms the presence of neurobiological abnormalities in bipolar disease, developing over time during decompensation episodes. Thus, future studies of bipolar disorder should focus on the mechanisms related to the onset and course of cognitive decline in bipolar patients in order to allow prevention and rehabilitation interventions upstream. Bipolar disorder seems to be associated with generalized age-related structural grey matter volume reductions and functional brain alterations thus suggesting the presence of neurodegenerative processes [25].

Conclusion

Mood disorders in the elderly have a heavy public health impact. It is currently proven that elderly subjects suffering from psychiatric pathologies present mortality rates 1.5 to 2.5 times higher than those of the general population and bipolar disorder in the elderly is not escaped [26]. The consequences on the quality of life of patients are not negligible (increase suicide risk and a number of hospitalizations, significant functional degradation). A demented-looking cognitive involution of bipolar disorder seems regularly noted, but its semiological contours remain ill-defined. This hypothesis of the existence of dementia specific to bipolar illness needs to be evaluated in the context of prospective studies, with a large number of patients in order to avoid bias and aspects such as the age of onset and duration of the disease, the frequency of decompensation, medical comorbidities and treatments used should also be studied. Moreover, knowledge of predictors of cognitive decline would help to personalize the care of bipolar patients, target subjects at risk of development of dementia, and carry out early interventions. Currently, even if drug iatrogeny cannot be the sole cause of the development of dementia following bipolarity [27]. The therapist must constrain himself to an optimal use of psychotropic treatments. Lithium has proved useful as a potential agent in slowing down this accelerated aging process in BD, potentially reversing effects induced by the disorder [28]. Continued treatment with lithium was associated with a reduced rate of dementia in patients with bipolar disorder in contrast to continued treatment with anticonvulsants, antidepressants, or antipsychotics [29].

1. Bourin M. Clinical aspects of depression in the elderly. Arch Depress Anxiety. 2018; 4: 26-30.
2. Dols A, Beekman A. Older Age Bipolar Disorder. Psychiatr Clin North Am. 2018 Mar;41(1):95-110. doi: 10.1016/j.psc.2017.10.008. Epub 2017 Dec 8. PMID: 29412851.
3. Diniz BS, Teixeira AL, Cao F, Gildengers A, Soares JC, Butters MA, Reynolds CF 3rd. History of Bipolar Disorder and the Risk of Dementia: A Systematic Review and Meta-Analysis. Am J Geriatr Psychiatry. 2017 Apr;25(4):357-362. doi: 10.1016/j.jagp.2016.11.014. Epub 2017 Jan 4. PMID: 28161155; PMCID: PMC5365367.
4. Brietzke E, Cerqueira RO, Soares CN, Kapczinski F. Is bipolar disorder associated with premature aging? Trends Psychiatry Psychother. 2019 Oct-Dec;41(4):315-317. doi: 10.1590/2237-6089-2019-0038. PMID: 31967192.
5. Elefante C, Brancati GE, Petrucci A, Gemmellaro T, Toni C, Lattanzi L, Perugi G. Risk of conversion to bipolar disorder in patients with late-onset major depression. Int Clin Psychopharmacol. 2022 Nov 1;37(6):234-241. doi: 10.1097/YIC.0000000000000421. Epub 2022 Jul 22. PMID: 35916593.
6. Meeks S. Bipolar disorder in the latter half of life: symptom presentation, global functioning and age of onset. J Affect Disord. 1999 Jan-Mar;52(1-3):161-7. doi: 10.1016/s0165-0327(98)00069-x. PMID: 10357029.
7. Shobassy A. Elderly Bipolar Disorder. Curr Psychiatry Rep. 2021 Jan 6;23(2):5. doi: 10.1007/s11920-020-01216-6. PMID: 33404961.
8. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005 Jun;62(6):593-602. doi: 10.1001/archpsyc.62.6.593. Erratum in: Arch Gen Psychiatry. 2005 Jul;62(7):768. Merikangas, Kathleen R [added]. PMID: 15939837.
9. Almeida OP, Fenner S. Bipolar disorder: similarities and differences between patients with illness onset before and after 65 years of age. Int Psychogeriatr. 2002 Sep;14(3):311-22. doi: 10.1017/s1041610202008517. PMID: 12475092.
10. Ritchie K, Artero S, Beluche I, Ancelin ML, Mann A, Dupuy AM, Malafosse A, Boulenger JP. Prevalence of DSM-IV psychiatric disorder in the French elderly population. Br J Psychiatry. 2004 Feb;184:147-52. doi: 10.1192/bjp.184.2.147. PMID: 14754827.
11. Depp CA, Jeste DV. Bipolar disorder in older adults: a critical review. Bipolar Disord. 2004 Oct;6(5):343-67. doi: 10.1111/j.1399-5618.2004.00139.x. PMID: 15383127.
12. Oostervink F, Boomsma MM, Nolen WA; EMBLEM Advisory Board. Bipolar disorder in the elderly; different effects of age and of age of onset. J Affect Disord. 2009 Aug;116(3):176-83. doi: 10.1016/j.jad.2008.11.012. Epub 2008 Dec 14. PMID: 19087895.
13. Bourin M. Emotions and Cognitions in Bipolar Disorder. In: Gargiulo PÁ, Mesones Arroyo HL. (eds) Psychiatry and Neuroscience Update. Springer. Cham. 2021; 589-597.
14. Gildengers AG, Mulsant BH, Al Jurdi RK, Beyer JL, Greenberg RL, Gyulai L, Moberg PJ, Sajatovic M, ten Have T, Young RC; GERI-BD Study Group. The relationship of bipolar disorder lifetime duration and vascular burden to cognition in older adults. Bipolar Disord. 2010 Dec;12(8):851-8. doi: 10.1111/j.1399-5618.2010.00877.x. PMID: 21176032; PMCID: PMC3038329.
15. Bourin M. Cognitive impact in bipolar disorder Arch Depress Anxiety 2019; 5: 052-058.
16. Serafini G, Pardini M, Monacelli F, Orso B, Girtler N, Brugnolo A, Amore M, Nobili F, Team On Dementia Of The Irccs Ospedale Policlinico San Martino DM. Neuroprogression as an Illness Trajectory in Bipolar Disorder: A Selective Review of the Current Literature. Brain Sci. 2021 Feb 23;11(2):276. doi: 10.3390/brainsci11020276. PMID: 33672401; PMCID: PMC7926350.
17. Szmulewicz AG, Samamé C, Martino DJ,. Strejilevich SA An updated review on the neuropsychological profile of subjects with bipolar disorder Arch Clin Psychiatry. 2015; 42:139-146.
18. Masouy A, Chopard G, Vandel P, Magnin E, Rumbach L, Sechter D, Haffen E. Bipolar disorder and dementia: where is the link? Psychogeriatrics. 2011 Mar;11(1):60-7. doi: 10.1111/j.1479-8301.2010.00348.x. PMID: 21447111.
19. Kessing LV, Andersen PK. Does the risk of developing dementia increase with the number of episodes in patients with depressive disorder and in patients with bipolar disorder? J Neurol Neurosurg Psychiatry. 2004 Dec;75(12):1662-6. doi: 10.1136/jnnp.2003.031773. PMID: 15548477; PMCID: PMC1738846.
20. Dhingra U, Rabins PV. Mania in the elderly: a 5-7 year follow-up. J Am Geriatr Soc. 1991 Jun;39(6):581-3. doi: 10.1111/j.1532-5415.1991.tb03597.x. PMID: 2037748.
21. Sajatovic M, Strejilevich SA, Gildengers AG, Dols A, Al Jurdi RK, Forester BP, Kessing LV, Beyer J, Manes F, Rej S, Rosa AR, Schouws SN, Tsai SY, Young RC, Shulman KI. A report on older-age bipolar disorder from the International Society for Bipolar Disorders Task Force. Bipolar Disord. 2015 Nov;17(7):689-704. doi: 10.1111/bdi.12331. Epub 2015 Sep 19. PMID: 26384588; PMCID: PMC4623878.
22. Phillips ML, Swartz HA. A critical appraisal of neuroimaging studies of bipolar disorder: toward a new conceptualization of underlying neural circuitry and a road map for future research. Am J Psychiatry. 2014 Aug;171(8):829-43. doi: 10.1176/appi.ajp.2014.13081008. PMID: 24626773; PMCID: PMC4119497.
23. Trifu SC, Trifu AC, Aluaş E, Tătaru MA, Costea RV. Brain changes in depression. Rom J Morphol Embryol. 2020 Apr-Jun;61(2):361-370. doi: 10.47162/RJME.61.2.06. PMID: 33544788; PMCID: PMC7864313.
24. Bourin M. Neurogenesis and Neuroplasticity in Major Depression: Its Therapeutic Implication. Adv Exp Med Biol. 2021;1305:157-173. doi: 10.1007/978-981-33-6044-0_10. PMID: 33834400.
25. Zovetti N, Rossetti MG, Perlini C, Brambilla P, Bellani M. Brain ageing and neurodegeneration in bipolar disorder. J Affect Disord. 2023 Feb 15;323:171-175. doi: 10.1016/j.jad.2022.11.066. Epub 2022 Nov 23. PMID: 36435402.
26. Valiengo Lda C, Stella F, Forlenza OV. Mood disorders in the elderly: prevalence, functional impact, and management challenges. Neuropsychiatr Dis Treat. 2016 Aug 24;12:2105-14. doi: 10.2147/NDT.S94643. PMID: 27601905; PMCID: PMC5003566.
27. Bourin M. Prescribed Psychotropic Drugs in the Elderly. In: Gargiulo P.Á., Mesones Arroyo H.L. (eds) Psychiatry and Neuroscience Update. Springer. Cham. 2021; 647-660.
28. Salarda EM, Zhao NO, Lima CNNC, Fries GR. Mini-review: The anti-aging effects of lithium in bipolar disorder. Neurosci Lett. 2021 Aug 10;759:136051. doi: 10.1016/j.neulet.2021.136051. Epub 2021 Jun 14. PMID: 34139318; PMCID: PMC8324565.
29. Kessing LV, Forman JL, Andersen PK. Does lithium protect against dementia? Bipolar Disord. 2010 Feb;12(1):87-94. doi: 10.1111/j.1399-5618.2009.00788.x. PMID: 20148870.