See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/46191737 Anxiety and depression in the elderly: Do we know any more? Article in Current opinion in Psychiatry · November 2010 DOI: 10.1097/YCO.0b013e32833f305f · Source: PubMed CITATIONS READS 21 146 2 authors: Gerard J Byrne Nancy A Pachana 177 PUBLICATIONS 2,083 CITATIONS 381 PUBLICATIONS 2,815 CITATIONS University of Queensland SEE PROFILE University of Queensland SEE PROFILE Some of the authors of this publication are also working on these related projects: DISABILITY ASSISTANCE ANIMALS OR NOT? PROBLEMS IN POLICY AND PRACTICE WORKSHOP View project All content following this page was uploaded by Nancy A Pachana on 03 January 2017. The user has requested enhancement of the downloaded file. All in-text references underlined in blue are added to the original document and are linked to publications on ResearchGate, letting you access and read them immediately. Anxiety and depression in the elderly: do we know any more? Gerard J. Byrnea,c and Nancy A. Pachanab a School of Medicine, bSchool of Psychology, University of Queensland and cMental Health Service, Royal Brisbane & Women’s Hospital, Brisbane, Australia Correspondence to Gerard J. Byrne, MBBS, PhD, FRANZCP, Discipline of Psychiatry, School of Medicine, University of Queensland, K Floor, Mental Health Centre, Royal Brisbane & Women’s Hospital, Herston, 4029 Queensland, Australia Tel: +61 7 3365 5148; fax: +61 7 3365 5488; e-mail: gerard.byrne@uq.edu.au Current Opinion in Psychiatry 2010, 23:504–509 Purpose of review The advent of global population ageing raises understandable concerns about the high-prevalence mental disorders in older people. Accordingly, this review covers recently published scientific articles concerning anxiety and depression. Recent findings There is a paucity of findings on anxiety in older people, although the availability of several new scales suggests increased interest in this topic. The low prevalence of latelife depression in many population surveys does not appear to be due to misattribution of depressive symptoms to physical disorders. Although it is well established that dementia leads to depression, there is now increasing evidence for the proposition that depression leads to cognitive decline and dementia. There is now good evidence also for a bidirectional relationship between obesity and depression. The prognosis of treated late-life depression varies with baseline neuropsychological function and the severity of white matter hyperintensities. Summary An excellent body of research on depression in older people is now available, although more work on both pharmacological and nonpharmacological treatments is needed. More research is urgently required into anxiety disorders in older people. These are highly prevalent and associated with considerable disease burden. As the literature on depression in older people reaches maturity, there should be greater research and clinical interest in anxiety. Keywords aged, aged 80 and over, anxiety, depression Curr Opin Psychiatry 23:504–509 ! 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins 0951-7367 Introduction In both developed and developing regions there is now increasing concern about ageing populations and their implications for mental healthcare delivery. As the postWorld War II generation of ‘baby boomers’ reaches retirement age, demand for high-quality geriatric psychiatry services is projected to rise dramatically. Although initial clinical and scientific interest has focused on the problem of dementia, there is now increasing concern about other high-prevalence mental disorders in later life, particularly the mood and anxiety disorders. There is a burgeoning research literature on this group of disorders, particularly on late-life depression. The literature on latelife anxiety is much smaller, but growing rapidly. In this article, recent developments are reviewed and important new research highlighted. Prevalence and risk factors In a European study of socioeconomic inequality and late-life depression using the 12-item EURO-D scale 0951-7367 ! 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins (N ¼ 22 777; 50–104 years), Ladin and colleagues [1"] found a clear North–South gradient. Southern European countries had more socioeconomic inequality and more late-life depression than Northern European countries and this relationship was not mitigated by greater individual income. In a Japanese study of 10 969 persons aged 50 years and over, Kaji and colleagues [2] examined the relationship between everyday stressors and late-life depression. This study used the Japanese version of the Center for Epidemiologic Studies – Depression scale (CES-D), using cut-off values of at least 16 and 26 points for mild to moderate and severe depression, respectively. Mild to moderate depression was present in 21.9% of participants and severe depression was present in 9.3%. The prevalence of both types of depression was greater in women and increased significantly with age. Following the work of Caspi and colleagues [3], there has been considerable interest in the idea that polymorphisms in the serotonin transporter gene (5-HTTLPR) DOI:10.1097/YCO.0b013e32833f305f Anxiety and depression Byrne and Pachana 505 might interact with life events in the genesis of depression, even in older cohorts. A European study of middleaged and older adults failed to find such a relationship [4], although a Korean study, with a quite different allelic frequency, did [5]. More recently, a further replication was attempted using a French cohort of 1421 participants aged 65 years and over [6"]. In this study, depression was defined at baseline using the CES-D self-report scale and the MINI diagnostic interview, and measured again 2 years later. This enabled both prevalent and incident cases to be identified. However, there was no interaction found between 5-HTTLPR genotype (using the rs25531 SNP) and life events in the prediction of either prevalent or incident depression in this late-life cohort. Both substantive and methodological explanations are possible. However, gene–environment interactions remain a topic of enormous interest. An important question has arisen about whether the lower rates of anxiety and depression in older people that are found almost universally in population-based epidemiological surveys can be attributed to age-specific limitations in the diagnostic interviews used to collect the data [7"]. Using data from the National Comorbidity Survey Replication (NCS-R), Kessler and colleagues [8""] investigated whether late-life depression is underdiagnosed because of misattribution of symptoms to physical disorders. In the NCS-R study, older people had both a later age of onset and more lifetime episodes of depression. However, older people had fewer severe episodes, fewer days out of role and less role impairment than younger people. As expected, older people had a higher prevalence of physical disorders than younger people. Despite this finding, older people had lower physical comorbidity with depression than younger people. These authors argue that this finding makes it unlikely that misattribution of physical symptoms would account for the lower rates of depression found in older people. It is well established that the prevalence and incidence of both anxiety and depressive disorders in later life are much higher in residential aged care settings than in the community. For example, a recent Norwegian nursing home study [9] found the prevalence of clinically significant depression to be 21.2%, with a 12-month incidence rate of 14.9% and a persistence rate of 44.8%. In addition, physical health status is known to be associated with risk for both depression and anxiety, although both the specificity and the direction of causality appear to vary from one general medical condition to another. Recent work [10] has demonstrated that depression predicts cardiovascular disease but not cerebrovascular disease, and that somatic symptoms of anxiety predict coronary heart disease, at least in women [11]. In a cross-sectional study of 1449 patients with Parkinson’s disease, depression was associated with disease severity and with dementia [12"]. However, it was not associated with age, age of onset of Parkinson’s disease or Parkinson’s disease duration. The prevalence of anxiety disorders in a cross-sectional study of patients with Parkinson’s disease was found to be 25% [13]. Once again, the severity but not the duration of Parkinson’s disease was predictive. With rising rates of obesity there has been an upsurge in research interest in its relationship with mental symptoms and mental disorders. In a meta-analysis of 15 longitudinal studies examining the bidirectional relationship between obesity and depression [14"] a reciprocal link was confirmed. In other words, obesity is a risk factor for depression and depression is a risk factor for obesity. This is a major issue in ageing populations, although this meta-analysis did not examine older people separately. In a prospective cohort study of 598 participants aged 60 years and over followed for up to 6 years, Köhler and colleagues [15""] found that level of depression at baseline predicted the rate of cognitive decline independently of the effect of apolipoprotein E allelic status. Cognitive decline was greatest in those with persistent or chronic depressive symptoms. The authors argued that depressive symptoms should be considered as targets for preventive interventions in later life with the implication that successful treatment might forestall the development of cognitive decline. In a smaller study, 35 people aged 60 years or older with major depression and 29 healthy controls were followed up over 18 months after baseline MRI brain scans [16]. White matter hyperintensities rather than salivary cortisol level or brain atrophy predicted cognitive decline over this period. Assessment In a fascinating descriptive study, Blass and Rabins [17"] report on depressive presentations in eight cases of fronto-temporal dementia (FTD) and emphasize the importance of considering FTD in the differential diagnosis of late-life depression. They make the point that some presentations meet DSM-IV criteria for major depression, whereas others are characterized more by mood lability or apathy. It is worth reflecting on the well established observation that minor depression is more common in older adults than younger adults and is more likely to present with a comorbid anxiety disorder in this population [18]. Interestingly, about 30% of nursing home residents have minor depression [19]. Our own group has undertaken further validation work on the 20-item Geriatric Anxiety Inventory [20,21], which is now established as a useful tool for the assessment of 506 Geriatric psychiatry generalized anxiety in older people [22,23]. We have also developed a five-item short form of the GAI [24"] for use in epidemiological surveys and in acute general medical settings. Both forms employ a dichotomous response scale, eschew somatic items and measure anxiety over the past week. A new 25-item anxiety scale has recently been published. The Geriatric Anxiety Scale (GAS; [25"]) has three subscales measuring somatic (nine items), cognitive (eight items) and affective (eight items) aspects of anxiety. Each item is rated in relation to the respondent’s last episode of significant anxiety on a four-point scale from ‘0’ not at all to ‘3’ all of the time. Thus the GAS does not necessarily rate current anxiety. However, it does exhibit excellent internal consistency and concurrent validity. The GAS has not yet been validated against any DSM-IV anxiety disorder diagnoses and cut points have not been established. Test–retest reliability has not yet been established and the potential confounding effects of either cognitive impairment or comorbid physical disorder have not yet been examined. With a group of colleagues, we have recently argued for screening measures to be developed specifically for use in residential aged care environments [26"]. In addition, the rationale for screening in such settings needs to be clear and to encompass disorders such as late-life anxiety, which have heretofore been neglected in such settings. Neuropsychology There is continuing interest in executive dysfunction in major depressive disorder (MDD). Kertzman and colleagues [27] applied the Stroop test to middle-aged and older outpatients with untreated MDD and a comparison group of normal controls. Older participants and those with MDD did worse. However, it is not clear whether the age-related changes in blue/green discrimination that commonly develop from the age of 50 years onwards might have influenced these findings. There is a version of the Stroop test [28] that employs colours (red, yellow, green) more readily discriminated by older people that might be preferable to use in studies involving people aged 50 years and over. Research on traumatic brain injury in ageing populations is uncommonly reported. However, SenathiRaja and colleagues [29"] have recently reported that poorer cognitive functioning is associated with older age at the time of injury and with increased time postinjury. These findings are likely to have implications for prognosis, treatment recommendations and longer-term issues of differential diagnosis and management planning. Neuroimaging Neuroimaging is a rapidly growing area and it is not possible to do justice to even recent advances here, particularly in relation to dementia. However, it is worthwhile considering two studies that have investigated the neuroimaging aspect of late-life depression. Nordanskog and colleagues [30] determined MRI hippocampal volume on a 3-Tesla machine in 12 depressed patients before and after a course of electroconvulsive therapy (ECT). Hippocampal volume was significantly increased bilaterally after ECT. The authors concluded that their findings supported the idea that the hippocampus is important for recovery from depression. However, other interpretations for their findings are possible. Kenny and colleagues [31"] used functional MRI (fMRI) resting state data from a 3-Tesla machine to compare functional connectivity between 16 older participants with a recent episode of depression and 17 normal controls. No brain regions showed greater connectivity in the nondepressed group in comparison with the depressed group. However, there was widespread increased connectivity in the depressed group in comparison with the nondepressed group, suggesting that functional connectivity is altered in late-life depression. Nonpharmacological treatment The utility of physical exercise in the prevention and treatment of anxiety and depression is subject to considerable debate. Against this background, Herring and colleagues [32"] conducted a meta-analysis of exercise training for anxiety reduction in patients with a variety of general medical and mental disorders. Forty articles including 2914 participants were reviewed. The mean effect size for anxiety reduction following exercise training was 0.29. Exercise training programs lasting no more than 12 weeks but involving training sessions of at least 30-min duration were most effective. Mead and colleagues [33] undertook a Cochrane review of physical exercise for depression in adults of all ages. We include it here because many of the trials included older adults and physical exercise is commonly prescribed for other reasons in later life. Although 28 randomized controlled trials met inclusion criteria, only 23 trials comparing exercise with a control condition or no treatment provided data that were satisfactory for metaanalysis. Of these, only three trials adequately concealed treatment allocation and used blinded outcome assessment. When the 23 trials were included, there was a large treatment effect [#0.82; 95% confidence interval (CI) #1.12, #0.51]. However, when only the three methodologically sound studies were included there was a more Anxiety and depression Byrne and Pachana 507 moderate and nonsignificant effect (#0.42; 95% CI #0.88, 0.03). The reviewers concluded that more methodologically sound trials were needed to help resolve this question. Pharmacological treatment The prognosis of depression complicated by comorbid anxiety has been reported to be worse than the prognosis of depression alone [34]. Nelson and colleagues [35"] undertook a meta-analysis to investigate whether response to second-generation antidepressants in depressed older adults was impaired by the presence of comorbid anxiety. Using a random-effects model, they compared the outcome for 2322 anxious and 1387 nonanxious depressed patients aged 60 years or older from published randomized placebo-controlled trials. There was no significant difference between the two groups in the outcome of antidepressant therapy. Sneed and colleagues [36"] randomized 174 people aged 75 years and over with MDD to an 8-week trial of citalopram 20–40 mg/day or placebo. At baseline they were assessed on a modified Stroop test administered via computer. The Stroop test measures response inhibition, one type of executive dysfunction. Those patients without deficient response inhibition on the Stroop who were treated with citalopram (n ¼ 58) did better than those without deficient response inhibition who were treated with placebo (n ¼ 61). In contrast, those patients with deficient response inhibition who were treated with citalopram (n ¼ 18) did worse than those patients with deficient response inhibition treated with placebo (n ¼ 21). These findings suggest an interaction between deficient response inhibition and citalopram in older people with major depression. The origin of this interaction is obscure, although it is well established that deficient response inhibition is associated with white matter ischaemic changes. However, these authors did not report MRI white matter findings. In a 12-week nonrandomized trial of sertraline in 217 participants aged 60 years and over with MDD, Fazekas scores were used to rate MRI white matter hyperintensities [37""]. Vascular risk factors correlated strongly with performance on a large battery of neuropsychological tests. Baseline neuropsychological function and white matter hyperintensities predicted Montgomery-Asberg Depression Rating Scale scores over the 12-week trial. Baseline neuropsychological function also predicted clinical remission. The findings from this study provide support for the vascular depression hypothesis in later life. It has been clear for some time that the initial treatment and ongoing management of moderate and severe depressive and anxiety disorders in later life should usually consist of combined therapy with antidepressant medication and some form of behavioural or psychological intervention. A variety of psychosocial and complementary therapies have attracted support for the treatment of mild and subsyndromal depressive and anxiety episodes. There is also an important role for ECT in the management of severe, treatment-resistant, depressive episodes in older people. In a randomized controlled trial of ultra-brief bifrontal and unilateral ECT [38], the bifrontal version was no less effective and was associated with less memory impairment. Although the prevalence of mood and anxiety disorders in noninstitutionalized older people appears to decline with advancing age, antidepressant drug use seems to rise. In a study based on officially collected Australian pharmaceutical data for citizens of all ages, the highest use of antidepressant drugs was in those aged 85 years and over [39"]. The authors suggest several potential explanations, including ‘off label’ prescribing for nonspecific emotional distress and insomnia. However, just why this should particularly affect prescribing to the oldest of the old is unclear. Given the association of antidepressant use with hyponatraemia and falls, these prescribing data suggest the need for increased physician education. On a lighter note, there is recent work suggesting that drinking coffee may reduce the risk of severe depression [40] and that subsyndromal depression may respond to physical activity with video-based exercise games [41]. The future In the draft criteria for DSM-5 MDD [42], it is proposed to remove the bereavement exclusion criterion, as there is now clear evidence that the depressive syndrome found commonly in the context of recent bereavement is very similar to the depressive syndrome found following other adverse life events [43,44]. There is also evidence that such bereavement-related depressive episodes respond to the usual treatments. It is also proposed to create a new condition in DSM-5 to be called chronic depressive disorder [42] to cover the existing DSM-IV syndromes of dysthymic disorder and MDD with chronic specification. Both of these proposed changes in the DSM-5 criteria for mood disorders are highly relevant to depression in older people, as bereavement occurs most commonly in older people and chronic depression increases in prevalence with advancing age. The main proposed changes in the DSM-5 criteria for the anxiety disorders include shortening the duration criterion for generalized anxiety disorder from 6 to 3 months and tightening up the criteria for post-traumatic stress disorder by making the A1 exposure criterion more 508 Geriatric psychiatry explicit and removing criterion A2, which required a defined psychological reaction to the traumatic event. Neither of these proposed changes has obvious agespecific implications. Conclusion There is a healthy level of research activity in relation to late-life depression, fuelled to some extent by the wider availability of advanced neuroimaging techniques. However, the research base for anxiety disorders in later life remains inadequate. Acknowledgements G.B. was funded in part by the National Health & Medical Research Council, the U.S. Alzheimer’s Association, the Wicking Trust, and the Royal Brisbane & Women’s Hospital Research Foundation. N.P. was funded in part by the National Health & Medical Research Council. References and recommended reading Papers of particular interest, published within the annual period of review, have been highlighted as: " of special interest "" of outstanding interest Additional references related to this topic can also be found in the Current World Literature section in this issue (pp. 605–606). Ladin K, Daniels N, Kawachi I. Exploring the relationship between absolute and relative position and late-life depression: evidence from 10 European countries. Gerontologist 2010; 50:48–59. Using data from 10 European countries, this study explores the relationship between late-life depression and socioeconomic inequality at both the country level and the individual level. 1 " 2 Kaji T, Mishima K, Kitamura S, et al. Relationship between late-life depression and life stressors: large-scale cross-sectional study of a representative sample of the Japanese general population. Psychiatry Clin Neurosci 2010; 64:426–434. 3 Caspi A, Sugden K, Moffitt TE, et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 2003; 301:386– 389. 4 Surtees PG, Wainwright NW, Willis-Owen SA, et al. Social adversity, the serotonin transporter (5-HTTLPR) polymorphism and major depressive disorder. Biol Psychiatry 2006; 59:224–229. 5 Kim JM, Stewart R, Kim SW, et al. Interactions between life stressors and susceptibility genes (5-HTTLPR and BDNF) on depression in Korean elders. Biol Psychiatry 2007; 62:423–428. Power T, Stewart R, Ancelin ML, et al. 5-HTTLPR genotype, stressful life events and late-life depression: no evidence of interaction in a French population. Neurobiol Aging 2010; 31:886–887. This European study explored whether polymorphisms in the serotonin transporter gene modified the risk of depression following adverse life events. 6 " O’Connor DW, Parslow RA. Differences in older people’s responses to CIDI’s depression screening and diagnostic questions may point to age-related bias. J Affect Disord 2010; 125:361–364. This study analysed data from an Australian population cohort to investigate whether there was an age-related variation in response to CIDI depression screening questions. 7 " Kessler RC, Birnbaum H, Bromet E, et al. Age differences in major depression: results from the National Comorbidity Survey Replication (NCS-R). Psychol Med 2010; 40:225–237. 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Increase in hippocampal volume after electroconvulsive therapy in patients with depression: a volumetric magnetic resonance imaging study. J ECT 2010; 26:62 – 67. 31 Kenny ER, O’Brien J T, Cousins DA, et al. Functional connectivity in late-life " depression using resting-state functional magnetic resonance imaging. Am J Geriatr Psychiatry 2010; 18:643–651. This study employs resting state fMRI data from a 3-T system to compare older people with depression with normal controls. 32 Herring MP, O’Connor PJ, Dishman RK. The effect of exercise training on " anxiety symptoms among patients: a systematic review. Arch Intern Med 2010; 170:321–331. This systematic review investigated the impact of exercise training on anxiety symptoms in patients of all ages. 33 Mead GE, Morley W, Campbell P, et al. Exercise for depression. Cochrane Database Syst Rev 2009; CD004366. 34 Steffens DC, McQuoid DR. Impact of symptoms of generalized anxiety disorder on the course of late-life depression. 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In this randomized controlled trial, response to antidepressant treatment in older people was modified by baseline neuropsychological function and a rating of white matter hyperintensity lesions. 38 Sienaert P, Vansteelandt K, Demyttenaere K, Peuskens J. Randomized comparison of ultra-brief bifrontal and unilateral electroconvulsive therapy for major depression: cognitive side-effects. J Affect Disord 2010; 122: 60–67. 39 Hollingworth SA, Burgess PM, Whiteford HA. Affective and anxiety disorders: " prevalence, treatment and antidepressant medication use. Aust N Z J Psychiatry 2010; 44:513–519. This pharmacoepidemiological study investigated antidepressant use by age. Older people were more likely to be dispensed antidepressant medication. 40 Ruusunen A, Lehto SM, Tolmunen T, et al. Coffee, tea and caffeine intake and the risk of severe depression in middle-aged Finnish men: the Kuopio Ischaemic Heart Disease Risk Factor Study. 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