© Springer International Publishing Switzerland 2017
Ana Verdelho and Manuel Gonçalves-Pereira (eds.)Neuropsychiatric Symptoms of Cognitive Impairment and DementiaNeuropsychiatric Symptoms of Neurological Disease10.1007/978-3-319-39138-0_88. Depression and Anxiety in Dementia Subjects
(1)
North East London NHS Foundation Trust, Department of Old Age Psychiatry, Brentwood Community Hospital, 2 Crescent Drive, Brentwood, Essex, CM15 8DR, UK
(2)
Retzdorffpromenade 3, Berlin, 12161, Germany
(3)
North East London NHS Foundation Trust, Department of Old Age Psychiatry, Sunflower Court, Goodmayes Hospital, Ilford, Essex, IG3 8XJ, UK
Abstract
Depression and cognitive disorders, including dementia and mild cognitive impairment, are common disorders in old age. Depression and anxiety are frequent in dementia, causing distress, reducing the quality of life, exacerbating cognitive and functional impairment and increasing caregiver stress. Even mild levels of depression can significantly add to the functional impairment of dementia patients, and the severity of psychopathological and neurological impairments increases with increasing severity of depression with increased disability, poor quality of life and higher mortality. Depressive symptoms may be both a risk factor and a prodrome of dementia and can often be difficult to distinguish in the early stages. Also, depression is often associated with deterioration in cognitive functioning which is not always completely reversible with treatment. Both depressive and anxiety symptoms are common in mild cognitive impairment and can coexist with higher rates of conversion to dementia.
Despite having a significant negative impact on the quality of life of people with dementia as well as their caregivers, both these conditions are usually under-recognised and as a consequence undertreated. Hence assessment and effective treatment of anxiety and depression in dementia could improve patient’s quality of life and should become more established in good clinical practice. Nonpharmacological approaches and watchful waiting should be attempted first in patients who present with mild to moderate symptoms. In cases not able to be managed through nonpharmacological means, treatment with medication should be considered.
Keywords
DementiaAlzheimer’s diseaseDepressionAnxietyAgitationMCIPhysical dependencyCaregiver burdenDisabilityMortalityPsychological therapiesAntidepressantsECTClinical Example
Mrs. EH is an 88 years old lady with a diagnosis of Alzheimer’s disease. Following a recent move to a care home, she presented with low mood, panic attacks, poor sleep and appetite, loss of confidence and withdrawal from previously enjoyed activities. Her mood continued to worsen and she started to express suicidal ideas at which point the home referred her to a psychiatrist in a dementia crisis team set up and run by one of the authors. She was seen by a psychiatrist who started her on antidepressants and a brief course of low dose benzodiazepines. Staff at the care home was advised on spending allocated time with her on a daily basis and on identifying and providing suitable daytime activities that she enjoyed. She was closely monitored over a few weeks with daily visits from the nurse in the dementia crisis team following which she made an excellent recovery with improved mood, sleep and appetite. The benzodiazepines were stopped after a 4-week period; she was maintained on an antidepressant in addition to an anticholinesterase which she was previously taking. On discharge from the team, she was cheerful, was interacting well with staff and other residents and was enjoying knitting and playing the piano which she previously used to enjoy.
It was possible for her to remain at the care home and receive treatment for a severe depressive episode without needing a hospital admission due to input from a specialised team for dementia in the community. The authors recognise that this might not be available in many places, but this example is cited to give the reader an insight into the value of diagnosing and good response for treatment of anxiety and depression shown by people with dementia.
Introduction
There are particular difficulties in defining and diagnosing depression in the context of dementia. It is only relatively recently that attempts have been made to produce inclusion and exclusion criteria for the diagnosis of depression specifically in Alzheimer’s disease (AD), based on affective and behavioural features [1]. The diagnostic criteria for major depression based on the Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV) have been used to diagnose depression in dementia without impressive results. They include symptoms like depressed mood, diminished interest, significant weight loss, insomnia, psychomotor agitation or retardation, loss of energy, feelings of worthlessness or guilt, diminished ability to concentrate and recurrent thoughts of death or suicidal ideation. Five (or more) of these symptoms have to be present during the same 2-week period and must represent a change from previous functioning. It has been recognised that these criteria do not satisfactorily reflect depression in AD, hence the development of provisional diagnostic criteria for depression of AD by a working group of the National Institute of Mental Health [1]. These provisional criteria differed from the original DSM-IV in that only three (or more) of the mentioned symptoms were required but were not needed to be present every day. Criteria were added for the presence of irritability and for social isolation or withdrawal. Finally, the criteria for loss of interest and poor concentration were omitted [2]. Thus, the NIMH criteria included patients who met DSM-IV criteria for major depression as well as less severe cases. In DSM-V, no changing of any of the core criteria of symptoms for major depression has been established, nor the requisite 2-week time period needed before it can be diagnosed. The DSM-V chapter on anxiety disorders no longer includes obsessive-compulsive disorder (which is included with the obsessive-compulsive and related disorders) or posttraumatic stress disorder and acute stress disorder (which are included with the trauma- and stress-related disorders). Changes in criteria for agoraphobia, specific phobia and social anxiety disorder (social phobia) include deletion of the requirement that individuals over age 18 years recognise that their anxiety is excessive or unreasonable. This change is based on evidence that older individuals often misattribute “phobic” fears to ageing. Instead, the anxiety must be out of proportion to the actual danger or threat in the situation, after taking cultural contextual factors into account. In addition, the 6-month duration, which was limited to individuals under age 18 in DSM-IV, is now extended to all ages. This change is intended to minimise overdiagnosis of transient fears. Nonetheless in the context of the questions discussed in this chapter, new developments of nomenclature such as DSM-V do not add much to the relevant problems [3].
For providing a better follow-up of the disease progression as well as of assessing the effect of therapeutic interventions, a number of other scales have been developed to assess depressive symptoms in dementia, e.g. the Cornell Scale for Depression in Dementia (CSDD), the Dementia Mood Assessment Scale (DMAS) and the Neuropsychiatric Inventory (NPI) [4]. The CSDD [5], derived from the Hamilton Depression Rating Scale (HAMD), is a 19-item observational instrument designed to rate depressive symptoms in individuals with dementia who can at least communicate basic needs. Scores are determined by a combination of prior observation and interviews with the patient as well as with the caregiver. The DMAS [6, 7] was modelled after the HAMD but did not include its subjective aspects, which make the scale too difficult for patients with dementia to complete. It is a 24-item observational scale used to rate mood and functional abilities on an objective basis. Rating scales like the Geriatric Depression Scale (GDS) [8] and structured interview schedules currently available are not without limitations when evaluating for depression in cognitively impaired subjects. Self-report measures in particular have their limitations when used for patients with MCI or dementia. It is well known that patients may underreport and caregivers may overreport symptoms, biased by own symptoms (e.g. stress), hence highlighting the need for the clinician to use both sources of information in a balanced manner.
Epidemiology
On reviewing current literature, the prevalence rates of depressive symptoms in people with dementia range from 10 to 62 % [9] with lower rates (0.9–4.8 %) reported when employing strict criteria for major depression [10]. A recent review shows that approximately 20–30 % of patients with AD have clinically significant depression, with higher rates in vascular dementia (VaD) and dementia with Lewy bodies (DLB) [9]. Risk of developing depression is higher if the person is younger in age, has significant medical conditions or has a family history of depression [11]. In mild cognitive impairment (MCI), rates of depressive symptoms are reported as moderate to high, ranging from 36 % [12] to 63 % [13].
Although anxiety symptoms are common both in dementia and MCI [14, 15], there is a lack of consensus about how to define and conceptualise anxiety in the presence of dementia and other forms of cognitive impairment. Studies have employed diagnostic criteria (e.g. the (DSM-IV)) or measures of anxiety symptomatology [16].
Also, there are contrasting views in the literature as to whether anxiety and agitation are the same or different constructs [17, 18] adding another complexity to diagnosing a pure anxiety disorder on a background of dementia. Another study [19] noted that anxiety and agitation are associated in dementia although the degree of correlation does not support the use of agitation as a measure of anxiety. Anxiety symptoms of autonomic sensitivity are not correlated with agitation and could be used to differentiate between the two if this is required.
Starkstein et al. [20] proposed a revision of diagnostic criteria for generalised anxiety disorder (GAD) in individuals with dementia consisting of excessive anxiety and worry (criteria A and B of the DSM-IV) and any three of the symptoms of restlessness, irritability, muscle tension, fears and respiratory symptoms. Rating of Anxiety in Dementia (RAID) [21] is a useful tool which is easy to use and has been shown to have high reliability for diagnosing anxiety in dementia. From reviewing available literature prevalence estimates in dementia range from 8 to 71 % for symptoms of anxiety [22] and 5–21 % for anxiety disorders [16].
In people with MCI, anxiety symptoms range from 10 to 74 % [23]. Relatively less is known about the prevalence of anxiety disorders in MCI, with rates up to 49 % [24] when using the Consortium to Establish a Registry for Alzheimer’s disease Behavioural Rating Scale for Dementia (CERAD-BRSD) criteria. It is notable that anxiety and depression can coexist in individuals with dementia and MCI with common symptoms across both affective states, which can add to the difficulties of definition [25].
Previous studies indicate that the frequency of depression and anxiety symptoms varies as a function of the severity of dementia. For example, experiencing or recognising depression is more common in patients with mild to moderate dementia, whereas elevated levels of anxiety may be more frequent in later stages of the disease [26]. Different types of dementia (e.g. vascular versus AD) have also been associated with different prevalence rates of depression and anxiety [27, 28].
Relationships Between Depression, Anxiety and Dementia
A recent review reported that a 2–5 fold increased risk of dementia is associated with depression [29]. There is a growing body of evidence to suggest that depression may be both a risk factor and a prodrome of dementia. The finding that the interval between diagnosis of depression and AD is positively related to increased risk of developing AD suggests that depression may be a risk factor for AD [30, 31]. This is further confirmed by a neuropathological study that demonstrated increased hippocampal plaque and tangle formation in AD patients with lifetime history of depression [32]. Other evidence indicates that depressive disorders are increased in the preclinical stage of AD [33], and the risk of developing dementia increases when depression is loaded with depression-executive dysfunction syndrome (DEDS) [34]. This increase may not be merely a by-product of self-perceived cognitive difficulties but the early manifestation of an underlying neurodegenerative disease, with shared risk factors. Further studies have found a much higher risk of developing Alzheimer’s disease in patients with very late-onset depression suggesting that depression might be a prodrome of AD but not of dementia of other etiology, with symptoms of depression emerging as a consequence of subjectively perceived worrisome cognitive deterioration. Furthermore, depression parameters and subjective memory impairment predicted AD independently of objective cognition [35].
There are likely biological mechanisms that link depression to dementia, such as vascular diseases, increased deposition of B-amyloid plaques, inflammatory changes and deficits of neurotrophic factors [36]. Damage to the hippocampus through depression-initiated alterations in glucocorticoid steroid levels [37] might explain the association between depression and dementia. Frontal and right parietal white matter hyperintensities are reported as the strongest brain structural correlates of apathy and depression in AD [37].
There is also some evidence for a genetic link between AD and depression. In a prospective study, the association of depressive symptoms on cognitive decline was increased among participants with one or more copies of the APOE-4 allele compared to those without the allele [38]. Another likely link is that depression occurs in response to the multiple psychological stresses involved with dementia. Starkstein and colleagues suggested that dysthymia in AD could be a negative emotional reaction to the progressive cognitive decline, whereas major depression in AD could be more strongly related to biological factors [39]. Depression can also unmask subclinical cognitive impairment and serves to compromise cognitive reserve [40]. It should be emphasised that none of these theories are mutually exclusive, and multiple factors, which can interact and propagate each other, might be involved.
Regarding the impact of these conditions on the person with dementia, consistent evidence suggests that the severity of depression increases the extent of neurological impairments, institutionalisation [41] and levels of caregiver burden [42]. Likewise, anxiety is associated with increased dependence [43] and increased risk of nursing home placement [44] and can lead to an overestimation of dementia severity [45]. Early symptoms of depression in MCI can be persistent and refractory to antidepressant medication [39] and increase the risk of developing dementia at follow-up [46]. In fact both depressive [47] and anxiety symptoms [12] in people with MCI predict higher rates of progression to AD [48] and are often implicated in greater impairments in activities of daily living [49].
Distinguishing Clinically Between Depression and Dementia
Distinguishing between depression and dementia can be challenging, even for an experienced clinician in the field, for both have a significant overlap. Normal age-related cognitive changes in the elderly that blur the distinction between normal ageing and early signs of dementia further complicate the diagnostic task. In old age, depression is associated with insomnia, hypochondriasis, somatisation, decreased appetite, weight loss, memory impairment and decreased activity, whereas in younger age groups active suicidal ideations, lifetime suicidal attempts, anhedonia and persistent depressive symptoms between episodes are more frequent [50]. Irritability appears to be one of the most prevalent depressive symptoms in nursing home residents diagnosed with comorbid depression [51]. Irritability should therefore alert caregivers to the presence of depression and could help early recognition. There are a number of cognitive deficits common to both depression and dementia, particularly in memory, attention, processing speed and executive functions, with memory showing the most overlap. Also, both depression and dementia can present with apathy, a syndrome of lack of motivation evidenced by diminished goal-directed motor behaviour, diminished goal-directed cognition and diminished emotional response [52]. The concepts of apathy and depression both share the predicate of reduced volition, which implies a particular phenomenological overlap. The frequency of apathy ranges from 25 % to more than 50 % among patients with AD [36] and is associated with a faster cognitive and functional decline [53]. Apathy may also have a differential impact in the conversion of MCI to dementia with greater conversion in patients showing apathy as a symptom [54]. Whereas apathy is increasingly recognised as a frequent behavioural problem in dementia, its nosological position remains unclear. Finally, affective dysregulation is also common to both depression and dementia, in the latter situation typically expressed with minimal provocation and with more rapid resolution. Despite the everyday relevance of fluctuation of mood symptoms in dementia, this has received little research interest apart from Lewy body dementia where fluctuations are very well recognised and have been studied extensively.
Rockwood and colleagues [55] focused on the variable expression of cognitive symptoms and described variability in mood and behaviour in patients with AD. On good days, patients showed improved global cognition, function, interest and initiation, whereas bad days were associated with frequent verbal repetition, poor memory, increased agitation and other disruptive behaviours. Looking at the available research findings, it would appear that temporary mood disturbances like these are common in Alzheimer’s disease patients and should be distinguished from the persistent mood disturbance that characterises patients with comorbid depression.
On taking a closer look at specific cognitive domains in comparing depression and dementing disorders, memory and executive functions appear to be the most relevant. Depression presents with several memory function deficits most common being those related to tasks of recall or remembering. Depressed patients perform better than AD patients on delayed recall measures, but motivational factors may play an important role. A great number of studies show that memory deficits in depression are considerably mild and transient when seen in comparison with dementia. Task switching or the set-shifting abilities have been the most commonly found impairments among executive functions in depressed patients [56]. Notably, studies suggest that depressed patients showing impairments on tasks of recall memory and executive functions may be at greater risk for AD than depressed patients without such decrements [57]. In a study by McCue and co-workers [58], patients with depression who were misclassified as having dementia tended to have more extreme degrees of depressive symptomatology and lower educational levels, thus adding another factor that may blur the clinical picture and complicate differential diagnosis. According to Emery and Oxman [59], depressive dementia sometimes appears to be a transitional stage in a disease progression from depression without dementia to a degenerative dementia for which the concept of “transitional dementia” to substitute the old term “pseudodementia” has arisen.
Elderly patients with depression often present with executive deficits, but these are markedly less than in conspicuous dementia, particularly AD patients. Additionally, decrements of activities of daily living are less pronounced compared to patients with dementia. Lower frequency of biological symptoms and signs of major depression (e.g. decreased appetite, disturbed sleep, weight loss) are found among dementia sufferers. A non-remitting depression in the elderly, particularly showing impairments on tasks of recall memory and executive functions, should be regarded as a possible prodrome of dementia. Finally, very often clinically it might be impossible to differentiate between the two, and a trial of treatment for depression might be the only way forward.
Overlap Between Depression and Anxiety in Dementia
Overlap between depressive and anxiety symptoms is routinely encountered in clinical practice, and anxiety is confounded with depression in individuals with dementia. In cognitively intact older adults, depression and anxiety are comorbid but form distinct constructs [60, 61]. In dementia, between 68 % and 75 % of individuals with dementia and GAD also meet the criteria for major depressive disorder [16–20] and GAD is associated with greater depressive symptoms in AD [62]. Studies examining the validity of instruments designed to assess anxiety symptoms have found strong overlap between the two constructs [63], and controlling for depression sometimes, but not always, eliminates the association between anxiety and other variables [58, 64–67]. A good impression of this problem is explored in a study where independent severe threat life events were associated with anxiety in the dementia patient group. Multivariate analyses suggested that this link was mediated by depressive symptoms [68].
Finally, in one study [69], anxiety loaded equally strongly on a depression/apathy factor and on a psychotic symptoms factor. Because the studies varied in more than one aspect (type of dementia, community sample versus patients from memory clinic, instrument used), it is difficult to ascertain which variables contributed to these findings.
In summary, the bulk of the evidence to date suggests that depression and anxiety are highly comorbid in individuals with dementia. Whether they form distinct constructs is unclear, as existing studies provide conflicting evidence. The main limitation to providing a more definitive conclusion is that, despite its importance, no study to date has yet focused specifically on this question. Rather, the existing evidence is indirect and incidental. Despite their overlap, treatment options for depression and anxiety have been considered separately in this chapter.
Treatment Options for Depression in Dementia
Pharmacological Treatment
Evidence for improvement in symptoms of depression in patients with dementia on antidepressant treatment, although suggestive, do not definitively confirm efficacy. Many trials have been carried out on small numbers of patients and are hence underpowered to detect differences, resulting in inconclusive findings. Variable trial methods, comorbid conditions and differences in the administered antidepressants further confound findings. Most studies showed a trend towards antidepressants being effective on depressive symptoms in patients with dementia, but the recent meta-analysis by Nelson and Devanand [70] could not confirm efficacy. A Cochrane review on antidepressants for treating depression in dementia, conducted by Bains et al. 2009 [71], came to the conclusion that it is not that antidepressants are necessarily ineffective, but rather that there is not much evidence to support their efficacy. Given that they may produce serious side effects, clinicians should therefore prescribe with due caution. In the light of large trials that have failed to detect efficacy, a Norwegian study in 52 nursing homes attracts interest. The study evaluated the effect of controlled treatment discontinuation of selective serotonin reuptake inhibitors (SSRIs) (e.g. escitalopram, citalopram, sertraline and paroxetine) in patients who were diagnosed with AD, vascular dementia or a mixture of both, who were prescribed SSRIs for at least 3 months. After 25 weeks, the discontinuation led to a statistically significant as well as clinically relevant increase in depressive symptoms, compared with those patients who continued with treatment [72].
Current practice is to use antidepressants, preferably selective serotonin reuptake inhibitors (SSRI), as a first-line treatment for depression in dementia, based on recommendations of several guidelines. In the UK, the National Institute for Health and Clinical Excellence (NICE) advocates antidepressants for major depression in dementia. Additionally, NICE advises that treatment should be started by staff with specialist training, who should follow the guidelines for depression after a careful risk-benefit assessment [73]. The American Psychiatric Association (APA) [74] recommends a trial of an antidepressant to treat clinically significant, persistent depressed mood in patients with dementia, and SSRIs may be preferred because they appear to be better tolerated than other antidepressants. Alternative agents to SSRIs are mentioned, including venlafaxine, mirtazapine and bupropion. The APA publication is the only guideline which refers to electroconvulsive therapy (ECT) as a possible treatment and considers it appropriate for patients with moderate to severe depression that is life threatening or refractory to other treatments. There is evidence from some trials for ECT as an effective and well-tolerated option for treating depression in people with dementia. The Hausner et al. study reported improvement in depressive symptoms with ECT with any cognitive deficits arising during therapy being transient [75]. All guidelines advise against antidepressant drugs with anticholinergic effects because of their potential to adversely affect cognition. Although SSRIs have a favourable side effect profile, a population-based cohort study [76] found that SSRIs and newer non-SSRI antidepressants were associated with an increased risk of several adverse outcomes compared with tricyclic antidepressants (TCAs). Hence this widely held belief of better tolerated SSRIs should be open to critical consideration and each patient treated after giving careful consideration to the risks like hyponatremia, gastrointestinal bleeding or falls versus benefits.
Psychosocial Interventions
There is an abundance of research trails to support that depression in older people can be effectively treated with psychological therapies, both alone and in combination with pharmacotherapy [77]. Despite the fact that dementias usually compromise higher cortical processes and thus have a negative impact on the possible results of most psychotherapeutic techniques, psychosocial interventions have been proposed and found useful for the treatment of major depression in dementia. Interpersonal psychotherapy (IPT), originally developed for younger adults and adapted for elderly as a late-life version (IPT-LL), was modified for depressed older adults with mild cognitive deficits (IPT-CI). This modified version includes the systematic incorporation of concerned caregivers into the treatment process, with joint patient–caregiver sessions to promote better understanding, communication and respect. In addition, IPT-CI helps both older adults and caregivers through the role transitions that result from cognitive deficits and functional limitations [78]. It has also been found to be useful for depression in mild stages of dementia and includes a comprehensive neuropsychological battery to assess the cognitive deficits and the cognitive strengths of the patient. The treatment consists of behavioural activation and the incorporation of memory aids (e.g. notepads and audio taping of sessions). It involves listing the pros and cons of situations and experimenting with new attitudes and cognitions in stressful situations [79]. Problem-solving therapy (PST) consists of five steps: identifying a problem and selecting a goal, brainstorming alternative solutions, applying a balanced review of the pros and cons of each solution, selecting a solution and creating an action plan and implementing and evaluating the action plan. In the case when one solution seems the obvious choice, participants usually are instructed to consider the pros and cons of each solution generated before finalising their decision. This process demonstrates to participants the value of weighing all options, rather than “going with your gut” in deciding on solutions for problems [80]. Preliminary data suggest that a home-delivered adaptation of PST that includes environmental adaptations and caregiver involvement is efficacious in reducing disability in depressed patients with advanced cognitive impairment or early dementia [81].
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