Formal diagnostic criteria for depression are derived from the symptom criteria in the Diagnostic and Statistical Manual, 4th edition (DSM-IV).8 Major depression, the most common mood disorder, is diagnosed when the individual exhibits, for at least 2 weeks, one or both of two core symptoms (depressed mood and lack of interest in most activities) along with four or more of the following symptoms: feelings of worthlessness or guilt; diminished ability to concentrate or make decisions; fatigue; psychomotor agitation or retardation; insomnia or hypersomnia; significant decrease or increase in weight or appetite; and recurrent thoughts of death or suicidal ideation.8 For the most part, depression is similarly experienced by older adults if there are no comorbid conditions;9 however, subtle differences with ageing may emerge. For example, depression with melancholia (symptoms of anhedonia, non-interactiveness and psychomotor retardation or agitation) appears to have a later age of onset than non-melancholic depression in clinical populations.10, 11 Older adults often experience depressive symptoms associated with bereavement after the loss of a loved one, symptoms consistent with those of a major depressive episode. Major depression may be diagnosed if the depressive symptoms are present at least 2 months or longer after the loss.

Minor, sub-syndromal or sub-threshold depression is diagnosed according to the Appendix of DSM-IV in the instance that one of the core symptoms is present (sad mood or loss of interest in most activities) along with one to three additional symptoms.1, 8 Other operational definitions of these less severe variants of depression include a score of 16 or more on the Center for Epidemiologic Studies Depression Scale (CES-D) but not meeting criteria for major depression,12, 13 a primarily biogenic depression not meeting criteria for major depression yet responding to antidepressant medication14 or a score of 11–15 on the CES-D.15

Dysthymic disorder is a long-lasting chronic disturbance of mood, less severe than major depression that lasts for 2 years or longer.8 It rarely begins in late life but may persist from mid life into late life.1, 16, 17 To be diagnosed with dysthymic disorder, the older adult must experience a depressed mood for at least 2 years along with two of the following symptoms: eating disturbance, sleep disturbance, low energy or fatigue, low self-esteem, poor concentration or difficulty in making decisions and feelings of hopelessness. Finally, other investigators have suggested a syndrome of depression without sadness, thought to be more common in older adults,18, 19 or a depletion syndrome manifested by withdrawal, apathy and lack of vigour.1, 20–22

Depression among individuals with dementia is fairly common, so much so that recently a group of investigators proposed a depression of Alzheimer’s disease (AD). In persons who meet criteria for dementia of the Alzheimer’s type, three of a series of symptoms that include depressed mood, anhedonia, social isolation, poor appetite, poor sleep, psychomotor changes, irritability, fatigue or loss of energy, feelings of worthlessness and suicidal thoughts must be present for the diagnosis to be made.1, 23

Depression in late life is frequently comorbid with physical conditions. When the depression derives from the physiological consequence of the medical condition, the disorder is diagnosed as mood disorder due to general medical condition.8

Depressive symptoms may also temporarily meet criteria for major depression in the midst of bereavement and acute adjustment disorders. The context of the depression therefore helps the clinician to determine whether a diagnosis of major depression should be made and treatment instituted or whether the symptoms will be expected to remit on their own when an appropriate time has elapsed. The clinician must remember, however, that what initially appears to be a case of bereavement or an adjustment disorder may evolve into major depression with time.

Depressive symptoms are no more or less frequent in late life than in mid life.1, 24–26 Several large epidemiological studies have been conducted to assess the prevalence of affective disorders in older populations. Generally, among the elderly, the prevalence of major depression is ∼1–3%1, 27, 28 and reports of clinically significant depressive symptoms in community-dwelling elderly have been ∼8–16%.1, 26, 29–31 Further, among individuals aged 85 years or older, the incidence of major depression appears to increase among the oldest of old,32 reaching ∼13%.33 However, this increased rate is explained by factors associated with ageing, including a higher proportion of women, more physical disability, more cognitive impairment and lower socioeconomic status.34, 35

Higher rates of depression and depressive symptoms have been consistently found for women compared with men in the general population and for the elderly.36, 37 Whereas some studies of the elderly have found few racial differences in the frequency of depressive symptoms29, 38, 39 or in the frequency of depressive diagnoses,31, 37, 40 others have found African American elders to have a higher frequency of depressive symptoms than Caucasians.41–44 Depressive symptoms may be greater in African Americans than Caucasians solely due to differences in socioeconomic status (SES).45, 46 Nevertheless, African Americans are generally thought by psychiatrists to have fewer depressive symptoms and are much less likely to be treated with antidepressant medications.47, 48 Some have also raised the issue of misclassification of African Americans as depressed.49

Comorbidity of Depression with Medical Illness

Depression late in life often occurs within the context of physical impairment,50 especially in the oldest individuals.1, 34 For example, in a study of patients hospitalized with acute myocardial infarction, investigators examined the degree of association between clinical depression and medical comorbidity and found that the adjusted odds ratios for having major depression increased linearly with medical comorbidity.51 Depression also adversely influences the outcome of comorbid health disorders in the elderly.1, 2, 52, 53

In a recent meta-analysis, chronic health problems were found to be a risk factor for depression among older adults.54 The quantitative meta-analysis showed that, compared with the elderly without chronic disease, those with chronic disease were at higher risk for depression [relative risk (RR), 1.53; 95% confidence interval (CI), 1.20–1.97]. Compared with the elderly with good self-rated health, those with poor self-rated health were at higher risk for depression [RR, 2.40; 95% CI, 1.94–2.97).

We have found the perception that one’s basic needs are not being met predicted future depressive symptoms in a highly controlled analysis. These results suggest that perception of inadequate basic needs, even when income and other known correlates of depression are controlled, is a strong predictor of future depressive symptoms.55

Depression and Cognitive Impairment

Depression is associated with both mild cognitive impairment56 and dementia.57 The prevalence of depression among the cognitively impaired has been found to range between 20 and 50%.23, 58, 59 Depression among individuals with dementia may be more frequent in those with vascular diseases compared with those with AD.60–62 Elevated rates of depression have also been found among individuals with dementia secondary to Parkinson’s disease.63a, 64, Depression may signal the onset of AD and may represent prodromal signs of dementia.65–67 Research suggests that depression initiated a glucocorticoid cascade that leads to damage of the hippocampus, a brain structure integral to memory, leading to subsequent cognitive decline.68

Major depression among those with dementia is associated with greater impairment of activities of daily living (ADLs), worse behavioural disturbance and more frequent wandering, even after adjusting for severity of dementia or comorbid health problems. Minor depression was also associated with non-mood behavioural disturbance and wandering.69

Depression is a chronic and recurring illness.70–75 In a meta-analysis76 of the prognosis of elderly medical inpatients with depression, researchers found that at 3 months 18% of patients were well, 43% were depressed and 22% were deceased. At 12 months or more, 19% were well, 29% were depressed and 53% were deceased. Factors associated with worse outcomes included more severe depression and more serious physical illness. Among those older depressed adults without significant comorbid medical illness or dementia and who are treated optimally, the outcome is more optimistic, with over 80% recovering and remaining well throughout follow-up.75

Medical comorbidity, functional impairment and comorbid dementing disorders all adversely influence the outcome of depression.1 Depression also adversely affects the outcome of the comorbid problems such as cardiovascular disease5 in which depressive disorder is associated with an increase in mortality,77 particularly for women and less so for men.78, 79 Problems in meeting one’s basic needs affects depression among older adults.55

Psychiatric disorders in general and severe depressive disorders increase the risk of non-suicide-related mortality.1, 5, 80 For example, in a review of 61 reports of this relationship from 1997 to 2001, 72% demonstrated a positive association between depression and mortality in elderly people.81a Both the severity and duration of depressive symptoms predict mortality in the elderly population in these studies.1, 82 Other studies, however, have suggested that the association between depression and mortality is related to the high correlation between depression and other medical problems. In one study, depression at baseline predicted earlier (3 and 5 year) mortality but not later (10 year) mortality. The interaction between self-rated health and depression independently and strongly predicted mortality at all endpoints,83 that is, depression impacts non-suicide mortality through intermediate risk factors.

In a recent study,84 both moderate [multivariate hazard ratio (MHR), 1.29; 95% CI, 1.03–1.61] and severe depression (MHR, 1.34; 95% CI, 1.07–1.68) predicted 10 year mortality after multivariate adjustment. Chronic depression was associated with a 41% higher mortality risk in a 6 year follow-up compared with subjects without depression.

The association of depression and suicide across the life cycle has been well established.85–91 Older adults are at a higher risk for suicide than any other age group. While older Americans comprise ∼13% of the US population, they account for 18% of all suicide deaths.92 Increased risk for suicide attempts in late life is associated with being widow(er)s, living alone, perception of poor health status, poor sleep quality, lack of a confidant and experience of stressful life events, such as financial discord and interpersonal discord.86, 91

The most common means of committing suicide in the elderly are use of a firearm88 and drug ingestion.1 Women attempt suicide more than men; however, men completed suicide more often than women.93 Although completed suicides increase with age, suicidal behaviours do not increase.94 This is consistent with the contention that older adults are more intent in their efforts to commit suicide.95

There are many risk factors for suicide, with depression being central.96 Perhaps the best studied factor is pervasive feelings of hopelessness.97, 98 Other psychological constructs include emotional pain,99 feelings of being a burden and social isolation.100a The lack of social networks and their disruption are significantly associated with risk for suicide in later life.95 Joiner et al. have identified key risk factors for individuals at high risk for suicide,101 and they (as others) have identified ‘mattering to others’ as an important protective factor.

Physical illness is strongly associated with suicide in the elderly. In one large epidemiological study the following medical illnesses were found to be associated with suicide:102 congestive heart failure [odds ratio (OR), 1.73; 95% CI, 1.33–2.24], chronic obstructive lung disease (OR, 1.62; 95% CI, 1.37–1.92), seizure disorder (OR, 2.95; 95% CI, 1.89–4.61), urinary incontinence (OR, 2.02; 95% CI, 1.29–3.17), anxiety disorders (OR, 4.65; 95% CI, 4.07–5.32), depression (OR, 6.44; 95% CI, 5.45–7.61), psychotic disorders (OR, 5.09; 95% CI, 3.94–6.59), bipolar disorder (OR, 9.20, 95% CI, 4.38–19.33), moderate pain (OR, 1.91; 95% CI, 1.66–2.20) and severe pain (OR, 7.52; 95% CI, 4.93–11.46). Treatment for multiple illnesses was strongly related to a higher risk and these patients often saw a primary care physician in preceding months before suicidal behaviour, underscoring the physician’s potential role in suicide. Indeed, almost half of the patients who committed suicide had visited a physician in the preceding week.

Older persons with mental disorders rarely seek help from mental health professionals, preferring to visit their primary care physician instead.103 The majority of older adults who die by suicide have been seen recently by a healthcare provider. Suicide prevention strategies rely on the identification of specific, observable risk factors. Depression, hopelessness and self-harming behaviours (such as food refusal) are possible indicators of suicide risk.95, 104 Living alone, feeling like one is a burden to others and having few social ties are each a risk factor for suicide. Individuals with a previous history of suicide are more likely to attempt suicide again.88 Increased risk is also associated with resolved plans, a sense of courage and/or competence regarding suicide and access to means of suicide (e.g. pills or gun).105 Other variables that increase suicide risk include substance abuse,106 marked impulsivity and personality disorder.107

Biological

As noted above, increased rates of depression are associated with many medical conditions, including dementing disorders,57 cardiovascular disease,81b hip fractures108 and Parkinson’s disease.109 Depression has been associated with pain in institutionalized elderly people110 and is also common among home-bound elders with urinary incontinence.111 In one study, initial medical burden, self-rated health and subjective social support were significant independent predictors of depression outcome.112 Therefore, any exploration of the aetiology of late-life depression must begin with the possibility that the depression is caused in part, and perhaps wholly, by physical illness.

The role of heredity, that is, genetic susceptibility, has been of great interest in exploring the origins of depression across the life cycle.113 Among elderly twins, genetic influences accounted for 16% of the variance in total depression scores on the CES-D and 19% of psychosomatic and somatic complaints. In contrast, genetics contributed minimally to the variance of depressed mood and psychological wellbeing.114 Attention has been directed to specific genetic markers for late-life depression. For example, a number of studies have focused on the susceptibility gene APOE (the e4 allele) for AD. No association was found in a community sample between APOE e4 allele and depression;115 however, the APOE e4 allele contributes to AD, which in turn is associated with increased rates of depression. In another study, hyperintensities in deep white matter but not in the periventricular white matter were associated with depressive symptoms, especially in elders carrying the e4 allele.116

Much attention has been directed to vascular risk for late-life depression, dating back at least 40 years, although the advent of magnetic resonance imaging (MRI) increased interest considerably.73, 117–120 Vascular lesions in some regions of the brain may contribute to a unique variety of late-life depression. MRI of depressed patients has revealed structural abnormalities in areas related to the cortical–striatal–pallidal–thalamus–cortical pathway,121 including the frontal lobes,122 caudate123 and putamen.124 These circuits are known to be associated with the development of spontaneous performance strategies demanded by executive tasks. Recent serotonin activity, specifically 5-HT2A receptor binding, decreases dramatically in a variety of brain regions from adolescence through mid life, but the declines slowly from mid life to late life. Receptor loss occurred across widely scattered regions of the brain (anterior cingulated, occipital cortex and hippocampus). Serotonin depletion can also be studied indirectly by the study of radioisotope-labelled or imipramine-binding (TIB) sites. There is a significant decrease in the number of platelet-TIB sites in elderly depressed patients compared with elderly controls and individuals.

In one study, healthy subjects showed a marked increase in cortisol levels 2–3 h into the procedure regardless of drink composition whereas recovered depressed subjects did not. In elderly patients who had recovered from depression, there was no evidence of greater vulnerability of hypothalamic 5-HT pathways to 5-HT depletion. However, they demonstrated reduced reactivity of the HPA axis compared with healthy subjects.125

Late-life depression is also associated with endocrine changes. Although the dexamethasone suppression test was long ago ruled out as a diagnostic test for depression, non-suppression of cortisol is associated with late-life depression compared with age-matched controls.126 Depression is also associated with an increase in corticotrophin-releasing factor (CRF), which mediates sleep and appetite disturbances, reduced libido and psychomotor changes.127 Ageing is linked to a heightened responsiveness of adrenocorticotropic hormone (ACTH), cortisol and dehydroepiandrosterone sulfate (DHEA-S) to CRF.128 Low levels of DHEA have been associated with higher rates of depression and a greater number of depressive symptoms in community-dwelling older women.129 Total testosterone levels have been found to be lower in elderly men with dysthymic disorder than in men without depressive symptoms.130 However, the efficacy of testosterone in treating depression has not been established.131

In addition, Tsai’s research suggests that decreased brain-derived neurotrophic factor (BDNF) is related to both AD and major depression.132 The author suggests that BDNF could be a bridge between AD and depression, explaining both the depressive symptoms in AD and cognitive impairment in depression.

Dementia and Depression

The prevalence of depression in dementia is estimated to range between 30 and 50%.58 Symptoms of depression are common among individuals with dementia, complicating both the diagnosis and treatment, and are often associated with a more severe clinical course, higher cost of treatment, poorer quality of life and worse outcomes. Further, psychiatric symptoms that occur in individuals with dementia are often the primary cause of family burden and distress. Depression in dementia often goes unrecognized, resulting in less effective therapeutic interventions.133 However, the identification and effective treatment of depressive disorder in individuals with dementia may substantially augment treatment outcome and improve the quality of life for the patient and family.

Depression among individuals with dementia may be more frequent in those with vascular diseases than in those with AD. Patients with vascular dementia have more frequent and more severe symptoms of depression, and also anxiety, than those with AD (after controlling for levels of cognitive impairment). Ballard et al. found that among patients with dementia, 25% had major depression and 27.4% had minor depression.60 Major depression occurred significantly more often and was significantly more severe in patients with vascular dementia than in patients with AD.

Psychological and Social

A variety of different psychological origins have been theorized for depression in later life, including behavioural, cognitive, developmental and psychodynamic theories. Among the behavioural explanations, learned helplessness134 was originally used to describe the increasingly passive behaviour of dogs who were exposed to inescapable shock. The theory has been expanded, suggesting that one cause of depression is learning that initiating action in an environment that cannot be changed is futile.134–136 As individuals face new challenges associated with ageing, coping strategies that were once useful may become less effective. Within this context, behavioural interventions (described below) encourage the individual to find new ways to cope successfully with environmental stress.

The most dominant current psychological model of depression is that of cognitive distortions.137 Several researchers have found consistent differences in the cognitive styles of depressed individuals compared with non-depressed individuals. Beck and co-workers have described the cognitive schema of depressed persons as having logical errors that promote depression.137–139 Cognitions may be distorted such that the elder has expectations that are not realistic, over-generalizes or over-acts to adverse events and personalizes events. Thus, in reaction to a negative life event (loss of a loved one, move into a nursing home, etc.), an individual’s cognitive style may increase the likelihood of a depressive episode.

A developmental theory of ageing, the disengagement theory of ageing,140 contends that there is a mutual social and affective withdrawal between the older adult and their social environment. Similarly, gerotranscendence141 is a concept in which the older individuals are thought to narrow their personal social world and to have a decreased investment in activities that were once important in younger years. Others have conceptualized this withdrawal as a subtype of geriatric depression that has been termed depletion.142 Some have attempted to couple the theory of social disengagement with ageing (much debated in the literature) with depression, suggesting that some symptoms of depression, such as lack of social interest and greater self-involvement, mirror attributes of older adults according to disengagement theory.143, 144 Other factors being equal, it is probable that elders who are less socially engaged are more depressed. For example, elders who stopped driving had a greater risk of worsening depressive symptoms.145 A more recent yet controversial theory complements the depletion theory, suggesting that successful ageing is associated with ‘selective optimization with compensation’.146 This model is based on the recognition by the elder of the realities of ageing, especially the losses. Such recognition leads to the selection of realistic activities, optimization of those activities and compensation for lost activities, which in turn leads to a reduced and transformed life. More recently, socioemotional selectivity theory147, 148 posits that decreasing rates of social contact reflect a greater selectivity in social partners.

Social engagement is a key concept related to depression and the association between late-life depression and impaired social support has been established for many years. Poor social support is strongly associated with depression in the elderly.149, 150 The quality of social support networks has been identified as an important factor in predicting relapse in depressive episodes and future levels of depressive symptoms.151, 152 Further, among the elderly, social support may serve as a buffer against disability,153 while social disengagement may be a risk factor for cognitive impairment.154

Perceived negative interpersonal events are associated with depression among individuals in general and also among elders, particularly in those who demonstrate a high need for approval and reassurance in the context of interpersonal relationships. While social support has been found to be critical in buffering an individual against depression, ironically the interpersonal behaviours of individuals who become depressed are often associated with the withdrawal of social support from friends and family.155

The diagnostic workup of late-life depression derives predominantly from what we know about symptom presentation and aetiology. The diagnosis is made on the basis of a history augmented with a physical examination and supplemented with laboratory studies. Importantly, there is no biological marker or test that creates the diagnosis of depression. However, for some subtypes of depression, such as vascular depression, the presence of subcortical white matter hyperintensities on MRI scanning are critical to confirming the diagnosis.135, 156

There are several standardized screening measures for depression that are often used by primary care physicians.157 Examples of such instruments include the Geriatric Depression Scale (GDS) and the Center for Epidemiologic Studies Depression Scale (CES-D).13, 158, 159 Screening in primary care is critical. Not only is the frequency of depression high, but also suicidal ideation can be detected by screening.

Despite the centrality of the clinical interview, other diagnostic tools must be employed to assess the depressed elder. Cognitive status should be assessed with the Mini Mental State Examination (MMSE) or a similar instrument, given the high likelihood of comorbid depression and cognitive dysfunction.57 Height, weight, history of recent weight loss, laboratory tests for hypoalbuminaemia and cholesterol are markers of nutritional status and are critical given the risk for frailty and failure to thrive in depressed elders, especially the oldest of old.34, 160 General health perceptions and also functional status (ADLs) should be assessed for all depressed elderly patients.161, 162 Assessment of social functioning,163 medications (many prescribed drugs can precipitate symptoms of depression), mobility and balance, sitting and standing blood pressure, blood screen, urinalysis, chemical screen (e.g. electrolytes, which may signal dehydration) and an electrocardiogram if cardiac disease is present (especially if antidepressant medications are indicated) round out the diagnostic workup.

Differential Diagnosis of Depression and Dementia

Dementia and depression have considerable symptom overlap.63b Hence distinguishing between late-life depression and depressive disorders in the elderly is one of the more challenging problems facing healthcare professionals.164 There are a cluster of cognitive deficits that are common to both dementia and depression. Memory impairment is the most frequent shared symptom.135, 165 In addition, apathy is a common symptom among individuals with dementia, including those with and without comorbid depression, and also among non-demented elderly individuals with depression.166

As described elsewhere (Ref, 135, pp. 230–2), clinicians often have difficulty in their attempt to distinguish a primary mood disorder from other problems associated with depressed mood, in particular with what some have referred to as ‘pseudodementia’ (Ref. 135, pp. 349–72). Pseudodementia is a syndrome in which dementia is mimicked, but the underlying cause is a psychiatric disorder which is typically, but not always, depression.167

Memory problems accompanying depression in older age may be present and similar in form to symptoms of dementia. However, depressed elderly patients (without dementia) tend to focus on their memory problems. In contrast, patients with dementia are typically unaware of the extent and severity of their cognitive dysfunction and use strategies to conceal their cognitive dysfunction from others. Wells167 compared the clinical features of patients with pseudodementia with those with true dementia and found that among the patients who present with depression and cognitive impairment, those who were eventually diagnosed with dementia were more likely to exhibit motivation-related symptoms, such as disinterest, low energy and concentration difficulties.

Biological

Evidence-based guidelines for the prevention of new episodes of depression are available, as are care-delivery systems that increase the likelihood of diagnosis and improve the treatment of late-life depression. However, in North America, public insurance covers these services inadequately.168

There is clear and mounting evidence for the efficacy of antidepressant medications (both alone and in combination with psychotherapy) in the treatment of older adults with major depression and also for the treatment of dysthymia.3 Antidepressant medications have become the foundation for the treatment of moderate to severe depression in older adults.1