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Published Online: 7 February 2022

Chapter 1. Introduction to Late-Life Depression

Art Walaszek, M.D.Authors Info & Affiliations

Publication: Late-Life Depression and Anxiety

https://doi.org/10.1176/appi.books.9781615379736.lg01

PRÉCIS

Depression is not a normal part of aging. But depression is common among older adults, and it is distressing, disabling, and sometimes fatal. Older adults with depression follow one of these clinical courses: earlier onset of major depressive disorder or bipolar disorder, with recurrence or chronicity into older adulthood; subclinical depression or anxiety through early adulthood or midlife, worsening into clinical depression in late life; or late-life onset of depression that is either a risk factor for or harbinger of dementia. A number of biological, psychosocial, cultural, and spiritual factors contribute to the development of late-life depression. Depression can manifest differently in older adults, including more somatic concerns, subtle psychotic symptoms (such as delusional guilt), and greater cognitive impairment—in fact, there is a strong two-way relationship between depression and dementia. Many older adults with depressive symptoms do not meet criteria for major depressive disorder but can still have significant dysfunction and worse outcomes. Whereas bereavement and grief are universal experiences, depression is pathological and can be clinically distinguished from grief. Late-life depression is associated with a number of negative outcomes, including suicide, increased all-cause and cardiovascular mortality, onset of or exacerbation of various medical conditions (e.g., stroke), disability, and caregiver burden. Comorbidities are common and include anxiety, dementia, substance use disorders, personality disorders, sleep disorders, and frailty. Thus, it is critical that clinicians assess for and address depression and associated conditions in older adults.

Public Health Impact of Late-Life Depression

The concept of depression dates back to Hippocrates, who defined melancholia, an ancient incarnation of depression, as “when fright or despondency lasts for a long time” (Scholtz 1941). Thomas Burton, a seventeenth-century cataloger of the disease and a sufferer himself, metaphorically linked melancholy and aging, referring to the former as “a kind of dotage” (Burton 2001, p. 169). Although Emil Kraepelin’s major diagnostic contribution to modern psychiatry was distinguishing manic-depressive insanity (bipolar disorder or recurrent major depressive disorder in the parlance of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition [DSM-5]; American Psychiatric Association 2013) from dementia praecox (schizophrenia), he also introduced involutional melancholia, that is, depression that arises later in life (Hirshbein 2009). Kraepelin described people suffering from involutional melancholia as having been free of psychiatric illness until involution—that is, menopause in women or a comparable age in men. American psychiatrists included involutional melancholia in their first diagnostic manual in 1918 and continued to diagnose patients with this condition well into the twentieth century, strongly linking aging with depression (Hirshbein 2009). Although DSM-5 does not include involutional melancholia, the false public perception that aging inevitably leads to depression remains pervasive.

Aging and depression are not synonymous. In fact, the prevalence of major depressive disorder (MDD) is lower in late life (roughly 65 years and older) than during midlife (Byers et al. 2010). Psychological well-being, resilience to adversity, an arc toward wisdom, and continued capacity for gratifying relationships are the norm in older adults.

When MDD does occur, it can be distressing, disabling, and even deadly for older adults. Late-life depression (LLD) has been associated with loss of quality of life, functional decline, increased mortality from comorbid medical conditions, and suicide (Fiske et al. 2009). (From here on, I use the term LLD when referring to depression in older adults in general and MDD when referring to the specific DSM diagnosis of major depressive disorder; people with LLD meet DSM criteria for MDD.) Depressed older adults, compared with older adults who are not depressed, are more likely to visit primary care, be hospitalized, and seek help within the home (e.g., nursing care, meals on wheels) (Luppa et al. 2012a). Depression in older adults is also associated with higher medical costs as compared with older adults without depression, including increased cost of outpatient care, inpatient care, emergency care, and medications (König et al. 2019). Severity also matters: health care costs, including the cost of informal caregiving for depressed elders, are higher in those with severe depression compared with those with mild depression (Luppa et al. 2012a). LLD contributes to and complicates other geriatric syndromes, including dementia, stroke, cardiac disease, falls, chronic pain, and frailty—in fact, LLD is one of the core geriatric syndromes affecting the quality of life and functioning of older adults and their caregivers. The number of older adults worldwide is projected to increase from 962 million in 2017 to 2.08 billion in 2050; therefore, clinicians should expect to see more cases of LLD over time (United Nations, Department of Economic and Social Affairs, Population Division 2017).

Older adults are more likely to seek mental health care from a primary care provider than from a mental health specialist (Fiske et al. 2009), but primary care providers have limited time to discuss mental health issues (median time of 2 minutes; Tai-Searle et al. 2007) and might easily miss the diagnosis. Further, older adults with depression may present with somatic symptoms such as fatigue, headache, or gastrointestinal distress, delaying the recognition of underlying LLD (Niles and O’Donovan 2019). Despite a number of public health and clinical interventions to promote the detection of LLD (e.g., U.S. Preventive Services Task Force recommendations for screening for depression), many elders with depression remain undiagnosed or undertreated (Rhee et al. 2018).

Ethnic and sexual minority elders face even more challenges. Compared with white older adults, ethnic minority elders are less likely to have their depression recognized, be prescribed antidepressants, or receive specialty mental health care and are more likely to have poorer outcomes (Mansour et al. 2020). Lesbian, gay, bisexual, transgender, and queer (LGBTQ+) elders may have experienced discrimination and threats to their safety for most of their lives, possibly preventing them from receiving appropriate mental health care (Yarns et al. 2016). We cover these topics in greater detail in Chapter 3, “Assessment of Late-Life Depression and Anxiety,” and Chapter 6, “Comprehensive Cultural Assessment of the Older Adult With Depression and Anxiety.”

Etiology of Depression

Understanding the clinical types of depression in late life is important for predicting clinical course and for choosing appropriate treatment. Clinical subtypes of depression in this older population include the following:

Major depressive disorder that arises in adolescence or early adulthood, likely has significant genetic and developmental roots, and then either recurs repeatedly as the person ages or becomes a chronic condition

Bipolar disorder that arises in early adulthood, likely has significant genetic and other biological causes, and then persists into late life, perhaps with more frequent mood episodes over time

Subclinical depression or anxiety that is present throughout early adulthood and midlife but is not disabling or even necessarily distressing but then emerges as clinically significant depression as the person ages

Major depressive disorder that arises in late life in a person with no prior psychopathology and either puts that person at high risk of developing a neurocognitive disorder or represents the prodrome of a neurocognitive disorder

Depression that arises after the onset of a neurodegenerative disorder (Alzheimer’s disease, Parkinson disease) or cerebrovascular disease, likely due to dysfunction of neural circuitry involved in emotion regulation compounded by psychological distress, and whose symptoms overlap with those of the syndrome of apathy

We might label the latter two subtypes as late-onset depression, a neuropsychiatric condition that is likely etiologically distinct from the first three presentations. Bearing in mind these manifold manifestations of LLD, we present multiple models of how depression can arise in older adults (for a synthesis, see Figures 1–1, 1–2, and 1–3).

Figure 1–1. Life course of late-life depression.

Figure 1–2. Mechanisms of late-life depression.

Figure 1–3. Neural networks involved in late-life depression.

NEUROBIOLOGY

LLD may arise from disruption of the neural circuitry involved in emotion regulation, especially frontal-executive and corticolimbic circuits (Rashidi-Ranjbar et al. 2020). Various networks are thought to be involved in emotion regulation, including the default mode network, an executive control network, and a network involved in reward and reinforcement (Kupfer et al. 2012). These networks include parts of the prefrontal cortex (e.g., the dorsolateral prefrontal cortex), hippocampus, amygdala, posterior cingulate cortex, and white matter tracts connecting these and other structures (see Figure 1–3). Anhedonia may arise from abnormalities in the reward network, executive dysfunction may arise from abnormalities in the executive control network, and rumination may arise from abnormalities in the default mode network.

Cerebrovascular disease, especially ischemic changes in white matter, is a primary cause of this disruption of neural circuitry (Alexopoulos 2019). Location of disease in white matter and extent of white matter disease have been associated with LLD, especially late-onset depression. Persons with LLD have been found to have decreased resting cerebral blood flow in the frontal lobes. Vascular risk factors in midlife, including hypertension and diabetes, are also risk factors for LLD. This strong link between cerebrovascular disease and depression has led to the construct of vascular depression, discussed in greater detail in the subsection “Vascular Depression.”

The high rate of depression in persons with Alzheimer’s disease and Parkinson’s disease suggests that neurodegeneration affects not only cognition but also emotional functioning. Several Alzheimer’s disease biomarkers (e.g., burden of amyloid plaques in the frontal cortex and hippocampus) have been associated with depression in older adults with and without dementia (Alexopoulos 2019). Depression, especially late-onset depression, may be a risk factor for dementia and for progression from mild cognitive impairment to dementia, suggesting a two-way relationship between dementia and depression; we discuss this in greater detail below.

Peripheral inflammatory markers have been associated with LLD, suggesting a pathway from aging to peripheral inflammation to central nervous system inflammation to depression (Martínez-Cengotitabengoa et al. 2016; Miller et al. 2013). For example, a large longitudinal study measured an inflammatory marker, C-reactive protein (CRP), in midlife, 7 years later, and another 14 years later, at which time depressive symptoms were also assessed; elevated CRP at two or more time points was associated with LLD (Sonsin-Diaz et al. 2020). This link raises the possibility of anti-inflammatory approaches to preventing or treating depression.

LLD has low to moderate heritability (14%–55%), suggesting a modest role for genetic factors (Tsang et al. 2017). Elders with early-onset depression are more likely to have a family history of depression than do those with late-onset depression (Gallagher et al. 2010). However, most genetic studies of LLD have not distinguished between early-onset and late-onset depression, making it hard to figure out how much of the genetic contribution to LLD is mediated by depression earlier in life. Carriers of the e4 allele of the APOE gene, an allele associated with increased risk of Alzheimer’s disease, may also be at slightly increased risk of LLD (Tsang et al. 2017). Cognitively intact elders with depression who are APOE ε4 carriers may be at higher risk for cognitive decline (Morin et al. 2019). Note that most subjects in the APOE studies have been non-Hispanic white people, limiting generalizability. Polymorphisms involving genes encoding neurotrophins such as brain-derived neurotrophic factor (BDNF) have also been associated with LLD (Miao et al. 2019; Tsang et al. 2017). In younger populations, carrying the S allele of SLCA64 (which results in less transcription of serotonin transporter) moderates the relationship between stressful life events and depression; the same polymorphism confers a slightly increased risk of LLD (Tsang et al. 2017). Depression has been associated with telomere shortening, a marker of cellular aging (Ridout et al. 2016).

Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is a hallmark of depression in younger adults. Older adults with depression can have either hypocortisolemia or hypercortisolemia, with the latter possibly associated with smaller hippocampal volumes (Bremmer et al. 2007; Geerlings and Gerritsen 2017). Women who undergo menopause later (i.e., have greater exposure to estrogen) have a lower risk of subsequently developing depression, even among women with a history of premenopausal depression (Georgakis et al. 2016). Estrogen has antidepressant and neuroprotective properties, although perhaps only during the perimenopausal period because estrogen has not been found to be effective for depression in women after menopause (Georgakis et al. 2016). The literature on the relationship between low testosterone and depression in older men is mixed (Walther et al. 2019).

Aside from neurodegenerative disorders, stroke, hypertension, and diabetes, other medical conditions have been associated with LLD. These conditions include coronary artery disease (including myocardial infarction), chronic pain, arthritis, hearing loss, vision loss, sleep apnea, cancer, thyroid disease, hyperhomocysteinemia, and vitamin B₁₂ deficiency (Aziz and Steffens 2013; Kerner and Roose 2016). This list becomes especially pertinent when we seek to identify reversible causes of depression in our patients, which we cover in Chapter 3. A number of medications have been associated with LLD, including steroids, β-blockers, benzodiazepines, opioids, and antiparkinsonian agents (Aziz and Steffens 2013). (Note that some of these medications can also cause euphoria or mania, in particular steroids and antiparkinsonian agents.) Excessive use of alcohol, benzodiazepine use disorder, and opioid use disorder have been associated with LLD (Wu and Blazer 2014).

PSYCHOSOCIAL, PSYCHOLOGICAL, AND PERSONALITY FACTORS

For a comprehensive review, readers are referred to incisive articles by Areán and Reynolds (2005) and Laird et al. (2019). Table 1–1 summarizes the findings from these reviews. In general, older adults experience a number of stressful life events, most notably the deaths of a partner and other loved ones, which in turn may result in loss of social supports and loneliness. Some stressors may be somewhat unique to aging, such as the loss of driving privileges due to physical or cognitive decline, which has been associated with a doubling of the risk of depression (Chihuri et al. 2016). The stressors do not have to be recent: older adults who had experienced one or more adverse childhood experiences (ACEs), especially those with low perceived social support, are at higher risk of LLD (Cheong et al. 2017). Older women, ethnic and racial minority elders, and sexual minority elders may continue to face sexism, racism, homophobia, and transphobia as they age. Increased living expenses while on a fixed income, neighborhood crime, food insecurity, and problems with access to and affordability of medical care may contribute to depression. Like younger adults, older adults may have a number of maladaptive personality traits and coping strategies that precipitate or perpetuate depression. Conversely, resilience may be protective (Laird et al. 2019).

TABLE 1–1. Psychosocial and psychological contributors to late-life depression

Stressful life events

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Interpersonal loss and bereavement

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Social isolation and decreased emotional support

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Medical illness and associated burden and disability

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Trauma, including interpersonal violence and fear of violence

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Role transitions (e.g., retirement)

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History of adverse childhood experiences

Socioeconomic factors

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Low income, difficulty affording medications, poor access to medical care

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Problems with transportation (e.g., following loss of driving privileges)

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Racism, sexism, homophobia, transphobia

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Stigma regarding mental illness and ageism

Personality factors

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Passive coping style (e.g., avoidance)

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Harm-avoidant or behaviorally inhibited temperament

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Insecure attachment

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Low extroversion, high neuroticism, low conscientiousness

Beliefs and values

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Low self-esteem

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Internalized mental illness stigma

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Negative stereotypes about aging

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Loss of sense of meaning and purpose

Source. Adapted from Areán and Reynolds 2005; Cheong et al. 2017; Laird et al. 2019.

In my practice, I have found older adults’ despair about a perceived loss of meaning and purpose to be an especially powerful and difficult-to-address component of LLD. For a more in-depth review of the role of meaning and purpose in psychological well-being, cognition, and survival, I recommend reading the section “Capacity Assessment” in Chapter 6.

It is helpful to understand how the psychology of LLD informs evidence-based psychotherapy (Kiosses et al. 2011). For example, the recognition that grief, loneliness, role transitions (e.g., retirement, becoming a caregiver), interpersonal skills deficits, and interpersonal conflicts can contribute to depression forms the basis of interpersonal psychotherapy. Cognitive-behavioral therapy seeks to address negative dysfunctional thoughts, distorted perceptions and beliefs, and the withdrawal or inactivity that accompany depression. Because cognitive impairment and executive dysfunction can accompany depression in older adults, problem-solving therapy focuses on “teaching patients skills for improving their ability to deal with specific everyday problems and life crises . . . . Patients identify problems, brainstorm different ways to solve their problems, create action plans, and evaluate their effectiveness in implementing the best possible solution” (Kiosses et al. 2011).

CULTURAL AND SPIRITUAL FACTORS

We devote Chapter 6 to a comprehensive review of cultural and spiritual factors in the care of older adults with depression and anxiety. Here we discuss the roles of culture and spirituality in contributing to LLD. Please note that I use the ethnic/racial terminology used in the original papers.

Culture refers to “a set of shared symbols, beliefs and customs that shapes individual and/or group behavior” (Dilworth-Anderson and Gibson 2002). Culture influences how people define a mental health problem, how they perceive the cause of the problem, how they cope with the problem, and whether and how they seek help for the problem (Aggarwal 2010). A tool such as the DSM-5 Cultural Formulation Interview, discussed in Chapter 6, can help the clinician better understand the role of culture in an elder with depression.

Culture may affect how depression manifests in older adults. For example, Black African, Caribbean, and South Asian elders in the United Kingdom are less likely to report guilt, hopelessness, and suicidal ideation than are White British elders. This could reflect a different presentation of LLD (fewer affective, more somatic symptoms) or lower acceptability of reporting such symptoms (Mansour et al. 2020).

The experience of being an ethnic minority or immigrant may contribute to developing LLD. Being an older adult who immigrated may be protective against depression (e.g., because of the healthy migrant effect, the hypothesis that the immigration process selects for more psychologically resilient people) or a risk factor (e.g., because of loss of power or status within the new culture) (Mansour et al. 2020; Sadavoy et al. 2004). Among immigrants to Western nations, intergenerational conflict over traditional versus Western-based values may serve as a stressor contributing to depression (Sadavoy et al. 2004). For example, Asian elders may feel disappointment in their adult children with respect to filial piety, “the spirit and principle of being considerate and respectful toward one’s parents and older family members”: Asian older adults’ satisfaction with their children’s filial piety is correlated with lower level of depression (Wu et al. 2018, p.370). Latinx elders may have expectations regarding familismo, the “intergenerational obligation, respect, and the duty to care for aging parents” (Wu et al. 2018, p.376).

Language barriers and challenges navigating social and medical systems may contribute to social isolation, in turn a risk factor for LLD (Sadavoy et al. 2004). Elders of various cultural backgrounds may view depression as a personal or familial matter not requiring a medical intervention (Flores-Flores et al. 2020; Ward et al. 2014). Ethnic minority elders may face challenges with respect to accessing linguistically and culturally appropriate services and are less likely to receive appropriate treatment, including antidepressants and psychotherapy (Mansour et al. 2020; Sadavoy et al. 2004). African American and other ethnic minority elders in the United States experience psychological distress as a result of racism, discrimination, prejudice, and poverty (Conner et al. 2010). African American elders are less likely to seek treatment for depression than are white elders because of mistrust of the health care system, stigma about mental illness, and alternative methods of coping (e.g., religious practices) (Conner et al. 2010). Depressed Black elders are 61% less likely to receive any depression treatment than are non-Hispanic white elders (Vyas et al. 2020).

In general, religion and spirituality have been associated with reduced risk of depression. There is some evidence that religious practices (such as attendance at religious services and prayer) are more protective against LLD than are religious beliefs alone (Laird et al. 2019). Spirituality may be especially important with respect to addressing LLD. For example, older African Americans may be more likely to turn to religious counsel (e.g., clergy) and may wish to incorporate religious practices into treatment of depression (Pickett et al. 2013).

We cover social determinants of health in Chapter 6.

Epidemiology of Depression

The prevalence of depression in older adults is around 5%–10%. Estimates across epidemiological studies vary, depending on how depression is defined (namely, using DSM-5 criteria [categorical] vs. using a rating scale with a cutoff score [dimensional]), on the population studied (e.g., some samples include older adults residing in nursing homes), and on which measure of prevalence is used (lifetime, 12-month, or point prevalence). Older adults with depressive symptoms may suffer from MDD (discussed in the following paragraphs) or from subsyndromal depression (sometimes also referred to as minor depression, discussed further in the subsection “Persistent Depressive Disorder (Dysthymia)”).

In general, the prevalence of MDD is lower among older adults than among younger adults and seems to decrease with age among older adults, although not all studies agree on the latter point. It is not clear why rates of depression are lower in older adults than younger adults. Possible explanations include cohort effects (i.e., current older adults had lower rates of depression as younger adults than do current younger adults), survivor effect (i.e., middle-age people with mood disorders are less likely to live into late life or are less likely to be ascertained because they become institutionalized), and methodological issues (e.g., older adults may have more difficulty recalling symptoms or may be less likely to report them) (Byers et al. 2010). The prevalence of MDD and depressive symptoms has uniformly been found to be higher among older women than older men. Relative rates of depression among ethnic minority elders have varied from study to study.

The National Comorbidity Survey Replication (NCS-R) examined the rates of depression among community-dwelling Americans 60 years and older. The lifetime prevalence of DSM-IV-defined MDD and dysthymia were 10.6% and 1.3%, respectively—lower than rates found in 18- to 59-year-old subjects (American Psychiatric Association 1994; Kessler et al. 2005). As would be expected, using 12-month prevalence yields lower rates than using lifetime prevalence. The 12-month prevalence of MDD in the NCS-R declined with age: ages 55–64, 6.2%; ages 65–74, 3.1%; ages 75–84, 1.1%; ages 85 and older, 1.8% (Byers et al. 2010). Older women had higher 12-month prevalence of mood disorders (including MDD, dysthymia, and bipolar disorder) than did older men (6.4% vs. 3.0%) (Byers et al. 2010). Comorbidity was common, with a 12-month prevalence of both a mood and an anxiety disorder of 3%.

The worldwide numbers are somewhat different, with higher rates of depression reported. A meta-analysis of 24 epidemiological studies from around the world estimated that the pooled point prevalence of MDD in adults 75 and older is 7.2% (95% CI, 4.4–10.6%), with higher rates for women than men; the lowest rates were in North America (Luppa et al. 2012b). When depression was defined dimensionally (i.e., using rating scales rather than diagnostic criteria), the pooled point prevalence was higher: 17.1% (95% CI, 9.7–26.1%). Note that this meta-analysis included studies of older adults residing in nursing homes, which may help explain the higher prevalence than in NCS-R, which included only community-dwelling older adults. See below for further discussion of depression among nursing home residents.

With respect to relationship status, the NCS-R data set yielded statistically significant differences in 12-month prevalence of mood disorder by marital status: divorced/separated/widowed, 6.6%; never married, 6.2%; married/cohabitating, 3.9% (Byers et al. 2010). Although the NCS-R study did not reveal significant differences in prevalence by years of education, other studies have found that lower educational attainment increases the risk of LLD (as will be discussed in greater detail in Chapter 6, section “Social Determinants of Late-Life Depression and Anxiety”).

Comparisons of rates of depression among older adults from various ethnic/racial groups have yielded conflicting results. Some studies have not found significant differences in prevalence of depression among ethnic/racial groups, whereas others have. For a detailed review of this literature, see Chapter 6, section “Ethnic and Racial Minority Elders.”

Clinicians should note that the prevalence of LLD is higher in clinical populations (e.g., in primary care or inpatient settings) than the numbers in other studies (e.g., Luppa et al. 2012b). Also, although most older adults reside in the community, others live in nursing homes and long-term care facilities, where the prevalence is also higher. In a meta-analysis of 32 studies conducted in nursing homes around the world, the prevalence of MDD in nursing home residents without dementia was found to be 18.9% (95% CI 14.8–23.8%) (Fornaro et al. 2020). An older meta-analysis that did not exclude residents with dementia found the prevalence of MDD to be 10% and prevalence of depressive symptoms to be 29% (Seitz et al. 2010). The prevalence of depression is especially high in persons with certain diagnoses (e.g., 42% in those with dementia due to Alzheimer’s disease; Zhao et al. 2016).

Rates of depression among LGBTQ+ elders are astonishingly high. At any given time, approximately 31% of LGB elders and 48% of transgender elders meet criteria for depression (Yarns et al. 2016).

As the population ages, the numbers of older adults experiencing homelessness and older adults who are incarcerated have been increasing. The prevalence of depression is 38.3% among homeless older adults and 25% among incarcerated older adults (Barry et al. 2017; Kaplan et al. 2019).

Clinical Presentation

As discussed in the section “Public Health Impact of Late-Life Depression,” the diagnosis of major depressive disorder (MDD) replaced involutional melancholia, regardless of the age of the patient. However, involutional melancholia included many symptoms that we recognize as present in LLD, especially when severe: apprehension and anxiety; confusion and other cognitive symptoms; delusions; and somatic symptoms such as headache, chest pain, and vertigo (Hirshbein 2009). Thus, MDD, as defined in DSM-5 (Box 1–1), paints only part of the picture of LLD. In this section, we review the many ways that depression manifests in older adults.

Box 1–1. DSM-5 Diagnostic Criteria for Major Depressive Disorder

Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.

Note: Do not include symptoms that are clearly attributable to another medical condition.

Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad, empty, hopeless) or observation made by others (e.g., appears tearful). (Note: In children and adolescents, can be irritable mood.)

Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation).

Significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day. (Note: In children, consider failure to make expected weight gain.)

Insomnia or hypersomnia nearly every day.

Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down).

Fatigue or loss of energy nearly every day.

Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick).

Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others).

Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.

The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

The episode is not attributable to the physiological effects of a substance or another medical condition.

Note: Criteria A–C represent a major depressive episode.

Note: Responses to a significant loss (e.g., bereavement, financial ruin, losses from a natural disaster, a serious medical illness or disability) may include the feelings of intense sadness, rumination about the loss, insomnia, poor appetite, and weight loss noted in Criterion A, which may resemble a depressive episode. Although such symptoms may be understandable or considered appropriate to the loss, the presence of a major depressive episode in addition to the normal response to a significant loss should also be carefully considered. This decision inevitably requires the exercise of clinical judgment based on the individual’s history and the cultural norms for the expression of distress in the context of loss.¹

The occurrence of the major depressive episode is not better explained by schizoaffective disorder, schizophrenia, schizophreniform disorder, delusional disorder, or other specified and unspecified schizophrenia spectrum and other psychotic disorders.

There has never been a manic episode or a hypomanic episode.

Note: This exclusion does not apply if all of the manic-like or hypomanic-like episodes are substance-induced or are attributable to the physiological effects of another medical condition.

Coding and Recording Procedures

The diagnostic code for major depressive disorder is based on whether this is a single or recurrent episode, current severity, presence of psychotic features, and remission status. Current severity and psychotic features are only indicated if full criteria are currently met for a major depressive episode. Remission specifiers are only indicated if the full criteria are not currently met for a major depressive episode. Codes are as follows:

Severity/course specifier	Single episode	Recurrent episode*
Mild (DSM-5 p. 188)	296.21 (F32.0)	296.31 (F33.0)
Moderate (DSM-5 p. 188)	296.22 (F32.1)	296.32 (F33.1)
Severe (DSM-5 p. 188)	296.23 (F32.2)	296.33 (F33.2)
With psychotic features** (DSM-5 p. 186)	296.24 (F32.3)	296.34 (F33.3)
In partial remission (DSM-5 p. 188)	296.25 (F32.4)	296.35 (F33.41)
In full remission (DSM-5 p. 188)	296.26 (F32.5)	296.36 (F33.42)
Unspecified	296.20 (F32.9)	296.30 (F33.9)

*For an episode to be considered recurrent, there must be an interval of at least 2 consecutive months between separate episodes in which criteria are not met for a major depressive episode. The definitions of specifiers are found on the indicated pages.

**If psychotic features are present, code the “with psychotic features” specifier irrespective of episode severity.

In recording the name of a diagnosis, terms should be listed in the following order: major depressive disorder, single or recurrent episode, severity/psychotic/remission specifiers, followed by as many of the following specifiers without codes that apply to the current episode.

Specify:

With anxious distress (DSM-5 p. 184)

With mixed features (DSM-5 pp. 184–185)

With melancholic features (DSM-5 p. 185)

With atypical features (DSM-5 pp. 185–186)

With mood-congruent psychotic features (DSM-5 p. 186)

With mood-incongruent psychotic features (DSM-5 p. 186)

With catatonia (DSM-5 p. 186). Coding note: Use additional code 293.89 (F06.1).

With peripartum onset (DSM-5 pp. 186–187)

With seasonal pattern (recurrent episode only) (DSM-5 pp. 187–188)

Source. Reprinted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, Arlington, VA, American Psychiatric Association, 2013. Copyright © 2013 American Psychiatric Association. Used with permission.

TYPICAL PRESENTATIONS

We begin by asking, what is depression? LLD is a sustained affective, cognitive, and behavioral syndrome that results in individuals having less ability to care for themselves and to engage in interpersonal relationships. The affective component of LLD has a negative valence that is experienced as discomfort or suffering; the predominant emotion is sadness, sometimes anxiety. People with depression also experience less positive affect, can lose pleasure and enjoyment in activities (i.e., anhedonia), and may not feel content or satisfied. The duration, intensity, and dysfunction of LLD distinguish it from the normal human emotion of sadness.

A person experiencing depression tends to have thoughts, beliefs, or cognitions that are inaccurate or incomplete:

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the belief that one is or not deserving of love

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the belief that one has done something wrong (regret or guilt); when severe, this belief can take on delusional intensity and can be complicated by hallucinations

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the belief that one is helpless or incapable of effective action

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hopelessness and the associated belief that life is not worth living (i.e., suicidal ideation)

Especially in older adults, depression is associated with cognitive impairment, including inattention, memory loss, and indecision.

The behaviors of depression include disturbances of core bodily functions: sleeping too much or too little; eating too much or too little; being withdrawn and inactive or being restless and purposelessly active; and somatization (e.g., nausea, headache, back pain). Depression increases the risk of suicidal behavior. Rarely, depression can result in catatonia.

The symptoms of depression result in distress, worse quality of life, and/or functional impairment. In older adults, we think about functioning in terms of instrumental activities of daily living (ADLs) and personal (or basic) ADLs (Katz 1983). Instrumental ADLs are higher-order functions described by the mnemonic SHAFT (University of Ottawa 2011):

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S = shopping for groceries, clothes, and other household items

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H = housekeeping

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A = accounting (i.e., managing one’s finances, including paying bills)

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F = food preparation

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T = transportation—not necessarily driving, but more broadly the ability to get around, whether by cab or bus or by driving oneself

Use the mnemonic DEATH to recall the list of basic or personal ADLs (University of Ottawa 2011):

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D = dressing oneself

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E = eating (i.e., feeding oneself)

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A = ambulating

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T = toileting

•

H = hygiene

LLD is a predictor of the onset of disability (the inability to carry out ADLs; Mendes de Leon and Rajan 2014), discussed below in the subsection “Disability.”

Older adults have a somewhat different pattern of depression symptoms than do younger adults. Older adults are more likely to endorse somatic symptoms (sleep disturbance, fatigue, psychomotor agitation or retardation) and less likely to endorse worthlessness or guilt and suicidal ideation than are younger adults; most but not all studies have found older adults more likely to report cognitive symptoms (poor concentration or memory) (Balsis and Cully 2008; Fiske et al. 2009). The prevalence of specific symptoms from the National Epidemiologic Survey on Alcoholism and Related Conditions (NESARC) study is presented in Table 1–2; this study included 1,808 community-dwelling older adults in the United States who had endorsed either low mood or anhedonia. Older adults with early-onset depression may be more likely to experience guilt and worthlessness than those with late-onset depression, although not all studies are consistent with respect to symptomatic differences between the two groups (Gallagher et al. 2010). There may be racial and ethnic differences in the symptoms of LLD, such as higher rates of rates of sadness, dysphoria, and psychomotor symptoms among Black and Hispanic elders (Vyas et al. 2020).

TABLE 1–2. Prevalence of specific symptoms in depressed older adults

Symptom	Prevalence
Low mood	92%
Anhedonia	68%
Weight or appetite change	58%
Sleep change	65%
Psychomotor agitation or retardation	33%
Fatigue	50%
Worthlessness or guilt	38%
Diminished concentration	51%
Thoughts of death or suicidal thoughts	31%
Source. National Epidemiologic Survey on Alcoholism and Related Conditions (adapted from Balsis and Cully 2008).

LLD tends to be episodic, with a remitting-relapsing course, although it can become chronic. Grief is especially common in older adults and shares many characteristics with LLD, except that a loss or other severe stressor does not necessarily precede an episode of depression and grief is usually not associated with significant dysfunction. (We spend more time on distinguishing grief from depression in the subsection “Depression and Grief”).

PSYCHOTIC DEPRESSION

Psychotic depression is a particularly severe form of LLD that is defined by the presence of delusions and/or hallucinations. The psychotic features are thought to be mood-congruent if their content includes “personal inadequacy, guilt, disease, death, nihilism, or deserved punishment” (American Psychiatric Association 2013, p. 186). Psychotic depression in older adults has been associated with frontal and temporal lobe atrophy, impairments in executive function and psychomotor speed, greater depression severity, poorer treatment response, and generally worse outcomes than in nonpsychotic depression (Gournellis et al. 2014).

Delusions are the hallmark of psychotic depression. The most common types of delusions are paranoia, somatic delusions, delusions of guilt, and the belief that one ought to be punished; somatic delusions are more common in older adults with depression than younger adults with depression (Gournellis et al. 2014). One-third of patients with psychotic depression have hallucinations, usually auditory (Gournellis et al. 2014). Psychotic depression is distinguished from schizophrenia and other psychotic disorders by the psychotic symptoms being present only when the patient is depressed. Clinicians should have a high index of suspicion for psychotic depression because treatment is different from that for nonpsychotic depression, including combining antidepressant and antipsychotic medication and earlier consideration of electroconvulsive therapy (for further discussion, see section “Pharmacological Interventions” in Chapter 5, “Management of Late-Life Depression and Anxiety”). A case example of psychotic depression is presented next.

CASE EXAMPLE 1: “I LOST MY MIND”

Mrs. Williams is a 72-year-old widowed, retired social worker with a history of MDD who presents with 3 months of withdrawing from activities, weight loss, low energy, and poor sleep. Her only prior episode of depression occurred 3 years ago, soon after her husband’s death, and resolved following treatment with sertraline and interpersonal psychotherapy. Recent medical evaluation (electrolytes, creatinine, hepatic enzymes, complete blood count, thyroid-stimulating hormone, vitamin B₁₂ level, erythrocyte sedimentation rate) was negative. Sertraline was resumed 2 months ago and titrated to 150 mg/day, without benefit—in fact, her depression has only worsened. Alarmed by her deterioration, her daughters urge her to seek a second opinion regarding her depression.

Today, Mrs. Williams’s chief complaint is “I lost my mind.” The clinician reassures her that she has not lost her mind but is instead suffering from a treatable mental health condition. However, she insists that she has lost her mind, so the clinician asks her to clarify. Mrs. Williams states that she no longer has a brain, and she requests an MRI to demonstrate this.

Mrs. Williams recounts more of her history: About 3 months ago, she felt a tingling sensation in her scalp. She found herself ruminating about it, could not concentrate on other tasks, and started falling behind on housework. She lay in bed at night, unable to fall asleep, worrying that she might die in the middle of the night. She lost interest in her hobbies, and she started canceling activities with her daughters and with her friends. She wondered if perhaps she had done something wrong—not eaten the right food, for example—and that was why her scalp tingled. She became terrified that she might eat the wrong food and started eating less; she has lost 25 pounds in 3 months. Eventually, she determined that the tingling in her scalp was due to her brain going missing, although she cannot explain how this might have happened. Once in a while, at night, she hears a voice whispering to her that she has lost her mind. She does not want to go on living like this, but at the same time she is afraid of dying and does not want to harm herself—“The Lord would send me straight to hell if I did that.” She does not endorse any religious, paranoid, or other delusions; other than the auditory hallucination of whispering and the possible tactile hallucination of scalp tingling, she does not endorse hallucinations. Mrs. Williams does not endorse any current or past manic symptoms, and there is no evidence of a substance use disorder. Bedside cognitive testing is slightly abnormal, with impairment in short-term memory.

The clinician diagnoses Mrs. Williams with MDD, recurrent, severe, with psychotic features, that is, psychotic depression. The clinician recommends psychiatric hospitalization and asks her to consider a course of electroconvulsive therapy.

CATATONIA

Catatonia is present in 18%–40% of patients admitted to a geriatric psychiatry inpatient unit, affecting about half of inpatient elders with depression in one study; depression was the most common cause (43%) of catatonia in this sample (Cuevas-Esteban et al. 2017). Catatonia is a severe behavioral syndrome whose features commonly include immobility and mutism but may also include agitation, catalepsy, waxy flexibility, negativism, posturing, mannerisms, stereotypies, grimacing, echolalia, and echopraxia (American Psychiatric Association 2013; Taylor and Fink 2003). Recognizing catatonia is critical because in older adults delayed treatment can result in adverse outcomes such as pneumonia, pulmonary embolus, physical restraint, misdiagnosis of dementia, and death (Swartz and Galang 2001).

BIPOLAR DEPRESSION

A full discussion of bipolar disorder is beyond the scope of this book; we provide only a brief review here. Bipolar I disorder includes episodes of mania, usually depression, and sometimes mixed states (features of both mania and depression). Bipolar II disorder is characterized by hypomanic and depressive episodes, with the latter being far more distressing and impairing. A medication (typically an antidepressant) or other substance may precipitate a manic episode with or without mixed features (in DSM-5 terms, substance/medication-induced bipolar disorder), or a manic episode could be due to another medical condition (formerly known as secondary mania but now referred to as bipolar and related disorder due to another medical condition).

The estimated prevalence of bipolar disorder among older adults is 0.5%–1.0%; it accounts for 6% of outpatient geriatric psychiatry visits and 8%–10% of inpatient geriatric psychiatry admissions (Sajatovic et al. 2015). As with MDD, people with bipolar disorder generally fall into two groups: those with early-onset bipolar disorder who have aged into older adulthood and those with onset after age 50 years (making up about 5%–10% of older adults with bipolar disorder) (Sajatovic et al. 2015). Early-onset illness tends to be associated with family history of mood disorders, more depressive and mixed episodes, and substance use, whereas late onset is associated with more cognitive impairment and medical comorbidity (Chen et al. 2017). The female-to-male ratio in bipolar disorder in older adults is about 2:1, compared with 1:1 in younger adults (Chen et al. 2017).

There are conflicting data regarding risk of recurrence of mood episodes in older adults with bipolar disorder. In one study following people with bipolar disorder and MDD up to 40 years after hospitalization, the risk of recurrence of bipolar disorder was twice as high as for MDD (0.4 vs. 0.2 episodes per year), with no change in frequency of episodes up to about age 70 (Angst et al. 2003). It is possible that antidepressants are less likely to “flip” an older adult with bipolar disorder into a manic or mixed episode compared with a younger adult (Chen et al. 2017). Older adults with bipolar disorder often have medical comorbidities (including metabolic syndrome, diabetes, hypertension, and cardiovascular disease) and, in one study, had life expectancy 10 years shorter than that of the general population (Sajatovic et al. 2015). Cognitive impairment is common (even when patients are euthymic), and bipolar disorder is a risk factor for the development of dementia (Ahearn et al. 2020).

The clinical presentation of bipolar disorder in older adults is similar to that in younger adults, except that hypersexuality, psychosis, anxiety, and suicide may be less common in older adults, although the latter is likely due to a survivor effect (Chen et al. 2017; Sajatovic et al. 2015). Misdiagnosis is common, and clinicians should maintain an index of suspicion of bipolarity in older adults who present with depression. Careful clinical history and family history are important. The onset of mania in late life raises the possibility of an organic disorder and necessitates a full medical workup that includes neuroimaging.

DEPRESSION IN DEMENTIA

Sadness is common among people with dementia, especially when they are aware of loss of cognition—in other words, an experience akin to grief. The functional impairment of dementia may itself contribute to feeling helpless, worthless, or hopeless. The pathophysiological changes that accompany the major causes of dementia—hippocampal degeneration in Alzheimer’s disease, dopaminergic dysfunction in Parkinson’s disease, and disruption of white matter tracts connecting the frontal lobes with the rest of the brain in vascular dementia—can also lead to depression. Figure 1–4 illustrates the relationship between dementia and depression; it should be noted that depression itself can contribute to cognitive impairment and may represent a reversible component of dementia.

Figure 1–4. Dementia as a cause of depression.

Depression is the second most common behavioral and psychological symptom of dementia (BPSD) overall (prevalence of 42%) and is the most common BPSD in mild dementia (25%) (Okura et al. 2010; Zhao et al. 2016). In 2002, a group of late-life depression and Alzheimer’s disease researchers proposed criteria for depression in Alzheimer’s disease (Olin et al. 2002). The prevalence of each criterion has been reported (Verkaik et al. 2009), and the criteria have been used in clinical trials of depression in Alzheimer’s disease (e.g., Munro et al. 2012). The criteria are as follows:

Clinically significant depressed mood (e.g., depressed, sad, hopeless, discouraged, tearful) (point prevalence of 90%)

Decreased positive affect or pleasure in response to social contacts and usual activities (i.e., a variant of the anhedonia typically seen in MDD) (59%)

Social isolation or withdrawal (presumably due to decreased ability to cope with social situations, as opposed to loss of pleasure) (55%)

Disruption in appetite (45%)

Disruption in sleep (19%)

Psychomotor changes (differing from the agitation or apathy commonly seen in dementia itself) (42%)

Irritability (note that this is not one of the DSM-5 criteria for major depressive disorder, but it is quite common in depression of Alzheimer’s disease) (64%)

Fatigue or loss of energy (61%)

Feelings of worthlessness, hopelessness, or excessive or inappropriate guilt (64%)

10.

Recurrent thoughts of death, suicidal ideation, suicide plan, or suicide attempt (33%)

For a diagnosis of depression of Alzheimer’s disease, a patient must have at least three of the above criteria, at least one of which must be the first or second criterion. A patient who had MDD well before the onset of Alzheimer’s disease may be considered to have recurrent MDD rather than depression of Alzheimer’s disease (Olin et al. 2002).

Distinguishing between depression and apathy (the most common BPSD) can be challenging; the following tips may be helpful: Guilt, worthless, and hopelessness are typically not present in patients with apathy (Walaszek 2019). Whereas patients with depression can be quite distressed, those with apathy may not be particularly bothered by their apathy; in fact, the family members of patients with apathy may be more frustrated with or distressed by the apathy than are the patients themselves (Walaszek 2019).

VASCULAR DEPRESSION

The observation of a strong relationship between cerebrovascular disease and LLD has led to the concept of vascular depression. People with vascular depression typically experience onset in late life, although exacerbation of early-onset depression is also possible (Alexopoulos 2019). The most common symptoms include psychomotor retardation, anhedonia, executive dysfunction, and poor insight into depression; guilt and family history of depression are less frequent than in patients with typical LLD (Alexopoulos 2019). The neurological signs associated with vascular depression vary and depend on the location and severity of ischemic changes—for example, patients with left temporal lobe stroke may have aphasia in addition to depression (Alexopoulos 2019).

A closely related concept is that of depression executive dysfunction syndrome. Disruption of frontal-subcortical networks leads to impairments in verbal fluency, inhibition, problem-solving, cognitive flexibility, working memory, and/or planning, in addition to anhedonia, psychomotor retardation, suspiciousness, and lack of insight (Alexopoulos 2019). My sense is that vascular depression and especially executive dysfunction syndrome represent syndromes that are actually closer to apathy (with respect to pathophysiology, presentation, and clinical course) than to what we would classically consider melancholic depression.

Why is this clinically relevant? When evaluating someone with late-onset depression, you should consider the possibility of underlying cerebrovascular disease, especially if the patient has not responded to antidepressants or psychotherapy. The prognosis of such patients is poorer, and other treatment options (e.g., psychostimulants, behavioral activation) may be more effective.

PERSISTENT DEPRESSIVE DISORDER (DYSTHYMIA)

Historically, dysthymia (or dysthymic disorder) represented a chronic syndrome of less intense depressive symptoms than seen with MDD. In DSM-5, persistent depressive disorder includes both dysthymia and chronic MDD. In addition to depressed mood, people with persistent depressive disorder experience at least two of the following: poor appetite or overeating, insomnia or hypersomnia, low energy or fatigue, low self-esteem, poor concentration or difficulty making decisions, or hopelessness (American Psychiatric Association 2013). Symptoms are present for at least 2 years, and no depression-free period lasts more than 2 months at a time. The symptoms cause clinically significant distress or functional impairment.

Most older adults with dysthymic disorder have onset of symptoms in late life (Devanand 2014). Family history of mood disorders is relatively uncommon, whereas bereavement, loss of social support, neurodegenerative disease, and/or cerebrovascular disease are prevalent (Devanand 2014).

MINOR DEPRESSION

Although the prevalence of DSM-diagnosable MDD is lower in older adults than in younger adults, depressive symptomatology is actually fairly common in older adults and can be associated with dysfunction and poorer quality of life. This observation has led to the interrelated constructs of minor depression, subsyndromal depression, and subthreshold depression—which may be two to three times more prevalent than major depression in older adults (Meeks et al. 2011). We will consider these together under the label of minor depression, the most commonly used term. In DSM parlance, this would be considered other specified depressive disorder, specifically, a depressive episode with insufficient (fewer than five) MDD symptoms.

About 8%–10% of older adults with minor depression convert to MDD each year; having minor depression roughly doubles (incidence rate ratio of 1.95) the risk of developing MDD (Lee et al. 2019; Meeks et al. 2011). Minor depression has been associated prospectively with suicidal ideation and behavior, increased cognitive impairment (including dementia), worse physical health, increased risk of disability, and increased health care utilization (Lee et al. 2019). Elders with minor depression have outcomes that are intermediate in severity compared with nondepressed elders and those meeting criteria for MDD (Meeks et al. 2011). Clinicians should be alert to minor depression as a marker for increased risk of development of MDD and other adverse outcomes.

DEPRESSION AND GRIEF

Bereavement, the loss of a loved one, is a universal experience. Grief is a normal emotional response to bereavement. The clinician caring for older adults faces two challenges: to not pathologize grief, while at the same time to not dismiss psychopathology as a normal part of aging. Acute grief can be quite distressing, is associated with physiological changes (e.g., sleep disturbance, increased cortisol, increased heart rate or blood pressure), and may increase the risk of myocardial infarction or Takotsubo cardiomyopathy (Shear 2015). Clinicians note that intense emotions of acute grief gradually wane, yet the patient’s sense of loss and of missing the loved one often persists. Adapting to the loss is the norm (Simon et al. 2020).

Pathological sequelae of bereavement include MDD, PTSD, and complicated grief. DSM-5 makes a significant point of describing how the manifestations of grief differ from the symptoms of MDD; I refer the reader to the notes to the DSM-5 criteria for MDD, which are summarized in Table 1–3. Bereavement is a severe stressful life event that can contribute to the development of a major depressive episode; grief is normal, but major depression is not.

TABLE 1–3. Distinguishing grief from depression

	Grief	Depression
Predominant emotions	Emptiness and loss	Depressed mood and anhedonia
Time course of emotions	Dysphoria decreases in intensity over days to weeks and occurs in pangs (waves) associated with thoughts or reminders of the deceased	Persistent; not tied to specific thoughts or preoccupations
Associated emotions	Positive emotions and humor may be present	Pervasive misery may be present
Thought content	Preoccupation with thoughts and memories of the deceased	Hopeless and pessimistic rumination
Cognitions about self	Self-esteem is preserved; if present, self-derogatory ideation refers to perceived failings with respect to the deceased	Worthlessness, self-loathing, self-critical thoughts
Thoughts of death	Focused on the deceased, including the possibility of “joining” the deceased	Suicidal ideation associated with feeling worthless, undeserving of life, or unable to cope with pain of depression
Hallucinations and delusions	Benign auditory or visual hallucination of the deceased or sensing the deceased’s presence	Paranoia, somatic delusions, delusions of guilt, or the belief that one ought to be punished; marker of psychotic depression
Source. American Psychiatric Association 2013.

PTSD can arise following the death of a loved one in a traumatic way (e.g., a motor vehicle accident) and may include guilt focused on the traumatic event or its aftermath and nightmares related to the traumatic event (Shear 2015). Detailed discussion of PTSD is beyond the scope of this chapter.

Complicated grief is a severe form of acute grief that lasts longer than expected (usually at least 6 months) given the person’s cultural and religious background and results in functional impairment (Shear 2015). It is estimated that complicated grief occurs in 10%–11% of adults bereaved by natural causes, with higher rates when the loved one died as a result of an accident, suicide, homicide, or disaster (Simon et al. 2020). Yearning and longing are core symptoms and are frequent and intense (Shear 2015). People with complicated grief may excessively avoid reminders of the loss and may angrily or guiltily ruminate about the circumstances or consequences of the death (Shear 2015). As of DSM-5-TR (American Psychiatric Association 2022), prolonged grief disorder is listed as a psychiatric diagnosis (Box 1–2). It is characterized by a maladaptive grief reaction that has persisted for at least 12 months after the death of a person who was close to the bereaved person. The core symptoms include intense yearning or longing for the deceased person and/or preoccupation with thoughts or memories of the deceased person. The International Classification of Diseases, 11th Revision (ICD-11) also includes prolonged grief disorder (Simon et al. 2020).

Box 1–2. DSM-5 Diagnostic Criteria for Prolonged Grief Disorder

The death, at least 12 months ago, of a person who was close to the bereaved individual (for children and adolescents, at least 6 months ago).

Since the death, the development of a persistent grief response characterized by one or both of the following symptoms, which have been present most days to a clinically significant degree. In addition, the symptom(s) has occurred nearly every day for at least the last month:

Intense yearning/longing for the deceased person.

Preoccupation with thoughts or memories of the deceased person (in children and adolescents, preoccupation may focus on the circumstances of the death).

Since the death, at least three of the following symptoms have been present most days to a clinically significant degree. In addition, the symptoms have occurred nearly every day for at least the last month:

Identity disruption (e.g., feeling as though part of oneself has died) since the death.

Marked sense of disbelief about the death.

Avoidance of reminders that the person is dead (in children and adolescents, may be characterized by efforts to avoid reminders).

Intense emotional pain (e.g., anger, bitterness, sorrow) related to the death.

Difficulty reintegrating into one’s relationships and activities after the death (e.g., problems engaging with friends, pursuing interests, or planning for the future).

Emotional numbness (absence or marked reduction of emotional experience) as a result of the death.

Feeling that life is meaningless as a result of the death.

Intense loneliness as a result of the death.

The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

The duration and severity of the bereavement reaction clearly exceed expected social, cultural, or religious norms for the individual’s culture and context.

The symptoms are not better explained by another mental disorder, such as major depressive disorder or posttraumatic stress disorder, and are not attributable to the physiological effects of a substance (e.g., medication, alcohol) or another medical condition.

Source. Reprinted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2022. Copyright © 2022 American Psychiatric Association. Used with permission.

Clinical Course

MDD tends to have a remitting-relapsing course, whereas dysthymic disorder is more chronic; a small subset of older adults may develop a steadily worsening course. Older adults with depression may experience a worse course than do younger adults with depression, including persistence of diagnosis of MDD or dysthymia, greater chronicity of symptoms, delayed time to remission, and worsening depression severity over time (Schaakxs et al. 2018). Many risk factors for worse trajectories of depression in older adults have been identified, including female gender; Black or Hispanic race/ethnicity; past psychiatric history of depression and/or anxiety; presence, number, and severity of medical conditions (e.g., ischemic heart disease, stroke, hypertension, diabetes mellitus, obesity, breast cancer); tobacco use; certain personality traits (e.g., avoidance coping, psychological inflexibility); lower educational level; severity of functional impairment; lack of social supports; and stressful life events (Musliner et al. 2016). Limitations in mobility (i.e., ability to do heavy housework, walk half a mile, and climb stairs) and adverse childhood experiences (in women) have also been associated with worse trajectories of LLD (Carrière et al. 2017). Interestingly, cognitive impairment has not been consistently identified as a predictor of a worse course of depression (Musliner et al. 2016).

In a primary care sample of older adults with MDD or dysthymia that had partially or fully remitted, 40% had recurrence of clinically significant depressive symptoms within a year (Katon et al. 2006). Predictors of relapse included severity of baseline depression and number of residual depressive symptoms at remission; for example, subjects with four residual symptoms had a 54% relapse rate versus 36% for those with only one residual symptom (Katon et al. 2006). The clinical implication is that a goal of treating depression in older adults should be complete remission of symptoms. In fact, persistence of depressive symptoms has been associated with a number of negative health outcomes, including increased mortality and increased risk of dementia, as discussed in the following section.

Consequences and Complications

A classic aphorism in geriatric psychiatry is that untreated depression in older adults can lead to a downward spiral of disability and worsening depression that culminates in death. In this section, we cover some of the consequences of LLD.

SUICIDE

Suicide is the topic of Chapter 4, “Suicide Risk Reduction in Older Adults,” and we very briefly summarize the chapter here. Age is a powerful predictor of suicide risk, with men 75 years old and older at the highest risk of dying from suicide (Figure 1–5) (Centers for Disease Control and Prevention 2020). Older adults are more likely than younger adults to choose lethal means (notably firearms) and are less likely to survive suicide attempts. Depression is the most common psychiatric diagnosis associated with suicide in older adults, although a significant proportion of older adults who die from suicide do not have a history of MDD. Interestingly, the risk of suicide does not appear to be higher in patients with dementia compared with elders without dementia, although the time immediately after the diagnosis of dementia is a period of higher risk of suicide (Seyfried et al. 2011). An essential part of the evaluation of any older adult with depression is conducting a suicide risk assessment, which is discussed in greater detail in Chapter 4.

MORBIDITY AND OTHER CAUSES OF DEATH

Older adults with depression are at heightened risk of dying from causes other than suicide. LLD is associated with a 34% increase in all-cause mortality and 31% increased cardiovascular mortality; for late-onset depression, the increases are 51% and 40%, respectively (Wei et al. 2019). In one cohort of 4,000 older adults with depression in the United Kingdom (mean age of 77 years), nearly 55% of subjects died within 3.5 years; predictors of mortality included older age, male gender, specific symptoms (cognitive impairment, apathy, lack of appetite), older age at diagnosis of depression, physical illness, impairments of ADLs, and (only in new-onset depression) depression severity (Cai et al. 2020). Another large cohort study of older adults, this time in Brazil, also found that LLD predicted mortality, although only in men; the authors estimated the population attributable risk of dying because of LLD—that is, the percentage of deaths that could be avoided if no one developed LLD—to be 8.5% (Diniz et al. 2014). Depression also increases the risk of death in patients with coronary heart disease and stroke. Possible explanations for the link between LLD and death include vascular disease; unhealthy behaviors such as tobacco use, binge drinking, or physical inactivity; poor adherence to medical treatment recommendations; or an inflammatory process (Wei et al. 2019).

Elders with depression are also at higher risk of developing coronary heart disease (or having another myocardial infarction), of having a stroke (or another stroke), of falling, of developing diabetes mellitus (or having worse diabetic course), of having more somatic symptoms (stomach problems, shortness of breath, dizziness, pain, and difficulties with eyesight) and of experiencing generally worse physical health (Fiske et al. 2009; Niles and O’Donovan 2019; Stubbs et al. 2016; Wu et al. 2019). Whether treating LLD has an impact on medical morbidity is unclear.

DISABILITY

LLD is a predictor of the onset of disability—that is, problems with carrying out personal or instrumental ADLs—with a roughly 40% increase in risk of developing disability among depressed elders compared with elders without depression (Mendes de Leon and Rajan 2014). The impact of depression on progression of disability is less clear, with conflicting evidence from various studies. The disability associated with LLD also leaves older adults less able to work and more likely to engage in unpaid family roles (e.g., babysitting grandchildren), with adverse financial implications (Snow and Abrams 2016; Zivin et al. 2013). Depression also contributes to physical frailty, which is discussed in greater detail in the subsection “Frailty and Failure to Thrive.”

IMPACT ON FAMILY AND OTHER CAREGIVERS

Because of decreased energy, motivation, and ability to carry out ADLs, older adults with depression may need to rely on family members and others for support. Compared with elders without depression, those with LLD receive up to 3 extra hours per week of informal caregiving (Zivin et al. 2013). This in turn takes an emotional and financial toll on caregivers. For example, family caregivers of elders suffering from depression are at higher risk of depression themselves, as well other negative health outcomes (Zivin et al. 2013). In 2016, the cost of unpaid caregiving of elders with either minor depression or MDD in the United States was estimated to be almost $13 billion (Snow and Abrams 2016). Strikingly, LLD can impact family members beyond direct caregivers: for example, young children living in the same household as a depressed elder have more problems with behavior, sleep, attention, and school (Zivin et al. 2013).

Comorbidities

LLD rarely manifests in isolation. About half of older adults with depression also have clinically significant anxiety; cognitive impairment is exceedingly common; excessive alcohol use and substance use disorders may complicate matters; and other medical conditions such as sleep disorders may be present. We provide an overview of these comorbidities next.

ANXIETY

Late-life anxiety is the other major topic of this book and thus will be covered extensively in Chapters 2, 3, 5, and 6. Here we briefly focus on the extensive comorbidity of depression and anxiety, both cross-sectionally and longitudinally. Up to half of elders with depression also have an anxiety disorder, and about one-quarter of those with anxiety also have depression (Beekman et al. 2000). Although much of the literature on this comorbidity specifically refers to generalized anxiety disorder (GAD), older adults with depression are more likely to have comorbid social phobia, panic disorder, and/or agoraphobia than GAD (van der Veen et al. 2015).

GAD tends to be chronic, with onset in early life for about half of older adults; in elders with both GAD and MDD, the onset of GAD usually precedes the onset of MDD (Lenze et al. 2005). Older adults with both depression and anxiety have worse outcomes than those with either one alone, including persistence of depressive symptoms, high rates of depression relapse, more cognitive decline, and higher risk of suicidal ideation or suicide (Lenze and Wetherell 2011). We go into greater detail about the comorbidity between depression and anxiety, including theories about why the two are so highly comorbid, in Chapter 2, “Introduction to Late-Life Anxiety and Related Disorders,” subsection “Depression.”

COGNITIVE IMPAIRMENT AND DEMENTIA

Cognitive impairment and neuropsychological deficits are common in depression and can be so severe as to mimic dementia—a construct sometimes referred to as pseudodementia (Brodaty and Connors 2020). Cognitive impairment may persist even after successful treatment of LLD, and depression roughly doubles the risk of dementia (Cherbuin et al. 2015).

Both early-onset and late-onset depression are associated with later cognitive impairment or development of dementia. In one large longitudinal study, compared with subjects with no depression, elders who had midlife depressive symptoms were 20% more likely to develop dementia, those with late-onset depression were 70% more likely, and those with depressive symptoms in both midlife and late life were 80% more likely (Barnes et al. 2012). In general, late-onset depression appears to be associated with a higher risk of cognitive decline than early-onset depression. For example, the Whitehall II study, which followed British civil servants over 28 years, found that people who went on to develop dementia were more likely to be depressed 11 years prior to the diagnosis of dementia but not earlier; at the time of diagnosis, people with dementia were 9 times more like to be depressed than were those without dementia (Singh-Manoux et al. 2017). However, it should be noted that at least one study found the opposite, namely, a higher risk of dementia with early-onset depression (Riddle et al. 2017).

The trajectory of symptoms may make a difference, too: for example, older adults with a pattern of “high and increasing” depression symptoms (greater depression severity at baseline, followed by increasing severity over the course of 5 years) have twice the risk of developing dementia than do those with minimal or moderate symptoms (Kaup et al. 2016). The risk that depression confers may be higher for vascular dementia than for dementia due to Alzheimer’s disease (Diniz et al. 2013). Depression results in increased risk of progression from mild cognitive impairment (mild neurocognitive disorder) to dementia (major neurocognitive disorder) (Dafsari and Jessen 2020). It is possible that LLD represents a modifiable risk factor for dementia, accounting for 4% of the population-attributable fraction of dementia risk (Livingston et al. 2020).

The exact nature of the relationship between depression and dementia remains unclear, with evidence supporting each of the following possibilities:

•

The pathophysiology of recurrent MDD (e.g., HPA axis dysfunction or dysfunctional neural networks) leads to or exacerbates the pathologies that lead to dementia.

•

Behaviors associated with recurrent MDD (e.g., substance use, physical inactivity, poor health habits) lead to or exacerbate the pathologies that lead to dementia (e.g., cerebrovascular disease).

•

MDD, in particular late-onset depression, that arises prior to dementia reflects an early clinical manifestation of underlying pathology (i.e., cerebrovascular disease or neurodegenerative disease) that will eventually lead to dementia.

•

Depression that arises after the onset of dementia is due to the pathological changes associated with dementia and/or represents a psychological reaction (grief) to memory loss, as discussed earlier in the subsections “Neurobiology” and “Vascular Depression.”

•

MDD and dementia are not causally related but instead have shared risk factors (e.g., genetic liability, social determinants of health, chronic medical problems).

•

Depression causes cognitive impairment during a depressive episode but otherwise is not associated with dementia.

These hypotheses are not mutually exclusive, and in a large heterogeneous population of people with depression and dementia, all could be true. Clinicians should take away the following from this discussion: 1) older adults with depression may have significant cognitive impairment, such that they appear to have dementia; 2) when assessing and caring for patients with dementia, it is important to keep in mind the possibility of depression, a potentially reversible cause of impairment; 3) elders experiencing their first episode of depression are at markedly higher risk for developing dementia. The following case illustrates these points further.

CASE EXAMPLE 2: “IT’S JUST NOT LIKE HIM TO FORGET TO PAY HIS BILLS”

Mr. Rodríguez is a 68-year-old retired accountant whose family has become increasingly concerned about his memory and behavior. His two adult daughters first noticed a change 8 months ago, soon after his wife died from ovarian cancer. He stopped showing interest in his usual activities, went to church on Sundays only after his children insisted, and no longer wanted to babysit his grandchildren. He stopped exercising, citing fatigue. He started sleeping excessively and had a hard time getting out of bed in the morning. His diet shifted to mostly junk food, and he gained 10 pounds. He seemed forgetful, was repetitive in his speech, and on a couple of occasions forgot to pay his bills (a new and surprising occurrence, given his background as an accountant). Mr. Rodríguez’s daughters thought that he might still be grieving, but his symptoms seemed excessive.

Mr. Rodríguez has no psychiatric history; his medical problems include hypertension (for which he takes a diuretic), hyperglycemia (which does not meet criteria for diabetes), and dyslipidemia (for which he takes a statin). There is no known family history of neuropsychiatric disease. His primary care provider ordered laboratory work (electrolytes, renal function, liver function, thyroid-stimulating hormone, complete blood count) and an electrocardiogram, all of which was normal except for elevated blood sugar. Mr. Rodríguez was referred to a psychiatrist for further evaluation.

On examination, Mr. Rodríguez is mildly disheveled, makes poor eye contact, and appears sullen, crying at times. He denies active suicidal ideation but states, “I wish God would take me away.” He denies psychotic and manic symptoms. He worries about his finances and whether he can continue to live alone. He reports rare use of alcohol and no use of illicit substances. He scores 10 out of 15 on the short version of the Geriatric Depression Scale (Yesavage et al. 1982), consistent with moderate to severe depression. Bedside cognitive testing is abnormal, with deficits in memory and executive function. However, Mr. Rodríguez may not have given his full effort during the testing.

You diagnose Mr. Rodríguez as having major depressive disorder, single episode, moderate. To complete the evaluation of other medical etiologies of depression, you order polysomnography to rule out sleep apnea and a test to measure his serum vitamin B₁₂ level. You explain to Mr. Rodríguez and his daughters that his cognitive impairment is likely due to depression and should improve with successful treatment of depression. You recommend a trial of sertraline and refer him for cognitive-behavioral therapy. He is then lost to follow-up.

Four years later, Mr. Rodríguez and his daughters return. They report that initially his mood, memory, and functioning improved markedly with the combination of an antidepressant and psychotherapy. He discontinued both after 6 months, and the depression did not recur, at least initially. About 1 year ago, however, his daughters noticed that he was becoming repetitive in his speech again; he got lost driving on two occasions and also got into a minor motor vehicle accident (without injury). He did not seem particularly depressed, just disinterested. His daughters insisted he resume sertraline, but this did not seem to help—in fact, his memory seemed even worse after restarting the medication. He was not interested in psychotherapy and declined all other offers of help. His responses to a recent Patient Health Questionnaire–9 (PHQ-9; Kroenke et al. 2001) were essentially normal, but bedside cognitive testing was worse than 4 years earlier.

You suspect that Mr. Rodríguez has now developed major neurocognitive disorder, and you refer him for neuropsychological assessment and neuroimaging to confirm the diagnosis and help establish the etiology.

SUBSTANCE USE DISORDERS

Problems with alcohol and substance use are common in older adults. The prevalence of at-risk alcohol use (two or more drinks on a usual drinking day in the past 30 days) or binge-drinking (five or more drinks on at least 1 day in the past 30 days) is 28% in older men and 11% in older women (Wu and Blazer 2014). Among older adults, at-risk alcohol use decreases with age and with prescription drug use, a proxy for diminished health (Foster and Patel 2019). In the 2005–2007 National Surveys on Drug Use and Health conducted among community-dwelling individuals in the United States, the prevalence of DSM-IV alcohol abuse and dependence among older adults was 0.9% and 0.6%, respectively (Wu and Blazer 2014); note that in DSM-5 the term alcohol use disorder replaces both alcohol abuse and alcohol dependence.

Older adults with greater alcohol use are more likely to have comorbid MDD and more likely to develop new-onset MDD: in a review of studies published between 2005 and 2013, Wu and Blazer (2014) found that about 4% of adults ≥ 60 years with alcohol use disorder developed MDD over the course of 3 years. Alcohol use disorders were the most common substance use disorders among older adults admitted to an inpatient psychiatric unit, constituting 73% of use disorders and 9% of all admissions; MDD was comorbid in 26% of patients with substance use disorders (Dombrowski et al. 2016). In another study, 26% of psychiatric inpatients had substance use disorders (most commonly, cocaine use disorder), and substance use disorders were associated with greater length of stay (Lane et al. 2018). Alcohol use can both contribute to depression and complicate its treatment, including interacting with antidepressants. Clinicians should screen all depressed elders for alcohol use, recognizing that use that does not meet criteria for alcohol use disorder can still be a problem in older adults.

A recent survey of older adults in a geriatrics clinic found that 15% had used cannabis within the past 3 years, and half of them reported daily or weekly use (Yang et al. 2021). Interestingly, 61% reported their first use of cannabis after age 60; 78% reported using cannabis for medical purposes only, including depression, anxiety, and insomnia; less than half had told their health care providers about their use of cannabis (Yang et al. 2021). Older adults who use cannabis and have MDD are more likely to misuse prescription pain relievers than are older adults who use cannabis and do not have MDD (Choi et al. 2021a). Reports to U.S. poison control centers of cannabis toxicity among older adults increased eighteenfold from 2009 to 2019, sometimes with serious consequences such as suicide attempts (Choi et al. 2021b). Older adults who used cannabis in the past year had high rates of depression: 17% in the past year and 32% lifetime (Vacaflor et al. 2020). Suicidal ideation in the past year was found in 14% of older adults who used cannabis combined with other drugs and in 5% of older adults who used only cannabis (compared with 2% of older adults who had never used cannabis) (Vacaflor et al. 2020). With the increasing use of cannabis among older adults, clinicians need to screen their patients for cannabis use and address comorbid depression and cannabis use.

Other substance use disorders in older adults, and their comorbidity with depression, have been less well studied. About 9% of older Americans smoke, and 4% meet criteria for nicotine dependence (Cawkwell et al. 2015; Wu and Blazer 2014). Older adults may be less likely than younger adults to report being interested in quitting smoking, and their primary care providers may be less likely to offer smoking cessation treatment, even though older adults have more success with smoking cessation (Cawkwell et al. 2015; Jordan et al. 2017). The comorbidity of smoking and depression has not been well studied. Older adults who continue to smoke have higher rates of psychological distress than do older adults who quit smoking (Cawkwell et al. 2015). In addition, they increase their cardiovascular risk factors, potentially contributing to vascular depression and potentially dementia in the long term. Given the tremendous benefits of smoking cessation at any age, all older adults presenting with depression should be screened for tobacco use and offered evidence-based smoking cessation techniques.

Illicit substance use is relatively uncommon among older adults, although comorbidity with depression is high. In the review by Wu and Blazer (2014), 7% of older adults with a substance use disorder (other than alcohol use disorder) developed MDD within 3 years. Twenty-seven percent of older adults accessing emergency care for psychiatric conditions had positive urine toxicology for illicit drug use (Wu and Blazer 2014). The opioid epidemic has not spared older adults, with 2.5% of older adults reporting misuse of prescription opioids in the past year; those misusing opioids were more likely to have depression; more likely to have alcohol use disorder; more likely to misuse sedatives or stimulants; and more likely to use tobacco, cocaine, or cannabis (Han et al. 2019).

PERSONALITY DISORDERS

As noted in the section “Clinical Course,” certain personality traits (e.g., avoidance coping, psychological inflexibility, neuroticism, harm avoidance) are associated with the development and persistence of LLD. Personality disorders are also common, found in about 24%–31% of older adults with depression (Devanand 2002). The most common personality disorders among this group are from cluster C (“anxious”) of the DSM-5 classification of personality disorders, specifically, obsessive-compulsive personality disorder and avoidant personality disorder (Devanand 2002). Personality pathology has been associated with worse treatment outcomes in LLD, including longer time to response and lower likelihood of remission (Kiosses et al. 2011). Personality disorders are more associated with early-onset depression than late-onset depression (Devanand 2002).

Interestingly, cluster B (“dramatic”) personality disorders such as borderline personality disorder are much less common in older adults with depression than in younger adults with depression. Why? Perhaps withdrawal and estrangement from family and friends replace self-harm behavior and volatile interpersonal relationships, or perhaps patients with these personality disorders are less likely to survive into old age because of suicide or other consequences of high-risk behavior (Devanand 2002). Nevertheless, given their likely history of one or more suicide attempts, their chronic depression and low self-esteem, and their lack of interpersonal supports, elders with comorbid LLD and borderline personality disorder require attentive clinical care.

SLEEP DISORDERS

About 30% of community-dwelling elders report sleep disturbance, which is a risk factor for the onset, exacerbation, and recurrence of depression (Bao et al. 2017). Short sleep duration (6 or fewer hours) is predictive of onset of depression, whereas long sleep duration (more than 9 hours) is not (Sun et al. 2018). Insomnia is also a risk factor for suicide attempts in older adults (Kay et al. 2016). Conversely, depressed elders are 70% more likely to develop problems with sleep than are nondepressed elders (Bao et al. 2017).

Of course, insomnia and hypersomnia are criteria for MDD, so some comorbidity would be expected. Beyond diagnostic overlap, possible mechanisms for this high level of comorbidity include changes in rapid eye movement (REM) sleep associated with aging (e.g., REM dysregulation is a predictor of recurrence of depression), changes in circadian rhythm (phase advance, i.e., going to sleep and waking up earlier), hyperarousal mediated by disturbances in the HPA axis, and structural and functional changes in the brain stem and hypothalamus (Bao et al. 2017). Some antidepressants can have negative effects on sleep, including changes in slow-wave (“deep”) sleep and REM sleep (Wichniak et al. 2017), whereas others are used to treat both depression and insomnia (Schroeck et al. 2016). Medications used in the treatment of insomnia, including benzodiazepines, “z-drugs” (zolpidem, zaleplon, and eszopiclone), and suvorexant, may exacerbate depression or suicidal ideation (McCall et al. 2017; Schroeck et al. 2016) and are not indicated for long-term use.

As noted earlier in the subsection “Neurobiology,” the possibility of obstructive sleep apnea (OSA) should be considered in the evaluation of older adults with depression. OSA at least doubles the risk of developing depression, perhaps via cerebral hypoperfusion associated with apneic episodes leading to or exacerbating cerebrovascular disease (Kerner and Roose 2016). Treatment of OSA has been found to reduce depressive symptoms in older adults, including in those who do not respond to antidepressants (Kerner and Roose 2016).

FRAILTY AND FAILURE TO THRIVE

Finally, we explore the relationship between frailty, failure to thrive, and depression. The frailty phenotype includes having three or more of the following five criteria: 1) weight loss (≥ 5% of body weight in the past year), 2) exhaustion (positive response to questions regarding effort required for activity), 3) weakness (decreased grip strength), 4) slow gait (> 6 seconds to walk 15 feet), and 5) decreased physical activity (measured in calories expended per week) (Fried et al. 2001). Frailty is associated with falls, hospitalizations, disability, and depression—which itself is a risk factor for frailty; in particular, slow gait predicts depression and vice versa (Brown et al. 2016). Frail elders are about four times more likely than nonfrail elders to have depression, with a prevalence of about 40% (Soysal et al. 2017).

There is significant diagnostic overlap between frailty and depression: weight loss, fatigue, and psychomotor slowing represent three of the nine DSM-5 criteria for MDD. In a reanalysis of the Epidemiologic Catchment Area study, 100% of severely depressed elders were considered frail (Brown et al. 2016). LLD and frailty are not synonymous, but they are highly comorbid; for example, a more recent study found that a quarter of depressed adults ≥ 60 years met the aforementioned Fried criteria for frailty and that roughly half had decreased grip strength, slow gait, or both (Brown et al. 2020). A meta-analysis of studies of elders diagnosed with MDD found that 18% were also frail (Soysal et al. 2017).

Mitochondrial dysfunction (resulting in fatigue and decreased mobility), dopaminergic dysfunction (resulting in cognitive and motor slowing), and chronic inflammation (discussed in the subsection “Neurobiology”) have been proposed as mechanisms for the relationship between frailty and depression (Brown et al. 2016). Cerebrovascular disease does not appear to be involved (Brown et al. 2020).

I should note that there is some controversy about the term failure to thrive (FTT). Physical frailty is a symptom—perhaps the core symptom—of FTT. FTT is included in the ICD and has been described as “a syndrome of weight loss, decreased appetite and poor nutrition, and inactivity, often accompanied by dehydration, depressive symptoms, impaired immune function, and low cholesterol” (Sarkisian and Lachs 1996, p. 1074). However, there is concern that the imprecision of the term and the implication that FTT is a psychosocial problem (as reflected in the pejorative concept of a “social admission”) may lead to delays in care and may perhaps reflect or contribute to ageism (Sarkisian and Lachs 1996; Tsui et al. 2020). In one study of older adults admitted for FTT, 88% were in fact found to have an acute medical condition (Tsui et al. 2020). Sarkisian and Lachs argue that a presumptive diagnosis of FTT should lead to a search for causes of impaired physical functioning, malnutrition, and cognitive decline—as well as identifying and addressing depression.

Summary: Understanding How Depression Arises and Progresses in Older Adults

Depression is a common, disabling, and potentially lethal syndrome in older adults. Neurobiological, psychosocial, cultural, and spiritual factors, as well as social determinants of health, contribute to depression, which can manifest somewhat differently in older adults than in younger adults. Late-onset depression may be a distinct disorder that represents a prodrome of dementia. Late-life depression is comorbid with (and exacerbates) a wide variety of other medical conditions, including anxiety disorders, substance use disorders, sleep disorders, personality disorders, cardiovascular disease, cerebrovascular disease, and neurodegenerative disorders. Suicide is of particular concern among depressed elders, who are also at risk of death from cardiovascular and other medical conditions. Unrecognized or undertreated depression can lead to many other negative outcomes, including worsening medical conditions, physical frailty, disability, and caregiver burden.

KEY POINTS

•

Late-life depression (LLD) is common, affecting at least 5%–10% of older adults and up to 48% in some subsets of older adults.

•

Depression can manifest differently in older adults than in younger adults, including more somatic symptoms, greater cognitive impairment, and subtle psychotic symptoms (e.g., delusional guilt).

•

Older adults with depression follow one of these clinical courses:

– Earlier onset of major depressive disorder (MDD) or bipolar disorder, with recurrence or chronicity into older adulthood

– Subclinical depression or anxiety through early adulthood or midlife, worsening into clinical depression in late life

– Late-life onset of depression that is either a risk factor for or harbinger of dementia. This is related to the construct of vascular depression, that is, depression that arises in the context of cerebrovascular disease and manifests with more executive dysfunction.

– Depression that arises after the onset of and is presumably due to a neurodegenerative disorder or cerebrovascular disease. This is to be distinguished from apathy (the most common behavioral and psychological symptom of dementia), which does not include the psychological distress associated with depression.

– Minor depression (not meeting full criteria for MDD) that nevertheless can result in disability and other negative outcomes

•

Depression arises in older adults from some combination of the following: genetic and developmental factors (e.g., childhood abuse); personality characteristics; social determinants of health; social and cultural factors, including race, ethnicity, and LGBTQ+ status; stressful life events, including the death of loved ones; dysfunction of the hypothalamic-pituitary-adrenal axis and/or reproductive hormone systems; cerebrovascular disease; neurodegenerative disease; inflammatory processes; use of alcohol and other substances; and dysfunction of neural networks involved in emotion regulation.

•

Cognitive impairment and depression are closely linked in older adults. LLD often includes cognitive symptoms, which may be so severe that the elder appears to have dementia. Conversely, Alzheimer’s disease and other causes of dementia can cause or contribute to depression. Clinicians evaluating older adults with depression should also assess their cognition; clinicians evaluating people suspected of having dementia should screen for depression.

•

Because LLD is comorbid with many other medical conditions, clinicians should also assess for anxiety, use of alcohol and other substances, sleep disorders (especially sleep apnea), and personality disorders.

•

In the United States, older men have the highest risk of suicide of any demographic. LLD is also associated with increased cardiovascular mortality and all-cause mortality.

Resources for Patients, Families, and Caregivers

National Suicide Prevention Lifeline

https://suicidepreventionlifeline.org

1-800-273-8255

1-800-799-4889 (TTY)

•

Older adults with depression are at especially high risk of suicide.

•

The National Suicide Prevention Lifeline provides free, confidential 24/7 support for people in distress and prevention and crisis resources for people in distress and their loved ones.

National Institute of Mental Health (NIMH)

www.nimh.nih.gov/health/publications/older-adults-and-depression/index.shtml

•

NIMH is the lead federal agency for research on mental disorders.

•

In addition to funding research, NIMH has developed educational materials on a number of topics, including “Older Adults and Depression,” available in English and Spanish.

National Institute on Aging (NIA)

www.nia.nih.gov/health/depression-and-older-adults

www.nia.nih.gov/health/mourning-death-spouse

•

NIA is a federal agency that studies the nature of aging and conducts research into Alzheimer’s disease and related dementias.

•

NIA has developed educational materials on a number of topics, including “Depression and Older Adults” and “Mourning the Death of a Spouse.”

Depression and Bipolar Support Alliance (DBSA)

www.dbsalliance.org

•

DBSA offers educational and support services for people suffering from depression or bipolar disorder and their family members.

•

Services are available online 24/7, in local support groups, in audiocasts and videocasts, or via printed materials.

Footnote

¹In distinguishing grief from a major depressive episode (MDE), it is useful to consider that in grief the predominant affect is feelings of emptiness and loss, while in an MDE it is persistent depressed mood and the inability to anticipate happiness or pleasure. The dysphoria in grief is likely to decrease in intensity over days to weeks and occurs in waves, the so-called pangs of grief. These waves tend to be associated with thoughts or reminders of the deceased. The depressed mood of an MDE is more persistent and not tied to specific thoughts or preoccupations. The pain of grief may be accompanied by positive emotions and humor that are uncharacteristic of the pervasive unhappiness and misery characteristic of an MDE. The thought content associated with grief generally features a preoccupation with thoughts and memories of the deceased, rather than the self-critical or pessimistic ruminations seen in an MDE. In grief, self-esteem is generally preserved, whereas in an MDE feelings of worthlessness and self-loathing are common. If self-derogatory ideation is present in grief, it typically involves perceived failings vis-à-vis the deceased (e.g., not visiting frequently enough, not telling the deceased how much he or she was loved). If a bereaved individual thinks about death and dying, such thoughts are generally focused on the deceased and possibly about “joining” the deceased, whereas in an MDE such thoughts are focused on ending one’s own life because of feeling worthless, undeserving of life, or unable to cope with the pain of depression.

References

Aggarwal NK: Reassessing cultural evaluations in geriatrics: insights from cultural psychiatry. J Am Geriatr Soc 58(11):2191–2196, 2010 20977437

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