Delirium and depression can cause cognitive changes that may be mistaken for dementia. Delirium can also be superimposed on dementia, particularly in older hospitalized patients. Clinicians and caregivers need to learn to distinguish the differences.

Delirium

Delirium is a neuropsychiatric syndrome with an acute onset and a fluctuating course. The term delirium literally means, “out of the track,” and was first used by Celsus, in the first century A.D. to describe either states of agitation or excessive somnolence.* Historically, this syndrome has been described under different names and classifications. Gradually the term delirium started to be more consistently used to designate reversible states of acute brain dysfunction associated with fever or medical/surgical conditions (Cerejeira & Mukaetova-Ladinska, 2011).

Somnolence: sleepiness or drowsiness, a desire to sleep for long periods of time during the day, falling asleep while working, during meals, or even in the middle of a conversation.

Delirium develops acutely—over hours or days—and is temporary and reversible. The most common causes of delirium, which are usually identifiable, are related to medication side effects, hypo- or hyperglycemia, fecal impactions, urinary retention, electrolyte disorders and dehydration, infection, stress, metabolic changes, an unfamiliar environment, injury, or severe pain.

Inattention is the most frequent clinical finding in a delirium episode. If severe enough, it can be detected during a clinical interview. In mild cases, impairment of attention can be uncovered only by formal cognitive testing (eg, naming the months in reverse order). Attention is impaired in early stages and throughout the course of a delirium episode, correlating with the severity of cognitive deficits (Cerejeira & Mukaetova-Ladinska, 2011).

A person experiencing delirium usually has difficulty with:

1. Orientation
2. Memory
3. Language and thought
4. Visuospatial abilities (Cerejeira & Mukaetova-Ladinska, 2011)

Specific deficits in visual perception have been described in people with delirium:

1. Illusions (misinterpretations of real sensory stimuli, as when the patient in a dark environment sees a threatening figure emanating from shadows on the walls)
2. Hallucinations (ranging from simple flashes or unstructured sounds to elaborate visions, that occur without corresponding sensory stimuli) (Cerejeira & Mukaetova-Ladinska, 2011).

The prevalence of delirium increases with age, and nearly 50% of patients over the age of 70 experience episodes of delirium during hospitalization. Delirium is under-diagnosed in almost two-thirds of cases or is misdiagnosed as depression or dementia (Hope et al., 2014).

Early diagnosis of delirium can lead to rapid improvement. Nevertheless, diagnosis is often delayed, and problems remain with recognition and documentation of delirium by healthcare providers. Although there are no definitive quantitative markers available to diagnose delirium, qualitative tools such as the Confusion Assessment Method (CAM) and modified Richmond Agitation and Sedation Scale have been validated. Unfortunately, these tools are underused and healthcare providers often simply record the patient’s mental status in narrative (Hope et al., 2014).

Depression

Although it presents with an array of physical symptoms, depression is considered a disorder of mood. It is also called an affective disorder to signify that one of its key aspects is a disturbance of emotions or feelings (Diamond, 2015).

The diagnosis of depression depends on the presence of two cardinal symptoms: (1) persistent and pervasive low mood, and (2) loss of interest or pleasure in usual activities. Depressive symptoms are judged to be of clinical significance when they interfere with normal activities and persist for at least 2 weeks, in which case a diagnosis of a depressive illness or disorder may be made (Diamond, 2015).

Along with apathy, depression is one of the most common affective symptoms in Alzheimer’s disease (Nowrangi et al., 2015). Almost one-third of long-term care residents have depressive symptoms, while an estimated 10% meet criteria for a diagnosis of major depressive disorder (Jordan et al., 2014).

Depression, although frequently present in those with Alzheimer’s disease, is much more persistent in dementia with Lewy bodies. Depressive symptoms in Alzheimer’s disease and dementia with Lewy bodies are associated with a greater cognitive decline and, in Alzheimer’s disease, significantly relate to lower survival rates over a 3-year period (Vermeiren et al., 2015).

Causes of Depression in Those with Dementia

Depression has been associated with an increased risk of dementia in old age, but the mechanisms underlying this association are not well understood. Several possible mechanisms have been proposed: (1) depression is a prodrome* of dementia, (2) depression reduces the threshold for dementia, and (3) depression leads to damage to neural systems, particularly the hippocampus, which contributes to the development of dementia (Olazarán et al., 2013).

*Prodrome: an early symptom that may indicate the presence of a disease.

Past or lifetime history of depression is known to increase the risk of developing both Alzheimer’s disease and vascular dementia. This is true even when depression occurred more than 10 years before the onset of dementia. A history of depression nearly doubles the risk of developing dementia. This is further confirmed by a study that demonstrated increased plaque and tangle formation in the hippocampus of Alzheimer’s patients who had a lifetime history of depression. Prolonged damage to the hippocampus due to hypercortisolemia* linked to depression has been proposed to underlie this finding (Muliyala & Varghese, 2010).

*Hypercortisolemia: abnormal, high levels of circulating cortisol, often cause by stress and leading to a “fight or flight” response.

Vascular factors may play a role in depression and dementia. Cerebrovascular disease, hypertension, diabetes, and other vascular factors may cause both cognitive impairment and depression. However, this potential role of cerebrovascular disease and other vascular factors in the association between depression and dementia has barely been investigated (Olazarán et al., 2013).

Management of Depression

In the long-term care population, depression is both common and under-treated. Depressive illness is associated with increased mortality, risk of chronic disease, and the requirement for higher levels of supported care (Jordan et al., 2014).

Long-term care staff can play a key role in the detection, assessment, management, and ongoing monitoring of mental health disorders among those they care for. However, staff members usually receive little training in mental health and often hold misconceptions about disorders such as depression and the behavioral and psychological symptoms of dementia. As a result, they have demonstrated poor skills in managing residents with these disorders (Jordan et al., 2014).

Pharmacologic interventions are targeted at alleviating depressive symptoms primarily to improve quality of life and improve function (Nowrangi et al., 2015). Treatment of depression in patients with dementia has involved the use of tricyclic agents1, SSRIs2, and MAO inhibitors3 even though the evidence to support the effectiveness of these agents is weak (Muliyala & Varghese, 2010).

¹Tricyclic agents: used to treat depression, bipolar disorder, anxiety, obsessive-compulsive disorder, and other disorders of mood.
²SSRIs: selective serotonin reuptake inhibitors are used to treat major depressive disorders and anxiety disorders.
³MAO inhibitors: monoamine oxidase inhibitors are prescribed for the treatment of depression.

Randomized controlled trials have evaluated the use of imipramine (Tofranil), citalopram (Celexa), fluoxetine (Prozac), sertraline (Zoloft), and moclobemide with beneficial results. However, a recent multicenter, randomized placebo-controlled trial did not demonstrate efficacy for the treatment of depression with sertraline (Zoloft) in patients with Alzheimer’s disease (Muliyala & Varghese, 2010).

Antidepressant treatment may reduce cognitive decline in depressed older Alzheimer’s patients. The use of cholinesterase inhibitors* with SSRI may improve activities of daily living and global functioning in patients with dementia. Non-pharmacologic management of depression involves both patient-focused interventions as well as family and caregiver support. In one study, treatment with donepezil (Aricept) delayed progression to Alzheimer’s disease among depressed subjects with mild cognitive impairment (Muliyala & Varghese, 2010).

*Cholinesterase inhibitor: a drug that prevents the breakdown of acetylcholine, a chemical that helps with memory and thinking.

Depression vs. Grief

The diagnosis of dementia can cause grief related to actual or anticipated losses associated with the dementia diagnosis (Vroomen et al., 2013). Good support following the initial diagnosis helps people adapt and provides opportunities to develop coping responses.

Grief, like depression, can cause physical symptoms such as shortness of breath, headaches, fatigue, a feeling of heaviness, and a lack of energy. Psychological symptoms associated with grief include clinical depression, hypochondria, anxiety, insomnia, and the inability to get pleasure from normal daily activities. These issues can lead to self-destructive behaviors, such as alcohol or drug abuse.

Grief is often associated with the many losses experienced by a person with dementia:

• Loss of physical strength and abilities
• Increased confusion
• Loss of income and savings
• Loss of health insurance
• Changes in housing and personal possessions, including loss of pets
• Loss of self-sufficiency, privacy, and self-esteem
• Changes in social contacts and roles

The onset of dementia in a friend, spouse, or relative can also cause family members and caregivers to grieve due to:

• Loss of companionship
• Loss of income
• Loss of privacy and free time
• Changes in social roles
• Changes in routine

In the early stage of dementia, counseling, assessment of co-morbid conditions, information about dementia, caregiver training, and development of a care plan can help a person deal with grief. Unfortunately, these resources are often lacking.

In later stages, moving a loved one to a care home can be the cause of immense grief and loss for people with dementia and for their caregivers. People with dementia newly admitted to an institution are often disoriented and disorganized in their new environment and feel grief due to a loss of control over their lives (Vroomen et al., 2013).

When a loved one dies, family members, and especially spouses, experience a period of acute grief that generally includes intrusive thoughts,* intense emotional distress, and withdrawal from normal daily activities. When a spouse dies, in addition to grief, about 28% of surviving spouses experience major depression. This period, along with the chronic grief that follows, may vary in length and intensity from individual to individual and often resembles clinical depression (Monk et al., 2013).

*Intrusive thoughts: unwanted, involuntary thoughts, images or ideas that can be obsessive, distressing, or upsetting.

This risk of depression appears to peak during the first six months of bereavement, although depressive symptoms can be present for up to two years. Even bereaved persons with minor depression may suffer, for they have a greater likelihood of functional impairment, poorer health, more physician visits and mental health counseling, and increased use of antidepressants than do non-bereaved individuals (Monk et al., 2013).