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Clinical features and diagnosis of cognitive impairment and delirium in patients with cancer

Clinical features and diagnosis of cognitive impairment and delirium in patients with cancer
Authors:
Jacynthe Rivest, MD
Jon Levenson, MD
Section Editors:
Jonathan M Silver, MD
Susan D Block, MD
Deputy Editor:
David Solomon, MD
Literature review current through: Jun 2022. | This topic last updated: May 16, 2022.

INTRODUCTION — Cognitive impairment and delirium are common in patients with cancer [1]. Delirium is distressing for patients and families, can interfere with recognition and management of symptoms such as pain, and is associated with increased mortality.

This topic reviews the clinical features of cognitive impairment and delirium in patients diagnosed with and treated for cancer, and also reviews the diagnosis of delirium. Other topics discuss cognitive function after cancer treatment, the clinical features and diagnosis of other psychiatric disorders in cancer patients, the clinical features and diagnosis of delirium in palliative care, and the management of delirium in cancer patients.

(See "Cognitive function after cancer and cancer treatment".)

(See "Clinical features and diagnosis of psychiatric disorders in patients with cancer: Overview".)

(See "Approach to symptom assessment in palliative care", section on 'Delirium'.)

(See "Management of psychiatric disorders in patients with cancer", section on 'Delirium'.)

COGNITIVE IMPAIRMENT — Patients with cancer, including cancer located outside of the central nervous system, often manifest cognitive impairment, based upon studies that compared cancer patients prior to treatment with healthy controls [2,3]. Although the prevalence of cognitive impairment varies due to differences in study populations and assessments [2,4], reviews estimate that impairment after diagnosis of cancer but prior to treatment occurs in 20 to 30 percent of patients [2,3].

Cognitive dysfunction can occur in several domains, including [2,3]:

Attention

Concentration

Executive function (eg, planning, problem solving, and response inhibition)

Information processing speed

Memory

However, the magnitude of the impairment is typically modest [2,4,5].

In addition, cancer treatments are associated with neuropsychological deficits in up to 75 percent of patients [2,3]. As an example, a meta-analysis of five cross-sectional studies examined cognition in patients with breast cancer who were receiving or had received adjuvant chemotherapy (n = 208), as well as controls (eg, breast cancer patients who did not receive adjuvant chemotherapy; n = 122) [6]. Executive functioning, language, memory, and spatial ability were each worse in patients treated with chemotherapy than controls, and the difference was small to moderate. Although many studies have focused upon chemotherapy (“chemobrain”), patients in these studies often received other treatments that can affect cognition, such as hormonal therapy, as well as radiation therapy and surgery involving the use of general anesthesia.

There are no established risk factors for cognitive impairment in patients with cancer, but increased age and decreased baseline cognitive reserve (capacity) may increase the risk [2,3].

Cognitive deficits related to cancer chemotherapy can persist after treatment is finished. (See "Cognitive function after cancer and cancer treatment".)    

In addition to studies that involved the use of clinician administered tests of cognition, self-reported cognitive impairment is greater in patients with cancer than the general public and may affect patient functioning (professional or personal) and quality of life. Patient self-reports may provide information about subtle cognitive changes that are not detected by standard neuropsychological tests, but self-reports are generally nonspecific and influenced by beliefs and stress [3]. A nationally representative survey identified individuals with a history of cancer (n >1300) and individuals with no history of cancer; after controlling for potential confounding factors (eg, age, education, and self-rated general health), the analyses found that self-rated memory problems were present in more individuals with a history of cancer than controls (14 versus 8 percent) [7].

The neurobiologic mechanisms by which cancer and cancer treatment impact cognitive function have not been elucidated, but both structural and functional central nervous system changes have been correlated with cognitive decline contribute. It is likely that many mechanisms contribute and that the observed cognitive dysfunction in some patients reflects an interaction between multiple factors, including baseline lower cognitive reserve. (See "Cognitive function after cancer and cancer treatment", section on 'Neurobiologic basis'.)

Clinicians who want to screen patients with cancer for cognitive impairment can use either the Mini Mental State Examination or the Montreal Cognitive Assessment. These tests should be interpreted using age- and education-based normative values; the Montreal Cognitive Assessment in particular is prone to yielding false positives. A study of patients with brain tumors (n = 58) found that sensitivity was superior with the Montreal Cognitive Assessment than the Mini Mental State Examination (62 versus 19 percent), and that specificity was superior with the Mini Mental State Examination (94 versus 56 percent) [8]. The Montreal Cognitive Assessment is accessible online and in multiple languages at www.mocatest.org. Additional information about these screening tests is discussed in the context of dementia. (See "Evaluation of cognitive impairment and dementia", section on 'Cognitive testing'.)

Cognitive impairment may be a symptom of a depressive syndrome, such as major depression (table 1) or minor depression (table 2), if the impairment occurs in conjunction with other depressive symptoms like dysphoria, anhedonia, and suicidal ideation or behavior. Impairment may also be a symptom of fatigue. (See "Clinical features, assessment, and diagnosis of unipolar depressive disorders in patients with cancer".)

DELIRIUM — Delirium is common in patients with cancer and is associated with distress in patients and families, prolonged hospitalizations, and increased morbidity and mortality [1]. As an example, a study of hospitalized cancer patients who developed delirium (n = 140) found that 30-day mortality was 25 percent [9].

The subsections below discuss delirium in patients with cancer. The clinical features, causes, assessment, diagnosis, and differential diagnosis of delirium in general clinical settings are discussed in detail separately, and delirium in patients approaching the end of life is also discussed separately. (See "Diagnosis of delirium and confusional states" and "Overview of managing common non-pain symptoms in palliative care", section on 'Delirium'.)

Prevalence — Delirium is a common complication of cancer and its treatment, especially in patients who are hospitalized and patients with advanced disease [10]. Reviews suggest that at a minimum, the prevalence of delirium in hospitalized patients is approximately 10 to 30 percent [1]. However, higher rates have been reported; as an example, a prospective study of 90 patients undergoing hematopoietic stem cell transplantation found that during five weeks of hospitalization, delirium occurred in 50 percent [11].

Pathogenesis — Delirium is due to a physiologic disturbance and often involves multiple etiologies [1,12]. Among patients with cancer, delirium is often due to medications used for chemotherapy (eg, corticosteroids, fluorouracil, ifosfamide, methotrexate, and vincristine), immunotherapy (eg, interferon), and/or control of pain, anxiety, and agitation (eg, opioids and benzodiazepines). In addition, the direct or indirect effects of cancer can cause delirium, including primary brain tumors, brain metastases (common with breast and lung cancer), dehydration, electrolyte imbalance, infection, major organ failure, paraneoplastic syndromes, and vascular complications. Substance intoxication or withdrawal can also contribute to delirium.  

Clinical features — The clinical features of delirium in patients with cancer include the following [1]:

Sudden onset of symptoms that typically fluctuate in severity during the day

Decreased level of consciousness (alertness or arousal)

Attentional disturbances and cognitive impairment in other domains

Apraxia

Agnosia

Executive functioning (eg, planning)

Language disturbances

Memory impairment

Visuospatial dysfunction

Disorientation

Delusions

Mood symptoms (eg, dysphoria and lability)

Neurologic findings (eg, asterixis, myoclonus, and tremor)

Perceptual disturbances (illusions or hallucinations)

Psychomotor activity increased or decreased

Sleep-wake cycle disturbances

Speech is incoherent

Thought process is disorganized

Screening — Screening tools can help clinicians diagnose delirium. Among the instruments that have been validated in patients with cancer, we suggest the Confusion Assessment Method (table 3) [1]. However, reasonable alternatives include the Memorial Delirium Assessment Scale (form 1A-B) and the Delirium Rating Scale-Revised 98. Delirium in cancer patients is frequently missed and is often misdiagnosed as akathisia, anxiety, dementia, depression, or psychosis [12,13].

Diagnosis — According to the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the diagnosis of delirium requires each of the following criteria [14]:

Disturbance in attention and awareness that develops quickly (usually hours to days) and tends to fluctuate each day.

Disturbance in cognition (eg, memory, orientation, language, visual spatial ability, and/or perception).

The disturbances in attention, awareness, and cognition are not better explained by another neurocognitive disorder and do not occur in the context of coma.

Evidence from the history, physical examination, or laboratory findings indicate that the disturbances are caused by a general medical condition, substance intoxication or withdrawal, and/or medication side effect.

Subtypes of delirium have been delineated, based upon the patient’s psychomotor behavior and level of arousal [1,14]:

Hypoactive subtype – Psychomotor retardation, lethargy, and decreased level of arousal.

Hyperactive subtype – Restlessness, agitation, and hypervigilance. Mood lability, failure to cooperate with care, and psychotic features may also be present.

Some patients may display alternating (mixed) features of each subtype.

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

Basics topic (see "Patient education: Delirium (confusion) (The Basics)")

Beyond the Basics topic (see "Patient education: Delirium (Beyond the Basics)")

SUMMARY

Patients with cancer often manifest acute and long-term cognitive impairment, the magnitude of which is typically modest. Cognitive dysfunction has been observed in attention, concentration, executive function, information processing speed, and memory. The prevalence of cognitive impairment in patients with cancer is high, reaching up to 75 percent of patients during treatment. Both cancer itself and cancer treatment are associated with cognitive impairment. Cognitive impairment in cancer patients may be temporary or permanent. (See 'Cognitive impairment' above.)

Delirium is common in patients with cancer and is associated with increased morbidity and mortality. (See 'Delirium' above.)

Delirium is a common complication of cancer and its treatment; at a minimum, the prevalence of delirium in patients hospitalized with cancer is approximately 10 to 30 percent. (See 'Prevalence' above.)

Delirium is due to a physiologic disturbance and often involves multiple etiologies. Among patients with cancer, delirium is often due to medications used for chemotherapy, immunotherapy, and/or control of pain, anxiety, and agitation. In addition, the direct or indirect effects of cancer can cause delirium, including primary brain tumors, brain metastases, dehydration, electrolyte imbalance, infection, major organ failure, paraneoplastic syndromes, and vascular complications. Substance intoxication or withdrawal can also contribute to delirium. (See 'Pathogenesis' above.)

The clinical features of delirium in patients with cancer include sudden onset of symptoms that typically fluctuate in severity during the day, decreased level of consciousness, attentional disturbances and cognitive impairment in other domains, neurologic findings, perceptual disturbances, sleep-wake cycle disturbances, incoherent speech, and disorganized thought process. (See 'Clinical features' above.)

Screening tools can help clinicians diagnose delirium. Among the instruments that have been validated in patients with cancer, we suggest the Confusion Assessment Method (table 3). (See 'Screening' above.)

The diagnosis of delirium requires each of the following criteria:

Disturbance in attention and awareness that develops quickly (usually hours to days) and tends to fluctuate each day.

Disturbance in cognition (eg, memory and/or orientation).

The disturbances in attention, awareness, and cognition are not better explained by another neurocognitive disorder and do not occur in the context of coma.

Evidence from the history, physical examination, or laboratory findings indicate that the disturbances are caused by a general medical condition, substance intoxication or withdrawal, and/or medication side effect.

(See 'Diagnosis' above.)

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  2. Ahles TA, Root JC, Ryan EL. Cancer- and cancer treatment-associated cognitive change: an update on the state of the science. J Clin Oncol 2012; 30:3675.
  3. Janelsins MC, Kesler SR, Ahles TA, Morrow GR. Prevalence, mechanisms, and management of cancer-related cognitive impairment. Int Rev Psychiatry 2014; 26:102.
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  6. Falleti MG, Sanfilippo A, Maruff P, et al. The nature and severity of cognitive impairment associated with adjuvant chemotherapy in women with breast cancer: a meta-analysis of the current literature. Brain Cogn 2005; 59:60.
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  10. Lawlor PG. Cancer patients with delirium in the emergency department: A frequent and distressing problem that calls for better assessment. Cancer 2016; 122:2783.
  11. Fann JR, Hubbard RA, Alfano CM, et al. Pre- and post-transplantation risk factors for delirium onset and severity in patients undergoing hematopoietic stem-cell transplantation. J Clin Oncol 2011; 29:895.
  12. Miller K, Massie MJ. Oncology. In: The American Psychiatric Association Publishing Textbook of Psychosomatic Medicine and Consultation-Liason Psychiatry, Third Edition, Levenson JL (Ed), American Psychiatric Association Publishing, Washington, DC 2019. p.625.
  13. Wada T, Wada M, Wada M, Onishi H. Characteristics, interventions, and outcomes of misdiagnosed delirium in cancer patients. Palliat Support Care 2010; 8:125.
  14. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), Washington, DC 2022.
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