Differentiating Delirium from Dementia from Depression: A Bedside Cognitive Assessment Framework for Internal Medicine Postgraduates

Dr Neeraj Manikath , claude.ai

Abstract

The "3 D's"—Delirium, Dementia, and Depression—represent a diagnostic trinity that challenges even seasoned internists. Misdiagnosis leads to inappropriate management, increased morbidity, and preventable mortality. This review provides a structured approach to differentiate these conditions at the bedside, emphasizing the Confusion Assessment Method (CAM) as the cornerstone tool, supplemented by clinical pearls derived from decades of teaching experience in internal medicine.

Introduction

Picture this clinical vignette: An 82-year-old woman is brought to the emergency department by her daughter who reports "confusion for two days." The patient has hypertension, diabetes, and "some memory problems" for the past year. She appears withdrawn and keeps asking, "Why am I here?" Is this acute delirium superimposed on chronic dementia? Is this worsening dementia? Or could this be depression presenting as cognitive impairment?

This scenario epitomizes the daily diagnostic challenge in hospital medicine. The consequences of misdiagnosis are profound. Treating delirium as dementia means missing reversible causes like infection or medication toxicity. Treating depression as dementia denies patients effective antidepressant therapy. Treating dementia as delirium leads to unnecessary investigations and delayed appropriate care planning.

The prevalence of delirium in hospitalized elderly patients ranges from 14% to 56%, with mortality rates of 25-33% within six months of diagnosis.[1,2] Dementia affects approximately 50 million people worldwide, while late-life depression occurs in 10-15% of community-dwelling elderly and up to 40% in hospitalized patients.[3,4] These conditions frequently coexist, creating a diagnostic labyrinth that demands systematic clinical reasoning.

The Foundation: Understanding the Pathophysiology

Delirium represents acute brain failure—a medical emergency analogous to acute renal failure or acute myocardial infarction. The underlying mechanism involves widespread disruption of neurotransmitter systems, particularly acetylcholine deficiency and dopamine excess, coupled with neuroinflammation.[5] Think of delirium as the brain's stress response to systemic illness, much like fever is to infection.

Dementia reflects chronic, progressive neurodegeneration with irreversible structural brain changes. Whether Alzheimer's disease, vascular dementia, or Lewy body dementia, the common thread is permanent neuronal loss and synaptic dysfunction.[6]

Depression in the elderly, particularly when presenting with cognitive symptoms (historically termed "pseudodementia"), involves functional rather than structural brain changes. Neuroimaging may show normal or minimal changes, and cognitive deficits typically reverse with treatment.[7]

The Bedside Framework: A Systematic Approach

The CAM: Your Diagnostic North Star

The Confusion Assessment Method (CAM), developed by Inouye et al. in 1990, remains the gold standard bedside tool for delirium diagnosis.[8] With a sensitivity of 94-100% and specificity of 90-95%, it outperforms clinical gestalt alone.

The Four CAM Criteria:

1. Acute onset and fluctuating course – Did the confusion start suddenly? Does it come and go throughout the day?
2. Inattention – Does the patient have difficulty focusing or maintaining attention?
3. Disorganized thinking – Is the patient's thinking unclear or illogical?
4. Altered level of consciousness – Is the patient anything other than alert (hyperalert, lethargic, stuporous)?

CAM is POSITIVE if: Features 1 AND 2 are present, PLUS either 3 OR 4.

Pearl #1: The Collateral History is Golden

Never diagnose any of the 3 D's without speaking to someone who knows the patient. The patient cannot reliably tell you if their cognition has acutely changed. Ask the family member or caregiver:

• "Was she like this yesterday?" (distinguishes acute vs. chronic)
• "Does the confusion come and go during the day?" (suggests delirium)
• "Has she seemed sad or lost interest in things she used to enjoy?" (suggests depression)

The Diagnostic Grid: Clinical Feature Comparison

Feature	Delirium (Acute Brain Failure)	Dementia (Chronic Decline)	Depression (Pseudodementia)
Onset	Acute (hours to days)	Insidious (months to years)	Subacute, often after a stressor (weeks to months)
Course	Fluctuating (waxing and waning)	Stable, progressive	Stable, but worse in morning
Attention	Severely impaired	Mildly impaired (late stage)	Intact (but with apathy)
Consciousness	Altered (hyper or hypoalert)	Clear	Clear
Hallucinations	Common (especially visual)	Rare until late stage	Rare
Psychomotor	Agitated (hyperactive) or lethargic (hypoactive)	Normal or slowed	Slowed (psychomotor retardation)
CAM Result	POSITIVE	NEGATIVE	NEGATIVE

Pearl #2: Attention is the Key Differentiator

Among the 3 D's, delirium uniquely causes severe attention impairment. Test this at the bedside:

The Months of Year Backwards Test: Ask the patient to recite months backward from December. Patients with delirium cannot get past October or November. Patients with early dementia or depression can usually complete this task, though they may be slow.

The Digit Span Test: Say a string of digits and ask the patient to repeat them. Normal adults can repeat 5-7 digits forward. Delirious patients typically cannot manage more than 3-4 digits.

Vigilance Test: Ask the patient to squeeze your hand every time they hear the letter "A" while you recite a random string of letters. Delirious patients will squeeze randomly or not at all.

Pearl #3: The "Fluctuation Sign"

Delirium's hallmark is fluctuation—lucid intervals interspersed with confusion. A patient who seems oriented at 9 AM but is confused by 3 PM almost certainly has delirium. Document multiple assessments throughout the day. Chart reviews showing "patient oriented × 3" in nursing notes followed by "patient confused and agitated" four hours later strongly suggest delirium.

In contrast, dementia patients have stable (though progressive over months) cognition, and depressed patients remain consistently slow and apathetic throughout the day, though symptoms may worsen in early morning.

Oyster #1: Hypoactive Delirium—The Silent Killer

Approximately 50% of delirium cases are hypoactive, not hyperactive.[9] These patients are quiet, withdrawn, and sleepy—often mistaken for depression or simply "old age." This subtype has the worst prognosis because it's frequently missed.

Clinical Hack: If an elderly hospitalized patient seems "pleasantly confused" or is sleeping 18 hours daily, assume hypoactive delirium until proven otherwise. Apply the CAM rigorously. Check attention with the months backward test. One study found that hypoactive delirium had twice the mortality of hyperactive delirium.[10]

Oyster #2: Delirium Superimposed on Dementia (DSD)

This combination occurs in 22-89% of hospitalized dementia patients.[11] The baseline cognitive impairment makes acute changes harder to detect. How do you diagnose delirium in someone who already has dementia?

Clinical Hack: Document baseline function from the family. "She usually knows our names but forgets what year it is. Today she doesn't recognize me at all." This acute worsening from baseline meets CAM criteria. Use the 3D-CAM, a modified version specifically validated for dementia patients.[12]

Oyster #3: Depression Presenting as "Pseudodementia"

Depression can mimic dementia so convincingly that older terminology called it "pseudodementia." However, approximately 25% of patients with depression-related cognitive impairment will develop true dementia within five years, suggesting these conditions exist on a spectrum.[13]

Distinguishing Features:

• Depressed patients often say "I don't know" to cognitive questions, while dementia patients confabulate or give wrong answers confidently
• Depressed patients typically have preserved attention (can focus when motivated)
• Depressed patients show little effort on cognitive testing, while dementia patients try hard but fail
• Depressed patients have prominent complaints of memory loss, while dementia patients minimize deficits (anosognosia)

Clinical Hack: Ask, "Over the past two weeks, have you felt down, depressed, or hopeless?" and "Over the past two weeks, have you felt little interest or pleasure in doing things?" These two questions comprise the PHQ-2, with 83% sensitivity for major depression.[14] A positive screen warrants full depression evaluation even if cognitive symptoms are prominent.

The Action Plan: What to Do When CAM is Positive

A positive CAM means delirium. This is a medical emergency requiring immediate intervention:

Step 1: Search for the Underlying Cause

Use the "I WATCH DEATH" mnemonic:

• Infections (UTI, pneumonia, COVID-19)
• Withdrawal (alcohol, benzodiazepines)
• Acute metabolic (hypoglycemia, hyponatremia, hypercalcemia)
• Toxins/drugs (anticholinergics, opioids, benzodiazepines)
• CNS pathology (stroke, seizure, encephalitis)
• Hypoxia (respiratory failure, cardiac failure)
• Deficiencies (thiamine, B12)
• Endocrine (thyroid, adrenal)
• Acute vascular (MI, shock)
• Trauma/surgery
• Heavy metals

Step 2: Essential Investigations

First-line labs: CBC, comprehensive metabolic panel, urinalysis and culture, chest X-ray, ECG, medication review

Second-line (based on clinical suspicion): Blood cultures, ammonia, TSH, B12, thiamine, arterial blood gas, toxicology screen, brain imaging (if focal neurologic signs or head trauma), lumbar puncture (if CNS infection suspected)

Step 3: Treat the Cause, Not Just the Symptoms

The Cardinal Rule: Antipsychotics do not treat delirium; they sedate agitated patients. Haloperidol and quetiapine have no mortality benefit and may cause harm.[15] Use them sparingly, only for severe agitation posing safety risk.

Instead, focus on:

• Treating infection with appropriate antibiotics
• Correcting metabolic derangements
• Discontinuing offending medications
• Ensuring adequate oxygenation
• Addressing pain appropriately

Step 4: Implement Non-Pharmacologic Prevention and Management

The ABCDEF bundle in ICU settings reduces delirium by 50%:[16]

• Assess, prevent, and manage pain
• Both SAT and SBT (sedation and breathing trials)
• Choice of analgesia and sedation
• Delirium monitoring and management
• Early mobility
• Family engagement

Adapt this for the general ward: Ensure glasses and hearing aids are in place, maintain day-night orientation, encourage family presence, mobilize early, avoid restraints, ensure adequate sleep (quiet environment at night), and maintain good hydration and nutrition.

Practical Teaching Point: The "Rule of Twos"

For your postgraduate students, teach them this memorable framework:

Delirium = 2 days (acute onset, hours to days) Depression = 2 weeks (DSM-5 requires symptoms present for at least two weeks) Dementia = 2 months (insidious onset over months to years)

This oversimplification works as a starting point for pattern recognition.

Special Populations: Additional Considerations

Postoperative Patients

Postoperative delirium occurs in 15-25% of major surgeries and up to 50% of hip fracture repairs.[17] Risk factors include age over 70, pre-existing cognitive impairment, polypharmacy, and major surgery. Use the CAM-ICU for intubated patients.

ICU Patients

ICU delirium affects 60-80% of mechanically ventilated patients.[18] The CAM-ICU, modified for intubated patients, should be performed every shift. Remember that sedation itself is a delirium risk factor—use the lightest effective sedation.

Palliative Care Patients

Terminal delirium occurs in up to 88% of dying patients.[19] The approach differs—comfort rather than investigation may be appropriate. However, always consider reversible causes (opioid toxicity, hypercalcemia, urinary retention) that can be simply addressed.

Conclusion: The Clinical Bottom Line

When faced with an elderly patient with altered cognition, apply this systematic approach:

1. Obtain collateral history – Determine baseline and acuteness of change
2. Apply the CAM – Is attention severely impaired? Is consciousness altered? Does confusion fluctuate?
3. If CAM positive: Think delirium FIRST – Search for medical causes aggressively
4. If CAM negative with chronic progressive course: Consider dementia – Refer for formal neuropsychological testing
5. If CAM negative with subacute onset and apathy: Screen for depression – Use PHQ-2/PHQ-9

Remember: Delirium is a medical emergency with the same urgency as septic shock or acute coronary syndrome. Dementia is a chronic neurologic condition requiring long-term planning. Depression is a treatable psychiatric condition that often responds well to intervention. Getting the diagnosis right determines whether your patient receives life-saving treatment, appropriate supportive care, or effective therapy for a reversible condition.

The CAM is your stethoscope for the brain—learn to use it with the same automaticity you use when auscultating the heart. Your patients' outcomes depend on it.

References

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3. Prince M, Wimo A, Guerchet M, et al. World Alzheimer Report 2015: The Global Impact of Dementia. Alzheimer's Disease International; 2015.

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