What is the differential diagnosis for confusion?

Differential Diagnosis for Confusion

The differential diagnosis for confusion must immediately distinguish between delirium (a medical emergency requiring urgent evaluation), dementia (chronic progressive cognitive decline), drug-induced cognitive impairment, and psychiatric conditions including depression and psychosis. 1

Critical First Step: Rule Out Delirium

Delirium represents a life-threatening medical emergency and must be assumed present until proven otherwise in any confused patient. 1 This acute confusional state develops over hours to days and carries significant mortality risk if untreated. 1

Key Features of Delirium:

• Acute onset (hours to days) with fluctuating course (symptoms vary within minutes to hours) 1
• Inattention as a cardinal feature 1
• Altered level of consciousness 1
• Disorganized thinking (disorientation, memory impairment, language alterations) 1
• Supportive features: sleep-wake cycle disturbances, hallucinations, delusions, emotional lability 1

Delirium Subtypes to Recognize:

• Hyperactive delirium: agitation, restlessness 1
• Hypoactive delirium: cognitive/motor slowing, sedated appearance (more common in elderly, higher mortality risk) 1
• Mixed delirium: alternating features 1

Common Precipitants of Delirium:

• Infections (urinary tract infections, pneumonia - most common) 1
• Toxic-metabolic disorders 1
• Electrolyte and hydration disturbances 1
• Medications (see below) 1
• Hypoxia 1
• Organ failure 1

Use the Confusion Assessment Method (CAM) for rapid bedside diagnosis - sensitivity 94%, specificity 89%, can be completed in under 5 minutes. 2, 3 The CAM requires: (1) acute onset and fluctuating course AND (2) inattention AND (3) either disorganized thinking OR altered consciousness. 3

Drug-Induced Cognitive Impairment

Medications cause delirium in 11-30% of hospitalized elderly patients and account for 2-12% of patients presenting with suspected dementia. 4 This is a critical and often reversible cause.

High-Risk Medications:

• Anticholinergic drugs (major cause of acute and chronic confusion; total anticholinergic burden determines risk more than any single agent) 4
• Benzodiazepines (especially long-acting agents - commonest drug cause of dementia exacerbation) 4
• Narcotics (major cause of postoperative delirium) 4
• Tricyclic antidepressants 4
• H2-receptor antagonists 4
• Cardiac medications (digoxin, beta-blockers) 4
• Corticosteroids 4
• NSAIDs 4
• Antibiotics 4

Polypharmacy with multiple anticholinergic compounds is particularly dangerous, especially in nursing home residents. 4

Dementia

Dementia presents as gradually progressive cognitive-behavioral syndrome developing over months to years, not hours to days. 1 Key distinction from delirium: chronic course without acute onset or minute-to-minute fluctuations.

Major Causes:

• Alzheimer's disease (most common irreversible cause) 5
• Vascular cognitive impairment 1
• Central nervous system damage 5
• HIV infection 5

Potentially Reversible Causes (rare - only 0.3-0.6% of dementia syndromes):

• Thyroid dysfunction 5
• Vitamin deficiencies (B12, folate) 5
• Normal-pressure hydrocephalus 5
• Hormonal deficiencies 1
• Metabolic disorders 1

Important caveat: Delirium frequently occurs superimposed on pre-existing dementia, causing accelerated decline, increased hospitalization, institutionalization, and death. 1

Psychiatric Causes

Major Depression with Cognitive Impairment

• Can present with confusion in elderly patients 5
• Distinguished by prominent mood symptoms and preserved attention (unlike delirium) 5

Psychosis

• Primary psychosis (schizophrenia, bipolar disorder, schizoaffective disorder) 1
• Secondary psychosis from medical conditions: endocrine disorders, autoimmune diseases, neurologic disorders, infections, neoplasms, nutritional deficiencies 1, 6
• Key distinction: Level of consciousness and awareness typically intact in psychosis (unlike delirium) 1
• Delusions and hallucinations are cardinal features 1

Metabolic and Systemic Causes

These rarely cause primary dementia but commonly precipitate delirium or worsen underlying cognitive impairment: 1

• Infections (systemic or CNS) 1
• Electrolyte disturbances 1
• Hypoxia 1
• Hepatic encephalopathy 1
• Autoimmune conditions 1
• Neoplastic/paraneoplastic syndromes 1
• Toxic exposures 1

Neurological Causes

• Stroke or transient ischemic attack 1
• Subdural or subarachnoid hemorrhage 1
• Meningitis or encephalitis 1
• Hydrocephalus 1
• Increased intracranial pressure 1
• Concussion (with disorientation/confusion immediately after head trauma) 1

Diagnostic Approach Algorithm

1. Establish timeline: Hours-to-days = delirium until proven otherwise; months-to-years = dementia 1, 5

2. Interview knowledgeable informant to determine baseline cognition, time course, and trajectory of changes 1

3. Apply CAM criteria for delirium screening 2, 3

4. Complete medication review focusing on anticholinergic burden and recent additions 4

5. Obtain cognitive lab panel: CBC, comprehensive metabolic panel, thyroid function, vitamin B12, urinalysis, chest X-ray 1

6. Neuroimaging (CT or MRI) when indicated for acute changes, focal findings, or atypical presentations 1

7. Treat underlying cause immediately if delirium identified - this is a medical emergency 1

Common pitfall: Attributing confusion to "normal aging" or pre-existing dementia without evaluating for superimposed delirium or reversible causes. 1, 7 Always assume a treatable cause exists until proven otherwise, as missed delirium doubles mortality risk. 1