Differentiating Delirium Versus Dementia in Older Adults

Etiology

Delirium is multifactorial and has various predisposing and precipitating factors.[4] Predisposing factors include age older than 70, male gender, and dementia, and the most common precipitating factors are medications, acute illness, infections, and exacerbation of chronic medical diseases.[11] 

On the other hand, dementia is a neurodegenerative process that can occur due to the accumulation of tau protein, beta-amyloid, or alpha-synuclein or due to multiple vascular insults to the brain. It is usually sporadic, sometimes genetic, eg, the APOE e4 allele for Alzheimer's disease, and seldomly due to prion infections as in the case of Creutzfeldt-Jakob disease.[7] Studies have shown delirium to be an independent risk factor for the development of dementia.[12]

Epidemiology

The incidence of delirium increases with age. The prevalence of delirium is as low as 1% to 2% in the community setting but rises to 8% to 17% in older patients presenting to the emergency center and can be as high as 40% among nursing home residents.[13] Alzheimer's disease is the most common type of dementia, followed by vascular and Lewy body dementia.[7] Frontotemporal type is the second most common type of dementia in patients younger than 65 years of age.[7] 

In adults older than 60, the incidence of postoperative delirium is 10% to 20%. Additionally, a mortality of 7% to 10% has been reported in patients with postoperative delirium at 30 days following surgery compared with 1% in those without delirium.[14] Moreover, delirium superimposed on dementia (DSD) ranges from 22% to 89% in hospital and community-dwelling individuals and is often underdiagnosed.[15] A study to assess nursing staff's knowledge showed that only 21% of the nursing staff could recognize hypoactive delirium.[16] According to data extrapolated from many studies, delirium may develop in an estimated 20% to 50% of patients with dementia who are hospitalized, which translates to a 3 to 4 times higher risk of delirium than patients without dementia.[13]

Pathophysiology

Delirium and dementia often coexist. The pathophysiology behind their interrelationship remains poorly understood. Some proposed theories explaining the underlying mechanisms include neuroinflammation, reactive oxygen species, neurotransmitter imbalance, and chronic stress.[4] The underlying pathophysiology differs depending on the subtype of dementia. Accumulation of beta-amyloid plaques, neurofibrillary tangles, and hyperphosphorylated tau protein are the characteristics of Alzheimer disease; aggregates of alpha-synuclein are seen in Lewy body dementia, Parkinson disease, and multiple system atrophy, corticobasal degeneration, progressive supranuclear palsy, and frontotemporal dementia (ie, Pick disease) which are all considered tauopathies.[8] Please see StatPearls' companion resource, "Major Neurocognitive Disorder (Dementia)," for further information on dementia pathologies.

History and Physical

History and physical examination are the mainstays in the diagnosis of delirium and dementia. Obtaining a history from both patients and family members is essential. The first step would be to get the patient's baseline mental and functional status. The second step would be to assess the acuity of the symptom onset, following which a timeline of progression needs to be established. Once a baseline is established, a brief cognitive screening assessment is performed via Mini-Cog and Short Portable Mental Status Questionnaire.[17]

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) requires the following criteria for delirium:

• Disturbance in attention and awareness develops acutely and tends to fluctuate in severity
• At least 1 additional disturbance in cognition
• Disturbances that are not better explained by preexisting dementia
• Disturbances that do not occur in the context of a severely reduced level of arousal or coma
• Evidence of an underlying organic cause or causes [6]

DSM-5 formulated the following criteria to diagnose dementia:

• A significant cognitive decline from the baseline level of performance in 1 or more cognitive domains. This can be based on the concern of the patient, the caregiver, or the significant informant, OR cognitive performance on the neuropsychological testing.
• The cognitive impairment interferes with the activities of daily living
• The cognitive decline does not occur exclusively in the context of delirium 
• Cognitive decline is not better explained by any other medical or psychiatric condition [18][6]

Evaluation

Cognitive Screening

Delirium, also referred to as acute brain failure, requires an urgent evaluation, whereas dementia is more of an outpatient diagnosis requiring a more detailed neurocognitive assessment. To diagnose delirium, evidence from history, physical exam, and medical or laboratory values that the change in mentation is secondary to an underlying medical condition, substance intoxication or withdrawal, medication or toxin exposure, or a combination of factors should be present.[19] 

The key element in delirium diagnosis remains a change from the patient's baseline mental status and the acuity of the change. The Confusion Assessment Method (CAM) algorithm includes the 4 main features of acute onset and fluctuating course of symptoms, inattention, and disorganized thinking or altered mentation, the most widely used criterion for diagnosing delirium. The 3-Minute Diagnostic Assessment (3D-CAM) provides a brief assessment consisting of 3 orientation items, 4 attention items, 3 symptom probes, and 10 observational items. This assessment has a sensitivity of 95% and specificity of 94% compared to a clinical reference standard rating in a prospective validation study in hospitalized patients.[20][21] 

Cognitive Testing

For a definitive diagnosis, an examination should be conducted by a trained healthcare professional with expertise who can perform cognitive testing. For delirium, the physician should test the key components of the CAM algorithm and establish an underlying etiology to explain the delirium. In addition to doing a targeted toxic, metabolic, and infectious workup in a case of delirium, neuroimaging should be performed. In some cases, Electroencephalography (EEG) is performed to rule out status epilepticus. A lumbar puncture is rarely needed when meningoencephalitis is suspected.[13] Inflammation is thought to be a key factor in the pathogenesis of delirium. None of the inflammatory markers have been validated for clinical application in the diagnosis of delirium to date.[17]

On the other hand, once an acute pathology is ruled out, patients with suspected dementia should undergo a thorough evaluation by a neurologist followed by neurocognitive testing and neuroimaging studies. Neurocognitive testing provides a more accurate diagnosis of the subtype of dementia based on the different domains affected. Neuroimaging such as magnetic resonance imaging (MRI) with neuro quant, nuclear positron emission test (PET), single-photon emission computed tomography (SPECT), and functional MRI are sometimes performed to look for the pattern of cerebral atrophy, hippocampal volume, and hypometabolic areas. The Dopamine Transporter Scan (DAT) is explicitly reserved for Parkinson and Parkinson plus syndromes. Genetic testing is seldom performed for cases such as Huntington's disease.

Treatment / Management

Treatment for delirium focuses on identifying and addressing underlying causes, reducing risk factors, and employing nonpharmacologic interventions. Once an etiology or multiple etiologies are identified for delirium, the first-line treatment is nonpharmacologic approaches, including removing or minimizing anticholinergic and psychoactive medications, reorienting the patients creating a quiet, soothing environment.[13][17] For hyperactive delirium, pharmacologic therapies can be used. American Geriatrics Society Clinical practice guidelines published guidelines for prevention and treatment of postoperative delirium. (B3)

In contrast, dementia management includes supportive care and pharmacologic treatments. Early and accurate differentiation between delirium and dementia is essential for effective management and improved patient outcomes. For patients with Alzheimer disease, pharmacotherapy with cholinesterase inhibitors (eg, galantamine, donepezil, rivastigmine) and memantine is approved for moderate to severe dementia in addition to supportive therapies, including cognitive training, cognitive stimulation therapy, and nutritional, physical exercise, and sleep therapies.[7][4][22][4]

Differential Diagnosis

The differential diagnoses for delirium and dementia includes:

• Delirium 
  • Infections: Urinary tract infections, pneumonia, sepsis, meningitis, encephalitis
  • Metabolic disturbances: Hypoglycemia, hyperglycemia, hyponatremia, hypercalcemia, hypoxia, hepatic or renal failure
  • Medications/toxins: Anticholinergics, benzodiazepines, opioids, polypharmacy, alcohol withdrawal
  • CNS disorders: Stroke, traumatic brain injury, epilepsy/postictal state, increased intracranial pressure
  • Systemic illnesses: Decompensated heart failure, malignancies, dehydration, thyroid dysfunction
  • Psychiatric conditions: Acute psychosis, severe depression, mania [5][4][7]
• Dementia
  • Neurodegenerative disorders: Alzheimer’s disease, Lewy body dementia, vascular dementia, frontotemporal dementia, Parkinson’s disease dementia
  • Chronic infections: Neurosyphilis, HIV-associated dementia, prion diseases (e.g., Creutzfeldt-Jakob disease)
  • Toxic/metabolic causes: Chronic vitamin B12 deficiency, Wilson’s disease, normal pressure hydrocephalus, chronic liver/kidney disease
  • Structural brain disorders: Brain tumors, chronic subdural hematomas
  • Autoimmune/inflammatory diseases: Multiple sclerosis, paraneoplastic syndromes, lupus cerebritis
  • Psychiatric conditions: Late-onset schizophrenia, severe depression with cognitive impairment (pseudodementia) [5][4][7][5]

Prognosis

Besides distinguishing delirium from dementia, identifying DSD is critical as it often leads to prolonged length of hospital stay, accelerated cognitive and functional decline, increased healthcare costs, and ultimately death.[17] For patients with delirium, the prognosis is generally guarded. Delirium is preventable in about 30% of the cases.[8] 

Complications

Studies have shown up to 2 to 4 times increased mortality in patients who develop delirium in the ICU setting, and up to 1.5-fold increased risk for death in a year following hospitalization in those admitted to general medical, geriatric service, and nursing home residents with comorbidities such as stroke and dementia.[13]