Continuing Education Activity

Delirium and dementia are the most common causes of altered mental status in elderly patients. With dementia being one of the predisposing factors for delirium, often the two coexist, and sometimes when the dementia is rapidly progressive, it can be difficult to differentiate the two in patients without a prior history of dementia. This activity highlights the interprofessional team's role in the evaluation and management of patients with delirium and dementia.

Objectives:

• Outline the features of delirium and dementia.
• Review the occurrence of superadded delirium in patients with dementia.
• Explain the importance of differentiating delirium and dementia in elderly patients.
• Review the distinct features of delirium and dementia based on the history, physical exam, and diagnostic modalities.

Introduction

Altered mental status is one of the most common presenting symptoms in elderly patients often related to 3 Ds- delirium, dementia, and depression.[1] Out of the 3 Ds, Delirium and dementia are more commonly encountered in clinical practice. Most of the time, the two terms are used interchangeably and therefore unrecognized on the initial assessment. It is critically important to understand that delirium and dementia are distinct syndromes with different prognoses and management.[2] While an acute confusional state that fluctuates and develops over days to weeks is likely to be delirium, a more persistent and chronic progression suggests dementia.[3] This distinction is blurred in cases of persistent delirium and reversible dementia. Cognition is assessed in six domains: memory and learning, language, executive functioning, complex attention, perceptual-motor, and social cognition.[4] 

Delirium is characterized by altered awareness mainly affecting attention, whereas dementia is defined as cognitive decline, which interferes with 1 or more domains.[5] Delirium is an abrupt onset of reduced orientation or awareness to the environment in contrast to dementia which is a gradual process leading to disturbance in the core features, and attention is affected much later in the disease course.[6] 

Typically, dementia is a neurodegenerative disorder seen in older age and is of various subtypes with the age of onset depending on the subtype. On the other hand, delirium is an age-independent process that occurs more commonly in elderly patients and can happen under variable circumstances. Delirium typically occurs from hours to days, versus dementia is a slow progressive course over months to years. Often the two coexists in the elderly, and sometimes when the dementia is rapidly progressive. It can be difficult to differentiate the two in patients without a prior history of dementia. Therefore, it becomes essential to distinguish between the two or to discern if superadded delirium in a pre-existing dementia patient (delirium superimposed dementia or DSD) leads to a prolonged hospital stay and accelerated cognitive and functional decline, increased healthcare costs, and ultimately death.[7]

Etiology

Delirium is multifactorial and has various predisposing and precipitating factors.[3] Predisposing factors include age above 70 years, male gender, and dementia, and the most common precipitating factors are medications, acute illness, infections, and exacerbation of chronic medical illnesses.[8] 

On the other hand, dementia is a neurogenerative process that occurs 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 such as the APOE e4 allele for Alzheimer's disease (AD), and seldomly due to prion infections as in the case of Creutzfeldt-Jakob disease (CJD).[5] Studies have shown delirium to be an independent risk factor for the development of dementia.[9]

Epidemiology

The incidence of delirium increases with age. In the community setting, it is a low as 1% to 2%. However, it increases to 8% to 17% in older patients presenting to the emergency center to as high as 40% among nursing home residents.[10] AD is the most common type of dementia, followed by vascular and Lewy body dementia (LBD).[5] Frontotemporal type is the second most common type of dementia in patients below 65 years of age.[5] DSD ranges from 22% to 89% in hospital and community-dwelling individuals and is often underdiagnosed.[11] A study to assess nursing staff's knowledge showed that only 21% of the nursing staff were able to recognize hypoactive delirium.[12]

Pathophysiology

Delirium and dementia often coexist. The pathophysiology behind their interrelationship remains poorly understood. Some of the proposed theories explaining the underlying mechanisms include neuroinflammation, reactive oxygen species, neurotransmitter imbalance, and chronic stress.[3] 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 and Corticobasal degeneration, Progressive supranuclear palsy, and frontotemporal dementia (Pick disease) are considered tauopathies.[6]

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 important. First and foremost is to get the patient's baseline mental and functional status. Secondly, acuity of the symptom onset and a timeline of the 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.[13]

The Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 requires the following criteria for delirium:[4]

• Disturbance in attention and awareness develops acutely and tends to fluctuate in severity.
• At least one 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.

DSM-5 formulated the following criteria to diagnose dementia:[4]

• A significant cognitive decline from the baseline level of performance in one or more cognitive domains. This can be based on the concern of the patient, or the caregiver or 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 a delirium 
• Cognitive decline is not better explained by any other medical or psychiatric condition.

Evaluation

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, there should be evidence from history, physical exam, medical or laboratory values that the change in mentation is the direct consequence of underlying medical condition or substance intoxication or withdrawal, medication or toxin exposure, or a combination of factors.[14] 

The key element in delirium diagnosis remains a change from the patient's baseline mental status and the change's acuity. The Confusion Assessment Method (CAM) algorithm includes the 4 main features (acute onset and fluctuating course of symptoms, inattention, and disorganized thinking or altered mentation). It is the most widely used criteria for diagnosing delirium. The 3-Minute Diagnostic Assessment (3D-CAM) provides a brief assessment (3 orientation items, 4 attention items, 3 symptom probes, and 10 observational items) has a sensitivity of 95% and specificity of 94% when compared to a clinical reference standard rating in a prospective validation study in hospitalized patients.[15][16] 

For a definitive diagnosis, an examination should be conducted by a trained 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 organic etiology or etiologies to explain the delirium. In addition to doing a targetted 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. Rarely a lumbar puncture (LP) is needed when suspecting meningoencephalitis.[10] 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.[13]

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. The neurocognitive testing provides a more accurate diagnosis of the subtype of dementia based on the different domains affected. Neuroimaging such as magnetic resonant (MR) with neuro quant, nuclear positron emission test (PET), SPECT, and functional MRI are sometimes performed to look for the pattern of cerebral atrophy, hippocampal volume, and hypometabolic areas. The rest of the diagnostic modalities are reserved for specific diagnoses, such as Dopamine Transporter Scan (DAT) for Parkinson and Parkinson plus syndromes. Seldomly, genetic testing is performed for cases such as Huntington's disease, some cases of AD (early and late-onset). 

Treatment / Management

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.[10][13] For hyperactive delirium, pharmacologic therapies can be used. American Geriatrics Society Clinical practice guidelines published guidelines for prevention and treatment of postoperative delirium. For patients with Alzheimer disease, pharmacotherapy with cholinesterase inhibitors (e.g., galantamine, donepezil, rivastigmine) and memantine is approved for moderate to severe dementia. The rest is supportive care.[5][3]

Differential Diagnosis

The differential diagnosis includes:[3][5]

• Dementia
• Depression
• Psychosis
• Vitamin B1 and B12 deficiency
• Thyroid disorders
• Infections such as HIV and neurosyphilis

Prognosis

Besides distinguishing delirium from dementia, it is crucial to identify superadded delirium in a pre-existing dementia patient as it leads to prolonged length of hospital stay, accelerated cognitive and functional decline, increased healthcare costs, and ultimately death.[13] For patients with delirium, the prognosis is generally guarded. Delirium is preventable in about 30% of the cases.[6] 

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.[10]

Pearls and Other Issues

1. The terms delirium and dementia are different entities yet are used interchangeably due to their overlapping features. 
2. Delirium is an abrupt onset of reduced orientation to the environment in contrast to dementia, a gradual neurodegenerative process leading to the disturbance in the core features, and attention is affected much later in the disease course.
3. Some exceptions to point #2 are sudden-onset cognitive decline with vascular dementia and gradual onset delirium with chronic aspirin exposure.[7]
4. Dementia is a precipitating factor for the development of delirium in elderly patients, and also delirium is an independent risk factor for the development of dementia. 
5. Delirium can be preventable and reversible, whereas dementia is not reversible except in normal pressure hydrocephalus and in the case of pseudodementia resulting from B12 deficiency, thyroid disorders, syphilis, and depression.[17]
6. Delirium can be superimposed on dementia due to multiple etiologies. Therefore it requires a thorough workup for the diagnosis.[18]
7. Unlike delirium, patients with dementia tend to have a state of wakefulness, and the baseline deficits tend to be fixed.[7] 
8. Delirium can signify some serious underlying medical condition and can be fatal in the elderly population. Early recognition and risk stratification can help improve the outcome.[13]
9. The fluctuation in cognition is one of the core features of Lewy Body Dementia (LBD), which can mimic a delirious state. Delirium and LBD have many similarities. Parkinsonian features, dysautonomia, neuroleptic sensitivity, and other supportive neuroimaging features can help with the accurate diagnosis.[19]
10.  DSD ranges from 22% to 89% in hospital and community-dwelling individuals. DSD is underdiagnosed due to a lack of proper evaluation. Failure to recognize DSD is associated with $38 to$152 billion annually.[11]

Enhancing Healthcare Team Outcomes

Differentiating delirium and dementia is critically important and can be challenging in many cases. Delirium is a common occurrence in elderly patients and is often overlooked in the elderly due to concurrent history of dementia. The two are distinct pathologic processes with different management and prognoses. Delirium suggests serious medical issues and usually carries a poor prognosis.

Interprofessional teamwork, including an emergency room provider, neurologist, neuropsychologist, geriatrician, and intensivist, is warranted. Besides, pharmacists, physical and occupational therapists, nursing, and case management staff also play a vital role. Pharmacists play an important role by providing us with important information about pharmacokinetics and potential drug interactions requiring frequent monitoring. Physical and occupational therapists help with mobility and structured activities to focus patients. The role of the nursing staff is pivotal in taking care of all the basic needs of demented patients. Social workers play a significant role by getting the providers in touch with their family and during transitions of care.

Some of the barriers that may hinder clinical improvement are failing to distinguish the two early on or identifying superadded delirium in a demented patient. Therefore a holistic and integrated approach via an interprofessional team can lead to early recognition and risk stratification, improving patient outcomes. [Level 5]