Major neurocognitive disorder

Last updated: December 5, 2022

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Major neurocognitive disorder (dementia) is an acquired disorder of cognitive function that is commonly characterized by impairments in the memory, language, attention, executive function, social cognition, and/or perceptual-motor domains. Most forms are associated with older age. The most common causes of dementia are neurodegenerative (e.g., Alzheimer disease) and vascular disease. While all subtypes of dementia share impairments in cognition, other clinical features may differ depending on the dementia subtype. Initial diagnosis should focus on patient history and neurological examination, including a cognitive assessment. Additional laboratory tests and neuroimaging studies are often necessary to investigate specific causes. An important differential diagnosis is pseudodementia. In contrast to patients with dementia, individuals with pseudodementia often recall the onset of their cognitive impairments, overestimate their symptoms, and are responsive to treatment with antidepressants. In general, specific pharmacotherapy to slow the loss of cognitive function in dementia is of modest benefit; management should focus on nonpharmacological measures.

Neurodegenerative brain diseases

Additional causes

Think DEMENTIAS for common etiologies of dementia: Degenerative (Alzheimer, Parkinson, Pick disease), Emotional (depression, psychosis), Metabolic (liver or kidney failure, toxins), Endocrine (hypothyroidism), Nutritional (vitamin deficiencies) or Neoplastic (carcinomatous meningitis), Traumatic (TBI), Infectious (syphilis, HIV, CJD), Autoimmune, Stroke.


  • General: memory impairment
  • Additional cognitive impairment
    • Speech: aphasia, word-finding difficulties, semantic paraphasia
    • Intellectual capacities, reasoning, planning capabilities, and self-control
    • Spatial-temporal awareness (however, the awareness of oneself remains stable for a long time)
    • Apathy
  • Changes in personality, mood, and behavior
    • Early stages: depression
    • Later stages: seemingly unconcerned mood and cognitive impairment is downplayed
  • Dementia associated with CNS infections


Approach [2][3]

The USPSTF has found insufficient evidence for or against screening for cognitive impairment in individuals with no symptoms; however, assessment for cognitive impairment is a routine part of the Medicare Annual Wellness Visit. [4]

Diagnostic criteria for neurocognitive disorders [2][5][6]

Diagnostic criteria for major neurocognitive disorder (dementia)

These criteria are in accordance with DSM-5. Unlike DSM-5, ICD-10 includes memory impairment as a diagnostic criterion.

DSM-5 diagnostic criteria for major neurocognitive disorder (dementia) [2][5]
Decline in ≥ 1 domain
Additional requirements

Diagnostic criteria for mild neurocognitive disorder (mild cognitive impairment)

Diagnostic criteria are similar to dementia, with the following differences:

  • Cognitive deficits are less severe, i.e., do not interfere with everyday life.
  • Patients are typically aware of their deficits.

The defining difference between MCI and dementia is the degree of functional impairment and cognitive decline.

Initial evaluation of major neurocognitive disorder [2][3]

Obtain the following studies in all patients with suspected dementia to identify the cause of dementia and/or rule out other causes (e.g., delirium).

Additional studies [2][10]

Obtain as indicated under specialist guidance in patients with a rapidly progressive course of dementia, early-onset dementia (< 65 years), or symptoms, risk factors, or other findings suggestive of a specific type of dementia.

General principles [2][3][13][14]

Obtain neuropsychological testing if there is diagnostic uncertainty despite the use of extensive screening tools.

Overview of cognitive screening tools

Overview of cognitive screening tools
Time requirement Test Domains assessed Important considerations
< 5 minutes

Clock-drawing test [15]

  • Free for general use
  • Commonly used as part of or in combination with other screening tools

Memory Impairment Screen (MIS) [16]

  • Free for general use
  • Scoring
    • Range: 0–8
    • ≤ 4 suggests cognitive impairment

Mini-Cog [17][18]

  • Free for general use
  • Reliable results across ethnolinguistically diverse populations
  • Scoring
    • Range: 0–5
    • < 3 suggests cognitive impairment

Six-item screener (SIS) [19]

  • Free for general use
  • Scoring
    • Range: 0–6
    • ≤ 4 suggests cognitive impairment
5–15 minutes

Mini Mental State Examination (MMSE) [20]

  • Proprietary test; requires a fee for use
  • Considered easier than MoCA
  • Scoring
    • Range: 0–30
    • < 24 suggests cognitive impairment

Montreal Cognitive Assessment (MoCA) [21]

  • One-hour training and certification are required before use.
  • Distinguishes between MCI and dementia better than MMSE
  • May be too difficult for patients with advanced dementia
  • Scoring
    • Range: 0–30
    • < 26 suggests cognitive impairment

Saint Louis University Mental Status Examination (SLUMS) [22]

  • Free for general use
  • More sensitive than MMSE, especially for detecting MCI
  • Accounts for level of education
  • Scoring
    • Range: 0–30
    • < 27 suggests cognitive impairment

Differential diagnosis of subtypes of dementia [23]

Course of disease

Distinctive clinical features

Studies & imaging


Normal aging
  • Insidious onset, typically starting in the sixth/seventh decade
  • Mild decline in some cognitive areas → episodic and working memory affected first
  • Procedural and semantic memory typically preserved
  • Independence in daily activities is preserved
  • No specific tests available
Pseudodementia [24]
  • Associated with major depression, especially in elderly patients
  • Cognitive deficits typically manifest after mood symptoms
  • Typically sudden onset
  • Mimics dementia
  • Complaints of memory loss
  • Mostly depressed mood
  • Patients are able to recall onset of symptoms.
  • Patient gives short answers, e.g., “I don't know”
  • Cognition usually improves after effective antidepressant therapy.
  • No specific tests available
  • Structural or metabolic abnormalities that are associated with depression (e.g., lesions of the limbic system)

Alzheimer disease (AD)

  • Slowly progressive, over ∼ 8–10 years
  • Episodic impairment of memory
  • Characteristic order of language impairment: naming → comprehension → fluency

Vascular dementia (VD)

  • May present with abrupt cognitive decline and stepwise deterioration

Dementia with Lewy bodies (DLB)

  • Steady decline; typically over ∼ 8–10 years but more rapid progression is possible

Frontotemporal dementia (FTD)

  • Usually manifests between ages 40–69
  • Behavioral variant FTD (most common) → early changes in personality, apathy

Normal pressure hydrocephalus (NPH)

  • Potentially reversible
  • CT/MRI: relative dilatation of ventricles with periventricular hyperintensities

  • Lumbar puncture alleviates symptoms
  • Cognitive impairment develops in advanced disease

Wernicke encephalopathy (WE) and Wernicke-Korsakoff syndrome (WKS)

  • Potentially reversible
Late neurosyphilis
  • Progresses many years after primary infection (∼ 20 years)

Wilson disease

  • Begins with subclinical hepatitis and progresses to liver cirrhosis and neuropsychiatric involvement if left untreated

Progressive multifocal leukoencephalopathy (e.g., in AIDS)

  • Symptoms due to PML are insidious in onset and can progress over several weeks
Creutzfeld-Jakob disease
  • Myoclonus triggered by startling (e.g., loud noises)
Huntington disease
  • Steady decline over 15–20 years

Think VITAMINS for the most common causes of rapidly progressive dementia: Vascular, Infectious, Toxic-metabolic, Autoimmune, Metastases, Iatrogenic, Neurodegenerative, Systemic/Seizures/Structural.

The differential diagnoses listed here are not exhaustive.

Approach [3][28][29]

  • Provide disease-specific treatment if available.
  • Initiate supportive management and management of associated conditions.
  • Arrange support for patients and their caregivers. [3][30][31]
  • Consider referral to hospice for eligible patients. [32]

Behavioral problems (e.g., physical agitation) and fecal incontinence in patients with dementia are associated with caregiver burnout and poor outcomes for patients (e.g., emergency department visits and institutionalization). [3][29][33]

Pharmacological treatment of dementia [3][28][30]

Antidementia medications provide limited improvement of cognitive symptoms. Use shared decision-making to review risks, benefits, and alternatives to pharmacotherapy. [28][31]

Supportive management of patients with dementia [3][28][31]

Memory training (i.e., cognition-oriented treatments) may modestly delay cognitive decline. However, these programs can lead to excessive frustration, which may exacerbate behavioral and neuropsychiatric symptoms. [28][31]

Patients with dementia are less likely to receive adequate pain management at the end of life. Consider using a nonverbal pain scale to assess pain, and follow a step-wise approach to analgesia.

Safety considerations

  • Inform the patient and caregivers about increased risk of driving accidents.
  • Consider referral for driving safety evaluation to assess for driving restrictions.
  • Consider the need for interventions (e.g., supervision) to prevent wandering.
  • Evaluate for risk of falls using the CDC STEADI algorithm.

Advance care planning (ACP) [35]

Management of neuropsychiatric conditions [3][32]

Avoid drugs with strong anticholinergic effects (e.g., tricyclic antidepressants, diphenhydramine) and use the lowest effective dose of psychoactive drugs. [30]

Management of conditions in advanced dementia [3][32]

Malnutrition and weight loss [38]

  • Perform a nutritional assessment for older adults every 3–6 months.
  • Assess for potential causes and initiate management accordingly.
  • Ensure support to enable adequate food intake as needed.
  • Avoid dietary restrictions and recommend providing food based on personal preference.
  • Avoid appetite stimulants.
  • Individualize decisions on artificial nutrition and hydration.
    • Consider time-limited use of a gastrointestinal tube in patients with mild to moderate dementia.
    • Do not initiate tube feeding in patients with severe or terminal-stage dementia.
    • Withholding nutrition and hydration at the end of life is not thought to cause discomfort. [32]

Fecal and urinary incontinence


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