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Major neurocognitive disorder

Last updated: June 12, 2020


Major neurocognitive disorder (previously called dementia) is an acquired disorder of cognitive function that is commonly characterized by impairments in memory, speech, reasoning, intellectual function, and/or spatial-temporal awareness. The potential causes of dementia are diverse, but the disorder is mainly due to neurodegenerative and/or vascular disease and as such, most forms are associated with increased age. Initial diagnosis should focus on the patient history, followed by cognitive assessments (e.g., the mini‑mental state exam) and physical examination. To confirm or rule out specific etiologies, additional laboratory tests or imaging studies are often necessary. Pharmacotherapy is available but is often met with little success because of the chronic and progressive nature of dementia.

An important differential diagnosis is pseudodementia, which is primarily associated with cognitive deficits in older patients with depression. In contrast to patients with dementia, individuals with pseudodementia can often recall the onset of their cognitive impairments, exaggerate their symptoms, and are remarkably responsive to treatment with antidepressants.


Neurodegenerative brain diseases

Additional causes


Clinical features

  • 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




  • Personal and collateral history of cognitive and behavioral changes
  • Drug history
  • Screening for depression
  • Physical and neurological examination

Diagnostic criteria for major neurocognitive disorder (previously dementia) in accordance with DSM-5

  • Significant cognitive decline in at least one of the following domains
  • Cognitive deficits interfere with everyday life, patient becomes dependent on help with complex activities (e.g., paying bills)
  • Cognitive deficits do not occur exclusively in the context of a delirium
  • Cognitive deficits are not better explained by another mental disorder (e.g., major depression)

Cognitive assessment

Mini-Mental State Examination (MMSE)

  • Definition: a screening tool that assesses the degree of cognitive impairment in individuals with suspected dementia
  • Diagnostic criteria
    • A maximum of 30 points is possible
    • A patient who scores 24 points or less is generally considered to have dementia.
      • 20–24 points: mild dementia
      • 13–20 points: moderate dementia
      • < 13 points: advanced dementia

Montreal Cognitive Assessment (MoCA)

  • Definition: a screening tool that assesses cognitive impairment
    • Includes testing of memory, visuospatial ability (e.g., by drawing a clock and copying a drawing of a cube), executive function, attention, language, abstraction (e.g., identifying similarity between a train and a bicycle), recall, and orientation to time and place.
  • Diagnostic criteria
    • A maximum of 30 points is possible
      • 18–25 points: mild cognitive impairment
      • 10–17 points: moderate cognitive impairment
      • < 10 points: severe cognitive impairment

Saint Louis University Mental Status Examination (SLUMS)

  • Definition: a screening tool to assess the degree of cognitive impairment in individuals with suspected dementia
  • Diagnostic criteria
    • A maximum of 30 points is possible
    • A patient who scores 19 points or less suffers from neurocognitive impairment

Clock-drawing test

  • Procedure: The patient is given a sheet of paper with an empty circle on which they are asked to draw a clock indicating the current time (including numbers and hands).
  • Purpose: If an individual is unable to correctly draw the numbers and hands on the clock, a deficit in spatial or abstract thinking may be present. These deficits are commonly already present during the early stages of dementia.

Neuropsychologic testing

Lab tests



Differential diagnoses

Course of disease

Distinctive clinical features

Studies & imaging


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
  • Lewy bodies (intracellular aggregations of mainly α-Synuclein)

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

Wernicke encephalopathy (WE) &

Wernicke-Korsakoff syndrome (WKS)

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


  • 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)
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
  • General loss of brain volume (white matter more affected than grey matter)


The differential diagnoses listed here are not exhaustive.


Memory training

  • Cognitive capabilities can be improved through targeted stimulation (e.g., practicing image recognition, completing arithmetic or combinatorial problems).
  • Recalling past memories

Antidementia drugs

Cholinesterase inhibitors

To remember Donepezil, rivastigmine, and galantamine, think of “Dona Riva dances at the nursing home gala.”


In general, anticholinergic substances (e.g., tricyclic antidepressants) should be avoided, as they may lead to further deterioration in cognitive functioning!



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