• Clinical science

Major neurocognitive disorder (Dementia)


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 dementia patients, individuals suffering from pseudodementia can often recall the onset of their cognitive impairments, exaggerate their symptoms, and are remarkably responsive to treatment with antidepressants.


Major neurocognitive disorder (previously dementia): Dementia is an acquired disorder of cognitive function, commonly characterized by impairments in memory, speech, reasoning, intellectual function, and/or spatial-temporal awareness


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
  • Dementia associated with CNS infections
    • Most types of CNS infections cause acute neurological or psychiatric symptoms rather than dementia.
    • Infections that may cause symptoms of dementia include:




  • 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
    • Learning and memory
    • Language
    • Executive function
    • Complex attention
    • Perceptual-motor
    • Social cognition
  • 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: : The MMSE is a screening tool that assesses the degree of cognitive impairment in individuals with suspected dementia.
    • Orientation capabilities: questions regarding year, season, date, day, month, country, state, city, address, and floor level
    • Registration (immediate memory): Three words are mentioned that must be repeated immediately.
    • Attention and calculation: Beginning with 100, the patient counts backwards every 7 numbers (100, 93, 86, 79, etc.). The patient is asked to spell a word backwards, e.g., “price”.
    • Recall (short-term memory): The patient is asked to repeat the 3 previously given words after some time.
    • Speaking capabilities and understanding: ability to rename objects shown, repeat a sentence, accomplish a 3-part order, read and follow a written request, write a complete sentence, and trace a geometric figure
  • Diagnostic criteria
    • A maximum of 30 points are 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

Saint Louis University Mental Status Examination (SLUMS)

  • Definition: a screening tool to assess the degree of cognitive impairment in individuals with suspected dementia
    • Orientation: questions regarding time (i.e., day of the week, year) and place (i.e., state)
    • Memory
      • Five objects are named and the patient is asked to recall them after later
      • A series of numbers are provided which the patient needs to recall backwards (e.g., if you say 42, they should say 24)
      • You tell the patient a short story and inform them to pay careful attention because you'll ask a few questions about it immediately afterwards (e.g., what is the main character's name and job)
    • Attention and calcuation
      • The patient is theoretically provided with a $100 budget and are told that they buy a dozen apples for $3 and a tricycle for $20
      • Ask how much money they have spent and how much they have left
    • Executive function
      • The patient is asked to draw the hour markers and a specific time within an empty clock face (i.e., circle)
      • Provide the patient with a drawing of a triangle, square (draw it larger than the other shapes), and rectangle, then ask them to place an X in the triangle and determine which figure is the largest in size
  • Diagnostic criteria
    • A maximum of 30 points is possible
    • A patient who scores 19 points or less suffers from neurocognitive impairment
High School education Less than High School education
Normal 27–30 20–30
Mild neurocognitive disorder 20–27 14–19
Dementia 1–19 1–14

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
  • Neuritic plaques (amyloid beta peptides, mainly accumulating extracellularly)
  • Neurofibrillary tangles (abnormally phosphorylated tau protein, which accumulates intracellularly)

Vascular dementia (VD)

  • May present with abrupt cognitive decline and stepwise deterioration
  • Asymmetric or focal deficits (e.g., hemiparesis)

Dementia with Lewy bodies (DLB)

  • Steady decline; typically over ∼ 8–10 years but more rapid progression is possible
  • Visual hallucinations and parkinsonian motor disorders
  • Attention impairment
  • SPECT: may reveal decreased occipital perfusion/metabolism
  • 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
  • CSF: ↑ Aβ 1–42
  • PET or SPECT to reveal metabolic disorders in the frontal and temporal lobes
  • Focal cortical atrophy
  • Neurons and glia cells show characteristic protein inclusions (in most cases tau and/or TDP-43, rarely FUS)

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
  • WE (classic clinical triad)
    • Confusion
    • Ataxia
    • Ophthalmoplegia
  • WKS
    • Severe anterograde and retrograde amnesia, apathy, confusion, anosognosia
    • Other cognitive capacities remain comparatively intact.
Late neurosyphilis
  • Progresses many years after primary infection (∼ 20 years)
  • Direct detection possible via darkfield microscopy


  • 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


Cholinesterase inhibitors


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

Adjuvant treatment

This section provides an overview of pharmacological and nonpharmacological strategies of treating associated disorders in patients suffering from dementia. The given measures do not necessarily apply to all types of dementia and individual indications and contraindications must always be considered.

Tricyclic antidepressants (e.g., imipramine) should generally NOT be administered because they may worsen cognitive function!

  • Sleep disorders
    • In general, nonpharmacological treatment is preferred
      • Environmental restructuring (e.g., moving the patient to a single bedroom, if possible)
      • General sleep hygiene (sufficient exercise, limited alcohol intake in the evening, stimulus control, consistent sleep-wake cycles, etc.)
      • Evaluation of drug effects or interactions that may disturb sleep; possible adjustment of medication
    • Pharmacotherapy: not generally recommended; in some cases, melatonin or trazodone may be beneficial.
    • If specific conditions (e.g., restless legs syndrome or insomnia due to depression) are identified, these conditions should receive specific treatment.
  • Pain: step-wise approach, starting with a low-dose trial in combination with systematic monitoring and reevaluation
  • Anxiety: Benzodiazepines should be used carefully and only for brief periods (e.g., during stressful changes in environment that cannot be avoided); drugs with shorter half-lives (e.g., oxazepam) are generally preferable.
  • Agitation/psychosis:
  • General nonpharmacologic measures
    • Avoid sudden changes in patient routine or environment; provide reassuring psychosocial interaction (e.g., speak softly and slowly; in general, avoid disagreeing with the patient).
    • Physical exercise (with specially trained personnel) may improve symptoms (especially in the case of Alzheimer disease).
    • Music therapy and animal‑assisted therapy may also be beneficial for some patients.