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
- Alzheimer disease (> 50% of dementia cases)
- Parkinson disease
- Frontotemporal dementia
- Dementia with Lewy bodies
- Progressive supranuclear palsy
- Huntington disease
Cerebrovascular disease (20% of dementia cases)
- Multi-infarct dementia
- Diffuse white matter disease (subcortical arteriosclerotic encephalopathy)
- Hypoxic brain damage
- Normal pressure hydrocephalus
- After head trauma, intracranial bleeding or brain tumors
- Drug/alcohol‑related (e.g., Wernicke‑Korsakoff syndrome)
- Wilson disease
- Vitamin deficiencies (thiamine, B6, B12, folate)
- Metabolic: exsiccosis, uremia, electrolyte imbalances
- Endocrine: hypothyroidism and hyperthyroidism, hypoparathyroidism and hyperparathyroidism
- Environmental toxins
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
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:
- Chronic meningitis
- HIV and HIV-related opportunistic infections
Perform a comprehensive clinical evaluation, including:
- Detailed history of cognitive decline
- Evaluation for risk factors for and/or symptoms of specific types of dementia
- Neurological examination, including a mental status examination and cognitive assessment
Assess for reversible causes of cognitive impairment, including; delirium and pseudodementia.
- See “Delirium vs. dementia.”
- Review medications on the Beers Criteria.
- Screen for major depressive disorder using PHQ-2.
- Confirm the diagnosis using DSM-5 diagnostic criteria for neurocognitive disorders.
- Obtain laboratory tests and neuroimaging to assess for underlying causes of major neurocognitive disorder.
- Refer patients with early-onset dementia, rapidly progressive dementia, or if more information is needed to guide management.
- Neurology: specialized testing, including neuroimaging, CSF evaluation, EEG, or genetic testing
- Geriatric psychiatry: full neuropsychological testing
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. 
Diagnostic criteria for neurocognitive disorders 
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) |
|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 
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).
- Vitamin B12 (cobalamin): assess for deficiency
- TSH: hypothyroidism
- CBC: anemia
- CMP: kidney disease, liver disease, and hypoglycemia or hyperglycemia
- Urinalysis: rule out infection
- Brain MRI is the preferred modality.
- Obtain to detect reversible or structural causes of dementia.
- Findings depend on the underlying disease and frequently include cortical atrophy.
- See “Differential diagnosis of subtypes of dementia” for a comparison of imaging findings.
Additional studies 
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.
- CBC with differential
- Folate (vitamin B9) and homocysteine: ↓ folate and ↑ homocysteine associated with cognitive impairment 
- ESR, CRP, ANA: inflammatory or autoimmune diseases
- RPR: if there is clinical suspicion for neurosyphilis
- Lyme titers: if there is clinical suspicion for chronic neuroborreliosis
- HIV screening: to rule out HIV-associated neurocognitive disorder
- Ceruloplasmin: to rule out Wilson disease
- Urine toxicology screen
Lumbar puncture to: 
- Assess for evidence of CNS inflammation (e.g., meningitis, encephalitis) or prion disease
- Detect specific biomarkers (e.g., in Alzheimer disease)
- Confirm normal pressure hydrocephalus (CSF tap test)
- PET scan or SPECT: to distinguish between specific neurodegenerative disorders
- Electroencephalogram (EEG): to evaluate for seizures, subcortical dementia, and frontal lobe degeneration 
General principles 
- Shorter screening tools (e.g., Mini-Cog) have adequate sensitivity and specificity for detecting dementia in most situations.
- Utilize a more extensive screening tool (e.g., Mini-Mental State Examination or Montreal Cognitive Assessment):
- For diagnostic clarity
- To assess the degree of cognitive impairment (e.g., MMSE < 24 suggests cognitive impairment)
- Factors such as education level, language, and illness can impact results.
- Repeat measurements to track disease progression over time.
- See “Mental status examination” for further details on cognitive domains.
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 
Memory Impairment Screen (MIS) 
Six-item screener (SIS) 
|5–15 minutes|| |
Mini Mental State Examination (MMSE) 
Montreal Cognitive Assessment (MoCA) 
Saint Louis University Mental Status Examination (SLUMS) 
|Differential diagnosis of subtypes of dementia |
Course of disease
|Distinctive clinical features|| |
Studies & imaging
|Normal aging|| || || || |
|Pseudodementia || || || || |
Alzheimer disease (AD)
| || || || |
Vascular dementia (VD)
| || || |
| || || || |
| || || |
| || || || |
|Parkinson|| || || |
Wernicke encephalopathy (WE) and Wernicke-Korsakoff syndrome (WKS)
| || || |
|Late neurosyphilis|| || || || |
| || || || |
Progressive multifocal leukoencephalopathy (e.g., in AIDS)
| || || || |
|Creutzfeld-Jakob disease|| || || || |
|Huntington disease|| || || |
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.
- Provide disease-specific treatment if available.
- Initiate supportive management and management of associated conditions.
- Arrange support for patients and their caregivers. 
- Consider referral to hospice for eligible patients. 
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). 
Pharmacological treatment of dementia 
- Antidementia medications may provide modest benefit for cognitive symptoms in some types of dementia.
Cholinesterase inhibitors (donepezil, galantamine, rivastigmine)
- Recommended for mild to moderate Alzheimer disease
- May be considered in patients with Parkinson dementia or Lewy body dementia
- NMDA-receptor antagonist (memantine): recommended for moderate to severe Alzheimer disease
- See “Antidementia medications” in “Alzheimer disease” for more information on indications and contraindications.
Antidementia medications provide limited improvement of cognitive symptoms. Use shared decision-making to review risks, benefits, and alternatives to pharmacotherapy. 
Supportive management of patients with dementia 
- Regularly evaluate for associated medical, psychiatric, or behavioral conditions.
- Manage risk factors (e.g., with ASCVD prevention).
- Use delirium prevention strategies.
- Treat hearing loss and vision loss if necessary.
- Periodically reassess care needs (see “Geriatric assessment”). 
- Coordinate functional status assessments.
- Offer psychoeducation.
- Assess for caregiver burnout and provide referrals for assistance.
- Encourage early advance care planning and financial planning.
- Recommend maintaining a:
- Predictable schedule
- Familiar home environment
- Encourage a healthy lifestyle, including:
- Recreational activities, e.g., social gatherings, art, puzzles, music, pet therapy
- Mediterranean diet
- Sleep hygiene, including a regular sleep schedule
- Personal hygiene
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. 
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.
- 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) 
- Discuss ACP at the time of diagnosis, or with changes in health status, residence, or financial situation.
- Document wishes and preferences, including a physician orders for life sustaining treatment, advance directive, and medical power of attorney.
- Consider a specific advance directive for dementia. 
- Assess decision-making capacity regularly.
Management of neuropsychiatric conditions 
Major depressive disorder and anxiety: Consider low dose of an SSRI (e.g., escitalopram or citalopram). 
- Consider low dose of an SSRI (e.g., escitalopram or citalopram).
- See “Depression in older adults.”
Agitation and psychosis 
- Avoid antipsychotic medications if possible.
- Focus on delirium prevention and nonpharmacological deescalation. 
- If other approaches have failed or the patient poses a substantial threat to themself or others, consider one of the following:
- Citalopram 
- Low dose of an antipsychotic
- If indicated, administer under medical supervision and in a time-limited fashion.
- See “Delirium management” and “Management of the agitated patient.”
Sleep disorders and disturbances 
- Nonpharmacological measures are preferred, e.g.:
- Sleep hygiene
- Environmental restructuring
- Address possible underlying causes (e.g., drug effects, nocturia, pain).
- Consider pharmacotherapy for insomnia (e.g., trazodone) if other methods have failed and benefits are expected to outweigh the risks.
- Avoid medications that increase the risk of delirium, disinhibition, daytime sedation, and/or falls.
- Nonpharmacological measures are preferred, e.g.:
Avoid drugs with strong anticholinergic effects (e.g., tricyclic antidepressants, diphenhydramine) and use the lowest effective dose of psychoactive drugs. 
Management of conditions in advanced dementia 
Malnutrition and weight loss 
- 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. 
Fecal and urinary incontinence
- Evaluate for potentially reversible causes.
- Ensure adequate hygiene to avoid skin breakdown and infections.
- Use pharmacotherapy with caution; conservative management is preferred, e.g., prompted voiding.
- See “General treatment of urinary incontinence”.
- Focus on prevention.
- Assess for aspiration risk factors.
- Avoid indwelling urine catheters.
- Monitor skin for pressure ulcers.
- Ensure antimicrobial treatment is only administered if patients meet indications. 
- If indicated, prescribe targeted antibiotic therapy in keeping with the patient's goals of care.
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