(Major Neurocognitive Disorder)

ByJuebin Huang, MD, PhD, Department of Neurology, University of Mississippi Medical Center
Reviewed/Revised Feb 2023
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Dementia is chronic, global, usually irreversible deterioration of cognition. Diagnosis is clinical; laboratory and imaging tests are usually used to identify treatable causes. Treatment is supportive. Cholinesterase inhibitors can sometimes temporarily improve cognitive function.

(See also Overview of Delirium and Dementia.)

Dementia may occur at any age but affects primarily older people. It accounts for more than half of nursing home admissions.

Dementias can be classified in several ways; one way is

  • Alzheimer or non-Alzheimer type

  • Cortical or subcortical

  • Irreversible or potentially reversible

  • Common or rare

Dementia should not be confused with delirium, although cognition is disordered in both. The following helps distinguish them:

  • Dementia affects mainly memory, is typically caused by anatomic changes in the brain, has slower onset, and is generally irreversible.

  • Delirium affects mainly attention, is typically caused by acute illness or drug toxicity (sometimes life threatening), and is often reversible.

Other specific characteristics also help distinguish the two disorders (see table Differences Between Delirium and Dementia).

Etiology of Dementia

Dementias may result from primary diseases of the brain or other conditions (see table Classification of Some Dementias).

The most common types of dementia are

Dementia also occurs in patients with Parkinson disease, Huntington disease, progressive supranuclear palsy, Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, other prion disorders, neurosyphilis, a traumatic brain injury (eg, chronic traumatic encephalopathy), or certain brain tumors located in cortical or subcortical brain areas involved in cognition. Patients can have > 1 type (mixed dementia). The most common mixed dementia is Alzheimer disease mixed with vascular cognitive impairment and dementia.

Some structural brain disorders (eg, normal-pressure hydrocephalus, subdural hematoma), metabolic disorders (eg, hypothyroidism, vitamin B12 deficiency), and toxins (eg, lead) cause a slow deterioration of cognition that may resolve with treatment. This impairment is sometimes called reversible dementia, but some experts restrict the term dementia to irreversible cognitive deterioration.

Depression may mimic dementia (and was formerly called pseudodementia); the two disorders often coexist. However, depression may be the first manifestation of dementia.

Age-associated memory impairment refers to changes in cognition that occur with aging. Older people have a relative deficiency in recall, particularly in speed of recall, compared with recall during their youth. These changes do not affect daily functioning and thus do not indicate dementia. However, the earliest manifestations of dementia are very similar.

Mild cognitive impairment (MCI) causes greater memory loss than age-associated memory impairment; memory and sometimes other cognitive functions are worse in patients with this disorder than in age-matched controls, but daily functioning is typically not affected. In contrast, dementia impairs daily functioning. Up to 50% of patients with mild cognitive impairment develop dementia within 3 years.

Subjective cognitive decline (SCD) is defined as a self-experienced persistent decline in cognitive capacity but normal performance on standardized cognitive tests used to classify MCI (1). The risk of MCI and dementia is increased in people with SCD.

Variousdisorders may exacerbate cognitive deficits in patients with dementia. Delirium often occurs in patients with dementia.


Prion-like propagation mechanisms appear to be involved in most or all neurodegenerative disorders that first manifest in older patients. A normal cellular protein sporadically (or via an inherited mutation) becomes misfolded into a pathogenic form or prion. The prion then acts as a template, causing other proteins to misfold similarly. This process occurs over years and in many parts of the central nervous system (CNS). Many of these prions become insoluble and, like amyloid, cannot be readily cleared by the cell. Evidence implies prion or similar mechanisms in Alzheimer disease (strongly), as well as in Parkinson disease, Huntington disease, frontotemporal dementia, and amyotrophic lateral sclerosis. These prions are not as infectious as those in Creutzfeld-Jacob disease, but they can be transmitted.

Rapidly progressive dementia (RPD) is a group of heterogeneous cognitive disorders that progress faster than other dementia syndromes, typically within 1 to 2 years (2). The most prominent presentation is cognitive decline (eg, memory loss, visuospatial and language deficits, executive dysfunction). However, other neuropsychiatric symptoms (eg, behavior disturbance, personality change, mood disorders, psychosis, sleep disturbance, altered alertness and/or awareness, involuntary movements such as tremor and myoclonus, gait disturbance, seizure-like activities, ataxia, parkinsonian features) also occur. Prion disease is the most common cause of RPD. Other common causes include autoimmune and paraneoplastic encephalitis. Sometimes the progression of other dementias is atypically rapid; they include Alzheimer disease, dementia with Lewy bodies, frontotemporal dementia,and dementia due to potentially reversible causes (eg, infectious, toxic/metabolic, neurovascular, psychiatric).


Etiology references

  1. 1. Jessen F, Amariglio RE, Buckley RF, et al: The characterisation of subjective cognitive decline. Lancet Neurol 19 (3):271–278, 2020. doi: 10.1016/S1474-4422(19)30368-0

  2. 2. Hermann P, Zen I: Rapidly progressive dementias — aetiologies, diagnosis and management. Nat Rev Neurol 18 (6):363–376, 2022. doi: 10.1038/s41582-022-00659-0

Symptoms and Signs of Dementia

(See also Behavioral and Psychologic Symptoms of Dementia.)

Dementia impairs cognition globally. Onset is gradual, although family members may suddenly notice deficits (eg, when function becomes impaired). Often, loss of short-term memory is the first sign. At first, early symptoms may be indistinguishable from those of age-associated memory impairment or mild cognitive impairment, but then progression becomes apparent.

Although symptoms of dementia exist in a continuum, they can be divided into

  • Early

  • Intermediate

  • Late

Personality changes and behavioral disturbances may develop early or late. Motor and other focal neurologic deficits occur at different stages, depending on the type of dementia; they occur early in vascular dementia and late in Alzheimer disease. Incidence of seizures is somewhat increased during all stages.

Psychosis—hallucinations, delusions, or paranoia—occurs in about 10% of patients with dementia, although a higher percentage may experience these symptoms temporarily.

Many disorders, particularly during exacerbations, can worsen the symptoms of dementia. These disorders include diabetes, chronic bronchitis, emphysema, infections, chronic kidney disease, liver disorders, and heart failure.

Drinking alcohol, even in moderate amounts, may also worsen the symptoms of dementia and contribute to its progression (eg, by reducing brain volume), and most experts recommend that patients with dementia stop drinking alcohol.

Early (mild) dementia symptoms

Recent memory is impaired; learning and retaining new information become difficult. Language problems (especially with word finding), mood swings, and personality changes develop. Patients may have progressive difficulty with independent activities of daily living (eg, balancing their checkbook, finding their way around, remembering where they put things). Abstract thinking, insight, or judgment may be impaired. Patients may respond to loss of independence and memory with irritability, hostility, and agitation.

Functional ability may be further limited by the following:

  • Agnosia: Impaired ability to identify objects despite intact sensory function

  • Apraxia: Impaired ability to do previously learned motor activities despite intact motor function

  • Aphasia: Impaired ability to comprehend or use language

Although early dementia may not compromise sociability, family members may report strange behavior accompanied by emotional lability.

Intermediate (moderate) dementia symptoms

Patients become unable to learn and recall new information. Memory of remote events is reduced but not totally lost. Patients may require help with basic activities of daily living (eg, bathing, eating, dressing, toileting).

Personality changes may progress. Patients may become irritable, anxious, self-centered, inflexible, or angry more easily. They may become more passive, with a flat affect; they may develop depression, become indecisive, lose spontaneity, or generally withdraw from social situations. Personality traits or habits may become more exaggerated (eg, concern with money becomes obsession with it).

Behavior disorders may develop: Patients may wander or become suddenly and inappropriately agitated, hostile, uncooperative, or physically aggressive.

By this stage, patients have lost all sense of time and place because they cannot effectively use normal environmental and social cues. Patients often get lost; they may be unable to find their own bedroom or bathroom. They remain ambulatory but are at risk of falls or accidents secondary to confusion.

Altered sensation or perception may culminate in psychosis with hallucinations and paranoid and persecutory delusions.

Sleep patterns are often disorganized.

Late (severe) dementia symptoms

Patients cannot walk, feed themselves, or do any other activities of daily living; they may become incontinent. Recent and remote memory is completely lost. Patients may be unable to swallow. They are at risk of undernutrition, pneumonia (especially due to aspiration), and pressure ulcers. Because they depend completely on others for care, placement in a long-term care facility often becomes necessary. Eventually, patients become mute.

Because such patients cannot relate any symptoms to a physician and because older patients often have no febrile or leukocytic response to infection, a physician must rely on experience and acumen whenever a patient appears ill.

End-stage dementia results in coma and death, usually due to infection.

Diagnosis of Dementia

  • Differentiation of delirium from dementia by history and neurologic examination (including mental status)

  • Identification of treatable causes clinically and by laboratory testing and neuroimaging

  • Sometimes formal neuropsychologic testing

Recommendations about diagnosis of dementia are available from the American Academy of Neurology (see also The diagnosis of dementia due to Alzheimer’s disease).

Distinguishing type or cause of dementia can be difficult; definitive diagnosis often requires postmortem pathologic examination of brain tissue. Thus, clinical diagnosis focuses on distinguishing dementia from delirium and other disorders and identifying the cerebral areas affected and potentially reversible causes.

Dementia must be distinguished from the following:

  • Delirium: Distinguishing between dementia and delirium is crucial (because delirium is usually reversible with prompt treatment) but can be difficult. Attention is assessed first. If a patient is inattentive, the diagnosis is likely to be delirium, although advanced dementia also severely impairs attention. Other features that suggest delirium rather than dementia (eg, duration of cognitive impairment) are determined by the history, physical examination, and tests for specific causes.

  • Age-associated memory impairment: Memory impairment does not affect daily functioning. If affected people are given enough time to learn new information, their intellectual performance is good.

  • Mild cognitive impairment: Memory and/or other cognitive functions are impaired, but impairment is not severe enough to interfere with daily activities.

  • Cognitive symptoms related to depression: This cognitive disturbance resolves with treatment of depression. Depressed older patients may experience cognitive decline, but unlike patients with dementia, they tend to exaggerate their memory loss and rarely forget important current events or personal matters. Neurologic examinations are normal except for signs of psychomotor slowing. When tested, patients with depression make little effort to respond, but those with dementia often try hard but respond incorrectly. When depression and dementia coexist, treating depression does not fully restore cognition.

Clinical criteria

The National Institute on Aging–Alzheimer's Association diagnostic guidelines specify that a general diagnosis of dementia requires all of the following:

  • Cognitive or behavioral (neuropsychiatric) symptoms interfere with the ability to function at work or do usual daily activities.

  • These symptoms represent a decline from previous levels of functioning.

  • These symptoms are not explained by delirium or a major psychiatric disorder.

The cognitive or behavioral impairment should be diagnosed based on a combination of history from the patient and from someone who knows the patient plus assessment of cognitive function (a bedside mental status examination or, if bedside testing is inconclusive, formal neuropsychologic testing). In addition, the impairment should involve ≥ 2 of the following domains:

  • Impaired ability to acquire and remember new information (eg, asking repetitive questions, frequently misplacing objects or forgetting appointments)

  • Impaired reasoning and handling of complex tasks and poor judgment (eg, being unable to manage a bank account, making poor financial decisions)

  • Language dysfunction (eg, difficulty thinking of common words, errors speaking and/or writing)

  • Visuospatial dysfunction (eg, inability to recognize faces or common objects)

  • Changes in personality, behavior, or comportment

If cognitive impairment is confirmed, history and physical examination should then focus on signs of treatable disorders that cause cognitive impairment (eg, vitamin B12 deficiency, neurosyphilis, hypothyroidism, depression—see table Causes of Delirium).

Assessment of cognitive function

The Mini-Mental Status Examination (see sidebar Examination of Mental Status) or the Montreal Cognitive Assessment (MoCA) is often used as a bedside screening test. When delirium is absent, the presence of multiple deficits, particularly in patients with an average or a higher level of education, suggests dementia. The best screening test for memory is a short-term memory test (eg, registering 3 objects and recalling them after 5 minutes); patients with dementia fail this test. Another test of mental status assesses the ability to name multiple objects within categories (eg, lists of animals, plants, or pieces of furniture). Patients with dementia struggle to name a few; those without dementia easily name many.

Neuropsychologic testing should be done when history and bedside mental status testing are not conclusive. It evaluates mood as well as multiple cognitive domains. It takes 1 to 3 hours to complete and is done or supervised by a neuropsychologist. Such testing helps primarily in differentiating the following:

  • Age-associated memory impairment, mild cognitive impairment, and dementia, particularly when cognition is only slightly impaired or when the patient or family members are anxious for reassurance

  • Dementia and focal syndromes of cognitive impairment (eg, amnesia, aphasia, apraxia, visuospatial difficulties, impairment of executive function) when the distinction is not clinically evident

Testing may also help characterize specific deficits due to dementia, and it may detect depression or a personality disorder that is contributing to poor cognitive performance.

Laboratory testing

Tests should include thyroid-stimulating hormone and vitamin B12 levels. Routine complete blood count (CBC), kidney and liver function tests are sometimes recommended, but yield is very low.

If clinical findings suggest a specific disorder, other tests (eg, for HIV or syphilis) are indicated. Lumbar puncture should be considered if a chronic infection or neurosyphilis is suspected or if prion disease or an autoimmune disorder is suspected in patients with rapidly progressive dementia. Other tests may be used to exclude causes of delirium.

Biomarkers for Alzheimer disease can be useful in research settings but are not yet routine in clinical practice. For example, in the cerebrospinal fluid (CSF), the tau level increases and beta-amyloid decreases as Alzheimer disease progresses. Also, for people with two epsilon-4 alleles of the apolipoprotein E4 gene, the risk of developing Alzheimer disease by age 75 is 10 to 30 times greater than that for people without the allele. However, routine genetic testing for the apolipoprotein E4 allele (apo epsilon-4) is not recommended, because the E4 allele is neither necessary nor sufficient to cause Alzheimer disease and because currently, no treatment can prevent or slow the progression of Alzheimer disease.


CT or MRI should be done in the initial evaluation of dementia and after any unexplained change in cognition or mental status. Neuroimaging can identify potentially reversible structural disorders (eg, normal-pressure hydrocephalus, brain tumors, subdural hematoma) and certain metabolic disorders (eg, pantothenate kinase-associated neurodegeneration [formerly known as Hallervorden-Spatz disease], Wilson disease) and irreversible disorders (eg, stroke, leukodystrophy, Creutzfeld-Jacob disease).

Occasionally, electroencephalography (EEG) is useful (eg, to evaluate episodic lapses in attention or bizarre behavior).

PET with fluorine-18 (18F)–labeled deoxyglucose (fluorodeoxyglucose, or FDG) or single-photon emission CT (SPECT) can provide information about cerebral perfusion patterns and help with differential diagnosis (eg, in differentiating Alzheimer disease from frontotemporal dementia and dementia with Lewy bodies).

Amyloid radioactive tracers that bind specifically to beta-amyloid plaques (eg, fluorine-18 [18F] florbetapir, [18F] flutemetamol, [18F] florbetaben) have been used with positron emission tomography (PET) to image amyloid plaques in patients with mild cognitive impairment or dementia. This testing should be used when the cause of cognitive impairment (eg, mild cognitive impairment or dementia) is uncertain after a comprehensive evaluation and when Alzheimer disease is a diagnostic consideration. Determining amyloid status via PET is expected to increase the certainty of diagnosis and management. [18F] flortaucipir-PET, using a tau radioactive tracer, can be used to estimate the density and distribution of aggregated tau neurofibrillary tangles in adults who have cognitive impairment and are being evaluated for Alzheimer disease (1).

Diagnosis reference

  1. 1. Fleisher AS, Pontecorvo MJ, Devous Sr MD, et al: Positron emission tomography imaging with [18F] flortaucipir and postmortem assessment of Alzheimer disease neuropathologic changes. JAMANeurol. Published online April 27, 2020. doi:10.1001/jamaneurol.2020.0528

Treatment of Dementia

  • Measures to ensure safety

  • Provision of appropriate stimulation, activities, and cues for orientation

  • Elimination of medications with sedating or anticholinergic effects

  • Assistance for caregivers

  • Arrangements for end-of-life care

Recommendations about treatment of dementia are available from the National Institute for Health and Care Excellence. Measures to ensure patient safety and to provide an appropriate environment are essential to treatment, as is caregiver assistance. Several medications are available.

Patient safety

Occupational and physical therapists can evaluate the home for safety; the goals are to

  • Prevent accidents (particularly falls)

  • Manage behavior disorders

  • Plan for change as dementia progresses

How well patients function in various settings (ie, kitchen, automobile) should be evaluated using simulations. If patients have deficits and remain in the same environment, protective measures (eg, hiding knives, unplugging the stove, removing the car, confiscating car keys) may be required. Some states require physicians to notify the Department of Motor Vehicles of patients with dementia because at some point, such patients can no longer drive safely.

If patients wander, signal monitoring systems can be installed, or patients can be registered in the Safe Return program. Information is available from the Alzheimer’s Association.

Ultimately, assistance (eg, housekeepers, home health aides) or a change of environment (living facilities without stairs, assisted-living facility, skilled nursing facility) may be indicated.

Environmental measures

Patients with mild to moderate dementia usually function best in familiar surroundings.

Whether at home or in an institution, the environment should be designed to help preserve feelings of self-control and personal dignity by providing the following:

  • Frequent reinforcement of orientation

  • A bright, cheerful, familiar environment

  • Minimal new stimulation

  • Regular, low-stress activities

Orientation can be reinforced by placing large calendars and clocks in the room and establishing a routine for daily activities; medical staff members can wear large name tags and repeatedly introduce themselves. Changes in surroundings, routines, or people should be explained to patients precisely and simply, omitting nonessential procedures. Patients require time to adjust and become familiar with the changes. Telling patients about what is going to happen (eg, about a bath or feeding) may avert resistance or violent reactions. Frequent visits by staff members and familiar people encourage patients to remain social.

Rooms should be reasonably bright and contain sensory stimuli (eg, radio, television, night-light) to help patients remain oriented and focus their attention. Quiet, dark, private rooms should be avoided.

Activities can help patients function better; those related to interests before dementia began are good choices. Activities should be enjoyable, provide some stimulation, but not involve too many choices or challenges.

Exercise to reduce restlessness, improve balance, and maintain cardiovascular tone should be done daily. Exercise can also help improve sleep and manage behavior disorders.

Occupational therapy and music therapy help maintain fine motor control and provide nonverbal stimulation.

Group therapy (eg, reminiscence therapy, socialization activities) may help maintain conversational and interpersonal skills.


Eliminating or limiting medications with central nervous system (CNS) activity often improves function. Sedating and anticholinergic medications, which tend to worsen dementia, should be avoided.

The cholinesterase inhibitors

, an NMDA (N-methyl-d-aspartate) antagonist, may help slow the loss of cognitive function in patients with moderate to severe dementia and may be synergistic when used with a cholinesterase inhibitor.

Medications to control behavior disorders (eg, antipsychotics) have been used.

Patients with dementia and signs of depression should be treated with nonanticholinergic antidepressants, preferably selective serotonin reuptake inhibitor (SSRIs).

Caregiver assistance

Immediate family members are largely responsible for care of a patient with dementia (see Family Caregiving for Older Adults). Nurses and social workers can teach them and other caregivers how to best meet the patient’s needs (eg, how to deal with daily care and handle financial issues); teaching should be ongoing. Other resources (eg, support groups, educational materials, Internet web sites) are available.

Caregivers may experience substantial stress. Stress may be caused by worry about protecting the patient and by frustration, exhaustion, anger, and resentment from having to do so much to care for someone. Health care practitioners should watch for early symptoms of caregiver stress and burnout and, when needed, suggest support services (eg, social worker, nutritionist, nurse, home health aide).

If a patient with dementia has an unusual injury, the possibility of elder abuse should be investigated.

Prognosis for Dementia

Dementia is usually progressive. However, progression rate varies widely and depends on the cause. Dementia shortens life expectancy, but survival estimates vary.

End-of-life issues

Because insight and judgment deteriorate in patients with dementia, appointment of a family member, guardian, or lawyer to oversee finances may be necessary. Early in dementia, before the patient is incapacitated, the patient’s wishes about care should be clarified, and financial and legal arrangements (eg, durable power of attorney, durable power of attorney for health care) should be made. When these documents are signed, the patient’s capacity should be evaluated, and evaluation results recorded. Decisions about artificial feeding and treatment of acute disorders are best made before the need develops.

In advanced dementia, palliative measures may be more appropriate than highly aggressive interventions or hospital care.

Key Points

  • Dementia, unlike age-associated memory loss and mild cognitive impairment, causes cognitive impairments that interfere with daily functioning.

  • Be aware that family members may report sudden onset of symptoms only because they suddenly recognized gradually developing symptoms.

  • Consider reversible causes of cognitive decline, such as structural brain disorders (eg, normal-pressure hydrocephalus, subdural hematoma), metabolic disorders (eg, hypothyroidism, vitamin B12 deficiency), medications, depression, and toxins (eg, lead).

  • Do bedside mental status testing and, if necessary, formal neuropsychologic testing to confirm that cognitive function is impaired in ≥ 2 domains.

  • Recommend or help arrange measures to maximize patient safety, to provide a familiar and comfortable environment for the patient, and to provide support for caregivers.

  • Consider adjunctive medications, and recommend making end-of-life arrangements.

More Information

The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.

  1. Alzheimer’s Association: This web site provides information about Alzheimer disease (eg, statistics, causes, risk factors, and symptoms) and resources for support (eg, information about daily care of people with Alzheimer disease and care for the caregiver).

  2. American Academy of Neurology: Practice parameter: Diagnosis of dementia (an evidence-based review): This 2001 review makes detailed recommendations for diagnosis of dementia and identification of its cause.

  3. Alzheimer’s Association: Dementia diagnosis: This web site provides links to free-access articles with the latest research about diagnostic criteria for Alzheimer disease and information about differential diagnosis, videos showing the disclosure of the diagnosis to patients, and up-to-date information about use of advanced imaging and biomarkers in the diagnosis of Alzheimer disease.

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