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Dementia

by Juebin Huang, MD, PhD

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.

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

Dementias can be classified in several ways:

  • Alzheimer or non-Alzheimer type

  • Cortical or subcortical

  • Irreversible or potentially reversible

  • Common or rare

Etiology

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

The most common types of dementia are

  • Alzheimer disease

  • Vascular dementia

  • Lewy body dementia

  • Frontotemporal dementias

  • HIV-associated dementia.

Dementia also occurs in patients with Parkinson disease, Huntington disease, progressive supranuclear palsy, Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, other prion disorders, and neurosyphilis. Patients can have > 1 type (mixed dementia).

Some structural brain disorders (eg, normal-pressure hydrocephalus, subdural hematoma), metabolic disorders (eg, hypothyroidism, vitamin B 12 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 2 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; these changes are not dementia. The elderly have a relative deficiency in recall, particularly in speed of recall, compared with recall during their youth. However, this change does not affect daily functioning.

Mild cognitive impairment 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 yr.

Any disorder may exacerbate cognitive deficits in patients with dementia. Delirium often occurs in patients with dementia. Drugs, particularly benzodiazepines and anticholinergics (eg, some tricyclic antidepressants, antihistamines, antipsychotics, benztropine), may temporarily cause or worsen symptoms of dementia, as may alcohol, even in moderate amounts. New or progressive kidney or liver failure may reduce drug clearance and cause drug toxicity after years of taking a stable drug dose (eg, of propranolol).

Prion mechanisms appear to be involved in most or all neurodegenerative disorders that first manifest in the elderly. 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 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.

Classification of Some Dementias

Classification

Examples

β-Amyloid deposits and neurofibrillary tangles

Alzheimer disease

Tau abnormalities

Frontotemporal dementia (including Pick disease)

Corticobasal ganglionic degeneration

Progressive supranuclear palsy

α-Synuclein abnormalities

Lewy body dementia

Parkinson disease dementia

Huntingtin gene mutation

Huntington disease

Cerebrovascular disease

Lacunar disease

Binswanger disease

Multi-infarct dementia

Strategic single-infarct dementia

Ingestion of drugs or toxins

Alcohol-associated dementia

Dementia due to exposure to heavy metals

Infections

Fungal: Dementia due to cryptococcosis

Spirochetal: Dementia due to syphilis or Lyme disease

Viral: HIV-associated dementia, postencephalitis syndromes

Prion disorders

Creutzfeldt-Jakob disease

Variant Creutzfeldt-Jakob disease

Alzheimer disease

Amyotrophic lateral sclerosis

Frontotemporal dementia

Huntington disease

Parkinson disease

Structural brain disorders

Brain tumors

Chronic subdural hematomas

Normal-pressure hydrocephalus

Other potentially reversible disorders

Depression

Hypothyroidism

Vitamin B 12 deficiency

Symptoms and Signs

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. Although symptoms of dementia exist in a continuum, they can be divided into early, intermediate, and 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.

Early

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 (see Agnosia)

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

  • Aphasia: Impaired ability to comprehend or use language (see Aphasia)

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

Intermediate

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, or they may become more passive, with a flat affect, depression, indecisiveness, lack of spontaneity, or general withdrawal from social situations. Behavior disorders may develop: Patients may wander or become suddenly and inappropriately agitated, hostile, uncooperative, or physically aggressive (see Behavioral and Psychologic Symptoms of Dementia).

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)

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 elderly 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

  • 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 .

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— Differences Between Delirium and Dementia*) 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 most recent National Institute on Aging–Alzheimer's Association diagnostic guidelines specify that 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 involve ≥ 2 of the following domains:

  • Impaired ability to acquire and remember new information (amnesia)

  • Language dysfunction (aphasia)

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

  • Impaired executive function, including reasoning, handling of complex tasks, and/or judgment (apraxia)

  • Changes in personality, behavior, or comportment.

Evaluation for dementia and cognitive impairment requires taking a history from the patient and from someone who knows the patient plus a test of cognitive function (a bedside mental status examination or neuropsychologic testing). If cognitive impairment is confirmed, history and physical examination should then focus on signs of treatable disorders that cause cognitive impairment (eg, vitamin B 12 deficiency, neurosyphilis, hypothyroidism, depression— Causes of Delirium).

Assessment of cognitive function

The Mini-Mental Status Examination (see Examination of Mental Status) 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 min); patients with dementia fail this test. Another test of mental status assesses the ability to name 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 h 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 B 12 levels. Routine CBC 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 is rarely needed but should be considered if a chronic infection or neurosyphilis is suspected. 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 CSF, the tau level increases and β-amyloid decreases as Alzheimer disease progresses. Also, routine genetic testing for the apolipoprotein E4 allele (apo ε4) is not recommended.(For people with 2 ε4 alleles, the risk of developing Alzheimer disease by age 75 is 10 to 30 times that for people without the allele.)

Neuroimaging

CT or MRI should be done in the initial evaluation of dementia or after any sudden 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, Hallervorden-Spatz disease, Wilson disease). Occasionally, EEG is useful (eg, to evaluate episodic lapses in attention or bizarre behavior). Functional MRI or single-photon emission CT can provide information about cerebral perfusion patterns and help with differential diagnosis (eg, in differentiating Alzheimer disease from frontotemporal dementia and Lewy body dementia).

Use of amyloid radioactive tracers that bind specifically to β-amyloid plaques (eg, Pittsburgh compound B [PiB], florbetapir) with PET to image amyloid plaques is under study and may be useful in the diagnosis of Alzheimer disease.

Prognosis

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

Treatment

  • Measures to ensure safety

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

  • Elimination of drugs with sedating or anticholinergic effects

  • Possibly cholinesterase inhibitors and memantine

  • Assistance for caregivers

  • Arrangements for end-of-life care

Recommendations about treatment of dementia are available from the American Academy of Neurology . Measures to ensure patient safety and to provide an appropriate environment are essential to treatment, as is caregiver assistance. Several drugs are available.

Patient safety

Occupational and physical therapists can evaluate the home for safety; the goals are to prevent accidents (particularly falls), to manage behavior disorders, and to 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

Large calendars and clocks and a routine for daily activities can help with orientation; 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.

The room 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 provides nonverbal stimulation. Group therapy (eg, reminiscence therapy, socialization activities) may help maintain conversational and interpersonal skills.

Drugs

Eliminating or limiting drugs with CNS activity often improves function. Sedating and anticholinergic drugs, which tend to worsen dementia, should be avoided.

The cholinesterase inhibitors donepezil, rivastigmine, and galantamine (see Treatment) are somewhat effective in improving cognitive function in patients with Alzheimer disease or Lewy body dementia and may be useful in other forms of dementia. These drugs inhibit acetylcholinesterase, increasing the acetylcholine level in the brain.

Memantine, 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.

Other drugs (eg, antipsychotics) have been used to control behavior disorders (see Drugs). Patients with dementia and signs of depression should be treated with nonanticholinergic antidepressants, preferably SSRIs.

Caregiver assistance

Immediate family members are largely responsible for care of a patient with dementia. 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.

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 (see also Capacity (Competence) and Incapacity). 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 B 12 deficiency), drugs, 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 drug therapy, and recommend making end-of-life arrangements.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • COGENTIN
  • INDERAL
  • NAMENDA
  • RAZADYNE
  • EXELON
  • ARICEPT

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