AD is characterized by insidious, severe, and progressive cognitive impairment that is irreversible and eventually fatal. AD accounts for roughly 60% to 80% of all dementias in the United States [4]. It proceeds relentlessly, gradually destroying all cognitive functions. While the number of adults with AD doubles for every five years after 65 years of age, the disease is also seen (less frequently) in younger people [1].

AD is characterized by insidious, severe, and progressive cognitive impairment that is irreversible and eventually fatal. AD accounts for roughly 60% to 80% of all dementias in the United States [4]. It proceeds relentlessly, gradually destroying all cognitive functions. While the number of adults with AD doubles for every five years after 65 years of age, the disease is also seen (less frequently) in younger people [1].

Approximately 1 million new cases of AD develop each year [4]. As the aging population increases, so will these numbers. Barring effective new treatments, there will be an estimated 13.8 to 16 million patients with AD in 2060 [4].

Parkinson disease and Huntington disease are examples of dementias related to diseases that begin primarily with subcortical dysfunction. Subcortical structures include the basal ganglia, thalamus, and brain stem. Motor coordination, vital functions, and central nervous system arousal, timing, and sequential activity are controlled by the subcortical structures. Movement disorders (e.g., tremors, rigidity, chorea) are a prominent and early manifestation of subcortical dementias. In cortical diseases such as AD, impaired motor function occurs late in the course of the illness [14].

The presence of neurofibrillary tangles and amyloid plaques are the structural hallmarks of AD. Beta-amyloid and tau are two proteins involved in the formation of these abnormal structures. A form of tau, A68, is the major component of these tangles. In healthy neurons, the internal structures (called microtubules) are formed like long parallel tracks with crosspieces that carry nutrients from the body of the cells to the ends of the axons. In AD, the structure has disintegrated; crosspieces formed from tau are twisted like two threads wound around each other. Amyloid plaques, made up of beta-amyloid mixed with dendritic debris from surrounding cells, are found in areas of the brain associated with memory. Knowledge of how beta-amyloid causes neuron death and forms plaques is incomplete, but it is known that the normally soluble amyloid becomes insoluble when the apolipoprotein E4 susceptibility gene (APOE4) protein latches onto the beta-amyloid.

The presence of neurofibrillary tangles and amyloid plaques are the structural hallmarks of AD. Beta-amyloid and tau are two proteins involved in the formation of these abnormal structures. A form of tau, A68, is the major component of these tangles. In healthy neurons, the internal structures (called microtubules) are formed like long parallel tracks with crosspieces that carry nutrients from the body of the cells to the ends of the axons. In AD, the structure has disintegrated; crosspieces formed from tau are twisted like two threads wound around each other. Amyloid plaques, made up of beta-amyloid mixed with dendritic debris from surrounding cells, are found in areas of the brain associated with memory. Knowledge of how beta-amyloid causes neuron death and forms plaques is incomplete, but it is known that the normally soluble amyloid becomes insoluble when the apolipoprotein E4 susceptibility gene (APOE4) protein latches onto the beta-amyloid.

There are many types of memory. How the information is used depends on how the memory was formulated. Episodic memory pertains to remembering specific events associated with a particular time and place. Episodic memory requires no effort at learning. Remembering the details of a child's birth, one's wedding, or perhaps a catastrophic event are other examples of episodic memory.

Semantic memory requires the conscious involvement of the learner. The knowledge is not associated with a particular time or place but is learned at some point in time. Skills such as using a telephone book, balancing a bank statement, cooking from a recipe, and reading a road map are examples of semantic type memories.

Implicit memory is information learned without the conscious involvement of the individual. It is established through early and frequent repetition. Reciting the Pledge of Allegiance and singing "Happy Birthday" are the result of implicit memory. Social customs and manners, such as saying please and thank you, develop through implicit memory.

Motor memory is required for tasks utilizing motor skills, such as riding a bicycle, jumping rope, and dancing. Once learned, these skills are rarely lost even if not used for some time.

Affective memory refers to feelings and emotions. Listening to a song may evoke memories of a person, place, or event. The aroma of a certain perfume may bring to mind a specific person. Cooking odors may elicit the memory of family holiday meals. Meeting a person for the first time may bring forth feelings of dislike until one realizes that the person resembles someone from the past.

The early stages are especially challenging for patients with AD, as they realize that they are slipping away and are unable to do anything about it; each stage brings with it additional mental, emotional, or physical losses. Inevitably, nearly all patients develop amnesia (memory impairment), aphasia (language impairment), agnosia (inability to identify common objects), apraxia (inability to use objects, despite knowing their function), and visuospatial deficit and may exhibit apathy, depression, or psychosis. Afflicted individuals will become dependent on caregivers for meeting even the most basic physical needs. The model of the progressive cognitive and functional decline in AD as "childhood development in reverse" (i.e., from the functional capacity of a child to that of an infant) is one that is easy for nonmedical family members and caregivers to understand [6].

The early stages are especially challenging for patients with AD, as they realize that they are slipping away and are unable to do anything about it; each stage brings with it additional mental, emotional, or physical losses. Inevitably, nearly all patients develop amnesia (memory impairment), aphasia (language impairment), agnosia (inability to identify common objects), apraxia (inability to use objects, despite knowing their function), and visuospatial deficit and may exhibit apathy, depression, or psychosis. Afflicted individuals will become dependent on caregivers for meeting even the most basic physical needs. The model of the progressive cognitive and functional decline in AD as "childhood development in reverse" (i.e., from the functional capacity of a child to that of an infant) is one that is easy for nonmedical family members and caregivers to understand [6].

A diagnosis of probable AD can be made based on the medical history, physical examination, diagnostic studies, caregiver interviews, and objective cognitive assessment including either neuropsychological testing or a "bedside" mental status examination [155]. The observation of signs and symptoms during cognitive assessment (with the ruling out of other disease processes) can support the diagnosis even in the absence of pathology reports. The earlier the diagnosis is made, the greater the benefit in managing the clinical course of the illness.

The goals of the diagnostic process are to:

The DSM-5-TR requires the following signs to be present before a diagnosis of major neurocognitive disorder (commonly referred to as dementia) is made [20]:

A functional assessment, to investigate the ability to complete activities of daily living, should be included in the diagnostic evaluation [159]. These activities include bathing, dressing, eating, and mobility within the home [2]. Instrumental activities of daily living include preparing meals, shopping, managing money, using the telephone, completing housework, and taking medications. Various tools are available that measure the person's ability to perform instrumental activities (e.g., Cognitive Performance Test, Executive Function Performance Test, Kitchen Task Assessment) [23]. These tests are also useful in determining whether or not someone can live independently or the degree of assistance that is required. Activities to consider include [23]:

Neuropsychological testing may be appropriate when the mental status test is abnormal but the functional test is normal; when a family member expresses concern or dementia is suspected and results of mental status tests are within the normal range; when the patient has an advanced academic degree; or when the patient's occupation indicates high premorbid intelligence [16]. Preferably, a specialist in neuropsychology should be employed.

Patients and family members should be encouraged to make long-term plans after a diagnosis of AD. When the diagnosis is made early in the course of the disease, the patient can and should fully participate. Decisions can be given some thought if they are made before a crisis occurs. The patient and family must be aware of the need for advance planning as a mechanism for protecting the individual's self-determination. The Patient Self-Determination Act (PSDA), legislated in 1990, is legally recognized in all states. The PSDA recognizes advance directives (the durable power of attorney and in some states, the living will) as legal documents providing direction when the patient is unable to make decisions. In some states, do not resuscitate (DNR) must be also written in the medical orders for those in healthcare facilities even if the advance directives contain this statement. Various states require that DNR orders must also be posted by or on the patient's bed. In the absence of advance directives, it may be necessary to initiate guardianship when the patient becomes incompetent. After a competency hearing, the judge decides incompetency based on the criteria of that state. The judge assigns a guardian to oversee the patient and his or her estate. Guardianship can protect a vulnerable person, but the process may be lengthy and complicated [28].

It is clear that to be restrained severely diminishes quality of life. This is in addition to the harmful effects of both physical and chemical restraints. The improper application of physical restraints may impede circulation, inhibit breathing, and predispose the patient to muscle atrophy, pressure ulcers, and incontinence [139,140]. The use of restraints increases disorientation and anxiety in many confused individuals. Restraints have not been proven to prevent falling and injury but have been shown to increase the risk of injury and death [140]. It is recommended that restraints only be used for medical emergencies [139].

ChEIs and memantine are the primary available modes of pharmacologic AD treatment. ChEIs prevent or delay the breakdown of acetylcholine in the brain, a neurotransmitter important for learning and memory. This has been shown to produce a small but measurable temporary improvement in cognitive function and behavioral symptoms in some patients with mild-to-moderate and moderate-to-severe disease [89]. A study published in 2009 showed that while most mild patients with AD respond only minimally to ChEIs, a small cohort respond substantially to treatment [165]. Because these agents do not produce a dramatic result, families and caregivers must be informed of realistic expectations [6].

A clinical need for the use of antipsychotic medications must be established. Psychotic behavioral disturbances, including agitation, hallucinations, delusions and paranoia, and physical and verbal aggressive behavior, may justify their use [49]. Wandering, impaired memory, depression, insomnia, and anxiety do not warrant their use unless patients present a danger to themselves or to others. Evidence suggests no single drug is more effective than any other, and when a drug is effective, it requires relatively low doses [134]. Greater clinical improvement has not been noted with higher doses [67]. The goal of the therapy is to find the dose at which the identified behaviors are eradicated without causing sedation [66]. Before antipsychotic medications are prescribed [66,152]:

The manifestations related to AD have a profound effect on the ability to perform activities of daily living. The rate at which those skills are lost varies from person to person. The degree to which function diminishes depends on the complexity of the task. After a skill is lost, it generally cannot be regained. Interventions are based on maintaining a skill for as long as possible. Basic self-care activities can usually be managed through the first two stages of the disease with varying degrees of assistance. The ability to complete instrumental activities of daily living, such as financial planning and driving, disappears early in the process. Disability associated with self-care deficits can be exacerbated by many factors other than the disease. Other illnesses, medication toxicity, increased fatigue, sensory deprivation, and inadequate support from the environment and caregivers can hasten the onset of functional loss.

AD predisposes patients to a number of complications. In the early stages of the disease, risk is highest for injury and trauma related to wandering; inability to recognize sensory cues for danger; impaired judgment; impulsiveness; memory deficits; altered nutrition related to shortened attention span, apraxia, and agnosia; and excessive energy expenditures due to wandering. In the later stages, there is increased risk for incontinence, pressure ulcers related to impaired mobility, and possibly undernutrition and aspiration related to impaired swallowing.

General management techniques are based on consistency, focusing on the individual's abilities, task breakdown, cueing, and the use of distraction.

When used judiciously, touch is very effective when working with people who have AD. The need to touch and be touched may increase with age as other senses such as vision and hearing tend to become diminished. "Skin hunger" may occur when there is lack of human physical contact with others, and researchers have compared lack of touch to malnutrition [40]. All forms of touch convey a message that is either positive or negative. Touch can be therapeutic and give the most pleasure of all senses. The significance of touch is often overlooked in this age of technology. Touching can build one's self-esteem when it implies acceptance of the person, and it can prevent feelings of rejection and loneliness. Touch can be functional or affectionate. Touch can be comforting and soothing. Gently rubbing the temples or giving a back massage has a calming influence. Caregivers use functional touch when they give a bath, take a pulse, or perform other nursing duties. Holding a hand or giving a hug reflects affection and caring. Touch can say, "I care about you." It builds trust and a feeling of security. Caregivers also "touch" with their voices, eyes, and facial expressions. Nonphysical touch occurs when you enter someone's personal space. The response of the individual depends on the situation. Patients may respond with verbal or physical violence if they are agitated or experiencing a catastrophic reaction.

For reasons that are not yet understood, changes in sexual behavior may become apparent in people with AD. Psychological reactions, such as depression and anxiety, that affect the general population, may also result in sexual dysfunction in the person with AD. Structural changes in the brain and nervous system may also account for sexual dysfunction. Coping with memory deficits may be so stressful that there is little energy or desire left for sexual activity.

Undernutrition may be identified by pale, scaling skin with dark areas on the cheeks and under the eyes. The tongue may be swollen and discolored and covered with lesions. Spongy, bleeding gums and dental cavities are other signs. Lack of subcutaneous fat and weak, atrophied muscles may also be noted. Disorientation is common with undernutrition. Signs of dehydration include dry oral mucous membranes, orthostatic hypotension, increases in pulse and respiration, decrease in blood pressure, disorientation, and diminished skin turgor [44].

All behavior has a reason, although the cause may not be immediately known. Behavior is a response to the environment, caregivers, or internal stimuli. Problems may develop when the expectations of the caregiver do not match the abilities of the patient. The patient has a need for supervision and assistance because of increasing functional disability. The management of behavior is directed toward adapting the environment and approaches to the needs of the individual. Caregivers cannot cure the disease or teach patients to remember. They cannot resolve behavioral issues by using logic, by trying to reason with the person, or by coaxing or using flattery. Caregivers should have a healthy sense of humor and be flexible, creative, and patient.

All behavior has a reason, although the cause may not be immediately known. Behavior is a response to the environment, caregivers, or internal stimuli. Problems may develop when the expectations of the caregiver do not match the abilities of the patient. The patient has a need for supervision and assistance because of increasing functional disability. The management of behavior is directed toward adapting the environment and approaches to the needs of the individual. Caregivers cannot cure the disease or teach patients to remember. They cannot resolve behavioral issues by using logic, by trying to reason with the person, or by coaxing or using flattery. Caregivers should have a healthy sense of humor and be flexible, creative, and patient.

Redirecting behaviors uses distraction techniques and patients' memory deficits, and short attention spans help to ensure the success of distraction. Used correctly, it avoids confrontation and the risk of catastrophic reactions.

The effective use of one's self as a therapeutic medium is the greatest intervention of all. Caregivers who are successful realize that the responses of the patient are frequently related to the approach of the caregiver. The most successful are those who are willing to "listen" to the patient's unspoken messages and use this information in their interactions. When a disturbing behavior occurs, they view it as a challenge for which they can find a solution rather than placing the responsibility for the behavior on the patient. They learn as much as they can about patients and their pasts through their contacts with the patients' families and others who know them.

If certain people or environments trigger shadowing, then adjustments or avoidance is necessary. If the behavior happens at a certain time of day, an activity may be planned to keep the person occupied, such as dusting or winding a ball of yarn. The Alzheimer's Association suggests, "gum therapy" or "cereal therapy" if the person can safely chew and swallow. Chewing is another form of distraction and redirection of energies.

Interventions for Wandering

Interventions for Sundowning

Interventions for Agitated Behavior

Reality orientation, reminiscence, and validation therapy are programs with specific purposes that may be utilized. Reminiscing is a natural process that people of all ages enjoy, but it is also stimulated in the elderly by the realization that life does not go on forever. For those with AD, reminiscing can be used as an intervention. In the early stage of AD, reminiscing can give a sense of pride and accomplishment to individuals who realize they are losing their grasp on reality.

Reality orientation (RO) was first described in the early 1960s by Taulbee and Folsom. RO is a planned, structured process designed to increase an individual's comprehension of person, place, time, and situation. This concept originated as a rehabilitation technique for traumatized war veterans [126]. However, it has been used for people who have moderate-to-severe degrees of confusion [56].

Naomi Feil developed validation therapy between 1963 and 1980 [119]. Feil de-emphasizes the significance of orientation and instead utilizes specific techniques to explore the meaning and motivation for confused statements [59]. Validation therapy is based on the premise that there is logic behind all behaviors and there are different stages and levels of disorientation among those diagnosed with an irreversible dementia. Validation assists disoriented individuals to restore the past, make closure, and justify their lives. The goal of validation therapy is to give the person a sense of identity, dignity, and self-worth through validation of the person's feelings. A structured learning program for the staff presented by a qualified consultant would be required in order to fully implement validation therapy as an intervention. Of the studies that have been performed to measure the efficacy of validation therapy, none have shown it to be significantly more effective than social contact or other therapies [119].

The primary goal of care during the terminal stage is to prevent complications associated with immobility and impaired physical functioning. Comfort should be paramount, with life extension generally no longer a consideration. Hospice services may be considered, with discontinuation of all life-sustaining measures or medicines. Special care should be exercised to prevent decubitus pressure ulcers, which may become a significant source of patient discomfort [6].

Severe cognitive impairment places the patient with AD at risk for sensory deprivation. Although the patient is minimally expressive, proper amounts of stimulation are needed to prevent continuous sleeping and agitation. The use of recliner type chairs enables dependent patients to be moved out of their room and to participate in appropriate activities. Listening to soothing music, hand massages, quiet talking, and olfactory stimulation with familiar odors are examples of sensory-centered activities.

Most families experience mixed emotions of relief and guilt when they realize they can no longer care for their loved one. The healthcare team must fully understand the impact of AD and institutionalization on the family so they can effectively help them deal with their grief. Intervention begins when the family visits the facility prior to admission. Their future adjustment may be influenced by what they observe during this time. Introduction to the staff gives the family the opportunity to identify key people in various departments. They should be provided information that describes the facility routine and a typical day. Most importantly, the family should be encouraged to communicate openly and honestly with staff. It is helpful if there is a specific person they can go to for discussion and answers. They should know that their feelings are normal and that staff is not judging them because of the patient's behavior.

Families may need suggestions for visiting. It is sometimes awkward to visit with a person who thinks the spouse is a sibling or the child is the spouse. The family is encouraged to bring old photos as a way of stimulating a response from the patient. The staff should direct them to other areas of the unit or building where they can take the patient when they come to visit and be invited to participate in care planning conferences and activities. Some families take great pleasure in feeding their loved ones, getting them ready for bed, or helping them bathe. On the other hand, there should be no pressure on those who choose not to help. Some families are exhausted from their caregiving demands prior to admission and welcome relief from further responsibilities.