Chapter 13: Neurocognitive Disorders Abnormal Psychology
Alzheimer's disease was first reported in 1907 by a German psychiatrist and neuropathologist, Alois Alzheimer (1864-1915), who documented the case of
"Auguste D.," a 51-year-old woman complaining of poor memory and disorientation regarding time and place. Eventually, Auguste D. became depressed and began to hallucinate. She showed the classic cognitive symptoms now understood as part of the diagnostic criteria for the disorder. Alzheimer was unable to explain this process of deterioration until after the patient had died, when an autopsy revealed that most of the tissue in her cerebral cortex had undergone severe degeneration. Upon examining the brain tissue under a microscope, Alzheimer also found that individual neurons had degenerated and formed abnormal clumps of neural tissue. Ninety years later, a discovery of brain slides from this famous case confirmed that the changes seen in Auguste D.'s brain were those of what now is known as Alzheimer's disease.
the anticholinesterases can have serious side effects that include
ainting, depression, anxiety, severe allergic reactions, seizures, slow or irregular heartbeat, fever, and tremor. Memantine's side effects can include hallucinations, seizures, speech changes, sudden and severe headache, aggressiveness, depression, and anxiety. Clinicians must weigh benefits against side effects when prescribing these medications, which themselves may interact with those the individual is receiving for other health conditions, such as aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs), Tagamet (used to treat heartburn), certain antibiotics, antidepressants, and medications that improve breathing.
Repeated injuries over time, such as those experienced by college and professional football players, may lead to
chronic traumatic encephalography (CTE), which causes a form of neurocognitive disorder and can lead to premature death. Football players are particularly likely to experience deficits in executive functioning associated with the damage to their frontal lobes. CTE's effects appear to be attributable, at least in part, to alterations in tau proteins, leading to the development of neurofibrillary tangles in areas of the brain active in both motor control and cognitive functioning.
Other reasons for the potentially misleading public information about Alzheimer's disease in the United States include
failure to take into account the education level of individuals who participate in epidemiological surveys, variations in the measurement of symptoms, and failure to account adequately for health status or other possible forms of neurocognitive disorder
Children and adolescents are most likely to suffer TBIs through
falls, sports injuries, and accidents. In older adults, falls are the most common cause of TBIs; falls are also the most deadly for this age group because they are generally associated with other severe injuries and complications.
The U.S. Food and Drug Administration-approved medications for treating mild to moderate Alzheimer's disease symptoms include
galantamine (Razadyne), rivastigmine (Exelon), and donepezil (Aricept). Clinicians only rarely prescribe another medication, tacrine (Cognex), due to concerns about its safety.
Apart from the cognitive symptoms of inattention and memory loss, individuals experiencing delirium may also have
hallucinations, delusions, abnormalities in sleep/wake cycles, changes in mood, and movement abnormalities. Once they experience this condition, people who have delirium are more likely to experience medical complications that can cause rehospitalization and a higher risk of mortality. Alzheimer's disease is another potential outcome due to the effects on the brain of inflammation of the immune system following a surgical procedure or injury.
Neurocognitive disorder with Lewy bodies is characterized by progressive loss of
memory, language, calculation, and reasoning, as well as other higher mental functions. The disorder gets its name from the presence in the brain of Lewy bodies, abnormal deposits of a protein called alpha-synuclein. These deposits affect dopamine and norepinephrine, which in turn affect motor functioning and memory. Individuals with neurocognitive disorder with Lewy bodies experience alterations in mood and movement in addition to cognitive changes.
A wide range of infectious diseases can cause the changes that occur with neurocognitive disorder. These include
neurosyphilis, encephalitis, tuberculosis, meningitis, human immunodeficiency virus (HIV), and localized infections in the brain. People who experience kidney failure may have symptoms of neurocognitive disorder as a result of the toxic accumulation of substances that the kidneys cannot cleanse from the blood. People with certain kinds of brain tumors also experience cognitive impairments and other symptoms of neurocognitive disorder.
Given that no medical treatments exist to cure the disease, behavioral psychologists are developing strategies to maximize the daily functioning of
people with Alzheimer's disease. They often target these efforts at the caregivers, who are the people (usually family members) primarily responsible for caring for the person with the disease. Caregivers often suffer adverse effects from the constant demands placed on them, effects that we call "caregiver burden". However, caregivers can learn behavioral strategies that promote the independence of their loved ones while also reducing the frequency of their distressing behaviors. Support groups can also provide a forum in which caregivers learn ways to manage the emotional stress that occurs with their role.
Trauma to the head that results in an alteration or loss of consciousness, or post-traumatic amnesia, is called
traumatic brain injury (TBI). The diagnostic criteria for neurocognitive disorder due to traumatic brain injury require evidence of impact to the head along with loss of consciousness, amnesia following the trauma, disorientation and confusion, and neurological abnormalities such as seizures. The symptoms must occur immediately after the trauma or after recovery of consciousness, and past the acute postinjury period.
As is true for Alzheimer's disease, there is no treatment to reverse the cognitive losses in
vascular neurocognitive disorder. However, individuals can take preventive actions throughout adulthood to protect themselves from the subsequent onset of this disease. Reducing the risk of hypertension and diabetes is one important way to lower the chances of developing cognitive disorders in later life.
The popular press widely but inaccurately reports the prevalence of Alzheimer's disease as 5 to 5.7 million in the United States, which would constitute
12 percent of the population over age 65 and 50 percent of those over age 85. The World Health Organization (2001) provides a far lower prevalence estimate of 5 percent of men and 6 percent of women worldwide. The incidence rate of new cases is less than 1 percent a year in those ages 60 to 65, or possibly as high as 6.5 percent in those 85 and older. Indeed, a study based on Canadian health insurance data reported a decline in the number of new cases reported in 2015, noting in addition that "since 60 to 80% of all major dementias have a vascular component, the falling incidence of stroke may have further contributed to the decline in dementia incidence"
Autopsy studies support the lower estimate. In one rural Pennsylvania community, researchers found Alzheimer's disease to be the cause of death in
4.9 percent of people age 65 and older. Of course, this estimate includes only those whose deaths were confirmed to have resulted from Alzheimer's disease. In many cases, another disease, such as pneumonia, is actually the immediate cause of death in people with advanced Alzheimer's disease. Nevertheless, this percentage is substantially lower than what we would expect on the basis of figures published in the media. Amazingly, among the 100-year-old and older participants in the New England Centenarian Study, approximately 90 percent were symptom-free until age 92.
Only an autopsy can produce a definitive diagnosis of
Alzheimer's disease by allowing pathologists to observe the characteristic changes in brain tissue. Assessments of individuals suspected of having the disease, particularly early in its progress, therefore depend on clinicians making a diagnosis by exclusion. In the later stages of the disease, the clinician can apply diagnostic guidelines that have 85 to 90 percent accuracy. A joint commission of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Diseases Association developed these in 1984, and they are referred to as the NINCDS/ADRDA Guidelines (McKhann et al., 1984). The diagnosis of Alzheimer's disease, which at present is based on the NINCDS/ADRDA criteria, requires thorough medical and neuropsychological screenings. Even with these very stringent and complete guidelines, the diagnoses to which they lead is at best one of "probable" Alzheimer's disease, again reflecting the fact that only through an autopsy can clinicians obtain a certain diagnosis.
Why do these overestimates occur?
Most importantly, report authors tend to include other forms of neurocognitive disorder due to Alzheimer's disease in their estimates. As many as 55 percent of neurocognitive disorders can be caused by disease processes other than Alzheimer's, including 20 percent caused solely by cardiovascular disease. Consequently, the "5.5 million" actually includes perhaps as many as 2 to 3 million people who have some form of vascular disease or other neurological disorder. Because cardiovascular disease is related to hypertension and diabetes, both of which people can control or prevent through diet and exercise, it is particularly important for older adults and their families to receive accurate diagnoses of any neurocognitive symptoms they experience.
As many as 12 to 20 percent of the U.S. veterans of the Iraq and Afghanistan wars may have experienced
TBIs resulting from injuries from improvised explosive devices (IEDs). Most of these cases are relatively mild in severity, meaning they involved loss of consciousness for 30 minutes or less, or post-traumatic amnesia of 24 hours or less. Most victims recover within 6 months of their injury, but a subgroup of veterans do not. Another group may have undetectable symptoms lasting until after their deployment. Not only does TBI carry significant health risks, but veterans who experienced it are at higher risk of developing PTSD, anxiety, and adjustment disorders. Unlike previous combat veterans, those who fought in the Iraq and Afghanistan wars are more likely to have had head injuries because their modern helmets offered better protection than those worn by soldiers in previous wars. Thus they will survive a blast only to suffer serious head (and other) injuries.
With the discovery of familial patterns of early-onset Alzheimer's disease along with advances in genetic engineering, researchers have identified several genes that may hold the key to understanding the cause of the disease.
The apoE gene on chromosome 19 has three common forms: e2, e3, and e4. Each produces a corresponding form of apolipoprotein E (apoE) called E2, E3, and E4. The presence of the e4 allele sets up the mechanism for production of the E4 form of apoE, which researchers believe damages the microtubules within the neuron, which in turn likely play an essential role in the cell's activity. Ordinarily, apoE2 and apoE3 protect the tau protein, which helps stabilize the microtubules. The theory is that if the tau protein is unprotected by apoE2 and apoE3, the microtubules will degenerate, eventually leading to the neuron's destruction.
While the genetic theory is compelling, it accounts for at most 50 percent of cases of people who develop Alzheimer's disease but have no known genetic risk, so behavioral factors would appear to be implicated.
These include cigarette smoking (Gons et al., 2011) and a sedentary lifestyle. Conversely, people who eat healthy diets have a lower risk of Alzheimer's disease. The Mediterranean diet includes foods that are high in tomatoes and olive oil, with low amounts of red meat and an occasional glass of red wine. Individuals who follow this diet have a lower risk of developing Alzheimer's disease.
Amyloid plaques are collections of clusters outside the neuron made up of
abnormal protein fragments called beta amyloid. Amyloid is a generic name for protein fragments that collect together in a specific way to form insoluble deposits (meaning that they do not dissolve). Amyloid plaques (also called beta-amyloid plaques) are formed when a substance found in the brain known as amyloid precursor protein (APP) embeds itself in the neuron's membrane. A small piece of APP lodges inside the neuron, and a larger part of it remains outside. In healthy aging, enzymes called secretases harmlessly trim away the extra length of the APP. In Alzheimer's disease, something goes wrong with this process so that the APP does not snip neatly at the cell membrane. The cut-off fragments of beta amyloid eventually clump together into beta-amyloid plaques that the body cannot dispose of or recycle.
The individual's cognitive functioning can also be negatively affected by
anoxia (oxygen deprivation to the brain), which may occur during surgery under general anesthesia or as a result of carbon monoxide poisoning. Anoxia can have severe effects on many brain functions because neurons die quickly if they are deprived of oxygen. Because brain neurons do not replace themselves, significant neuron loss can lead to impairments in concrete thinking and functions such as new learning ability, attention, concentration, and tracking. The emotional effects of brain damage due to anoxia can include affective dulling and disinhibition, as well as depression. These changes can drastically reduce the person's ability to plan, initiate, and carry out activities.
Treatment of delirium includes a pharmacological approach that relies on
antipsychotics including haloperidol and risperidone. In one study, this combination was found to resolve symptoms of delirium in as many as 84 percent of cases over a period of 4 to 7 days. Although haloperidol is considered potentially useful in reducing delirium in high-risk patients, research does not support its efficacy as a preventive.
the biological perspective has not yet produced a viable treatment for one of the most devastating of these disorders, Alzheimer's disease. Until researchers find a cure, individuals and their families whose lives are touched by the disease must be willing to try a
ariety of approaches to alleviate the suffering. Many research programs are currently underway to explore strategies for reducing the stress placed on caregivers. Some of these strategies make use of innovative, high-tech methods such as computer networks. Others take the more traditional approach of providing emotional support to individuals with Alzheimer's disease and their families. The application of cognitive-behavioral and other methods of therapy to help people cope with Alzheimer's is another useful approach. It seems that the bottom line in all this research on understanding and treating those affected by Alzheimer's disease is that it is not necessary for psychologists to wait until biomedical researchers discover a cure. They can do quite a bit to improve the quality of life for people with Alzheimer's and to help them maintain their functioning and dignity for as long as possible.
Professional athletes may also suffer mild TBIs, particularly those who play contact sports such as football and hockey. Their injuries may not be properly
assessed when they occur, leading them to return to play before they are fully ready to do so. Although they may appear to have recovered enough to go back onto the field, they may nevertheless suffer mental impairments that are only evident later. In one study of male and female college athletes engaged in high-contact sports, researchers found memory impairments even in players who did not appear to have suffered a concussion. Unlike trauma victims, athletes are more likely to return to pre-injury functioning within 2 to 14 days.
People diagnosed with delirium temporarily experience disturbances in their
attention and awareness. The symptoms tend to appear abruptly and fluctuate over the duration of the disorder. The core of delirium is an acute state of confusion or impairment in cognitive processing that affects memory, orientation, executive functioning, ability to use language, visual perception, and learning.
There are two main implications of research documenting the behavioral risk factors for Alzheimer's disease. First, people can reduce their risk of Alzheimer's disease by
avoiding behaviors that contribute to its development. Second, these risk factors also increase the likelihood of an individual's developing cerebrovascular disease, depression, and other causes of neurocognitive disorder. This finding supports the contention that estimates of Alzheimer's prevalence statistics are inflated by the existence of other preventable neurocognitive disorders related to risk factors within the aging population. Advances in public health efforts intended to reduce obesity, diabetes, and smoking should lead to a decrease in the estimates of Alzheimer's disease, if not actual reductions in the number of people who truly have the disorder.
Several indicators can help the clinician differentiate depression from neurocognitive disorder. For example, depressed individuals are more keenly
aware of their impaired cognition and frequently complain about their faulty memory. In contrast, individuals with Alzheimer's usually try to hide or minimize the extent of impairment or explain it away when they cannot conceal the loss. As the disorder progresses, people with Alzheimer's disease lose awareness of the extent of their cognitive deficits and may even report improvement as they lose their capacity for critical self-awareness.
Exposure to certain drugs and environmental toxins can cause
brain damage and result in a condition called substance/medication-induced neurocognitive disorder. Such toxins can come from intense fumes from house paint, styrene used in plastics manufacturing, and fuels distilled from petroleum.
One of the reasons current medical treatments for Alzheimer's disease are not proving effective is that
changes other than the development of amyloid plaques and neurofibrillary tangles may occur in its development and progression. Changes in cardiovascular functioning and diabetes must also be accounted for as possible contributors.
Instead of using medications as a prevention for the development of delirium,
clinicians can provide high-risk patients with cognitively stimulating activities such as discussions of current events or word games. In this approach, multidisciplinary staff addresses the risk factors of delirium as soon as a patient is admitted to an acute care facility for rehabilitation (after, for example, a hip fracture) rather than wait for delirium to develop.
The common overestimation of the incidence of Alzheimer's disease reinforces the false notion that any
cognitive changes experienced by people in later life (or earlier) reflect the disease's onset. Loss of working memory occurs normally in later life for most individuals. Once people become self-conscious about their memory, however, they tend to exaggerate even small losses, thinking they have Alzheimer's disease. Unfortunately, this self-consciousness only worsens their memory, which further perpetuates the cycle. Rather than taking preventive steps, such as engaging in memory exercises or other cognitively challenging activities, people in this situation are likely to give in to despair
In DSM-5, the term neurocognitive disorder replaces dementia, used in DSM-IV-TR to refer to a form of
cognitive impairment in which individuals undergo progressive loss of cognitive functions severe enough to interfere with their normal daily activities and social relationships. The DSM-5 work group considered the term dementia to be acceptable for use in medical settings, but there is hope that this overly general term will eventually be replaced altogether.
Prior to the introduction of antiretroviral therapies for acquired immune deficiency syndrome (AIDS), the disease that can result from HIV, neurocognitive disorder in the late stages of the disease was a
common and devastating complication. With improvements in treatment, this condition, known as AIDS dementia complex, has become less prevalent; however, cases continue to rise among people who go undiagnosed and untreated, a situation particularly common in developing countries.
Other approaches to treating neurocognitive disorder due to Alzheimer's disease target the free radicals, which are molecules that form when beta amyloid breaks into fragments. Free radicals can
damage neurons in the surrounding brain tissue (Wani et al., 2017). Antioxidants can disarm free radicals and therefore may be another treatment for Alzheimer's disease. Bioflavonoid, a substance that occurs naturally in wine, tea, fruits, and vegetables, is one such antioxidant. Researchers view naturally occurring bioflavonoids (in, for example, blueberries) as having important preventive roles in reducing the extent of memory loss in later adulthood (Joseph, Shukitt-Hale, & Casadesus, 2005). A longitudinal study of over 1,300 French people found that bioflavonoids were beneficial in reducing the risk of Alzheimer's disease
The neurocognitive disorders specifically describe
decline acquired in one or more domains of cognition associated with alterations in the brain.
Adding to the complexity of separating the causes of neurocognitive disorder in disorders other than Alzheimer's is the fact that
depression can lead to symptoms similar to those apparent in the early stages of Alzheimer's disease. The condition is known as pseudodementia, or false neurocognitive disorder, is a severe form of depression that has primarily cognitive symptoms.
The Alzheimer's Association also uses the term "Alzheimer's dementia" in its estimates, including to
describe "those with mild cognitive impairment due to Alzheimer's and asymptomatic individuals who have verified biomarkers of Alzheimer's" (Alzheimer's Association, 2018). This expanded terminology is not consistent with DSM-5 (which does not use the term dementia in the diagnosis) and also expands the definition beyond individuals who meet the actual diagnostic criteria.
There are several specialized tests to assess delirium. The Delirium Rating Scale-Revised (DRS-R-98) is a widely used measure that has been translated into several languages (Table 2) and has well-established validity and reliability. The advantage of this scale is that although it was
designed for psychiatrists, other professionals (physicians, nurses, psychologists) and researchers can also use it. When completing the instrument, the clinician can use information gathered from family members, visitors, hospital staff, physicians, medical charts, and even hospital roommates.
Substance-induced persisting amnestic disorder occurs when
drugs or medications cause serious memory impairment. An array of substances may cause this condition, including prescribed medications, illicit drugs, industrial solvents, and environmental toxins such as lead, mercury, and insecticides. The most common cause of this form of neurocognitive disorder is chronic alcohol use. The memory loss must persist over time for the clinician to assign the diagnosis of neurocognitive disorder due to another general medical condition. For some people, especially chronic abusers of alcohol, the neurocognitive disorder due to another general medical condition persists for life, causing such severe impairment that the individual may require custodial care. For others, such as those whose condition results from medications, full recovery is possible.
Behavioral strategies aimed at increasing the patient's independence include
giving prompts, cues, and guidance for self-maintenance. For example, the clinician can encourage the patient to relearn the steps in getting dressed and then positively reward him or her with praise and attention for having completed them. Through modeling, the patient relearns old skills through imitation. The caregiver can also learn time management, which encourages following a strict daily schedule. As a result, the patient is more likely to fall into a regular routine of everyday activities. All these methods benefit both the patient and the caregiver. The patient regains some measure of independence, which reduces the caregiver's burden to the extent that the patient can engage in self-care tasks.
In 2013, there were an estimated 2.8 million TBI-related hospitalizations, emergency department visits, and deaths (Taylor, Bell, Breiding, & Xu, 2017). (Figure 7). Children aged 0 to 4 years, adolescents and young adults aged 15 to 24 years, and adults 75 years and older have the
greatest risk of TBI. The highest rates of hospitalization and death due to TBI occur in adults 75 years of age and older. People within these age groups sustain accidental TBIs for different reasons.
The group recognized that there is still no infallible way of diagnosing the disorder in a living person, proposing that clinicians diagnose an individual as
having "probable" or "possible" Alzheimer's disease. They also suggested a third diagnostic category, "probable or possible," with evidence of brain pathology. This would not be a clinical diagnosis but would be intended for research purposes only. However, the authors of DSM-5 adopted this terminology, which is now used to indicate a level of certainty of the diagnosis.
Clinicians use neuropsychological testing and neuroimaging techniques, as well as an individual's medical history, to decide whether an
individual's symptoms fall into the category of a neurocognitive disorder. Neuropsychological testing helps clinicians identify specific patterns of responses that appear to fit known disease profiles. They combine this knowledge with their client's medical history to see whether a specific event triggered the symptoms. In addition, neuroimaging provides clinicians with an inside look at the brain to help them connect symptoms with specific illnesses or injuries. Both forms of assessment are required for an individual to receive a diagnosis of one of these disorders.
Infection is another precipitating factor in at-risk individuals. In a survey of nearly 1.3 million patients studied over the years 1998 to 2005, researchers found that the most frequent causes of delirium were
infections, including respiratory infections, cellulitis, and urinary tract and kidney infections. The next largest cause was some type of central nervous system disorder, including cancer, neurocognitive disorder, stroke, and seizure. The third most frequent cause of delirium included metabolic disorders, cardiovascular disease, and orthopedic procedures. However, over the course of the study, drug-induced delirium increased in prevalence among older adults, suggesting that either hospital workers became more attuned to this diagnosis or that people in this age group are becoming increasingly likely to receive delirium-inducing medications. Making health professionals aware of adverse drug effects may ultimately help to reduce the prevalence of delirium in high-risk individuals
The clinical tool clinicians most commonly use for providing a quick screening for Alzheimer's disease is a specialized form of the
mental status examination, known as the MiniMental State Examination (MMSE) (Folstein, Folstein, & McHugh, 1975) (Table 5). People with Alzheimer's disease respond in certain ways to several items on this instrument. They tend to be circumstantial, repeat themselves, and lack richness of detail when describing objects, people, and events. As a screening tool, the MMSE can provide preliminary indications that an individual may have the neurocognitive disorder, but it should not be used as the sole basis for a diagnosis.
The diagnosis of mild neurocognitive disorder is applied when the individual shows
modest levels of cognitive decline. These declines are not severe enough to interfere with the individual's capacity for living independently.
The biological theories of Alzheimer's disease attempt to explain the development of two characteristic abnormalities in the brain:
neurofibrillary tangles and amyloid plaques. Neurofibrillary tangles are made up of a protein called tau (Figure 3), a protein which seems to play a role in maintaining the stability of microtubules, supporting the axon's internal structure. The microtubules are like train tracks that guide nutrients from the cell body down to the axon's ends. The tau proteins are like the railroad ties or crosspieces of the microtubule train tracks. In Alzheimer's disease, the tau changes chemically and loses its ability to separate and support the microtubules. With their support gone, the tubules begin to wind around each other and can no longer perform their function. This collapse of the transport system within the neuron may first result in malfunctions in communication between neurons and may eventually lead to the neuron's death. The development of neurofibrillary tangles appears to occur early in the disease process and may progress quite substantially before the individual shows any behavioral symptoms.
Current medications inhibit the action of acetylcholinesterase, the enzyme that
normally destroys acetylcholine after its release into the synaptic cleft and which is implicated as a contributor to memory loss. Because these slow the breakdown of acetylcholine, they allow higher levels to remain in the brain, thus facilitating memory. All have significant side effects. Memantine falls into a separate category of FDA-approved medications for treatment of Alzheimer's disease in the moderate to severe stages. An NMDA antagonist, memantine regulates glutamate, which, in excessive amounts, may destroy neurons.
By definition, the symptoms of Alzheimer's disease become progressively worse
over time. However, not all people who show early symptoms of Alzheimer's disease actually have this disease. As you can see from Figure 2, some individuals remain healthy until death. Some experience memory problems (referred to here as "amnestic mild neurocognitive disorder") but are able to compensate for them and never develop Alzheimer's disease. In those individuals who develop Alzheimer's disease, however, the loss of independent function continues in a progressive manner until death. Factors related to more rapid decline in the early stages of the disease include being younger at the age of onset, having higher education, and having poorer cognitive status when symptoms of the disease are first recognized
Although it is primarily a loss of motor control, neurocognitive disorder due to Huntington's disease is a degenerative neurological disorder that can also affect
personality and cognitive functioning. Researchers have traced Huntington's disease to an abnormality on chromosome 4 that causes a protein, now known as huntingtin, to accumulate and reach toxic levels. The symptoms first appear during adulthood, between ages 30 and 50. The disease results in the death of neurons in subcortical structures that control motor behavior.
Rather than manifesting as a decline in memory, as we see in Alzheimer's disease, frontotemporal neurocognitive disorder is reflected in
personality changes, such as apathy, lack of inhibition, obsessiveness, and loss of judgment. Eventually, the individual becomes neglectful of personal habits and loses the ability to communicate. The onset of the disorder is slow and insidious. On autopsy, the brain shows atrophy in the frontal and temporal cortex, but there are no amyloid plaques or arterial damage.
People undergoing mild TBI may experience a related condition known as
postconcussion syndrome (PCS) in which they continue to have symptoms such as fatigue, dizziness, poor concentration, memory problems, headache, insomnia, and irritability. Individuals most at risk of developing PCS are those who had an anxiety or depressive disorder prior to their injury and acute post-traumatic stress for approximately 5 days after their injury. However, PCS may also develop in traumatized individuals with these characteristics who do not actually suffer a mild TBI.
Neurocognitive disorder due to prion disease, also known as Creutzfeldt-Jakob disease, is a rare neurological disorder known as
prion disease, which researchers believe is caused by an infectious agent and that results in abnormal protein accumulations in the brain. Initial symptoms include fatigue, appetite disturbance, sleep problems, and concentration difficulties. As the disease progresses, the individual shows increasing signs of neurocognitive loss and eventually dies. Underlying these symptoms is widespread damage known as spongiform encephalopathy, meaning that large holes develop in brain tissue. The disease appears to be transmitted to humans from cattle that have eaten the body parts of dead farm animals infected with the disease (particularly sheep, in which the disease is known as scrapie). In 1996, an epidemic in England of "mad cow disease," along with reported cases of the disease in humans, led to a ban on importation of British beef. Concerns about this disease continue to exist in European countries, as well as in the United States.
The benefits of the current medications to treat Alzheimer's disease symptoms are short-lived. Administering higher levels of anticholinesterases may slow the
progression somewhat but does not prevent deterioration in cognitive functioning over the long term. Donepezil may reduce the perception by caregivers of their burden and of the other symptoms shown by the patients they care for, but these effects have not been studied past 12 weeks of treatment. Another medication, galantamine (Razadyne), acts as an anticholinesterase and may have positive effects for up to 3 years, but it also has a higher associated death rate. Medications that address the deleterious changes in tau are being developed but at present are not suitable for use in humans.
Neurocognitive disorder due to Alzheimer's disease is a disorder associated with
progressive, gradual declines in memory, learning, and at least one other cognitive domain. The first symptoms of memory loss precede a cascade of changes that eventually ends in death due to the development of medical illness resulting from infection or failure of vital bodily organs.
The cognitive losses that occur with physical disorders and toxic reactions may be reversible if the person receives
prompt and appropriate medical treatment. However, if intervention for a treatable neurocognitive disorder is not introduced in the early stages, the brain damage becomes irreversible. The more widespread the structural damage to the brain, the lower the chance that the person will ever regain lost functions.
Nutritional deficiencies can also cause cognitive decline. People who are severely undernourished are
prone to develop a deficiency of folate, a critical nutrient, leading to progressive cerebral atrophy. If the deficiency is not corrected by dietary improvements, the individual can become depressed and show various cognitive impairments, such as poor memory and impaired abstract reasoning.
Amnesia is the inability to
recall information that was previously learned or to register new memories. In DSM-5, people with amnesia receive a diagnosis of major neurocognitive disorder due to another general medical condition. Their memory loss can result from a wide variety of medical problems, including head trauma, loss of oxygen, and herpes simplex.
To receive a diagnosis of delirium, the individual must show these changes in consciousness or awareness over a very
short period of time, on the order of hours or days. The diagnosis also requires that a general medical condition must cause the disturbance. Clinicians, therefore, specify whether the delirium results from substance intoxication, substance withdrawal, a medication, or other medical condition(s). The clinician also rates the delirium as acute (occurring a few hours or days) or persistent (occurring over weeks or months).
Most early-onset familial Alzheimer's disease cases occur with defects in the
so-called presenilin genes (PS1 and PS2), which, as the name implies, are most likely involved in causing the brain to age prematurely. The mean age of onset in families with mutations in the PS1 gene is 45 years (ranging from 32 to 56 years) and age 52 years for people with PS2 gene mutations (ranging from 40 to 85 years). The pattern of inheritance for the presenilin genes is autosomal dominant, meaning that if one parent carries the allele that occurs with the disease, the offspring has a 50 percent chance of developing the disorder. Researchers are attempting to determine how presenilin genes 1 and 2 interact with APP, beta-amyloid plaques, and tangles. Researchers estimate that the four genes, presenilin 1 and 2, APP, and apoE, account for approximately half the genetic risk for Alzheimer's disease.
A number of disturbances occur with Huntington's disease, ranging from altered cognitive functioning to
social and personality changes. We associate the disease with mood disturbances, changes in personality, irritability and explosiveness, suicidality, changes in sexuality, and a range of specific cognitive deficits. Because of these symptoms, clinicians may incorrectly diagnose the disorder as schizophrenia or a mood disorder, even if the individual has no history suggestive of these disorders. People with Huntington's disease can also appear apathetic because of their decreased ability to plan, initiate, or carry out complex activities. Their uncontrolled motor movement interferes with sustained performance of any behavior, even maintaining an upright posture, and eventually most people with Huntington's disease become bedridden.
Major neurocognitive disorders are diagnosed when individuals show significant cognitive decline from a previous level of performance in the six domains of Table 1 based on a
standardized neuropsychological or other quantified clinical assessment. These cognitive deficits must interfere with the individual's ability to perform necessary tasks in everyday living, not occur exclusively with delirium, and lack a better explanation as another psychological disorder.
Delirium can develop for a variety of reasons, including
substance intoxication or withdrawal, head injury, high fever, and vitamin deficiency. People of any age can experience delirium, but it is more common among older adults who have been hospitalized for medical or psychiatric reasons. In addition to age, the risk factors for delirium include a previous history of stroke, neurocognitive disorder, sensory impairment, and use of multiple prescription medications ("polypharmacy"). People at risk may develop delirium following infections, urinary retention or use of catheters, dehydration, loss of mobility, and disorders affecting heart rate. Increases in immune system inflammatory responses may also contribute to delirium
Another possible cause of neurocognitive disorder is cardiovascular disease affecting the
supply of blood to the brain. This condition, called vascular neurocognitive disorder, is highly prevalent, and researchers link it to a variety of cardiovascular risk factors. The most common form is multi-infarct dementia (MID), caused by transient attacks in which blood flow to the brain is interrupted by a clogged or burst artery. The damage to the artery deprives the surrounding neurons of blood and oxygen, which causes the neurons to die. Although each infarct is too small to be noticed at first, over time the progressive damage caused by the infarcts leads the individual to lose cognitive abilities. Memory impairment appears to be similar to that observed in Alzheimer's disease; however, there are some significant differences between these two disorders. People with vascular neurocognitive disorder show a particular set of physical abnormalities, such as walking difficulties and weakness in the arms and legs, and a pattern of cognitive functioning distinctly different from that in people with Alzheimer's.
Pick's disease is a relatively rare, progressive degenerative disease that affects
the frontal and temporal lobes of the cerebral cortex. It is caused by the accumulation in neurons of unusual protein deposits called Pick bodies. In addition to having memory problems, people with this disorder become socially disinhibited, either acting inappropriately and impulsively or appearing apathetic and unmotivated. In contrast to the sequence of changes people with Alzheimer's disease show, those with Pick's disease undergo personality alterations before they begin to have memory problems. For example, they may experience deterioration in social skills, language abnormalities, flat emotionality, and a loss of inhibition.
Neurocognitive disorder due to Parkinson's disease brings about neuronal degeneration of the basal ganglia,
the subcortical structures that control motor movements. Deterioration of diffuse areas of the cerebral cortex may occur. Cognitive changes do not occur in all people with Parkinson's disease, but researchers estimate rates as high as 60 percent, mostly among those who are older and at a more advanced stage of the disease. Parkinson's disease is usually progressive, with various motor disturbances being the most striking feature of the disorder. For example, at rest, the person's hands, legs, or head may shake involuntarily. The muscles become rigid, and it is difficult for the person to initiate movement, a symptom called akinesia. A general slowing of motor activity, known as bradykinesia, also occurs, as does a loss of fine motor coordination. Some people with Parkinson's disease walk with a slowed, shuffling gait. They have difficulty starting to walk, and once they start, they have difficulty stopping. In addition to these motor abnormalities, they show signs of cognitive deterioration, such as slowed scanning on visual recognition tasks, diminished conceptual flexibility, and slowed motor responses. The individual's face also appears expressionless and speech becomes stilted, losing its normal rhythmic quality. The individual has difficulty producing words on tests that demand verbal fluency. However, many cognitive functions, such as attention, concentration, and immediate memory, remain intact.
Although researchers are testing various theories to identify the causes of Alzheimer's disease, the most probable is that an
underlying defect in the genetic programming of neural activity triggers the formation of tangles and plaques. The genetic theory was given impetus with the discovery that a form of the disease called early-onset familial Alzheimer's disease, which begins at the unusually young ages of 40 to 50, occurs with higher than expected prevalence in certain families. Other genes appear to be involved in a form of late-onset familial Alzheimer's disease that starts at the more expected ages of 60 to 65. Researchers postulate that these genes lead to the formation of excessive amounts of beta-amyloid protein.
Behavioral strategies can also eliminate, or at least reduce the frequency of,
wandering and aggression in an Alzheimer's patient. One possible approach, which is not always practical, is extinction. The caregiver ignores certain disruptive behaviors, with the intention of eliminating the reinforcement that has helped maintain them. Extinction is not practical for behaviors that may lead to patient harm, however, such as leaving the house and wandering into the street. One possibility is to give the patient positive reinforcement for staying within certain boundaries; however, this may not be sufficient, and at that point the caregiver needs to install protective barriers. Another possible approach is for the caregiver to identify situations that are particularly problematic for the patient, such as the bathtub or the dining table. The caretaker can then use behavioral methods in these circumstances. For example, if the problem occurs while eating, it may be that the caretaker can encourage the patient to relearn how to use a knife and fork, rather than feeding him or her. Again, such an intervention can reduce caregiver burden as well as increasing the patient's functional skills.
