Dementia: Disorders of the Brain

Dementia Overview

       In 1901 Auguste Deter, a woman in her early 50s, became the first person diagnosed with Alzheimer's disease, a form of dementia. The disease is named after the doctor who first described it, Alois Alzheimer.
The disease is characterized by odd behavior, memory problems, paranoia, disorientation, agitation, and hallucinations.

What Is Dementia?

       Dementia refers to a group of symptoms that can be caused by several different brain disorders. In general, dementia is characterized by impaired intellectual functioning that interferes with daily activities or personal relationships. This impairment can include memory loss, language difficulty, decreased perception, and impaired reasoning.

 

What Are the Different Kinds of Dementia?

       There are several different classifications of dementia. Dementia can be classified by either the area of the brain that is affected, whether it is progressive, or whether it results from another disorder (primary or secondary). The following slides discuss some causes and types of dementia.

Alzheimer's Disease

       The most common cause of dementia is Alzheimer's disease. More than 5 million people are living with Alzheimer's disease, and ½ million die each year from it. It is the 6th leading cause of death in the U.S., and the 5th leading cause of death for seniors 65 and older. Two-thirds of seniors with Alzheimer's are women. Up to 5% of those living with Alzheimer's have the early-onset form of the disease, and are diagnosed in their 40s or 50s. Alzheimer's disease usually causes a decline in thinking ability, memory, movement, and language. Bizarre, withdrawn, or paranoid behavior may also occur as the disease progresses.
       On the microscopic level, Alzheimer's disease shows up in the brain with two characteristic abnormalities: amyloid plaques and neurofibrillary tangles. Amyloid plaques are abnormal clumps of protein (beta amyloid) found between the nerve cells of the brain that impair communication between nerve cells. Neurofibrillary tangles are damaged proteins (tau proteins) that collect into "tangles," which cause improper functioning of nerve cells, leading them to disintegrate.
It is unknown if amyloid plaques and neurofibrillary tangles cause Alzheimer's or if they result from the disease itself.

 

       Patients with Alzheimer's disease suffer progressive disability over the course of the illness. Generally, patients with Alzheimer's can live from 2 to 20 years from diagnosis; on average patients life expectancy is 8-10 years. Early in the disease, patients may only have subtle symptoms such as changes in personality or lapses in memory. As the disease worsens, patients may experience bouts of disorientation, and may notice difficulty in performing daily tasks. In later stages of the disease, patients can no longer care for themselves, and they may become paranoid or hostile. In the last stages of the disease patients lose the ability to swallow and control bladder and bowel functions. They may no longer recognize family members and may not be able to speak.
Complications of Alzheimer's that can be fatal include loss of ability to swallow that can lead to aspiration pneumonia, and incontinence leading to urinary tract infections or sepsis (severe infection).

 

Vascular (Multi-Infarct) Dementia

       After Alzheimer's disease, the second most common cause of dementia is vascular dementia. Vascular dementia may be caused by brain damage such as from strokes, atherosclerosis, endocarditis, or amyloidosis. Structural damage to the brain tissue, either by blocked arteries, blood clots, or bleeding (hemorrhage) causes symptoms of vascular dementia. Vascular dementia may coexist with Alzhemier's disease and many of the symptoms overlap. However, people with vascular dementia only usually maintain their personality. Other symptoms of vascular dementia include nighttime wandering, depression, incontinence, or one-sided body weakness associated with larger strokes.  One type of vascular dementia called multi-infarct dementia (MID) is caused by multiple small strokes in different areas of the brain. When the smaller blood vessels of the brain become blocked tiny areas of the brain, especially in the "white matter" (outer part of the brain), become damaged. These small strokes can be in "silent areas" (areas of the brain that when damaged do not show outward signs of disability), or may occur in important regions of the brain such as the hippocampus or parts of the left hemisphere where damage causes disability to be apparent.
Other types of vascular dementia include Binswanger's disease and CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy).

 

Lewy Body Dementia (LBD)

       The third most common type of dementia is Lewy body dementia (LBD), also called dementia with Lewy bodies (DLB). The "Lewy body" is an abnormal protein found microscopically in the brain of patients with this type of dementia.
Symptoms of Lewy body dementia are similar to Alzheimer's, including impaired memory, confusion, and poor judgment. LBD also includes symptoms such as hallucinations and parkinsonian symptoms (shuffling gait, inability to stand straight, and shaking).

Frontotemporal Dementia (FTD)

       Frontotemporal dementia, also called frontal lobe dementia and previously known as Pick's disease, is caused by degeneration of nerve cells in the frontal and temporal regions of the brain. The frontal and temporal regions of the brain control behavior, judgment, emotions, speech, and some movement. Damage to these areas accounts for the symptoms that separate frontotemporal dementia from other types of dementia.
Symptoms of frontotemporal dementia generally occur in younger patients in their 50s and 60s, and it is believed to account for 10% to 15% of all cases of dementia. Behavioral changes appear early on in the disease with frontotemporal dementia, differing from the late onset in Alzheimer's disease.

HIV-associated Dementia (HAD)

       HIV-associated dementia (HAD), also called AIDS-dementia complex (ADC), is a brain disorder caused by infection with HIV (human immunodeficiency virus), the virus that causes AIDS. It is not clear how the virus causes the brain damage that leads to the symptoms of dementia. The main symptoms of HAD include impaired memory, lack of concentration, withdrawal from social activities, and speech difficulties. Medications to treat HIV/AIDS may delay the onset of the dementia symptoms.

Huntington's Disease

       Huntington's disease is a genetic disorder that causes an abnormal protein (huntingtin protein) to form in the brain. This leads to brain changes that cause abnormal movements, a decline cognitive skills, irritability, depression, and anxiety. Some patients may progress to show psychotic behavior.
Huntington's disease begins earlier in life than other types of dementia, typically between the ages of 30 to 50. Life expectancy after onset of symptoms is between 10 to 15 years.

Dementia Pugilistica

       Boxer's syndrome, or dementia pugilistica, is a form of chronic brain injury caused by repetitive head trauma. It's name comes from symptoms experienced by boxers who have had years of being punched in the head. Primary symptoms – which may not develop for years after the trauma - include slurred speech, poor motor coordination, and difficulty walking. Patients may also experience memory problems.

Corticobasal Degeneration (CBD)

       Corticobasal degeneration (CBD) is a loss of nerve cells (atrophy) in the cerebral cortex and the basal ganglia areas of the brain. This progressive disorder worsens over the course of 6 to 8 years due to degeneration of multiple brain areas. Symptoms of CBD have features of parkinsonianism (poor coordination, muscle rigidity, and shaking), as well as Alzheimer's disease (memory loss, speech difficulty, and trouble swallowing). Patients with CBD deteriorate to the point where they can no longer care for themselves, and often die from secondary medical issues such as pneumonia or severe infection (sepsis).

Creutzfeldt-Jakob Disease (CJD)

       Creutzfeldt-Jakob disease (CJD) is a type of human and animal disease known as transmissible spongiform encephalopathies (TSEs). It is thought to be caused by an abnormal protein called a "prion." It is in the same family of diseases as bovine spongiform encephalopathy (BSE, or "mad cow" disease). There are three main types of CJD: sporadic, familial, and infectious. Eighty-five percent of cases are sporadic, with no known cause. Familial cases account for 10% to 15%, and are genetically passed on to family members. The remaining cases are infectious, resulting from exposure to an external source of the abnormal prion protein, such as in BSE.
Symptoms of CJD include personality changes, problems with muscular coordination, impaired vision, and insomnia. Progression to death is more rapid than in other types of dementia.

Dementias in Children

       Dementia can also occur in children. Though rare, there are some disorders that can cause the disease in pediatric patients including Niemann-Pick disease, Batten disease, Lafora body disease, and certain types of poisonings.

What Other Conditions Can Cause Dementia?

Many other conditions can cause dementia, including:

• Low oxygen in the blood (anoxia/hypoxia), either from a specific incident (heart attack, stroke, surgical complications), or chronic disease (heart disease, asthma, COPD/emphysema) can cause damage to brain tissue.
• Acute infections such as meningitis, encephalitis, untreated syphilis, and Lyme disease.
• Brain tumors or metastases from other cancers in the body.
• Thiamine (vitamin B1), B6, or B12 deficiencies, and severe dehydration.
• Acute traumatic injury to the brain such as a subdural hematoma.
• Side effects from medications taken for other medical conditions.
• Electrolyte abnormalities.
• Poisoning such as exposure to lead, other heavy metals, alcohol, recreational drugs or other poisonous substances.

What Conditions Are Not Dementia?

       Though many conditions may have similar symptoms to dementia, not all are considered to be dementia. These include:

• Depression
• Delirium
• Age-related cognitive decline
• B12 deficiency
• Reactions to drugs (recreational or prescription)

What Causes Dementia?

       All forms of dementia are the end result of either cell degeneration and death, or abnormalities impeding communications between brain cells (neurons). In many of the common types of dementia, abnormal proteins (or abnormal amounts of normally-occurring proteins) are found in the brain tissue on the microscopic level. It is unknown if these proteins cause dementia or if they result from the diseases themselves. While some types of dementia are hereditary, many are a result of a combination of genetics, environment, and lifestyle.

 

What Are the Risk Factors for Dementia?

Several risk factors for developing some types of dementia have been identified. These factors include:

• Age
• Genetics
• Smoking and alcohol use
• Atherosclerosis (hardening of arteries)
• High cholesterol
• Plasma homocysteine
• Diabetes
• Mild cognitive impairment
• Down syndrome

How Is Dementia Diagnosed?

       Most often, dementia is diagnosed by exclusion, which means doctors rule out other conditions that can cause the symptoms that resemble dementia.
Tests to diagnose dementia include:

• Physical examination with detailed neurological testing
• Cognitive and neuropsychological tests
• Brain scans (CT scans and MRIs)
• Blood tests, urinalysis, toxicology screen, thyroid tests
• Psychiatric evaluation
• Genetic testing

Treatment for Dementia?

There is no known cure for dementia, but many patients may benefit from combination treatments.

• Medications for Alzheimer's disease and some other forms of dementia can improve symptoms and slow the progression of the disease.
• Cognitive training, such as memory training, note-taking, and computerized recall devices can aid in memory.
• Behavior modification can help control behaviors that may put the patient in danger.

Medications for Alzheimer's Disease

       Drugs approved by the U.S. Food and Drug Administration (FDA) to treat Alzheimer's disease are called cholinesterase inhibitors. These drugs temporarily improve or stabilize memory and thinking skills in some individuals. These drugs include:

• donepezil (Aricept)
• rivastigmine (Exelon)
• galantamine (Razadyne – previously called Reminyl)
• tacrine (Cognex) – not used much due to side effects

       Doctors may also prescribe other drugs, such as anticonvulsants, sedatives, and antidepressants to treat problems that may be associated with dementia such as insomnia, anxiety, depression, and sleep disorders.

 

Medications for Vascular Dementia

       Because vascular dementia is caused by the death of brain tissue and atherosclerosis, there is no standard drug treatment for it. Drugs used to treat other atherosclerotic vascular diseases such as cholesterol medications, blood pressure medications, and anti-blood clotting medications, may be used to slow the progression of vascular dementia. In some cases, cholinesterase inhibitors and antidepressants may help improve symptoms associated with vascular dementia.

Medications for Other Dementias

       For the more rare forms of dementia, there are no standard medical treatments. Cholinesterase inhibitors, such as those used to treat Alzheimer's disease, may reduce behavioral symptoms in some patients with Parkinson's dementia.
In most cases, medications are given to patients with dementia to relieve specific symptoms associated with their disorder. Doctors may prescribe other drugs, such as anticonvulsants, sedatives, and antidepressants to treat problems that may be associated with dementia such as insomnia, anxiety, depression, and sleep disorders.

Can Dementia be Prevented?

       In some people, moderating known risk factors for dementia may help prevent or delay the onset of the disease. These factors include:

• Diabetics should keep glucose levels under control
• Keep healthy cholesterol levels
• Exercise
• Maintain healthy blood pressure
• Lose weight if overweight
• Quit smoking and moderate alcohol consumption
• Keep the mind active and engaged with intellectually stimulating activities

Caring for People with Dementia

       Patients with moderate and advanced dementia cannot adequately care for themselves and usually require around-the-clock care. Patients often do best when they are able to remain in a familiar environment such as their own home, when possible. The patient's environment should be made safe by following safety measures as recommended by the Alzheimer's Association: Caregivers can help patients with dementia by managing their environment to reduce frustrations.

• Limit visitors
• Limit noise and stimulation such as radios and televisions
• Keep areas safe and free of clutter
• Keep familiar objects nearby and in predicable places
• Follow a set routine
• Have calendars and clocks available to aid the patient's memory
• Engage in intellectually stimulating activities that the person is able to participate in

Driving and Dementia

       Driving with dementia is unsafe for both the driver, passengers, and those they share the road with. The patient with dementia may have slower reaction times, and can easily get confused or lost. It is up to the patient's family and caregivers to ensure the patient does not have access to a car or to drive a vehicle.

What Research Is Being Done on Dementia?

Research on dementia is ongoing.

• There is a lot of focus on new treatments to slow the progression of cognitive dysfunction.
• Other research is aimed at decreasing the progression and damage to the brain due to abnormal proteins (tau and beta amyloid).
• Researchers are also trying to identify the genes that may contribute to Alzheimer's disease and to develop drugs to modify these genes.
• Another area of research is trying to identify causes and treatments for inflammation to the brain, which is a key factor in Alzheimer's dementia.
• Research into the brain cells' utilization of insulin may lead to novel treatments for dementia.

Source:medicinenet