Alzheimer's Disease and other Dementias.


Submitted Aug 22, 2003   Updated Sep 26, 2010
By Ray Fosterrlf@mt-rushmore.net

 

What is Dementia?

Dementia refers to an acquired persistent loss of intellectual functions due to a brain disorder. This is not a normal part of the aging process, even though the vast majority of persons who experience a dementia are persons over 65 years of age.

What are some of the effects of Dementia?

Dementia typically unfolds gradually over a period of many years but it can begin abruptly. It affects some or all of the following brain functions:

Memory

Orientation

Language

Judgement

Visuospatial skills

Concentration

Ability to sequence tasks

What are some of the reversible dementias?

There are numerous causes of dementia including reversible conditions and other conditions that may be stabilized. These include:

Medications

Infections

Metabolic disorders

Depression

Brain tumor and subdural hematoma

Normal pressure hydrocephalus

 

 


Normal pressure hydrocephalus (NPH) is a relatively uncommon brain disorder that involves an obstruction in the normal flow of cerebral spinal fluid. This blockage causes a buildup of cerebral spinal fluid in the ventricle (space) in the brain. The clinical symptoms of NPH are urinary incontinence, poor balance and gait, and dementia. NPH is sometimes treatable with a neurosurgical procedure in which a shunt is inserted to divert the cerebral spinal fluid away from the brain. 

The presence of a brain tumor or traumatic brain injury can result in dementia depending on the location of the mass or injury in the brain. These problems are diagnosed using brain imaging techniques such as a CT scan or MRI.

Depression is a psychiatric disorder with the principle symptoms of sadness, difficulty in thinking and concentration, decreased activity, feelings of helplessness and hopelessness, and sometimes suicidal ideation. Many severely depressed people will have some cognitive deficits, like poor concentration and attention, which can mimic a dementia. This condition is sometimes called pseudodementia. These people may not receive treatment for their depression unless it is differentiated from the symptoms of dementia. Depression is treatable but requires prompt evaluation and treatment. Another challenge is the presence of both dementia and depression. In this situation, the intellectual presentation may be more extreme for the stage of the dementia. A skilled diagnosis by a psychiatrist, neurologist, or geriatrician is important to sort out this complex clinical picture. Depression is treatable, whether alone or in combination with dementia.

There are numerous metabolic disturbances associated with dementia. These include vitamin deficiencies, chronic kidney failure, thyroid, liver and pancreatic disorders.

An infection in one's blood or central nervous system can cause dementia. Laboratory tests usually reveal such infections causing dementia.

Older adults are often on complex medication regimens. Dementia can be related to toxic effects of these medications or drug-food interactions. Moreover, many classes of drugs are known to affect mental status such as psychotropics, anticonvulsants, antibiotics, and antihypertensives.

Most dementias are irreversible in nature. Sometimes two or more types of these dementias may occur together as a "mixed dementia." There are several dozen causes but the major types are listed below.

What are some of the so-called irreversible Dementia's?


Performing any task requires the ability to put a series of steps together in the right order. Someone with dementia may forget the steps in preparing a meal or shopping for groceries.

The ability to pay attention or concentrate may also be impaired. This may be seen in difficulty with making change or balancing a checkbook.

Distortions in interpreting one's environment may also be seen in dementia. Although eyesight itself may be well preserved, the brain's ability to accurately interpret what one is seeing may be impaired.

Reasoning skills, especially with respect to abstract tasks, are often impaired resulting in poor judgement.

Word finding difficulty is also typically seen among persons with dementia. Comprehension of spoken language may also be impaired. Rules of syntax and grammar may be impaired although speech itself may be intact.

The inability to know one's place and time may also be indicative of dementia - for example, getting lost outside one's home or not knowing the month or year.
The hallmark of dementia is impairment with respect to recent events, what is often referred to as "working memory." Forgetting appointments, conversations, and the like typically herald the onset of dementia. New learning becomes defective whereas memories from the distant past may be intact.

 

 

"Irreversible Dementias"

Alzheimer's

Muli-Infarct

Creutzfeldt-Jakob disease

Proof Positive

Can dementia be passed on from meat?

Researchers at the University of Pittsburgh studied patients that were thought to have died from Alzheimer’s Disease. On closer examination they found that some of them had actually died from the prion-related Creutzfeldt-Jakob disease.

Despite carefully searching the medical literature, I have not come across any systematic study of the number of CJD patients misclassified as having Alzheimer’s Disease. The experience of a couple of dementia research neuropathologists left me with a reasonable guess that anywhere between 1 in 50 to 1 in 200 patients who are clinically diagnosed with Alzheimer’s really have unequivocal autopsy evidence of CJD. This may not sound like a very large percentage. However, when you consider the total number with Alzheimer’s, this small percentage of cases accounts for a significant number of people. Currently, some four million Americans have Alzheimer’s disease.41 According to a Harvard medical report, the estimates are that by 2050 the number will be over 10 million.42 If even one in 100 diagnosed Alzheimer’s patients had CJD, this would translate into 40,000 cases currently and 100,000 by the middle of the next century.

Pick's Disease, Lewy Body Disease, Huntington's disease, AIDS dementia complex, Prgressive aphasia

How is Alzheimer's disease diagnosed?

 

Diagnostic Evaluation of Dementia

History from patient and relative or friend

Clinical Exam

Blood Work: CBC, Chem Profile, Thyroid function tests, Syphilis serology, Vitamin B12, Folate

CR or MRI

If Indicated: Psychological testing, HIV, Brain Biopsy, SPECT or PET scan, Lumbar puncture, EEG

There is no single test available to diagnose Alzheimer’s disease such as a blood test, as is the case with diabetes for example. However, when other disorders have been ruled out and typical symptoms of AD have been documented, there is a high probability for obtaining an accurate diagnosis by an experienced physician.

How do we suspect Alzheimer's?

 

 

Criteria for Probable Alzheimer's Disease

Dementia established by clinical and neuropsychological exam

Deficits in at least two areas of cognition

Progressive worsening of memory and other cognitive functions

No disturbances of consciousness

Onset between age 40 and 90

Absence of other disorders to account for dementia

Since there is currently no simple and reliable biological test to diagnose AD, criteria have been established to guide physicians in making the diagnosis. In the vast majority of cases, these criteria are useful in helping physicians differentiate between Alzheimer's disease and other forms of irreversible dementia. Any doubts about the accuracy of the diagnosis should be addressed to a medical specialist, most likely a neurologist, in the form of a second opinion.

How common is Alzheimer's?

 

Prevalence of Alzheimer's

Over 4 million Americans (affects their families too), Number doubles about every 5 years after age 65, Estimated cost of $100 billion annually, Numbers may triple by 2050

AD is far and away the most common form of dementia.

According to a large, community-based study by Evans and his colleagues in East Boston during the 1980s, about 3 percent of persons aged 65-74 have AD, nearly 1 in 5 persons aged 75-84 years have the disease, and almost half of those over age 85 years have the disease. The 85+ age group is currently the fastest growing segment of the U.S population. Taking into account these figures, it is now estimated that there are over four million Americans with the disease. U.S. Census projections of the aging population clearly show that the number of Americans with AD will grow dramatically in the coming decades unless means of prevention are found.

What is the progression of symptoms of Alzheimer's?

 

 

Early-Stage Symptoms

Memory

Recent memory loss much of the time

Language

Mild aphasia

Orientation

Seeks the familiar and avoids the unfamiliar

Motor

Some difficulty writing and using objects

Mood and Behavior

Apathy, depression

Activities of Daily Living (ADLs)

Needs reminders with some ADLs

Middle-Stage Symptoms

 

Memory

Routine loss of recent memory

Language

Moderate aphasia

Orientation

May get lost at times, even inside the home

Motor

Repetitive actions, apraxia

Mood and Behavior

Possible mood and behavioral disturbances

Activities of Daily Living (ADL's)

Need reminder and help with most ADL's

Late-Stage Symptoms

 

Memory

Mixes up past and present

Language

Expressive and receptive aphasia

Orientation

Misidentifies familiar persons and places

Motor

Bradykinesia, falls

Mood and Behavior

Greater incidence of mood and behavioral disturbances

ADL's

Need Reminders with all ADL's

Terminal Stage Symptoms

 

Memory

No apparent link to present or past

Language

Mute or few incoherent words

Orientation

Oblivious to surroundings

Motor

Little spontaneous movement; dysphagia, myoclonus, seizures

Mood and Behavior

Completely passive

ADL's

Requires total care

What are some risk factors?

Proof Positive

Does Smoking affect dementia?

Compared to nonsmokers, smokers face double the risk of developing dementia.

Risk Factors for Alzheimer's

Definite

Possible

Increasing Age, Family History, Female gender, Down Syndrome

Environmental toxins, Low formal education and occupational attainment, previous head trauma, cerebrovascular disease

Circumstances that put one at risk for diseases are referred to as risk factors. A common risk factor for acquiring many diseases involves exposure to environmental toxins. For example, inhaling tobacco smoke is known to increase one’s risk of getting lung and heart diseases. Also, high blood pressure, high cholesterol levels, and obesity significantly increase one’s chances for heart disease. Identification of these risk factors has led to advances in prevention, treatments, and cures.

Another common risk factor for developing diseases involves heredity. Some genetic disorders may be well known and easily identified through genetic testing, even before birth. For example, someone with Huntington’s disease inherits the gene associated with this disease from one parent. In turn, the affected person may put his or her offspring at a 50 percent chance of inheriting the

disease. Other diseases may not have a clear-cut genetic cause and may not be triggered unless combined with environmental factors. Such diseases pose an uncertain risk of inheritance or genetic susceptibility. Clear risk factors for Alzheimer’s disease include:

Increasing age

Aging is clearly the main risk factor. The older you grow, the greater your risk, as shown by the above noted graph based on the community-based study on the prevalence of AD.

Family history

Having a close blood relative who develops Alzheimer’s increases one’s personal risk. In a 1996 study, researchers with the MIRAGE project tracked the lifetime Alzheimer’s risk of nearly 13,000 people who had a first-degree relative (mother, father, sister, brother, son, daughter) with the condition. By age 80, people with AD in both parents had a 54 percent risk, 1.5 times the risk of the the disease in people with just one affected parent, and 5 times the risk of people with two unaffected parents. Furthermore, if one identical twin develops AD, the other’s risk is unusually high–40 to 50 percent–which argues for a genetic predisposition. Several genes now associated with AD are described below.

Female gender

Women tend to live longer than men and thus are more likely to develop AD due to longevity alone. Some studies have shown that at all ages, women have a higher risk of AD than men, but other studies have contradicted this finding.

Down syndrome

Over age 40, all persons with Down syndrome, a genetic disorder, evidence plaques and tangles at autopsy although not all are symptomatic during lifetime. We obviously do not have the luxury of choosing our biological parents, whose genetic makeup may influence our health. For better or worse, we inherit a set of genes from both mother and father that may protect or put us at risk for certain diseases. Advances in understanding the human genetic map may ultimately lead to ways of blocking the action of defective genes and promoting drugs that mimic genes that have protective effects. In the meantime, the search continues for factors in the environment that put us at risk for developing certain diseases so that we can modify our lifestyles. We are just beginning to understand risk factors for AD. If potentially reversible risk factors can be identified, we may discover clues about prevention, treatment, or a cure.

What are possible risk factors?

Possible risk factors are those suspected of being linked somehow to AD, but the linkage has not been proven. Weak or strong associations with AD may be attributed to a complex number of factors still unidentified. In the meantime, possible risk is associated with the following factors: 

Hazardous elements in the environment may play a contributing role in AD, but researchers have not yet been able to identify any with certitude. Experts agree that environmental factors may influence a genetic predisposition to AD. Because ingestion of heavy metals such as lead can cause brain damage, there has been a constant search for something in the environment that we eat or breathe that may be a culprit. Studies of identical twins show that genetics play a key role in AD but also show that genetic makeup is not destiny. Identical twins are genetically the same, but AD develops in only about half of identical twin pairs. In addition, when both identical twins develop Alzheimer’s, their age at diagnosis often differs by as much as 15 years. For many years, the role of aluminum in AD was studied; however, aluminum is no longer a major consideration in spite of occasional published reports suggesting it may play a role.

Low education & occupational attainment

Another risk factor with major social implications relates to one’s level of education and occupation. Growing evidence suggests that people with low educational and occupational attainment may be at greater risk of developing AD than the rest of the population. Conversely, those with high educational and occupational attainment may be at lower risk for developing AD than the rest of the population. Two possible explanations have been put forth about the role of education and occupation. First, the more educated people perform better on tests of intellectual ability than others and are not easily identified as having symptoms of AD. Second, higher levels of education may increase brain reserve, delaying onset of symptoms for many years. These theories have not yet been proven. Whether education and occupation represent true risk factors or are merely markers for some other disease-related factors will not be known without further research.

Head trauma

It is well known that professional boxers who suffer repeated blows to the head are at great risk of brain damage resulting in permanent impairment of memory, language, and other cognitive functions. Recent studies have shown that anyone who suffers a severe blow to the head at any time in life is more prone to getting AD than those without such experience. It has also been speculated that even a minor head injury occurring early in life may have dormant yet lasting effects that make one vulnerable to AD late in life. Head trauma may put a person at risk for developing AD, but whether the risk is large or small is not yet fully understood.

Cerebrovascular disease

A study of Catholic nuns by Dr. David Snowden and colleagues at the University of Kentucky suggests that the presence of tiny strokes or TIAs in combination with the plaques and tangles characteristic of AD significantly increases its clinical manifestations. Further study is needed to clarify the role of vascular disease in the onset of AD.

What can be done?

Strategies for Medcical Treatment of Alzheimer's disease

Prevention, Delay onset, Slow rate of progression, Treat primary and secondary symptoms

Prevention

Slow down progression

Treat primary symptoms

Treat secondary symptoms

Besides some of the standard drugs such as tacrine and donnezepril what drugs might be used?

Potential Treatments/Prevention

Non-Steroidal Anti-Inflamatory Drugs, Anti-Oxidant Agents, Estrogen, Alternative medicine, Others?

 

Many other cholinesterase inhibitors are now in various stages of development. Meanwhile, several other approaches are under investigation: 

Some years ago, researchers noticed that people with severe arthritis have strikingly low rates of AD. Treatment of arthritis involves large doses of medications known as non-steroidal anti-inflammatory drugs (NSAIDs). These drugs include such common, over-the-counter medications as aspirin, ibuprofen (Motrin, Advil), and naproxen (Naprosyn), plus many prescription drugs--but not acetaminophen (Tylenol). Meanwhile, researchers have discovered that inflammation of brain tissue may play a key role in the development of neurofibrillary tangles and beta-amyloid plaques, the anatomical hallmarks of AD. These observations suggest that NSAIDs might treat. prevent, or delay the onset of AD. The main problem with NSAIDs is that they carry a significant risk of adverse effects. Newer drugs for treating arthritis known as COX-2 inhibitors have overcome this obstacle but their benefits in treating or preventing AD have not yet been proven.

Antioxidants

Daily intake of 2000 International Units vitamin E showed some slowed progression among a group of 350 persons with AD. Vitamin E is now being tested in a nationwide Memory Study to find out if it may actually delay the onset of the disease.

Estrogen

Growing evidence suggests that estrogen-replacement therapy for postmenopausal women may protect brain cells from AD. Again, several retrospective studies show that women who have taken estrogen seem to be at a lowered risk for AD than women who have not taken estrogen. A large study known as The Women’s Health Initiative is currently exploring this possibility in depth. Moreover, another study is examining the effects of estrogen among women who already have AD. The "Estrogen and Alzheimer’s Disease" fact sheet available through ADEAR (800-438-4380) is a good resource for further information.

Alternative medicine

Walking and Alzheimer's Disease

One interesting study involved an attempt to improve the communication skills of two groups of Alzheimer’s patients. One group was put in a walking exercise program, and the other group was given lessons in conversation. Over 40 percent of the exercise group experienced significant improvement in communication skills, while the "conversation therapy" group experienced no significant improvement in their communication skills. Proof Positive Neil Nedley, M.D.

Natural agents and food supplements such as gingko biloba have been touted as treatments for AD and related dementias but there is little scientific credence to such claims. The "Gingko Biloba" fact sheet available through ADEAR (800-438-4380) is a good source of information.

Some social interventions that may be helpful include:

Care of Persons with Alzhiemer's disease

Create a supportive atmosphere

Structure appropriate activities and routine

Design "dementia friendly" environments

Facilitate peer groups (for emotional support and shared activities)

 

In the absence of completely effective medical treatments of AD right now, much attention must be given to psychosocial approaches to caring for affected individuals. The rest of the training program will focus on meeting their needs as well as helping families in their traditional role as caregivers. Major areas of concern for persons with the disease include:

Creating a supportive atmosphere

Developing programs of structured activities

Designing "dementia friendly" environments

Enabling persons with AD to talk about their challenges together in peer groups

 

and give them a voice in their own care. 
that offer cues to simplify surroundings,
 that promote remaining abilities and minimize the effects of compromised abilities,
by understanding how the person with AD perceives his or her world,

 

 

NSAIDs


If the cognitive symptoms of AD cannot be successfully treated, the next best approach is to treat behavioral symptoms often associated with the disease: insomnia, agitation, hallucinations, delusions, etc. A variety of behavioral and pharmacologic approaches aim to alleviate these symptoms.

If none of the above steps can be accomplished, the next best approach is to improve memory and other brain functions impaired by AD. By treating these symptoms, there is a hope of slowing down progression too. Again, current drugs and experimental drugs are directed toward this goal but have thus far fallen short of expectations for dramatic benefits.

After early symptoms of the disease develop, the goal then is to maintain individuals at their highest possible level of functioning. Stopping or slowing down the usual advance of the disease could theoretically enable individuals to remain independent and living in their own homes with minimal supports. Drugs currently approved and in testing phases aim to accomplish this goal but have thus far fallen short of expectations.

The ideal approach to deal with any disease is to prevent it altogether, for example, with a vaccine. Since the causes of AD are not known at this time, it is difficult to arrive at such a simple solution. However, as understanding of risk factors grows, there may be ways of reducing personal risk for the disease that ultimately prevent the onset of the AD.

 

Environmental factors

The Alzheimer's Disease Education and Referral Center (ADEAR Center) is a service of the National Institute on Aging (NIA). The NIA is part of the Federal Government's National Institutes of Health located in Bethesda, Maryland. ADEAR (800-438-4380) is a good source of information.