Chronic Stress as Risk Factor for Alzheimer’s Disease

Stress is inherent in every human being. It is the way we respond to a real or imaginary threat.  It is the fight-or-flight mechanism which enables our bodies to initiate the chain of biochemical reactions in response to a hazard, whether real or perceived. While your mind and emotions develop through the learning experience of life, instincts were given to you as a survival protection tool.

What is stress?

Stress is a normal physical response to events that make you feel threatened or upset your balance in some way. When you sense danger – whether it’s real or imagined – the body's defenses kick into high gear in a rapid, automatic process known as the “fight-or-flight” reaction, or the stress response.

When you perceive a threat, your nervous system responds by releasing a flood of stress hormones, including adrenaline and cortisol. These hormones rouse the body for emergency action.

Your heart pounds faster, muscles tighten, blood pressure rises, breath quickens, and your senses become sharper. These physical changes increase your strength and stamina, speed your reaction time, and enhance your focus – preparing you to either fight or flee from the danger at hand.

The stress response is the body’s way of protecting you. When working properly, it helps you stay focused, energetic, and alert. In emergency situations, stress can save your life – giving you extra strength to defend yourself, for example, or spurring you to slam on the brakes to avoid an accident.

The stress response also helps you rise to meet challenges. Stress is what keeps you on your toes during a presentation at work, sharpens your concentration when you’re attempting the game-winning free throw, or drives you to study for an exam when you'd rather be watching TV.

But beyond a certain point, stress stops being helpful and starts causing major damage to your health, your mood, your productivity, your relationships, and your quality of life.

Chronic Stress Danger

What happens with chronic stress then? If we are chronically stressed and experience chronic distress as a result, then we are constantly releasing cortisol. Like red wine, too much of a good thing can be bad. Chronically high cortisol has been shown to cause brain cell dysfunction, to kill brain cells, and to cause atrophy of the brain.

With aging, something additional happens. Biological systems become deregulated. Our ability to shut down biological systems once they are turned on becomes impaired with aging. Cortisol levels go up, but they stay up longer and go down slower. We become more prone to the psychological effects of stress if we are distressed, and the effects last longer. More brain cells may dysfunction and more may be killed.

Over the course of a lifetime, the effects of chronic stress can accumulate and become a risk factor for cognitive decline and Alzheimer's disease. Several studies have shown that stress, and particularly one's individual way of reacting to stress (the propensity to become distressed often found in neurotic people for example), increases the risk for Alzheimer's disease.

Clinical Research – Stress as Risk Factor for Alzheimer’s Disease

UC San Diego Study, 2010

In 2010, a research group led by Mark Tuszynski at the University of California, San Diego, performed a study on monkeys to see how different environments affect the development of Alzheimer’s disease. Some monkeys were put in very small cages when they were young, while others were in larger cages. The monkeys in the small cages were unable to get enough exercise and released larger amounts of stress hormones. These stress hormones can reduce the number of nerve synapses. Upon study of the monkeys’ brains, it was confirmed that monkeys raised in smaller cages had, on average, a higher density of plaques and lower number of synapses, the same brain pathology seen postmortem in Alzheimer’s patients.

University of Houston, 2010

In another study in March, 2010, Karim Alkadhi at the University of Houston led a research team to study the effects of stress on rodents in a water maze. Some rats were injected with amyloid peptides, while other rats were subjected to stress by placing an intruder rat in their home cage. The rats were divided into 4 groups to see the effects of the amyloid proteins and stress singly and combined.

The study results showed that only one group of students had difficulty learning the new task, reflecting substantial memory impairment - the animals that received both the amyloid dose and were regularly stressed out.”

Utah State University, 2010

Chronic psychological stress throughout a lifespan might increase an individual's risk for Alzheimer's and dementia later in life, according to research from the Emma Eccles Jones College of Education and Human Services at Utah State University.

The research, led by Maria Norton, Ph.D., built off the recently completed 15-year Cache County Memory Study (CCMS) and used that data to focus on the role psychological stress has on dementia. The findings are consistent with the hypothesis that chronic stress can expose an individual to long-term levels of stress-related hormones, which results in chronically high levels of glucocorticoids, a natural chemical, shown in both animal and human studies to increase the rate of neuronal cell death with long-term exposure.

"Using this objective data, such as death records, medical information, and the cognitive evaluations from the CCMS, we were able to see that people who experienced particularly stressful life events, such as a parent's death during one's childhood, death of a child or spouse, or living with a spouse who is afflicted with dementia is associated with significantly higher rates of dementia later in life," Norton said.

Norton also found that there were some factors that were associated with lower rates of depression and stress, such as individuals who had high levels of religious involvement, thus indicating that the ability to cope with psychological adversity might reduce the risk of Alzheimer's.

University of South California, 2011

While there were multiple studies, which confirmed the causal relationship between chronic stress and Alzheimer’s Disease development, scientists at the University of Southern California (USC) have now found an scientifically backed up mechanism: chronic stress (physical or mental) causes over expression of the RCAN1 gene, in turn leading to neurodegenerative disease.

The mechanism involves the following steps:

1. In a healthy person, the RCAN1 gene helps cells cope with stress. However, chronic overproduction of RCAN1 causes hyperphosphorylation of tau proteins in the brain.
2. Tau proteins stabilize microtubules, which are like scaffolding, used to build the brain’s neurons. Previous research has shown that when the tau protein binds too much phosphate (hyperphosphorylation), it forms snarls that prevent the brain’s signals from effectively traveling.
3. These neurofibrillary tangles eventually choke the life out of neurons, killing off brain function a tiny piece at a time in what is outwardly recognized as degenerative brain disease.

The researchers suggests that overexpression of RCAN1 is also connected to Amyloid beta (overproduction of the Amyloid beta peptide), a competing theory of neurodegeneration.

Further supporting the RCAN1 role are observations that it has been also shown to be chronically overexpressed from birth in the brains of patients with Down syndrome. These patients develop neurofibrillary tangles and typically start to experience the onset of Alzheimer’s disease around age 40.

Sources and Additional Information:

http://www.myinnerchi.com/health_managing_stress.html

http://helpguide.org/mental/stress_signs.htm

http://www.psychologytoday.com/blog/alzheimers-hope-the-horizon/201003/stress-the-brain-aging-and-alzheimers-disease

http://www.alzheimersreadingroom.com/2011/02/can-stress-cause-alzheimers-disease.html

http://www.kurzweilai.net/how-chronic-stress-causes-alzheimers-other-brain-diseases

http://www.news-medical.net/news/20110728/Chronic-psychological-stress-linked-to-increased-risk-of-Alzheimers.aspx

Bacopa Preventing Alzheimer’s and Dementia

What is Bacopa?

An extract of a little-known herb called Bacopa can dramatically increase your brain function and memory — and may even help prevent dementia and Alzheimer’s disease. Its therapeutic use has its origins from traditional Ayurvedic medicine in India, where it has been used for its adaptogenic, tranquilizing and antioxidant properties.

Bacopa is a creeping perennial herb that can be found in Nepal, China, India, Sri Lanka, Taiwan, Vietnam and some parts of the United States, including Hawaii, Florida and other Southern states. Bacopa (also called Bacopa monnieri or brahmi) thrives in wetlands, on muddy shores and around ponds or bog gardens. Be careful not to confuse brahmi (Bacopa monnieri) with gotu kola and other natural medicines that are also sometimes called brahmi.

Used in India for thousands of years for both traditional and medicinal purposes, Bacopa had a central role in religious consecration ceremonies for infants: The botanical was believed to open a gateway to intelligence for children.

Bacopa herb contains many compounds including bacopasaponins such as bacoside A, bacopaside II, bacopaside I, bacopaside X, bacopasaponin, bacopaside N2 and minor components bacopasaponin F, bacopasaponin E, bacopaside N1 bacopaside III, bacopaside IV and bacopaside V. The total saponin content in samples, plant materials and extracts vary from 5 to 22%. Dammarane-type triterpenoid saponins classified as pseudojujubogenin and jujubogenin glycosides are reported as some of active components in this plant.

Shamanic Memory

Researchers may first have been intrigued by Bacopa monnieri because of the effect they believed it had on ancient shamans, who reportedly used the herb to help them memorize epic poems. Researchers theorized that perhaps the Bacopa plant enhanced the shamans’ brain function and improved their memory, concentration and recall. It’s no wonder researchers suspected a link, since some of these epic poems — when they were finally written down — exceeded 900 pages, and the shamans could recite them word for word!

Mind Booster

Today, modern science is confirming traditional wisdom about Bacopa. In research conducted in Australia and the United States, Bacopa improved study subjects’ ability to retain new information — and it also helped them increase their visual processing speed in as little as three weeks.

Research into the benefits of Bacopa includes:

• A study by the psychology department at the University of Wollongong in Australia that demonstrated Bacopa could increase memory and recall ability.
• Research in 1996 presented at the International Brain Research Conference that showed that Bacopa reduced the time needed to learn new tasks by almost half. Participants taking Bacopa mastered mental exercises in as little as six days compared to 10 days for the control group.
• An extensive 2001 rigorous, randomized double-blind, placebo-controlled experiment in Victoria, Australia confirmed the herb’s benefits for learning. After 12 weeks, those taking Bacopa scored significantly better on all higher order cognitive processing tests.

Bacopa monnieri has been extensively tested and proven as a memory and concentration enhancer, but the benefits of Bacopa extend to other mental and emotional functions, as well.
In many areas of the world, Bacopa is also used to treat:

• Depression
• Stress
• Anxiety
• Attention Deficit Disorder
• Epilepsy
• Alzheimer’s disease
• Mental deficiency

Bacopa May Combat Cognitive Decline

In addition to its short-term cognitive benefits, Bacopa may also prevent long-term cognitive decline. A study in the Journal of Alternative and Complementary Medicine showed that elderly participants who used 300 mg per day of Bacopa demonstrated improved mental functions in comparison to a placebo group. Improvement was most profound in the areas of attention and verbal-information processing — and researchers concluded that Bacopa could be effective in preventing cognitive decay.

Since research has shown a link between mild cognitive decline and eventual dementia and Alzheimer’s disease, preventing even mild memory difficulties may play an important role in warding off those memory-related diseases that are so prevalent among baby boomers and elderly people.

News of the many health benefits of Bacopa recently seeped into mainstream news. In his TV show on May 30, 2011, Dr. Mehmet Oz (also known as “America’s Doctor”) recommended Bacopa for brain health. Dr. Oz said, “Bacopa Monnieri will make you smarter, enhance your memory and help you focus better.”

Mechanism of action

Bacopa contains bacosides A and B, which enhance neuron repair and speed up information transfer between brain cells. This herb also has powerful antioxidant properties which protect the brain cells from damage.

The mode of action of brain cell protective effects is due to the antioxidants that suppress neuronal oxidative stress and the acetylcholinesterase inhibitory activities. Treating patients with bacopa extract may be a way to treat neurodegenerative disorders associated with oxidative stress as well as perhaps Alzheimer's disease.

There is some evidence to suggest that it might relax muscles in the blood vessels, airways, and the small intestine. It might also act as a tranquilizer to promote relaxation as well as a pain reliever.

How to Use Bacopa

Adults can use a dosage of Bacopa herb between 200 mg to 500 mg a few times a week. Many preparations are in the form of extracts with various potencies. If you buy a bacopa extract product, your dosage would be less than that of the regular bacopa powder. How much less depends on how potent and concentrated the extract.

A 225 mg tablet of Bacopa taken up to three times daily is recommended by many health practitioners, although consultation with a qualified herbalist is advised to determine your ideal dosage.

To be most effective, Bacopa extract is usually taken in the recommended dosage daily for 12 weeks. In low doses, Bacopa is mild and non-addictive. Although overdose is uncommon, Bacopa has been known to be toxic in very high doses, so caution is advised. However, it is reported that any symptoms of toxicity will immediately subside once Bacopa supplementation is discontinued.

Bacopa is relatively inexpensive and can be found at health food stores and through a variety of online retailers.

Precautions and Side Effects

Women who are pregnant or nursing should first talk to their doctor before taking. Bacopa also may cause sleepiness if taken in high doses.

Sources and Additional Information:

http://www.easyhealthoptions.com/alternative-medicine/bacopa-may-help-prevent-alzheimers-and-dementia/

http://www.bacopa-monnieri.com/

http://www.holistic-herbalist.com/bacopa.html

http://www.herbslist.net/bacopa.html

http://www.webmd.com/vitamins-supplements/ingredientmono-761-BRAHMI.aspx

Early Detection Alzheimer’s in Elderly Patients

Detecting Dementia

Making the diagnosis of dementia is reasonably straightforward in the moderate and severe stages, but it can be problematic to distinguish the early stages of Alzheimer’s from “normal” ageing in elderly patients, although recent development has helped to clarify which neuropsychological tests discriminate most effectively. Most people who present with concerns about memory problems do not in fact have dementia, and it is also important to note that in specialist clinical practice professionals see an atypical group of patients. O’Connor (1994) found that only 3% of people identified in a community survey as having mild dementia had been referred to specialist services, along with 18% of those with moderate dementia and 33% of those with severe dementia.

Early Detection

Interest in the early detection of Alzheimer’s has increased with the recent licensing of anti-cholinesterase inhibiting medication as a treatment for the cognitive impairment of early-stage Alzheimer’s. This detection on early-stage of the disease is increasingly undertaken in the context of multidisciplinary memory clinics, where neuropsychological assessment plays a critical role in establishing a diagnosis. Early detection of DAT offers the possibility of introducing psychosocial and pharmacological interventions at an early stage. It has been demonstrated that memory clinics can provide an effective focus for early intervention and for the development of integrated psychosocial approaches. Early detection of Alzheimer’s remains a challenge, however, and there are a number of barriers to early detection. People with dementia, and their families, may interpret certain memory impairment of the patients as part of normal ageing process or deny that there have been any changes, and rates of detection by general medical practitioners are low.

Distinguishing Dementia from “Normal” Ageing

The boundaries between dementia and normal forgetfulness still appear somewhat fluid, and it remains unclear how the difference between dementia and normal ageing should be conceptualized. Although many older people and their families expect to observe a decline in memory functioning, there is a great deal of variation in the general population as regards the kinds of memory changes seen as part of “normal” ageing, and the issue is compounded by cohort effects. A broad overview suggests that, although memory functioning becomes less efficient from about 67 years onwards there is no general decline in memory ability and no uniform decline across the range of different memory tasks. Memory functioning is relatively more affected in the very old, so that diagnostic criteria do not allow for a dementia diagnosis made after the age of 90. The following general observations can be made with regard to memory changes in healthy older people:

• Working memory may be affected.
• Episodic memory is affected to a much greater degree than semantic or procedural memory.
• Immediate recall is affected more than delayed recall, while recognition memory is unaffected.
• Retrieval is slower and less efficient, with more rapid and extensive forgetting.
• Prospective memory remains as good as that of younger people if external aids and reminders can be used, but is poorer if no such aids are available.
• Autobiographical memory does not show the stereotypical discrepancy between vivid memories of the distant past and hazy memories of more recent events; instead, memories across the lifespan show loss of detail and become vaguer.
• Alterations in memory functioning can be offset by intelligence, expertise and use of compensatory strategies, enabling the person to cope well despite any changes.

What is “Normal” Memory Loss?

• Forgetting people’s names occasionally;
• sometimes not being able to find the right word;
• taking longer to learn new things;
• sometimes forgetting where one has put things, like keys, for example;
• sometimes forgetting what one has come into a room to do.

What are the Symptoms of More Serious Memory Loss?

A more serious memory problem is one that affect’s a person’s ability to carry out everyday life activities such as driving a car, shopping or managing money. Some of the signs are:

• asking the same questions over and over;
• getting lost in familiar places;
• not being able to follow directions;
• confusion over time, people and places;
• forgetting to eat right and regularly;
• not bathing;
• poor judgment about safety;
• driving problems.

Medicines That Cause Forgetfulness

Forgetfulness is common among drug and alcohol abusers, but certain medicines also list forgetfulness as one of their side effects. Due to the age-related medical conditions, elderly people are more affected by the negative side effects, caused by medications. Approximately 163,000 people in the United States are estimated to experience serious cognitive impairment either caused or worsened by drugs.

For example, a beta-blocker medication, such as Inderal, generic name propranolol, or Lopressor, generic name metoprolol, may cause short-term memory problems. Similar results have been reported in patients who use such medications which contain the active ingredient methyldopa. Additionally, many antidepressants cause memory-related problems, especially in the beginning of the treatment. The same applies to anti-anxiety medicines like lorazepam and alprazolam or sleeping pills like triazolam. Benzodiazepines that are used to treat such disorders as anxiety, restless legs and social phobias seem to cause forgetfulness. Tranquilizers that are used to treat such conditions as Tourette syndrome and irritable bowel syndrome also seem to cause forgetfulness in some patients. Some drugs aimed at reducing high levels of cholesterol have also been criticized for such side effects. Even over-the-counter medicines, such as the antihistamine diphenhydramine, have been linked to forgetfulness.

The Boundaries between Dementia and “Normal” Ageing

As a general rule, the lower the score on cognitive tests, the more likely it is that the person has dementia. However, Storandt & Hill (1989) found that scores of patients with very mild Alzheimer’s overlapped considerably with those of both normal older people and people with mild Alzheimer’s. Furthermore, even where people do show some degree of memory impairment, progression to dementia is not inevitable.

The area of uncertainty between “normal” ageing and dementia has attracted a number of attempts to define diagnostic categories. Among the diagnostic labels suggested are age-associated memory impairment (AAMI), mild cognitive impairment, benign senescent forgetfulness, and minimal or questionable dementia. These concepts remain controversial, and practice varies regarding their use. The category of AAMI, for example, would include large numbers of older people, and it is questionable whether changes that are essentially normative should be labeled in this way.

Which Tests Are Useful in Discriminating between Dementia and Normal Ageing?

The CERAD studies suggest that the best discriminator is performance on delayed recall tasks. A 10-word list presented in three learning trials and tested after a 5–8 min delay correctly classified 94% of controls and 86% of patients with mild dementia, using a cutting score of 2 SDs below the control group mean. Performance on naming tests was found to be useful as an adjunctive measure. If patients have impairment in delayed recall and problems in naming or verbal fluency, this is a very strong indicator for dementia. Other studies have also emphasized the value of delayed recall. Tierney et al. (1996) found that problems in delayed recall and attention were the best predictors of whether people with mild memory problems would go on to develop Alzheimer’s disease.

Sources and Additional Information:

The Book of Memory Disorders by Alan D. Baddeley

http://www.suite101.com/content/memory-loss-in-the-elderly-a57376

http://www.livestrong.com/article/161728-what-are-the-causes-of-sudden-forgetfulness-in-the-elderly/

http://www.wrongdiagnosis.com/sym/forgetfulness.htm

Deep brain stimulation technique to fight Alzheimer’s

Insertion of a deep brain stimulator (DBS), a device similar to a pacemaker for the brain, may improve memory and function for patients with Alzheimer’s disease.  The National Institute of Neurological Disorders and Stroke (NINDS) explains that the set up for deep brain stimulation involves three parts: an electrode; a neurostimulator, which is the battery pack; and the extension. The surgeon implants the electrode in a specific region of the brain, which he or she identifies using an imaging scan, such as a magnetic resonance imaging (MRI) scan or computed tomography (CT) scan. With the neurostimulator, the surgeon implants that near the collarbone, then connects the two parts with the extension, which is also underneath the skin. The electrical signals are sent from the neurostimulator through the extension and up through the electrode to the brain.

Recent research showed that after implanting a DBS in six patients with Alzheimer’s, half of the patients had either improved memory, or a slower rate of decline.

“We showed that not only is this a safe procedure, but that the evidence is there to warrant a bigger trial,” according to Dr. Andres Lozano and colleagues at Toronto Western Hospital, who conducted the research. “Any amount of time that extends quality of life and quality years to someone with Alzheimer’s may be a benefit.”

Alzheimer’s disease (AD) is the most common form of dementia among older people, and affects more than five million Americans, according to the Alzheimer’s Organization. 

“Alzheimer’s disease (AD) is characterized by functional impairment in the neural elements and circuits underlying cognitive and memory functions,” according to Lozano. Initially, affected individuals have mild memory problems, which progress over time, to the point of needing total care.  Other, later symptoms can include anxiety, wandering, and aggression.  No treatment can stop the disease. However, some drugs, may delay the progression of the disease, and others, including antipsychotics, may help treat certain symptoms for a limited time.

Lozano and his team investigated the theory that electrical stimulation of structures deep in the brain, including the hypothalamus, might improve symptoms by enrolling six willing participants with early signs of Alzheimer’s in their study.

Each patient left the hospital within three days after the study and continued their standard medical therapy for Alzheimer’s disease, as well as continuous stimulation from the implanted device for one year.

During that time, the subjects were assessed in several ways, including cognitive testing, brain mapping, and imaging.  Their cognitive function was evaluated by several different types of measurement scales. Positive emission tomography (PET) scans, a type of brain scan that measures metabolic activity, were used to assess the way the DBS device changed glucose metabolism in the brain.  (Alzheimer’s disease can alter how glucose is used in the brain.) 

In half of the patients, by six or 12 months, their cognitive function had either improved or had declined at a slower rate than expected.  “Evaluation of the Alzheimer’s Disease Assessment Scale cognitive subscale and the Mini Mental State Examination suggested possible improvements and/or slowing in the rate of cognitive decline at 6 and 12 months in some patients,” according to the researchers.

In addition, the PET scans showed that the abnormal glucose metabolism typically seen in patients with Alzheimer’s disease improved after insertion of the DPS device, and the improvement continued throughout the year of follow-up.

None of the patients had any serious side effects during the year after the device was implanted.

Although Lozano’s  study is small, the results are encouraging. Future, larger studies may provide more information on a potentially effective therapy for treating Alzheimer’s disease, or slowing the decline, which could complement additional therapies.

“There is an urgent need for novel therapeutic approaches for Alzheimer’s disease. Modulating pathological brain activity in this illness with DBS merits further investigation.”

“It’s a very intriguing study,” says Laurie Ryan, program director of Alzheimer’s disease clinical trials at the National Institute on Aging, who was not involved in the research. “I don’t think we can predict how it will turn out with a larger number of subjects, but they did have some very interesting data, particularly the PET data [on glucose metabolism]."

Although Lozano is careful to stress that deep brain stimulation is a potential therapy, aiming to improve symptoms of Alzheimer’s without necessarily tackling the underlying cause, he does feel that it opens up a new way of looking at the disease. “We should think of Alzheimer’s as a brain circuit disorder,” he says. This is in keeping with some of the research being done on the effects of normal aging on brain circuits, says Ryan. “I think this is another piece of the puzzle that is pointing us in that direction.” Lozano and his colleagues now plan to undertake a larger, Phase II, clinical trial.

Patients with milder forms of Alzheimer's seemed to benefit the most from the deep brain stimulation.

The procedure seems to work by driving the activity in less-damaged areas of the brain, "reactivating these brain circuits that are responsible and cognitive functioning," Lozano explained.

However, the deep brain stimulation is an invasive technique. "This is not a procedure free of risk," noted Dr. Richard Lipton, an attending neurologist at Montefiore Medical Center in New York City. "It involves taking often frail, older adults and drilling a hole through the skull, then pressing a needle through the tissue of the brain till the tip gets into a crucial area where you want to leave it. If you go through a blood vessel, you can produce bleeding that can cause serious harm. This is not a benign procedure. So, the device would have to be approved before it is available for widespread use."

Dr. Lozano first discovered the potential for DBS to treat Alzheimer's disease while treating a patient for obesity using DBS back in 2003. While signaling areas of the brain, Dr. Lozano and his team triggered memories in the patient. In follow-up testing the patient's memory improved and Dr. Lozano set in motion the first ever DBS trial of patients with early signs of Alzheimer's disease.

Sources and Additional Information:

http://psychcentral.com/news/2010/08/10/potential-new-therapy-for-alzheimers-disease/16605.html

http://www.sciencedaily.com/releases/2010/08/100804122707.htm

http://www.dana.org/news/features/detail.aspx?id=29578

http://www.empowher.com/alzheimer039s-disease/content/can-deep-brain-stimulation-help-alzheimers-disease-patients

http://www.medicinenet.com/script/main/art.asp?articlekey=118908

Diagnostic criteria of Dementia of the Alzheimer's Type

This form of progressive dementia named for Alois Alzheimer begins gradually, and is usually diagnosed after other specific causes have been ruled out through appropriate diagnostic procedures.

DSM-IV-TR: Diagnostic criteria for Dementia of the Alzheimer's Type (cautionary statement)  

A. The development of multiple cognitive deficits manifested by both  (1) memory impairment (impaired ability to learn new information or to recall previously learned information)  (2) one (or more) of the following cognitive disturbances:
  (a) aphasia (language disturbance)
  (b) apraxia (impaired ability to carry out motor activities despite intact motor function)
  (c) agnosia (failure to recognize or identify objects despite intact sensory function)
  (d) disturbance in executive functioning (i.e., planning, organizing, sequencing, abstracting)

B. The cognitive deficits in Criteria A1 and A2 each cause significant impairment in social or occupational functioning and represent a significant decline from a previous level of functioning. 

C. The course is characterized by gradual onset and continuing cognitive decline. 

D. The cognitive deficits in Criteria A1 and A2 are not due to any of the following:
(1) other central nervous system conditions that cause progressive deficits in memory and cognition (e.g., cerebrovascular disease, Parkinson's disease, Huntington's disease, subdural hematoma, normal-pressure hydrocephalus, brain tumor)
(2) systemic conditions that are known to cause dementia (e.g., hypothyroidism, vitamin B or folic acid deficiency, niacin deficiency, hypercalcemia, neurosyphilis, HIV infection)
(3) substance-induced conditions 

E. The deficits do not occur exclusively during the course of a delirium. 

F. The disturbance is not better accounted for by another Axis I disorder (e.g., Major Depressive Episode, Schizophrenia). 

Code based on presence or absence of a clinically significant behavioral disturbance:

294.10 Without Behavioral Disturbance: if the cognitive disturbance is not accompanied by any clinically significant behavioral disturbance.

294.11 With Behavioral Disturbance: if the cognitive disturbance is accompanied by a clinically significant behavioral disturbance. (e.g., wandering, agitation)

Specify subtype:

With Early Onset: if onset is at age 65 years or below 

With Late Onset: if onset is after age 65 years 

Coding note: Also code 331.0 Alzheimer's disease on Axis III. Indicate other prominent clinical features related to the Alzheimer's disease on Axis I (e.g., 293.83 Mood Disorder Due to Alzheimer's Disease, With Depressive Features, and 310.1 Personality Change Due to Alzheimer's Disease, Aggressive Type).

What Is the DSM-IV TR?

The Diagnostic and Statistical Manual of Mental Disorders, 4th edition text revision (DSM-IV TR) is used by clinicians and psychiatrists to diagnose psychiatric illnesses. The DSM-IV TR is published by the American Psychiatric Association and covers all categories of mental health disorders for both adults and children. The manual is non-theoretical and focused mostly on describing symptoms as well as statistics concerning which gender is most affected by the illness, the typical age of onset, the effects of treatment, and common treatment approaches.

The DSM-IV was originally published in 1994 and listed more than 250 mental disorders. An updated version, called the DSM-IV TR, was published in 2000 and contains minor text revision in the descriptions of each disorder. Mental health providers use the manual to better understand a client's potential needs as well as a tool for assessment and diagnosis.

The DSM-IV TR is based on five different dimensions. This multiaxial approach allows clinicians and psychiatrists to make a more comprehensive evaluation of a client's level of functioning, because mental illnesses often impact many different life areas.

• Axis I: Clinical Syndromes
  This axis describes clinical symptoms that cause significant impairment. Disorders are grouped into different categories, including adjustment disorders, anxiety disorders, and pervasive developmental disorders.
• Axis II: Personality and Mental Retardation
  This axis describes long-term problems that are overlooked in the presence of Axis I disorders. Personality disorders cause significant problems in how a patient relates to the world and include antisocial personality disorder and histrionic personality disorder. Mental retardation is characterized by intellectual impairment and deficits in other areas such as self-care and interpersonal skills.
• Axis III: Medical Conditions
  These include physical and medical conditions that may influence or worsen Axis 1 and Axis II disorders. Some examples may include HIV/AIDS and brain injuries.
• Axis IV: Psychosocial and Environmental Problems
  Any social or environmental problems that may impact Axis I or Axis II disorders are accounted for in this assessment. These may include such things as unemployment, relocation, divorce, or the death of a loved one.
• Axis V: Global Assessment of Functioning
  This axis allows the clinician to rate the client's overall level of functioning. Based on this assessment, clinicians can better understand how the other four axes are interacting and the effect on the individual's life.

While the DSM-IV TR is an important tool, it is important to note that only those who have received specialized training and possess sufficient experience are qualified to diagnose and treat mental illnesses. Clinicians also use the DMS-IV to classify patients for billing purposes, since the government and many insurance carriers require a specific diagnosis in order to approve payment for treatment.

DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), published in 1994 was the last major revision of the DSM. It was the culmination of a six-year effort that involved over 1000 individuals and numerous professional organizations. Much of the effort involved conducting a comprehensive review of the literature to establish a firm empirical basis for making modifications. Numerous changes were made to the classification (i.e., disorders were added, deleted, and reorganized), to the diagnostic criteria sets, and to the descriptive text based on a careful consideration of the available research about the various mental disorders.

In anticipation of the fact that the next major revision of the DSM (i.e., DSM-V) will not appear until 2010 or later (i.e., at least 16 years after DSM-IV), a text revision of the DSM-IV called DSM-IV-TR was published in July 2000. The primary goal of the DSM-IV-TR was to maintain the currency of the DSM-IV text, which reflected the empirical literature up to 1992. Thus, most of the major changes in DSM-IV-TR were confined to the descriptive text. Changes were made to a handful of criteria sets in order to correct errors identified in DSM-IV. In addition, some of the diagnostic codes were changed to reflect updates to the ICD-9-CM coding system adopted by the US Government.

Sources and Additional Information:

http://www.behavenet.com/capsules/disorders/alzheimersTR.htm

http://psychology.about.com/od/psychotherapy/f/faq_dsm.htm

http://psyweb.com/Mdisord/DSM_IV/jsp/dsm_iv.jsp

Predicting Alzheimer ’s Disease Progression Rate

Mental status exam - Mental status exams assess memory, concentration, and other cognitive skills. The most frequently used mental status exam is called the Mini-Mental State Exam (MMSE), a research-based set of questions that results in a score representing a person's general level of cognitive functioning.

The MMSE is generally a reliable and valid indicator of cognitive impairment that can correctly distinguish between individuals with dementia, individuals with pseudo-dementia due to depression, and individuals with depression and no cognitive impairment. However, the test must be used with caution in certain groups of people. For example, highly educated people frequently score high on the MMSE, even if they have Alzheimer's Disease (AD). Similarly, people with less than an eighth grade education or whose first language is not English often score poorly on the MMSE, even though they may not have cognitive impairment.

The latest research states that not only the patient current mental status may be evaluated based on the MMSE assessment results, but also Alzheimer's disease (AD) progression rate. The new approach is able to reliably predict how quickly the individual patient will lose cognitive and other abilities with significant degree of reliability.

Rachelle Doody, MD, PhD, and colleagues from Baylor College of Medicine in Houston, Texas, report initial results using the prognosis indicator with 597 patients followed up for 15 years published online February 23, 2010 in Alzheimer's Research & Therapy.

“Patients and families frequently ask clinicians to predict expected rates of cognitive and functional decline, and clinicians currently have little basis for making such decisions," Dr. Doody told Medscape Neurology.

"We’ve found that a simple, calculated progression rate at the initial visit gives reliable information regarding performance over time," she said. "The slowest progression group also survives longer."

Calculating AD Progression Rate

The pre-progression rate is calculated using a standard assessment of symptom duration in years and the baseline Mini-Mental State Examination (MMSE) score. The estimate of duration includes a series of questions about the duration of specific symptoms that might be a sign of AD, medical records review, and informant interview.

The study authors explain, “Since a cognitively intact individual should obtain the maximum MMSE score of 30, the pre-progression rate is given by the formula: (30 baseline MMSE)/estimated duration of symptoms in years.”

Those with an MMSE score decrease of less than 2 points per year were classified as slow progressors. Intermediate progressors were defined as having a 2- to 4-point decrease per year and rapid progression as a 5 point or greater decrease per year in MMSE score.

Dr. Doody told Medscape Neurology, “The procedures for obtaining and using the information are not yet in common use, but they could be. With further refinement, physicians could use this work to tell patients whether they fall into a slow, intermediate, or rapidly progressing category with respect to the intrinsic progression of their AD. They might decide upon follow-up intervals and how aggressive to be with medications based upon the progression rate. Once started on therapy, it might be possible to alter the intrinsic rate, but this requires further study.”

The researchers examined outcomes for patients annually for up to 15 years using the MMSE, the Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAScog – cognitive MMSE sub-scale), the Verbal Series Attention Test, the Clinical Dementia Rating Scale Sum of Boxes, and the Lawton and Brody Activities of Daily Living Scale, which combines the Physical Self-Maintenance Scale and the Instrumental Activities of Daily Living Scale.

Slow Progressors Also Live Longer

The investigators found that patients in the slow and intermediate groups maintained better performance on tests of cognitive function, global function, and complex activities of daily living than the rapid progressors. For example, slow progressors gained 0.6 fewer points per year on the ADAScog and intermediate progressors 0.8 fewer points per year than rapid progressors.

At study entry, the slow progressors also had a longer estimated duration of symptoms than intermediate or fast progressors, as well as higher IQ and education.

Slow progressors also lived longer. Median survival was 4.7 years for slow, 4.1 years for intermediate, and 2.5 years for rapid progressors, adjusted for age, sex, education, and baseline severity (hazard ratio, 0.62 for slow vs. fast progressors).

“Our results suggest that prognostications based upon initial progression rate are most reliable for slow and fast progressors but that long duration reliability of an intermediate progression rate may depend upon the patient's age and life expectancy at diagnosis," the study authors conclude. "It would be safe to say that an intermediate progressor may remain so for several years, but that, if the patient lives for a long time after diagnosis, the rate may increase sufficiently to affect both abilities and survival."

Next Question: Can Drugs Alter Progression Rate?

Whether these “apparently intrinsic” progression rates can be modified by anti-dementia drug treatment is a key unanswered question that must be answered before the progression rate tool can be adopted for clinical use, the study authors say.

For now, Dr. Doody said, “Physicians could tell patients that people do not progress naturally at the same rate and that their individualized progression characteristics should be taken into account in planning their treatment and in monitoring their response to therapy. They could also say that the proposed rate requires some procedures that are not yet in everyday use (a standardized estimate of duration) and that they will decide over time whether or not to incorporate these procedures into what they do based upon continued studies of its utility.”

This study also has implications for AD clinical trial design. “Currently, parallel group studies count on randomization to yield comparable placebo and treatment groups," the study authors write. "Preprogression rates are not assessed, yet imbalances across the treatment groups in this important variable could obscure or create treatment differences. Future clinical trials may benefit from gathering systematic data regarding individual symptom onset in order to perform a formal estimate of duration and to calculate preprogression rates.”

Not Ready for Routine Use

Cognitive neurologist Alireza Atri, MD, PhD, agreed that this might be useful. Dr. Atri, who recently analyzed long-term effectiveness of combination therapy in AD (Alzheimer Dis Assoc Disord. 2008;11:209-221), is director of the Memory Disorders & Special Dementia Units at the Veterans' Affairs Geriatric Research Education and Clinical Center in Bedford, Massachusetts, and assistant in neurology at Massachusetts General Hospital/Harvard Medical School in Boston.

Asked by Medscape Neurology to comment on this study, Dr. Atri said, “I think this is an important study with several exceptional strengths, including utilization of a large, well-characterized longitudinal clinical cohort with useful measure and endpoints and analysis using sophisticated methods guided by good clinical and scientific knowledge from a leader in the field who has an uncommon perspective and expertise, working at the interface of clinical care and clinical trials and utilizing quantitative methodology to address important questions with great practical implications that, thus far, have been mostly neglected, overlooked, and/or underappreciated.”

Dr. Atri noted that although this model for predicting risk and prognosis in AD is not yet ready for routine use, it “provides a very good enhancement/upgrade from previous work and prognostication models, including some of Dr. Doody's own work, that integrate patient demographics and clinical characteristics and measures, including test scores, type and duration of symptoms, and physical exam findings, at a first clinical visit to a neurologist/physician in order to better predict the highly variable individual course we see in patients with Alzheimer's disease.”

Dr. Atri said that the study raises questions that need to be addressed further, including the effect of antidementia medications, vitamins and dietary supplements, vascular risk factors, behavioral symptoms, physical findings, especially parkinsonism and extrapyramidal signs, and genetic susceptibility factors, such as APOE-e4 status.

“We are a ways away still, but we desperately need to be wiser and more efficient in our approaches to gathering and using clinical data," Dr. Atri said. "I agree that clinical trials should heed Dr. Doody’s findings and incorporate more data and approaches like this to minimize risk of imbalances between or within treatment groups that can easily obscure signals of efficacy in Alzheimer's disease trials.”

Sources and Additional Information:

http://www.alzcwva.org/news.php?article=1724

http://alzheimers-review.blogspot.com/2009/12/psychologicalpsychiatric-evaluation-to.html

http://www.medafile.com/scr/chopra07.pdf

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2763071/

Greater purpose in life as weapon against Alzheimer’s Disease

The United States is currently experiencing the early stages of what is expected to be an epidemic of Alzheimer's Dementia. It is predicted that the current number of cases of Alzheimer's Dementia will double by 2020, and double again by 2040. Some unfortunate individuals are born with genes that strongly predispose them to developing Alzheimer's Dementia. However, this is true for only a minority of people. The familial, early onset form of Alzheimer's Dementia, which is so strongly linked to genetic abnormalities, is responsible for about five percent of cases of this illness. There is compelling evidence that the rest of us can escape, or at least postpone or diminish the severity of Alzheimer's, by improving our diets, maintaining our health and generally living healthier lifestyles. In most cases, it appears Alzheimer's Dementia can be avoided.

An underappreciated but scientifically substantiated fact is that getting a good education, challenging your mind, maintaining friendships and staying socially active can also help reduce the risk of developing Alzheimer's Dementia in later life. A new report in the American Medical Association journal, Archives of General Psychiatry, now compliments those findings in showing that simply having a sense of purpose in life can help to reduce this risk.

People who say their lives have a purpose are less likely to develop Alzheimer's disease or its precursor, mild cognitive impairment, a new study suggests. Purpose -- which the researchers define as a "psychological tendency to derive meaning from life's experiences and to possess a sense of intentionality and goal directedness that guides behavior" -- has long been thought to protect against adverse health outcomes. For example, it was recently reported to be associated with longevity, they noted. But there was little information on the association of purpose with Alzheimer's disease.

As the population ages and dementia becomes a more frequent diagnosis, there's increasing impetus to determine the causes of the disease, associated risk factors and how to prevent it, explained study co-author Dr. Aron S. Buchman, an associate professor in the department of neurological sciences at Rush University Medical Center in Chicago.

"There has been a lot of interest in psychosocial factors and their association with cognitive decline and dementia in later life," he said.

The study looked at the positive aspects of life and their possible effect on keeping dementia at bay, "looking at happiness, purposefulness in life, well-being and whether those kind of concepts are associated with a decreased risk of dementia," Buchman explained.

For the study, published in the March issue of the Archives of General Psychiatry, Buchman and his colleagues collected data on 951 older people without dementia who participated in the Rush Memory and Aging Project. The participants were asked to respond to statements such as: "I feel good when I think of what I have done in the past and what I hope to do in the future," and "I have a sense of direction and purpose in life."

After an average four years of follow-up, 16.3% of the people in the study developed Alzheimer's disease. Taking into account other factors that could account for Alzheimer's, the researchers found that people who responded most positively to statements about their lives were the least likely to develop the condition. Also, people who said they had more purposeful lives were less likely to develop mild cognitive impairment and had a slower rate of cognitive decline.

People who scored 4.2 out of 5 on the purpose-in-life measure were about 2.4 times less likely to develop Alzheimer's disease, compared with people who scored 3.0, the study found.

It's not known whether there is a biological reason for this finding, the researchers noted.

"One possibility is that, truly, somebody with high purpose in life might have a lower risk of developing dementia because of what's involved in purpose in life," Buchman said.

"The importance of the study," he added, "is this doesn't prove anything, but it points researchers in the direction of a link between purpose in life and cognition in late life. And now we have to find out what the biological basis is."

Still, the researchers think these findings could have implications for public health. "In particular, these findings may provide a new treatment target for interventions aimed at enhancing health and well-being in older adults. Purpose in life is a potentially modifiable factor that may be increased via specific behavioral strategies that help older persons identify personally meaningful activities and engage in goal-directed behaviors," the authors continue. "Even small behavioral modifications ultimately may translate into an increased sense of intentionality, usefulness and relevance."

"More social activity, more physical activity, higher cognitive activities, high purpose in life -- all these psychosocial factors seem to be linked with longer life, decreased mortality, decreased disability and provide important clues to a public health approach to try to increase independence in older people in later life," Buchman said.

Greg M. Cole, a neuroscientist at the Greater Los Angeles VA Healthcare System, wondered if the study is really measuring depression, not a purposeful life.

"I am unclear about how low scores on the purpose-in-life measures can be separated from mild depression," Cole said. "Depression has been repeatedly associated with increased Alzheimer's disease risk. So psychiatrists can make a distinction, but they seem likely closely related."

"One wonders whether this is a treatable psychiatric condition contributing to risk or an early symptom of decline," he added.

William H. Thies, chief medical and scientific officer at the Alzheimer's Association, said the new study "contributes to the literature that says there is a linkage between behavior and disease."

The study begs the question whether there is more Alzheimer's disease because more people have a lower sense of purpose, or is a lower sense of purpose an early, subtle, sign of dementia, he said.

"As we get better and better at having biological measures of the disease, we will shed a lot of light on these kinds of studies and whether these behaviors are simply a symptom or they are a place where you can intervene," Thies said.

Previous researches have shown that people that have long histories of Major Depression are twice as likely to develop Alzheimer's Dementia than those that do not. Reduction of stress further decreases the likelihood of dementia. Indeed, studies have shown that people who describe themselves as calm, relaxed, and self-satisfied can reduce their risk of Alzheimer's by one half. The East Boston study showed that every year of education after high school reduces the risk of Alzheimer's by 17 percent. A study at Duke University showed that having intellectually challenging work in adult life can reduce the risk of dementia even further beyond what a good education alone can do. In the Honolulu-Asia Aging Study it was found that maintaining friendships in later life significantly improves the likelihood of avoiding dementia. Another interesting study found that people already diagnosed with Alzheimer's Dementia who have large social networks of family and friends can maintain better cognitive function, even with higher levels of amyloid plaque damage in their brains, than can those without such social support. Scientific studies have also shown that people with deeply held religious beliefs and dedication to religious practices, regardless of the type, have a slower rate of cognitive decline when Alzheimer's dementia is already diagnosed. The current study now adds to this list of things we can do and ways we can approach life that can reduce our risk of dementia. Having a sense of purpose in life can reduce this risk.

Sources and Additional Information:

http://www.medicinenet.com/script/main/art.asp?articlekey=113908

http://www.huffingtonpost.com/scott-mendelson-md/a-sense-of-purpose-in-lif_b_488528.html

http://www.sciencedaily.com/releases/2010/03/100301165619.htm

http://abcnews.go.com/Health/AlzheimersNews/purpose-life-stave-off-alzheimers/story?id=9986018

Is there a Link Between Level of Education and Alzheimer's Disease?

An interesting association between low education level and Alzheimer’s disease has been noticed by the professional, however the exact reason for this phenomenon is not clear. Some scientists believe it has to do with synaptic concentration (the amount of alternative routes a neuron can use to communicate with other neurons). The suggestion is that the higher your education level, the more synaptic connections your neurons have had to make in order to process all the information stored in your brain, and this is considered as cognitive or neurological reserve.

This threshold model proposes that a more educated person might have more synapses to lose before behavioral problems how up or that they exhibit dementia only if their cognitive reserve capacity falls below a specific threshold.

A 2008 research confirmed the theory that education can delay the onset of the dementia and cognitive decline that are characteristic of the disorder. Scientists at the Alzheimer's Disease Research Center at Washington University School of Medicine in St. Louis found that some study participants who appeared to have the brain plaques long associated with Alzheimer's disease still received high scores on tests of their cognitive ability. Participants who did well on the tests were likely to have spent more years in school.

"The good news is that greater education may allow people to harbor amyloid plaques and other brain pathology linked to Alzheimer's disease without experiencing decline of their cognitive abilities," says first author Catherine Roe, Ph.D., research instructor in neurology.

Roe and her colleagues at the Alzheimer's Disease Research Center used the study participants' education levels to approximate a theoretical quality called cognitive reserve: improved abilities in thinking, learning and memory that result from regularly challenging and making use of the brain. Neurologists have long speculated that this quality, roughly equivalent to the benefits that accrue in the body via regular physical exercise, can help the brain cope with the damage caused by Alzheimer's disease.

Doctors still cannot conclusively diagnose Alzheimer's disease in any manner other than post-mortem brain examination. But Washington University scientists have shown that an imaging agent for positron emission tomography scans, Pittsburgh Compound B (PIB), can reveal the presence of amyloid plaques, a key brain change that many neurologists suspect either causes Alzheimer's or is closely linked to its onset.

In addition to scanning the participants' brains with PIB, the participants took several tests that assessed their cognitive abilities and status. They also ranked their educational experience: high-school degree or less, college experience up to an undergraduate degree, and graduate schooling.

As expected, those whose brains showed little evidence of plaque buildup scored high on all the tests. But while most participants with high levels of brain plaque scored poorly on the tests, those who had done postgraduate work still scored well. Despite signs that Alzheimer's might already be ravaging the brains of this subgroup, their cognitive abilities had not declined and they had not become demented.

The obtained results were reproduced by the recent 2009 study at the Department of Psychiatry, Klinikum rechts der Isar, Technische Universität München, investigated the effects of formal education on the symptoms of Alzheimer's disease. They researchers were able to show that education diminishes the impact of Alzheimer's disease on cognition even if a manifest brain volume loss has already occurred. Dr. Robert Perneczky explains: "We know that there is not always a close association between brain damage due to Alzheimer's disease and the resulting symptoms of dementia. In fact, there are individuals with severe brain pathology with almost no signs of dementia, whereas others with only minor brain lesions exhibit a considerable degree of clinical symptoms."

These phenomena are often ascribed to the theoretical concept of cognitive reserve. A high level of cognitive reserve results in a strong individual resilience against symptoms of brain damage; cognitive reserve can therefore be seen as protective against brain damage.

However, while education level and brain activity has proven to allow certain delay (protection) for the Alzheimer’s disease development, but it is not able to slow memory loss once it starts, says another study. Reporting in the Feb. 3, 2009 issue of Neurology, scientists say they found that education does not appear to protect against how fast people lose memory once forgetfulness begins.

"This is an interesting and important finding because scientists have long debated whether aging and memory loss tend to have a lesser effect on highly educated people," says study author Robert S. Wilson, PhD, with the Alzheimer's Disease Center at Rush University Medical Center in Chicago. "While education is associated with the memory's ability to function at a higher level, we found no link between higher education and how fast the memory loses that ability."

He and colleagues tested the thinking skills of 6,500 people from the Chicago area with an average age of 72 and varying levels of education. The level of education of people in the study ranged from eight or fewer years of school to 16 or more years. Interviews and tests about memory and thinking functions were given every three years, up to 14 years.

When the study started, people with more education were found to have better memory and thinking skills than those with lesser education. The results remained the same regardless of other factors related to education, such as job status, race, and the effects of practice with the tests.

Further analysis, however, showed that the "rate of cognitive decline at average or high levels of education was slightly increased" during early years of follow-up study, but then decreased slightly later, compared to people with low levels of education. "The results suggest that education is robustly associated with level of cognitive function, but not with rate of cognitive decline," they conclude.

Sources and Additional Information:

http://mednews.wustl.edu/news/page/normal/12951.html

http://www.webmd.com/alzheimers/news/20090202/education-protects-against-alzheimers

http://www.medicalnewstoday.com/articles/164056.php

http://esciencenews.com/articles/2009/08/11/formal.education.lessens.impact.alzheimers.disease